Vaccine

A vaccine is a biological preparation that provides active acquired immunity to a particular disease. A vaccine typically contains an agent that resembles a disease-causing microorganism and is often made from weakened or killed forms of the microbe, its toxins, or one of its surface proteins. The agent stimulates the body's immune system to recognize the agent as a threat, destroy it, and to further recognize and destroy any of the microorganisms associated with that agent that it may encounter in the future. Vaccines can be prophylactic (example: to prevent or ameliorate the effects of a future infection by a natural or "wild" pathogen), or therapeutic (e.g., vaccines against cancer are being investigated).[1][2][3][4]

The administration of vaccines is called vaccination. Vaccination is the most effective method of preventing infectious diseases;[5] widespread immunity due to vaccination is largely responsible for the worldwide eradication of smallpox and the restriction of diseases such as polio, measles, and tetanus from much of the world. The effectiveness of vaccination has been widely studied and verified; for example, vaccines that have proven effective include the influenza vaccine,[6] the HPV vaccine,[7] and the chicken pox vaccine.[8] The World Health Organization (WHO) reports that licensed vaccines are currently available for twenty-five different preventable infections.[9]

The terms vaccine and vaccination are derived from Variolae vaccinae (smallpox of the cow), the term devised by Edward Jenner to denote cowpox. He used it in 1798 in the long title of his Inquiry into the Variolae vaccinae known as the Cow Pox, in which he described the protective effect of cowpox against smallpox.[10] In 1881, to honor Jenner, Louis Pasteur proposed that the terms should be extended to cover the new protective inoculations then being developed.[11]

Vaccine
SalkatPitt
Jonas Salk in 1955 holds two bottles of a culture used to grow polio vaccines.
MeSHD014612

Effectiveness

RougeoleDP
A child with measles, a vaccine-preventable disease[12]

Vaccines have historically been the most effective means to fight and eradicate infectious diseases. Limitations to their effectiveness, nevertheless, exist.[13] Sometimes, protection fails because the host's immune system simply does not respond adequately or at all. Lack of response commonly results from clinical factors such as diabetes, steroid use, HIV infection, or age. It also might fail for genetic reasons if the host's immune system includes no strains of B cells that can generate antibodies suited to reacting effectively and binding to the antigens associated with the pathogen.

Even if the host does develop antibodies, protection might not be adequate; immunity might develop too slowly to be effective in time, the antibodies might not disable the pathogen completely, or there might be multiple strains of the pathogen, not all of which are equally susceptible to the immune reaction. However, even a partial, late, or weak immunity, such as a one resulting from cross-immunity to a strain other than the target strain, may mitigate an infection, resulting in a lower mortality rate, lower morbidity, and faster recovery.

Adjuvants commonly are used to boost immune response, particularly for older people (50–75 years and up), whose immune response to a simple vaccine may have weakened.[14]

Hilleman-Walter-Reed.jpeg
Maurice Hilleman's measles vaccine is estimated to prevent 1 million deaths every year.[15]

The efficacy or performance of the vaccine is dependent on a number of factors:

  • the disease itself (for some diseases vaccination performs better than for others)
  • the strain of vaccine (some vaccines are specific to, or at least most effective against, particular strains of the disease)[16]
  • whether the vaccination schedule has been properly observed.
  • idiosyncratic response to vaccination; some individuals are "non-responders" to certain vaccines, meaning that they do not generate antibodies even after being vaccinated correctly.
  • assorted factors such as ethnicity, age, or genetic predisposition.

If a vaccinated individual does develop the disease vaccinated against (breakthrough infection), the disease is likely to be less virulent than in unvaccinated victims.[17]

The following are important considerations in the effectiveness of a vaccination program:

  1. careful modeling to anticipate the effect that an immunization campaign will have on the epidemiology of the disease in the medium to long term
  2. ongoing surveillance for the relevant disease following introduction of a new vaccine
  3. maintenance of high immunization rates, even when a disease has become rare.

In 1958, there were 763,094 cases of measles in the United States; 552 deaths resulted.[18][19] After the introduction of new vaccines, the number of cases dropped to fewer than 150 per year (median of 56).[19] In early 2008, there were 64 suspected cases of measles. Fifty-four of those infections were associated with importation from another country, although only 13% were actually acquired outside the United States; 63 of the 64 individuals either had never been vaccinated against measles or were uncertain whether they had been vaccinated.[19]

Vaccines have contributed to the eradication of smallpox, one of the most contagious and deadly diseases in humans. Other diseases such as rubella, polio, measles, mumps, chickenpox, and typhoid are nowhere near as common as they were a hundred years ago. As long as the vast majority of people are vaccinated, it is much more difficult for an outbreak of disease to occur, let alone spread. This effect is called herd immunity. Polio, which is transmitted only between humans, is targeted by an extensive eradication campaign that has seen endemic polio restricted to only parts of three countries (Afghanistan, Nigeria, and Pakistan).[20] However, the difficulty of reaching all children as well as cultural misunderstandings have caused the anticipated eradication date to be missed several times.

Vaccines also help prevent the development of antibiotic resistance. For example, by greatly reducing the incidence of pneumonia caused by Streptococcus pneumoniae, vaccine programs have greatly reduced the prevalence of infections resistant to penicillin or other first-line antibiotics.[21]

Adverse effects

Vaccination given during childhood is generally safe.[22] Adverse effects if any are generally mild.[23] The rate of side effects depends on the vaccine in question.[23] Some common side effects include fever, pain around the injection site, and muscle aches.[23] Additionally, some individuals may be allergic to ingredients in the vaccine.[24] MMR vaccine is rarely associated with febrile seizures.[22]

Severe side effects are extremely rare.[22] Varicella vaccine is rarely associated with complications in immunodeficient individuals and rotavirus vaccines are moderately associated with intussusception.[22]

Some countries such as the United Kingdom provide compensation for victims of severe adverse effects via its Vaccine Damage Payment. The United States has the National Childhood Vaccine Injury Act. At least 19 countries have such no-fault compensation.[25]

Types

Vaccine
Vaccine
ReverseGeneticsFlu
Avian flu vaccine development by reverse genetics techniques.

Vaccines are dead or inactivated organisms or purified products derived from them.

There are several types of vaccines in use.[26] These represent different strategies used to try to reduce the risk of illness while retaining the ability to induce a beneficial immune response.

Inactivated

Some vaccines contain inactivated, but previously virulent, micro-organisms that have been destroyed with chemicals, heat, or radiation.[27] Examples include the polio vaccine, hepatitis A vaccine, rabies vaccine and some influenza vaccines.

Attenuated

Some vaccines contain live, attenuated microorganisms. Many of these are active viruses that have been cultivated under conditions that disable their virulent properties, or that use closely related but less dangerous organisms to produce a broad immune response. Although most attenuated vaccines are viral, some are bacterial in nature. Examples include the viral diseases yellow fever, measles, mumps, and rubella, and the bacterial disease typhoid. The live Mycobacterium tuberculosis vaccine developed by Calmette and Guérin is not made of a contagious strain but contains a virulently modified strain called "BCG" used to elicit an immune response to the vaccine. The live attenuated vaccine containing strain Yersinia pestis EV is used for plague immunization. Attenuated vaccines have some advantages and disadvantages. They typically provoke more durable immunological responses and are the preferred type for healthy adults. But they may not be safe for use in immunocompromised individuals, and on rare occasions mutate to a virulent form and cause disease.[28]

Toxoid

Toxoid vaccines are made from inactivated toxic compounds that cause illness rather than the micro-organism. Examples of toxoid-based vaccines include tetanus and diphtheria. Toxoid vaccines are known for their efficacy. Not all toxoids are for micro-organisms; for example, Crotalus atrox toxoid is used to vaccinate dogs against rattlesnake bites.

Subunit

Protein subunit – rather than introducing an inactivated or attenuated micro-organism to an immune system (which would constitute a "whole-agent" vaccine), a fragment of it can create an immune response. Examples include the subunit vaccine against Hepatitis B virus that is composed of only the surface proteins of the virus (previously extracted from the blood serum of chronically infected patients, but now produced by recombination of the viral genes into yeast) or as an edible algae vaccine, the virus-like particle (VLP) vaccine against human papillomavirus (HPV) that is composed of the viral major capsid protein, and the hemagglutinin and neuraminidase subunits of the influenza virus. Subunit vaccine is being used for plague immunization.

Conjugate

Conjugate – certain bacteria have polysaccharide outer coats that are poorly immunogenic. By linking these outer coats to proteins (e.g., toxins), the immune system can be led to recognize the polysaccharide as if it were a protein antigen. This approach is used in the Haemophilus influenzae type B vaccine.

Experimental

Agile Pulse In Vivo
Electroporation System for experimental "DNA vaccine" delivery

A number of innovative vaccines are also in development and in use:

  • Dendritic cell vaccines combine dendritic cells with antigens in order to present the antigens to the body's white blood cells, thus stimulating an immune reaction. These vaccines have shown some positive preliminary results for treating brain tumors [29] and are also tested in malignant melanoma.[30]
  • Recombinant Vector – by combining the physiology of one micro-organism and the DNA of the other, immunity can be created against diseases that have complex infection processes. An example is the RVSV-ZEBOV vaccine licensed to Merck that is being used in 2018 to combat ebola in Congo.[31]
  • DNA vaccination – an alternative, experimental approach to vaccination called DNA vaccination, created from an infectious agent's DNA, is under development. The proposed mechanism is the insertion (and expression, enhanced by the use of electroporation, triggering immune system recognition) of viral or bacterial DNA into human or animal cells. Some cells of the immune system that recognize the proteins expressed will mount an attack against these proteins and cells expressing them. Because these cells live for a very long time, if the pathogen that normally expresses these proteins is encountered at a later time, they will be attacked instantly by the immune system. One potential advantage of DNA vaccines is that they are very easy to produce and store. As of 2015, DNA vaccination is still experimental and is not approved for human use.
  • T-cell receptor peptide vaccines are under development for several diseases using models of Valley Fever, stomatitis, and atopic dermatitis. These peptides have been shown to modulate cytokine production and improve cell-mediated immunity.
  • Targeting of identified bacterial proteins that are involved in complement inhibition would neutralize the key bacterial virulence mechanism.[32]

While most vaccines are created using inactivated or attenuated compounds from micro-organisms, synthetic vaccines are composed mainly or wholly of synthetic peptides, carbohydrates, or antigens.

Valence

Vaccines may be monovalent (also called univalent) or multivalent (also called polyvalent). A monovalent vaccine is designed to immunize against a single antigen or single microorganism.[33] A multivalent or polyvalent vaccine is designed to immunize against two or more strains of the same microorganism, or against two or more microorganisms.[34] The valency of a multivalent vaccine may be denoted with a Greek or Latin prefix (e.g., tetravalent or quadrivalent). In certain cases, a monovalent vaccine may be preferable for rapidly developing a strong immune response.[35]

Heterotypic

Also known as heterologous or "Jennerian" vaccines, these are vaccines that are pathogens of other animals that either do not cause disease or cause mild disease in the organism being treated. The classic example is Jenner's use of cowpox to protect against smallpox. A current example is the use of BCG vaccine made from Mycobacterium bovis to protect against human tuberculosis.[36]

Nomenclature

Various fairly standardized abbreviations for vaccine names have developed, although the standardization is by no means centralized or global. For example, the vaccine names used in the United States have well-established abbreviations that are also widely known and used elsewhere. An extensive list of them provided in a sortable table and freely accessible, is available at a US Centers for Disease Control and Prevention web page.[37] The page explains that "The abbreviations [in] this table (Column 3) were standardized jointly by staff of the Centers for Disease Control and Prevention, ACIP Work Groups, the editor of the Morbidity and Mortality Weekly Report (MMWR), the editor of Epidemiology and Prevention of Vaccine-Preventable Diseases (the Pink Book), ACIP members, and liaison organizations to the ACIP."[37] Some examples are "DTaP" for diphtheria and tetanus toxoids and acellular pertussis vaccine, "DT" for diphtheria and tetanus toxoids, and "Td" for tetanus and diphtheria toxoids. At its page on tetanus vaccination,[38] the CDC further explains that "Upper-case letters in these abbreviations denote full-strength doses of diphtheria (D) and tetanus (T) toxoids and pertussis (P) vaccine. Lower-case "d" and "p" denote reduced doses of diphtheria and pertussis used in the adolescent/adult-formulations. The 'a' in DTaP and Tdap stands for 'acellular,' meaning that the pertussis component contains only a part of the pertussis organism."[38] Another list of established vaccine abbreviations is at the CDC's page called "Vaccine Acronyms and Abbreviations", with abbreviations used on U.S. immunization records.[39] The United States Adopted Name system has some conventions for the word order of vaccine names, placing head nouns first and adjectives postpositively. This is why the USAN for "OPV" is "poliovirus vaccine live oral" rather than "oral poliovirus vaccine".

Developing immunity

The immune system recognizes vaccine agents as foreign, destroys them, and "remembers" them. When the virulent version of an agent is encountered, the body recognizes the protein coat on the virus, and thus is prepared to respond, by (1) neutralizing the target agent before it can enter cells, and (2) recognizing and destroying infected cells before that agent can multiply to vast numbers.

When two or more vaccines are mixed together in the same formulation, the two vaccines can interfere. This most frequently occurs with live attenuated vaccines, where one of the vaccine components is more robust than the others and suppresses the growth and immune response to the other components. This phenomenon was first noted in the trivalent Sabin polio vaccine, where the amount of serotype 2 virus in the vaccine had to be reduced to stop it from interfering with the "take" of the serotype 1 and 3 viruses in the vaccine.[40] This phenomenon has also been found to be a problem with the dengue vaccines currently being researched, where the DEN-3 serotype was found to predominate and suppress the response to DEN-1, −2 and −4 serotypes.[41]

Adjuvants and preservatives

Vaccines typically contain one or more adjuvants, used to boost the immune response. Tetanus toxoid, for instance, is usually adsorbed onto alum. This presents the antigen in such a way as to produce a greater action than the simple aqueous tetanus toxoid. People who have an adverse reaction to adsorbed tetanus toxoid may be given the simple vaccine when the time comes for a booster.

In the preparation for the 1990 Persian Gulf campaign, whole cell pertussis vaccine was used as an adjuvant for anthrax vaccine. This produces a more rapid immune response than giving only the anthrax vaccine, which is of some benefit if exposure might be imminent.

Vaccines may also contain preservatives to prevent contamination with bacteria or fungi. Until recent years, the preservative thimerosal was used in many vaccines that did not contain live virus. As of 2005, the only childhood vaccine in the U.S. that contains thimerosal in greater than trace amounts is the influenza vaccine,[42] which is currently recommended only for children with certain risk factors.[43] Single-dose influenza vaccines supplied in the UK do not list thiomersal (its UK name) in the ingredients. Preservatives may be used at various stages of production of vaccines, and the most sophisticated methods of measurement might detect traces of them in the finished product, as they may in the environment and population as a whole.[44]

Schedule

For country-specific information on vaccination policies and practices, see: Vaccination policy

In order to provide the best protection, children are recommended to receive vaccinations as soon as their immune systems are sufficiently developed to respond to particular vaccines, with additional "booster" shots often required to achieve "full immunity". This has led to the development of complex vaccination schedules. In the United States, the Advisory Committee on Immunization Practices, which recommends schedule additions for the Centers for Disease Control and Prevention, recommends routine vaccination of children against:[45] hepatitis A, hepatitis B, polio, mumps, measles, rubella, diphtheria, pertussis, tetanus, HiB, chickenpox, rotavirus, influenza, meningococcal disease and pneumonia.[46] A large number of vaccines and boosters recommended (up to 24 injections by age two) has led to problems with achieving full compliance. In order to combat declining compliance rates, various notification systems have been instituted and a number of combination injections are now marketed (e.g., Pneumococcal conjugate vaccine and MMRV vaccine), which provide protection against multiple diseases.

Besides recommendations for infant vaccinations and boosters, many specific vaccines are recommended for other ages or for repeated injections throughout life—most commonly for measles, tetanus, influenza, and pneumonia. Pregnant women are often screened for continued resistance to rubella. The human papillomavirus vaccine is recommended in the U.S. (as of 2011)[47] and UK (as of 2009).[48] Vaccine recommendations for the elderly concentrate on pneumonia and influenza, which are more deadly to that group. In 2006, a vaccine was introduced against shingles, a disease caused by the chickenpox virus, which usually affects the elderly.

History

Prior to the introduction of vaccination with material from cases of cowpox (heterotypic immunisation), smallpox could be prevented by deliberate inoculation of smallpox virus, later referred to as variolation to distinguish it from smallpox vaccination. The earliest hints of the practice of inoculation for smallpox in China come during the 10th century.[49] The Chinese also practiced the oldest documented use of variolation, dating back to the fifteenth century. They implemented a method of "nasal insufflation" administered by blowing powdered smallpox material, usually scabs, up the nostrils. Various insufflation techniques have been recorded throughout the sixteenth and seventeenth centuries within China.[50]:60 Two reports on the Chinese practice of inoculation were received by the Royal Society in London in 1700; one by Dr. Martin Lister who received a report by an employee of the East India Company stationed in China and another by Clopton Havers.[51]

Edward Jenner manuscript
Jenner's handwritten draft of the first vaccination

Sometime during the late 1760s whilst serving his apprenticeship as a surgeon/apothecary Edward Jenner learned of the story, common in rural areas, that dairy workers would never have the often-fatal or disfiguring disease smallpox, because they had already had cowpox, which has a very mild effect in humans. In 1796, Jenner took pus from the hand of a milkmaid with cowpox, scratched it into the arm of an 8-year-old boy, James Phipps, and six weeks later inoculated (variolated) the boy with smallpox, afterwards observing that he did not catch smallpox.[52][53] Jenner extended his studies and in 1798 reported that his vaccine was safe in children and adults and could be transferred from arm-to-arm reducing reliance on uncertain supplies from infected cows.[10] Since vaccination with cowpox was much safer than smallpox inoculation,[54] the latter, though still widely practised in England, was banned in 1840.[55]

Centenaire de la découverte de la vaccine par Jenner CIPB0429
French print in 1896 marking the centenary of Jenner's vaccine

The second generation of vaccines was introduced in the 1880s by Louis Pasteur who developed vaccines for chicken cholera and anthrax,[11] and from the late nineteenth century vaccines were considered a matter of national prestige, and compulsory vaccination laws were passed.[52]

The twentieth century saw the introduction of several successful vaccines, including those against diphtheria, measles, mumps, and rubella. Major achievements included the development of the polio vaccine in the 1950s and the eradication of smallpox during the 1960s and 1970s. Maurice Hilleman was the most prolific of the developers of the vaccines in the twentieth century. As vaccines became more common, many people began taking them for granted. However, vaccines remain elusive for many important diseases, including herpes simplex, malaria, gonorrhea, and HIV.[52][56]

Timeline

اللقاح
Vaccine timeline

Economics of development

One challenge in vaccine development is economic: Many of the diseases most demanding a vaccine, including HIV, malaria and tuberculosis, exist principally in poor countries. Pharmaceutical firms and biotechnology companies have little incentive to develop vaccines for these diseases, because there is little revenue potential. Even in more affluent countries, financial returns are usually minimal and the financial and other risks are great.[57]

Most vaccine development to date has relied on "push" funding by government, universities and non-profit organizations.[58] Many vaccines have been highly cost effective and beneficial for public health.[59] The number of vaccines actually administered has risen dramatically in recent decades.[60] This increase, particularly in the number of different vaccines administered to children before entry into schools may be due to government mandates and support, rather than economic incentive.

Patents

The filing of patents on vaccine development processes can also be viewed as an obstacle to the development of new vaccines. Because of the weak protection offered through a patent on the final product, the protection of the innovation regarding vaccines is often made through the patent of processes used in the development of new vaccines as well as the protection of secrecy.[61]

According to the World Health Organization, the biggest barrier to local vaccine production in less developed countries has not been patents, but the substantial financial, infrastructure, and workforce expertise requirements needed for market entry. Vaccines are complex mixtures of biological compounds, and unlike the case of drugs, there are no true generic vaccines. The vaccine produced by a new facility must undergo complete clinical testing for safety and efficacy similar to that undergone by that produced by the original manufacturer. For most vaccines, specific processes have been patented. These can be circumvented by alternative manufacturing methods, but this required R&D infrastructure and a suitably skilled workforce. In the case of a few relatively new vaccines such as the human papillomavirus vaccine, the patents may impose an additional barrier.[62]

Production

Preparation of measles vaccines
Two workers make openings in chicken eggs in preparation for production of measles vaccine.

Vaccine production has several stages. First, the antigen itself is generated. Viruses are grown either on primary cells such as chicken eggs (e.g., for influenza) or on continuous cell lines such as cultured human cells (e.g., for hepatitis A).[63] Bacteria are grown in bioreactors (e.g., Haemophilus influenzae type b). Likewise, a recombinant protein derived from the viruses or bacteria can be generated in yeast, bacteria, or cell cultures. After the antigen is generated, it is isolated from the cells used to generate it. A virus may need to be inactivated, possibly with no further purification required. Recombinant proteins need many operations involving ultrafiltration and column chromatography. Finally, the vaccine is formulated by adding adjuvant, stabilizers, and preservatives as needed. The adjuvant enhances the immune response of the antigen, stabilizers increase the storage life, and preservatives allow the use of multidose vials.[64][65] Combination vaccines are harder to develop and produce, because of potential incompatibilities and interactions among the antigens and other ingredients involved.[66]

Vaccine production techniques are evolving. Cultured mammalian cells are expected to become increasingly important, compared to conventional options such as chicken eggs, due to greater productivity and low incidence of problems with contamination. Recombination technology that produces genetically detoxified vaccine is expected to grow in popularity for the production of bacterial vaccines that use toxoids. Combination vaccines are expected to reduce the quantities of antigens they contain, and thereby decrease undesirable interactions, by using pathogen-associated molecular patterns.[66]

In 2010, India produced 60 percent of the world's vaccine worth about $900 million(€670 million).[67]

Excipients

Beside the active vaccine itself, the following excipients and residual manufacturing compounds are present or may be present in vaccine preparations:[68]

  • Aluminum salts or gels are added as adjuvants. Adjuvants are added to promote an earlier, more potent response, and more persistent immune response to the vaccine; they allow for a lower vaccine dosage.
  • Antibiotics are added to some vaccines to prevent the growth of bacteria during production and storage of the vaccine.
  • Egg protein is present in influenza and yellow fever vaccines as they are prepared using chicken eggs. Other proteins may be present.
  • Formaldehyde is used to inactivate bacterial products for toxoid vaccines. Formaldehyde is also used to inactivate unwanted viruses and kill bacteria that might contaminate the vaccine during production.
  • Monosodium glutamate (MSG) and 2-phenoxyethanol are used as stabilizers in a few vaccines to help the vaccine remain unchanged when the vaccine is exposed to heat, light, acidity, or humidity.
  • Thimerosal is a mercury-containing antimicrobial that is added to vials of vaccine that contain more than one dose to prevent contamination and growth of potentially harmful bacteria. Due to the controversy surrounding thimerosal it has been removed from most vaccines except multi-use influenza, where it was reduced to levels so that a single dose contained less than 1 microgram of mercury, a level similar to eating 10g of canned tuna.[69]

Role of preservatives

Many vaccines need preservatives to prevent serious adverse effects such as Staphylococcus infection, which in one 1928 incident killed 12 of 21 children inoculated with a diphtheria vaccine that lacked a preservative.[70] Several preservatives are available, including thiomersal, phenoxyethanol, and formaldehyde. Thiomersal is more effective against bacteria, has a better shelf-life, and improves vaccine stability, potency, and safety; but, in the U.S., the European Union, and a few other affluent countries, it is no longer used as a preservative in childhood vaccines, as a precautionary measure due to its mercury content.[71] Although controversial claims have been made that thiomersal contributes to autism, no convincing scientific evidence supports these claims.[72]

Delivery systems

VaccineBySandraRugio
Woman receiving rubella vaccination, Brazil, 2008.

The development of new delivery systems raises the hope of vaccines that are safer and more efficient to deliver and administer. Lines of research include liposomes and ISCOM (immune stimulating complex).[73]

Notable developments in vaccine delivery technologies have included oral vaccines. Early attempts to apply oral vaccines showed varying degrees of promise, beginning early in the 20th century, at a time when the very possibility of an effective oral antibacterial vaccine was controversial.[74] By the 1930s there was increasing interest in the prophylactic value of an oral typhoid fever vaccine for example.[75]

An oral polio vaccine turned out to be effective when vaccinations were administered by volunteer staff without formal training; the results also demonstrated increased ease and efficiency of administering the vaccines. Effective oral vaccines have many advantages; for example, there is no risk of blood contamination. Vaccines intended for oral administration need not be liquid, and as solids, they commonly are more stable and less prone to damage or to spoilage by freezing in transport and storage.[76] Such stability reduces the need for a "cold chain": the resources required to keep vaccines within a restricted temperature range from the manufacturing stage to the point of administration, which, in turn, may decrease costs of vaccines.

A microneedle approach, which is still in stages of development, uses "pointed projections fabricated into arrays that can create vaccine delivery pathways through the skin".[77]

An experimental needle-free[78] vaccine delivery system is undergoing animal testing.[79][80] A stamp-size patch similar to an adhesive bandage contains about 20,000 microscopic projections per square cm.[81] This dermal administration potentially increases the effectiveness of vaccination, while requiring less vaccine than injection.[82]

Plasmids

The use of plasmids has been validated in preclinical studies as a protective vaccine strategy for cancer and infectious diseases. However, in human studies, this approach has failed to provide clinically relevant benefit. The overall efficacy of plasmid DNA immunization depends on increasing the plasmid's immunogenicity while also correcting for factors involved in the specific activation of immune effector cells.[83]

Veterinary medicine

US Navy 060815-N-0411D-018 U.S. Army Veterinarian, Capt Gwynne Kinley of Cape Elizabeth, Maine, immunizes a goat with the help of U.S. Navy Operations Specialist 2nd Class Jessica Silva
Goat vaccination against sheep pox and pleural pneumonia

Vaccinations of animals are used both to prevent their contracting diseases and to prevent transmission of disease to humans.[84] Both animals kept as pets and animals raised as livestock are routinely vaccinated. In some instances, wild populations may be vaccinated. This is sometimes accomplished with vaccine-laced food spread in a disease-prone area and has been used to attempt to control rabies in raccoons.

Where rabies occurs, rabies vaccination of dogs may be required by law. Other canine vaccines include canine distemper, canine parvovirus, infectious canine hepatitis, adenovirus-2, leptospirosis, bordatella, canine parainfluenza virus, and Lyme disease, among others.

Cases of veterinary vaccines used in humans have been documented, whether intentional or accidental, with some cases of resultant illness, most notably with brucellosis.[85] However, the reporting of such cases is rare and very little has been studied about the safety and results of such practices. With the advent of aerosol vaccination in veterinary clinics for companion animals, human exposure to pathogens that are not naturally carried in humans, such as Bordetella bronchiseptica, has likely increased in recent years.[85] In some cases, most notably rabies, the parallel veterinary vaccine against a pathogen may be as much as orders of magnitude more economical than the human one.

DIVA vaccines

DIVA (Differentiating Infected from Vaccinated Animals) vaccines make it possible to differentiate between infected and vaccinated animals.

DIVA vaccines carry at least one epitope less than the microorganisms circulating in the field. An accompanying diagnostic test that detects antibody against that epitope allows us to actually make that differentiation.

First DIVA vaccines

The first DIVA vaccines (formerly termed marker vaccines and since 1999 coined as DIVA vaccines) and companion diagnostic tests have been developed by J.T. van Oirschot and colleagues at the Central Veterinary Institute in Lelystad, The Netherlands.[86] [87] They found that some existing vaccines against pseudorabies (also termed Aujeszky's disease) had deletions in their viral genome (among which the gE gene). Monoclonal antibodies were produced against that deletion and selected to develop an ELISA that demonstrated antibodies against gE. In addition, novel genetically engineered gE-negative vaccines were constructed.[88] Along the same lines, DIVA vaccines and companion diagnostic tests against bovine herpesvirus 1 infections have been developed.[89][90]

Use in practice

The DIVA strategy has been applied in various countries and successfully eradicated pseudorabies virus. Swine populations were intensively vaccinated and monitored by the companion diagnostic test and, subsequently, the infected pigs were removed from the population. Bovine herpesvirus 1 DIVA vaccines are also widely used in practice.

Other DIVA vaccines (under development)

Scientists have put and still, are putting much effort in applying the DIVA principle to a wide range of infectious diseases, such as, for example, classical swine fever,[91] avian influenza,[92] Actinobacillus pleuropneumonia[93] and Salmonella infections in pigs.[94]

Trends

Vaccine development has several trends:[95]

  • Until recently, most vaccines were aimed at infants and children, but adolescents and adults are increasingly being targeted.[95][96]
  • Combinations of vaccines are becoming more common; vaccines containing five or more components are used in many parts of the world.[95]
  • New methods of administering vaccines are being developed, such as skin patches, aerosols via inhalation devices, and eating genetically engineered plants.[95]
  • Vaccines are being designed to stimulate innate immune responses, as well as adaptive.[95]
  • Attempts are being made to develop vaccines to help cure chronic infections, as opposed to preventing disease.[95]
  • Vaccines are being developed to defend against bioterrorist attacks such as anthrax, plague, and smallpox.[95]
  • Appreciation for sex and pregnancy differences in vaccine responses "might change the strategies used by public health officials".[97]
  • Scientists are now trying to develop synthetic vaccines by reconstructing the outside structure of a virus, this will help prevent vaccine resistance.[98]

Principles that govern the immune response can now be used in tailor-made vaccines against many noninfectious human diseases, such as cancers and autoimmune disorders.[99] For example, the experimental vaccine CYT006-AngQb has been investigated as a possible treatment for high blood pressure.[100] Factors that affect the trends of vaccine development include progress in translatory medicine, demographics, regulatory science, political, cultural, and social responses.[101]

Plants as bioreactors for vaccine production

Transgenic plants have been identified as promising expression systems for vaccine production. Complex plants such as tobacco, potato, tomato, and banana can have genes inserted that cause them to produce vaccines usable for humans.[102] Bananas have been developed that produce a human vaccine against hepatitis B.[103] Another example is the expression of a fusion protein in alfalfa transgenic plants for the selective directioning to antigen presenting cells, therefore increasing vaccine potency against Bovine Viral Diarrhea Virus (BVDV).[104][105]

See also

References

  1. ^ Melief CJ, van Hall T, Arens R, Ossendorp F, van der Burg SH (September 2015). "Therapeutic cancer vaccines". J. Clin. Invest. 125 (9): 3401–12. doi:10.1172/JCI80009. PMC 4588240. PMID 26214521.
  2. ^ Bol KF, Aarntzen EH, Pots JM, Olde Nordkamp MA, van de Rakt MW, Scharenborg NM, et al. (March 2016). "Prophylactic vaccines are potent activators of monocyte-derived dendritic cells and drive effective anti-tumor responses in melanoma patients at the cost of toxicity". Cancer Immunol. Immunother. 65 (3): 327–39. doi:10.1007/s00262-016-1796-7. PMC 4779136. PMID 26861670.
  3. ^ Brotherton J (2015). "HPV prophylactic vaccines: lessons learned from 10 years experience". Future Medicine. 10 (8): 999–1009. doi:10.2217/fvl.15.60.
  4. ^ Frazer IH (May 2014). "Development and implementation of papillomavirus prophylactic vaccines". J. Immunol. 192 (9): 4007–11. doi:10.4049/jimmunol.1490012. PMID 24748633.
  5. ^
  6. ^ Fiore AE, Bridges CB, Cox NJ (2009). Seasonal influenza vaccines. Curr. Top. Microbiol. Immunol. Current Topics in Microbiology and Immunology. 333. pp. 43–82. doi:10.1007/978-3-540-92165-3_3. ISBN 978-3-540-92164-6. PMID 19768400.
  7. ^ Chang Y, Brewer NT, Rinas AC, Schmitt K, Smith JS (July 2009). "Evaluating the impact of human papillomavirus vaccines". Vaccine. 27 (32): 4355–62. doi:10.1016/j.vaccine.2009.03.008. PMID 19515467.
  8. ^ Liesegang TJ (August 2009). "Varicella zoster virus vaccines: effective, but concerns linger". Can. J. Ophthalmol. 44 (4): 379–84. doi:10.3129/i09-126. PMID 19606157.
  9. ^ World Health Organization, Global Vaccine Action Plan 2011-2020. Archived 2014-04-14 at the Wayback Machine Geneva, 2012.
  10. ^ a b Baxby D (January 1999). "Edward Jenner's Inquiry; a bicentenary analysis". Vaccine. 17 (4): 301–7. doi:10.1016/s0264-410x(98)00207-2. PMID 9987167.
  11. ^ a b Pasteur, Louis (1881). "Address on the Germ Theory". Lancet. 118 (3024): 271–72. doi:10.1016/s0140-6736(02)35739-8.
  12. ^ "Measles | Vaccination | CDC". 2018-02-05.
  13. ^ Grammatikos AP, Mantadakis E, Falagas ME (June 2009). "Meta-analyses on pediatric infections and vaccines". Infect. Dis. Clin. North Am. 23 (2): 431–57. doi:10.1016/j.idc.2009.01.008. PMID 19393917.
  14. ^ Neighmond, Patti (2010-02-07). "Adapting Vaccines For Our Aging Immune Systems". Morning Edition. NPR. Archived from the original on 2013-12-16. Retrieved 2014-01-09.open access publication – free to read
  15. ^ Sullivan, Patricia (2005-04-13). "Maurice R. Hilleman dies; created vaccines". Wash. Post. Archived from the original on 2012-10-20. Retrieved 2014-01-09.open access publication – free to read
  16. ^ Schlegel M, Osterwalder JJ, Galeazzi RL, Vernazza PL (August 1999). "Comparative efficacy of three mumps vaccines during disease outbreak in Eastern Switzerland: cohort study". BMJ. 319 (7206): 352. doi:10.1136/bmj.319.7206.352. PMID 10435956.
  17. ^ Préziosi MP, Halloran ME (September 2003). "Effects of pertussis vaccination on disease: vaccine efficacy in reducing clinical severity". Clin. Infect. Dis. 37 (6): 772–9. doi:10.1086/377270. PMID 12955637.
  18. ^ Orenstein WA, Papania MJ, Wharton ME (2004). "Measles elimination in the United States". J Infect Dis. 189 (Suppl 1): S1–3. doi:10.1086/377693. PMID 15106120.
  19. ^ a b c "Measles—United States, January 1 – April 25, 2008". Morb. Mortal. Wkly. Rep. 57 (18): 494–98. May 2008. PMID 18463608. Archived from the original on October 11, 2017.open access publication – free to read
  20. ^ "WHO South-East Asia Region certified polio-free". WHO. 27 March 2014. Archived from the original on 27 March 2014. Retrieved November 3, 2014.
  21. ^ 19 July 2017 Vaccines promoted as key to stamping out drug-resistant microbes "Immunization can stop resistant infections before they get started, say scientists from industry and academia." Archived 22 July 2017 at the Wayback Machine
  22. ^ a b c d Maglione MA, Das L, Raaen L, Smith A, Chari R, Newberry S, Shanman R, Perry T, Goetz MB, Gidengil C (August 2014). "Safety of vaccines used for routine immunization of U.S. children: a systematic review". Pediatrics. 134 (2): 325–37. doi:10.1542/peds.2014-1079. PMID 25086160.
  23. ^ a b c "Possible Side-effects from Vaccines". Centers for Disease Control and Prevention. 2018-07-12. Archived from the original on 17 March 2017. Retrieved 24 February 2014.
  24. ^ "Seasonal Flu Shot – Seasonal Influenza (Flu)". CDC. 2018-10-02. Archived from the original on 2015-10-01.
  25. ^ Looker, Clare; Heath, Kelly (2011). "No-fault compensation following adverse events attributed to vaccination: a review of international programmes". Word Health Organisation.
  26. ^ "Vaccine Types". National Institute of Allergy and Infectious Diseases. 2012-04-03. Archived from the original on 2015-09-05. Retrieved 2015-01-27.
  27. ^ "Types of Vaccines". Archived from the original on 2017-07-29. Retrieved October 19, 2017.
  28. ^ J.K. Sinha; S. Bhattacharya. A Text Book of Immunology (Google Book Preview). Academic Publishers. p. 318. ISBN 978-81-89781-09-5. Retrieved 2014-01-09.
  29. ^ Kim W, Liau LM (2010). "Dendritic cell vaccines for brain tumors". Neurosurg Clin N Am. 21 (1): 139–57. doi:10.1016/j.nec.2009.09.005. PMC 2810429. PMID 19944973.
  30. ^ Anguille S, Smits EL, Lion E, van Tendeloo VF, Berneman ZN (June 2014). "Clinical use of dendritic cells for cancer therapy". Lancet Oncol. 15 (7): e257–67. doi:10.1016/S1470-2045(13)70585-0. PMID 24872109.
  31. ^ McKenzie, David (26 May 2018). "Fear and failure: How Ebola sparked a global health revolution". CNN. Retrieved 26 May 2018.
  32. ^ Meri S, Jördens M, Jarva H (December 2008). "Microbial complement inhibitors as vaccines". Vaccine. 26 Suppl 8: I113–7. doi:10.1016/j.vaccine.2008.11.058. PMID 19388175.
  33. ^ "Monovalent" at Dorland's Medical Dictionary
  34. ^ Polyvalent vaccine at Dorlands Medical Dictionary Archived March 7, 2012, at the Wayback Machine
  35. ^ "Questions And Answers On Monovalent Oral Polio Vaccine Type 1 (mOPV1)'Issued Jointly By WHO and UNICEF'". Pediatric Oncall. 2 (8). 3. What advantages does mOPV1 have over trivalent oral polio vaccine (tOPV)?. 2005-01-08. Archived from the original on 2012-02-29.
  36. ^ Scott (April 2004). "Classifying Vaccines" (PDF). BioProcesses International: 14–23. Archived (PDF) from the original on 2013-12-12. Retrieved 2014-01-09.
  37. ^ a b Centers for Disease Control and Prevention, U.S. Vaccine Names, archived from the original on 2016-05-26, retrieved 2016-05-21.
  38. ^ a b Centers for Disease Control and Prevention (2018-08-07), Tetanus (Lockjaw) Vaccination, archived from the original on 2016-05-16, retrieved 2016-05-21.
  39. ^ Centers for Disease Control and Prevention (2018-02-02), Vaccine Acronyms and Abbreviations [Abbreviations used on U.S. immunization records], archived from the original on 2017-06-02, retrieved 2017-05-22.
  40. ^ Sutter RW, Cochi SL, Melnick JL (1999). "Live attenuated polio vaccines". In Plotkin SA, Orenstein WA. Vaccines. Philadelphia: W. B. Saunders. pp. 364–408.
  41. ^ Kanesa-thasan N, Sun W, Kim-Ahn G, et al. (2001). "Safety and immunogenicity of attenuated dengue virus vaccines (Aventis Pasteur) in human volunteers". Vaccine. 19 (23–24): 3179–88. CiteSeerX 10.1.1.559.8311. doi:10.1016/S0264-410X(01)00020-2. PMID 11312014.
  42. ^ "Institute for Vaccine Safety – Thimerosal Table". Archived from the original on 2005-12-10.
  43. ^ Wharton, Melinda E.; National Vaccine Advisory committee "U.S.A. national vaccine plan" Archived 2016-05-04 at the Wayback Machine
  44. ^ http://www.npl.co.uk/environment/vam/nongaseouspollutants/ngp_metals.html Archived 29 September 2007 at the Wayback Machine
  45. ^ "ACIP Vaccine Recommendations Home Page". CDC. 2013-11-15. Archived from the original on 2013-12-31. Retrieved 2014-01-10.
  46. ^ "Vaccine Status Table". Red Book Online. American Academy of Pediatrics. April 26, 2011. Archived from the original on December 27, 2013. Retrieved January 9, 2013.
  47. ^ "HPV Vaccine Safety". Centers for Disease Control and Prevention (CDC). 2013-12-20. Archived from the original on 2009-11-10. Retrieved 2014-01-10.
  48. ^ "HPV vaccine in the clear". NHS choices. 2009-10-02. Archived from the original on 2014-01-10. Retrieved 2014-01-10.open access publication – free to read
  49. ^ Needham, Joseph. (2000). Science and Civilization in China: Volume 6, Biology and Biological Technology, Part 6, Medicine. Cambridge: Cambridge University Press. p.154
  50. ^ Williams, Gareth (2010). Angel of Death. Basingstoke: Palgrave Macmillan. ISBN 978-0-230-27471-6.
  51. ^ Silverstein, Arthur M. (2009). A History of Immunology (2nd ed.). Academic Press. p. 293. ISBN 978-0-08-091946-1..
  52. ^ a b c Stern AM, Markel H (2005). "The history of vaccines and immunization: familiar patterns, new challenges". Health Aff. (Millwood). 24 (3): 611–21. doi:10.1377/hlthaff.24.3.611. PMID 15886151. Archived from the original on 2014-04-24.open access publication – free to read
  53. ^ Dunn PM (January 1996). "Dr Edward Jenner (1749–1823) of Berkeley, and vaccination against smallpox" (PDF). Arch. Dis. Child. Fetal Neonatal Ed. 74 (1): F77–78. doi:10.1136/fn.74.1.F77. PMC 2528332. PMID 8653442. Archived from the original (PDF) on 2011-07-08.
  54. ^ Van Sant JE (2008). "The Vaccinators: Smallpox, Medical Knowledge, and the 'Opening' of Japan". J Hist Med Allied Sci. 63 (2): 276–79. doi:10.1093/jhmas/jrn014.
  55. ^ Dudgeon JA (1963). "Development of smallpox vaccine in England in the eighteenth and nineteenth centuries". BMJ (5342): 1367–72. doi:10.1136/bmj.1.5342.1367. PMC 2124036. PMID 20789814.
  56. ^ Baarda, Benjamin I.; Sikora, Aleksandra E. (2015). "Proteomics of Neisseria gonorrhoeae: the treasure hunt for countermeasures against an old disease". Frontiers in Microbiology. 6: 1190. doi:10.3389/fmicb.2015.01190. ISSN 1664-302X. PMC 4620152. PMID 26579097; Access provided by the University of Pittsburgh.
  57. ^ Goodman, Jesse L. (2005-05-04). "Statement by Jesse L. Goodman, M.D., M.P.H. Director Center for Biologics, Evaluation and Research Food and Drug Administration U.S. Department of Health and Human Services on US Influenza Vaccine Supply and Preparations for the Upcoming Influenza Season before Subcommittee on Oversight and Investigations Committee on Energy and Commerce United States House of Representatives". Archived from the original on 2008-09-21. Retrieved 2008-06-15.
  58. ^ Olesen OF, Lonnroth A, Mulligan B (2009). "Human vaccine research in the European Union". Vaccine. 27 (5): 640–45. doi:10.1016/j.vaccine.2008.11.064. PMID 19059446.
  59. ^ Jit, Mark; Newall, Anthony T.; Beutels, Philippe (1 April 2013). "Key issues for estimating the impact and cost-effectiveness of seasonal influenza vaccination strategies". Human Vaccines & Immunotherapeutics. 9 (4): 834–840. doi:10.4161/hv.23637. PMC 3903903. PMID 23357859.
  60. ^ Newall, A.T.; Reyes, J.F.; Wood, J.G.; McIntyre, P.; Menzies, R.; Beutels, P. (February 2014). "Economic evaluations of implemented vaccination programmes: key methodological challenges in retrospective analyses". Vaccine. 32 (7): 759–65. doi:10.1016/j.vaccine.2013.11.067. PMID 24295806.
  61. ^ Hardman Reis T (2006). "The role of intellectual property in the global challenge for immunization". J World Intellect Prop. 9 (4): 413–25. doi:10.1111/j.1422-2213.2006.00284.x.
  62. ^ "www.who.int" (PDF). Archived (PDF) from the original on 2015-11-23.
  63. ^ "Three ways to make a vaccine" (infographic). Archived from the original on 2015-12-23. Retrieved 2015-08-05, in Stein, Rob (24 November 2009). "Vaccine system remains antiquated". The Washington Post. Archived from the original on 19 October 2017.
  64. ^ Muzumdar JM, Cline RR (2009). "Vaccine supply, demand, and policy: a primer". J Am Pharm Assoc. 49 (4): e87–99. doi:10.1331/JAPhA.2009.09007. PMID 19589753.
  65. ^ "Components of a vaccine". Archived from the original on 2017-06-13.
  66. ^ a b Bae K, Choi J, Jang Y, Ahn S, Hur B (2009). "Innovative vaccine production technologies: the evolution and value of vaccine production technologies". Arch Pharm Res. 32 (4): 465–80. doi:10.1007/s12272-009-1400-1. PMID 19407962.
  67. ^ Staff (15 November 2011). "India produces 60 percent of world's vaccines". Indonesia. Antara. Archived from the original on 19 September 2015. Retrieved 2015-08-05.
  68. ^ CDC (2018-07-12). "Ingredients of Vaccines — Fact Sheet". Archived from the original on December 17, 2009. Retrieved December 20, 2009.
  69. ^ The mercury levels in the table, unless otherwise indicated, are taken from: Mercury Levels in Commercial Fish and Shellfish (1990-2010) Archived 2015-05-03 at the Wayback Machine U.S. Food and Drug Administration. Accessed 8 January 2012.
  70. ^ "Thimerosal in vaccines". Center for Biologics Evaluation and Research, U.S. Food and Drug Administration. 2007-09-06. Archived from the original on 2013-01-06. Retrieved 2007-10-01.
  71. ^ Bigham M, Copes R (2005). "Thiomersal in vaccines: balancing the risk of adverse effects with the risk of vaccine-preventable disease". Drug Saf. 28 (2): 89–101. doi:10.2165/00002018-200528020-00001. PMID 15691220.
  72. ^ Offit PA (2007). "Thimerosal and vaccines—a cautionary tale". N Engl J Med. 357 (13): 1278–79. doi:10.1056/NEJMp078187. PMID 17898096.
  73. ^ Morein B, Hu KF, Abusugra I (2004). "Current status and potential application of ISCOMs in veterinary medicine". Adv Drug Deliv Rev. 56 (10): 1367–82. doi:10.1016/j.addr.2004.02.004. PMID 15191787.
  74. ^ American Medicine. American-Medicine Publishing Company. 1926.
  75. ^ South African Institute for Medical Research (1929). Annual report [Jaarverslag]. South African Institute for Medical Research – Suid-Afrikaanse Instituut vir Mediese Navorsing.
  76. ^ Firdos Alam Khan (2011-09-20). Biotechnology Fundamentals. CRC Press. p. 270. ISBN 978-1-4398-2009-4.
  77. ^ Giudice EL, Campbell JD (2006). "Needle-free vaccine delivery". Adv Drug Deliv Rev. 58 (1): 68–89. doi:10.1016/j.addr.2005.12.003. PMID 16564111.
  78. ^ WHO to trial Nanopatch needle-free delivery system| ABC News, 16 Sep 2014| "Needle-free polio vaccine a 'game-changer'". 2014-09-16. Archived from the original on 2015-04-02. Retrieved 2015-09-15.
  79. ^ "Australian scientists develop 'needle-free' vaccination". The Sydney Morning Herald. 18 August 2013. Archived from the original on 25 September 2015.
  80. ^ "Vaxxas raises $25m to take Brisbane's Nanopatch global". Business Review Weekly. 2015-02-10. Archived from the original on 2015-03-16. Retrieved 2015-03-05.
  81. ^ "Australian scientists develop 'needle-free' vaccination". Chennai, India: The Hindu. 28 September 2011. Archived from the original on 1 January 2014.
  82. ^ "Needle-free nanopatch vaccine delivery system". News Medical. 3 August 2011. Archived from the original on 11 May 2012.
  83. ^ Lowe (2008). "Plasmid DNA as Prophylactic and Therapeutic vaccines for Cancer and Infectious Diseases". Plasmids: Current Research and Future Trends. Caister Academic Press. ISBN 978-1-904455-35-6.
  84. ^ Patel, JR; Heldens, JG (March 2009). "Immunoprophylaxis against important virus disease of horses, farm animals and birds". Vaccine. 27 (12): 1797–810. doi:10.1016/j.vaccine.2008.12.063. PMID 19402200.
  85. ^ a b Berkelman, Ruth L. (1 August 2003). "Human Illness Associated with Use of Veterinary Vaccines". Clinical Infectious Diseases. 37 (3): 407–14. doi:10.1086/375595. PMID 12884166.open access publication – free to read
  86. ^ Van Oirschot JT, Rziha HJ, Moonen PJ, Pol JM, Van Zaane D (1986). "Differentiation of serum antibodies from pigs vaccinated or infected with Aujeszky's disease virus by a competitive enzyme immunoassay". The Journal of General Virology. 67 (6): 1179–82. doi:10.1099/0022-1317-67-6-1179. PMID 3011974.
  87. ^ Van Oirschot JT (1999). "Diva vaccines that reduce virus transmission". Journal of Biotechnology. 73 (2–3): 195–205. doi:10.1016/S0168-1656(99)00121-2. PMID 10486928.
  88. ^ Van Oirschot JT, Gielkens AL, Moormann RJ, Berns AJ (1990). "Marker vaccines, virus protein-specific antibody assays and the control of Aujeszky's disease". Veterinary Microbiology. 23 (1–4): 85–101. doi:10.1016/0378-1135(90)90139-M. PMID 2169682.
  89. ^ Van Oirschot JT (1999). "Diva vaccines that reduce virus transmission". Journal of Biotechnology. 73 (2–3): 195–205. doi:10.1016/S0168-1656(99)00121-2. PMID 10486928.
  90. ^ Kaashoek MJ, Moerman A, Madic J, Rijsewijk FA, Quak J, Gielkens AL, Van Oirschot JT (1994). "A conventionally attenuated glycoprotein E-negative strain of bovine herpesvirus type 1 is an efficacious and safe vaccine". Vaccine. 12 (5): 439–44. doi:10.1016/0264-410X(94)90122-8. PMID 8023552.
  91. ^ Hulst MM, Westra DF, Wensvoort G, Moormann RJ (1993). "Glycoprotein E1 of hog cholera virus expressed in insect cells protects swine from hog cholera". Journal of Virology. 67 (9): 5435–42. PMC 237945. PMID 8350404.
  92. ^ Capua I, Terregino C, Cattoli G, Mutinelli F, Rodriguez JF (February 2003). "Development of a DIVA (Differentiating Infected from Vaccinated Animals) strategy using a vaccine containing a heterologous neuraminidase for the control of avian influenza". Avian Pathol. 32 (1): 47–55. doi:10.1080/0307945021000070714. PMID 12745380.
  93. ^ Maas A, Meens J, Baltes N, Hennig-Pauka I, Gerlach GF (2006). "Development of a DIVA subunit vaccine against Actinobacillus pleuropneumoniae infection". Vaccine. 24 (49): 7226–32. doi:10.1016/j.vaccine.2006.06.047. PMID 17027123.
  94. ^ Leyman B, Boyen F, Van Parys A, Verbruggh E, Haesebrouck F, Pasmans F (2011). "Salmonella Typhimurium LPS mutations for use in vaccines allowing differentiation of infected and vaccinated pigs". Vaccine. 29 (20): 3679–85. doi:10.1016/j.vaccine.2011.03.004. hdl:1854/LU-1201519. PMID 21419163. Archived from the original on 2017-10-28.
  95. ^ a b c d e f g Plotkin SA (2005). "Vaccines: past, present and future". Nat Med. 11 (4 Suppl): S5–11. doi:10.1038/nm1209. PMID 15812490.
  96. ^ Carlson B (2008). "Adults now drive growth of vaccine market". Gen. Eng. Biotechnol. News. 28 (11). pp. 22–3. Archived from the original on 2014-01-10.open access publication – free to read
  97. ^ Klein SL, Jedlicka A, Pekosz A (May 2010). "The Xs and Y of immune responses to viral vaccines". Lancet Infect Dis. 10 (5): 338–49. doi:10.1016/S1473-3099(10)70049-9. PMID 20417416.
  98. ^ Staff (28 March 2013). "Safer vaccine created without virus". The Japan Times. Agence France-Presse – Jiji Press. Archived from the original on 30 March 2013. Retrieved 2013-03-28.
  99. ^ Spohn G, Bachmann MF (2008). "Exploiting viral properties for the rational design of modern vaccines". Expert Rev Vaccines. 7 (1): 43–54. doi:10.1586/14760584.7.1.43. PMID 18251693.
  100. ^ Samuelsson O, Herlitz H (2008). "Vaccination against high blood pressure: a new strategy". Lancet. 371 (9615): 788–89. doi:10.1016/S0140-6736(08)60355-4. PMID 18328909.
  101. ^ Poland GA, Jacobson RM, Ovsyannikova IG (2009). "Trends affecting the future of vaccine development and delivery: the role of demographics, regulatory science, the anti-vaccine movement, and vaccinomics". Vaccine. 27 (25–26): 3240–44. doi:10.1016/j.vaccine.2009.01.069. PMC 2693340. PMID 19200833.
  102. ^ Sala F, Manuela Rigano M, Barbante A, Basso B, Walmsley AM, Castiglione S (January 2003). "Vaccine antigen production in transgenic plants: strategies, gene constructs and perspectives". Vaccine. 21 (7–8): 803–8. doi:10.1016/s0264-410x(02)00603-5. PMID 12531364.
  103. ^ Kumar, G. B. Sunil; T. R. Ganapathi; C. J. Revathi; L. Srinivas; V. A. Bapat (October 2005). "Expression of hepatitis B surface antigen in transgenic banana plants". Planta. 222 (3): 484–93. doi:10.1007/s00425-005-1556-y. PMID 15918027.
  104. ^ Ostachuk A; Chiavenna SM; Gómez C; Pecora A; Pérez-Filgueira MD; Escribano JA; Ardila F; Dus Santos MJ; Wigdorovitz A (2009). "Expression of a ScFv–E2T fusion protein in CHO-K1 cells and alfalfa transgenic plants for the selective directioning to antigen presenting cells". Veterinary Immunology and Immunopathology. 128 (1): 315. doi:10.1016/j.vetimm.2008.10.224. Archived from the original on 2018-05-01.
  105. ^ Peréz Aguirreburualde MS, Gómez MC, Ostachuk A, Wolman F, Albanesi G, Pecora A, Odeon A, Ardila F, Escribano JM, Dus Santos MJ, Wigdorovitz A (February 2013). "Efficacy of a BVDV subunit vaccine produced in alfalfa transgenic plants". Vet. Immunol. Immunopathol. 151 (3–4): 315–24. doi:10.1016/j.vetimm.2012.12.004. PMID 23291101.

External links

External video
Modern Vaccine and Adjuvant Production and Characterization, Genetic Engineering & Biotechnology News
Andrew Wakefield

Andrew Jeremy Wakefield (born 1957) is a discredited former British doctor who became an anti-vaccine activist. He was a gastroenterologist until he was struck off the UK medical register for unethical behaviour, misconduct and dishonesty. In 1998 he was the lead author of a fraudulent research paper claiming that there was a link between the measles, mumps and rubella (MMR) vaccine and autism and bowel disease.After the publication of the paper, other researchers were unable to reproduce Wakefield's findings or confirm his hypothesis of an association between the MMR vaccine and autism, or autism and gastrointestinal disease. A 2004 investigation by Sunday Times reporter Brian Deer identified undisclosed financial conflicts of interest on Wakefield's part, and most of his co-authors then withdrew their support for the study's interpretations. The British General Medical Council (GMC) conducted an inquiry into allegations of misconduct against Wakefield and two former colleagues. The investigation centred on Deer's numerous findings, including that children with autism were subjected to unnecessary invasive medical procedures such as colonoscopies and lumbar punctures, and that Wakefield acted without the required ethical approval from an institutional review board.

On 28 January 2010, a five-member statutory tribunal of the GMC found three dozen charges proved, including four counts of dishonesty and 12 counts involving the abuse of developmentally delayed children. The panel ruled that Wakefield had "failed in his duties as a responsible consultant", acted both against the interests of his patients, and "dishonestly and irresponsibly" in his published research. The Lancet fully retracted the 1998 publication on the basis of the GMC's findings, noting that elements of the manuscript had been falsified. The Lancet's editor-in-chief Richard Horton said the paper was "utterly false" and that the journal had been "deceived". Three months following The Lancet's retraction, Wakefield was struck off the UK medical register, with a statement identifying deliberate falsification in the research published in The Lancet, and was thereby barred from practising medicine in the UK.In January 2011, an editorial accompanying an article by Brian Deer in BMJ described Wakefield's work as an "elaborate fraud". In a follow-up article, Deer said that Wakefield had planned to launch a venture on the back of an MMR vaccination scare that would profit from new medical tests and "litigation driven testing". In November 2011, another report in BMJ revealed original raw data indicating that, contrary to Wakefield's claims in The Lancet, children in his research did not have inflammatory bowel disease.Wakefield's study and his claim that the MMR vaccine might cause autism led to a decline in vaccination rates in the United States, United Kingdom and Ireland and a corresponding rise in measles and mumps, resulting in serious illness and deaths, and his continued claims that the vaccine is harmful have contributed to a climate of distrust of all vaccines and the reemergence of other previously controlled diseases. Wakefield has continued to defend his research and conclusions, saying there was no fraud, hoax or profit motive. In February 2015, he publicly repeated his denials and refused to back down from his assertions, even though—as stated by a British Administrative Court Justice in a related decision—"There is now no respectable body of opinion which supports (Dr. Wakefield's) hypothesis, that MMR vaccine and autism/enterocolitis are causally linked".

BCG vaccine

Bacillus Calmette–Guérin (BCG) vaccine is a vaccine primarily used against tuberculosis (TB). In countries where tuberculosis or leprosy is common, one dose is recommended in healthy babies as close to the time of birth as possible. In areas where tuberculosis is not common, only children at high risk are typically immunized, while suspected cases of tuberculosis are individually tested for and treated. Adults who do not have tuberculosis and have not been previously immunized but are frequently exposed may be immunized as well. BCG also has some effectiveness against Buruli ulcer infection and other nontuberculous mycobacteria infections. Additionally it is sometimes used as part of the treatment of bladder cancer.Rates of protection against tuberculosis infection vary widely and protection lasts up to twenty years. Among children it prevents about 20% from getting infected and among those who do get infected it protects half from developing disease. The vaccine is given by injection into the skin. Additional doses are not supported by evidence.Serious side effects are rare. Often there is redness, swelling, and mild pain at the site of injection. A small ulcer may also form with some scarring after healing. Side effects are more common and potentially more severe in those with poor immune function. It is not safe for use during pregnancy. The vaccine was originally developed from Mycobacterium bovis which is commonly found in cows. While it has been weakened, it is still live.The BCG vaccine was first used medically in 1921. It is on the World Health Organization's List of Essential Medicines, the most effective and safe medicines needed in a health system. Between 2011 and 2014 the wholesale price was $0.16 to $1.11 USD a dose in the developing world. In the United States it costs $100 to $200 USD. As of 2004 the vaccine is given to about 100 million children per year globally.

DPT vaccine

DPT (also DTP and DTwP) is a class of combination vaccines against three infectious diseases in humans: diphtheria, pertussis (whooping cough), and tetanus. The vaccine components include diphtheria and tetanus toxoids and killed whole cells of the bacterium that causes pertussis (wP).

DTaP and Tdap refer to similar combination vaccines in which the component "P" or "p" with lower case "a" is acellular.

Also available are the DT and Td vaccines, which lack the pertussis component.

In the United Kingdom, the Netherlands and France, the abbreviation DTP refers to a combination vaccine against diphtheria, tetanus, and poliomyelitis. In the Netherlands, pertussis is known as kinkhoest and DKTP refers to a combination vaccine against diphtheria, kinkhoest, tetanus, and polio.

The usual course of childhood immunization in the USA is five doses between 2 months and 15 years. For adults, Td boosters are recommended every 10 years.

In the latter 20th century, vaccinations helped to reduce the incidence of childhood pertussis in the United States. Despite this, reported instances of the disease increased twenty-fold in the early 21st century, resulting in numerous fatalities. Over this time, many parents declined to vaccinate their children against pertussis for fear of side effects. In 2009, the journal Pediatrics concluded the largest risk among unvaccinated children was not the contraction of side effects, but rather the disease that the vaccination aims to protect against.DTP was licensed in 1949.

HPV vaccine

Human papilloma virus (HPV) vaccines are vaccines that prevent infection by certain types of human papillomavirus. Available vaccines protect against either two, four, or nine types of HPV. All vaccines protect against at least HPV type 16 and 18 that cause the greatest risk of cervical cancer. It is estimated that they may prevent 70% of cervical cancer, 80% of anal cancer, 60% of vaginal cancer, 40% of vulvar cancer, and possibly some mouth cancer. They additionally prevent some genital warts with the vaccines against 4 and 9 HPV types providing greater protection.The World Health Organization (WHO) recommends HPV vaccines as part of routine vaccinations in all countries, along with other prevention measures. The vaccines require two or three doses depending on a person's age and immune status. Vaccinating girls around the ages of nine to thirteen is typically recommended. The vaccines provide protection for at least 5 to 10 years. Cervical cancer screening is still required following vaccination. Vaccinating a large portion of the population may also benefit the unvaccinated. In those already infected the vaccines are not effective.HPV vaccines are very safe. Pain at the site of injection occurs in about 80% of people. Redness and swelling at the site and fever may also occur. No link to Guillain–Barré syndrome has been found.The first HPV vaccine became available in 2006. As of 2017, 71 countries include it in their routine vaccinations, at least for girls. They are on the World Health Organization's List of Essential Medicines, the most effective and safe medicines needed in a health system. The wholesale cost in the developing world is about US$47 a dose as of 2014. In the United States it costs more than US$200. Vaccination may be cost effective in the developing world.

Influenza vaccine

Influenza vaccines, also known as flu shots or flu jabs, are vaccines that protect against infection by influenza viruses. A new version of the vaccine is developed twice a year, as the influenza virus rapidly changes. While their effectiveness varies from year to year, most provide modest to high protection against influenza. The United States Centers for Disease Control and Prevention (CDC) estimates that vaccination against influenza reduces sickness, medical visits, hospitalizations, and deaths. When an immunized worker does catch the flu, they are on average back at work a half day sooner. Vaccine effectiveness in those under two years old and over 65 years old remains unknown due to the low quality of the research. Vaccinating children may protect those around them.The World Health Organization (WHO) and the CDC recommend yearly vaccination for nearly all people over the age of six months, especially those at high risk. The European Centre for Disease Prevention and Control also recommends yearly vaccination of high risk groups. These groups include pregnant women, the elderly, children between six months and five years of age, those with other health problems, and those who work in healthcare.The vaccines are generally safe. Fever occurs in five to ten percent of children vaccinated. Temporary muscle pains or feelings of tiredness may occur as well. In certain years, the vaccine has been linked to an increase in Guillain–Barré syndrome among older people at a rate of about one case per million doses. It should not be given to those with severe allergies to previous versions of the vaccine. Although most influenza vaccines are produced using egg-based techniques, influenza vaccines are nonetheless recommended for people with egg allergies, even if severe. The vaccines come in both inactive and weakened viral forms. The inactive version should be used for those who are pregnant. They come in forms that are injected into a muscle, sprayed into the nose, or injected into the middle layer of the skin.Vaccination against influenza began in the 1930s with large scale availability in the United States beginning in 1945. It is on the World Health Organization's List of Essential Medicines, the most effective and safe medicines needed in a health system. The wholesale price in the developing world is about $5.25 USD per dose as of 2014. In the United States, it costs less than $25 USD as of 2015.

Jenny McCarthy

Jennifer Ann McCarthy (born November 1, 1972), sometimes credited as Jenny Wahlberg, is an American anti-vaccine activist, actress, model, television host, author, and screenwriter. She began her career in 1993 as a nude model for Playboy magazine and was later named their Playmate of the Year. McCarthy then parlayed her Playboy fame into a television and film acting career starting as a co-host on the MTV game show Singled Out, then some eponymous sitcoms, as well as films such as BASEketball, Diamonds, Scream 3, and Santa Baby. She is a former co-host of the ABC talk show The View.

McCarthy has written books about parenting and has become an activist promoting research into environmental causes and alternative medical treatments for autism. She has promoted the disproven idea that vaccines cause autism and that chelation therapy helped cure her son of autism. Both claims are unsupported by medical consensus, and her son's autism diagnosis has been questioned. McCarthy has been described as "the nation's most prominent purveyor of anti-vaxxer ideology", but she has denied the charge, stating: "I am not anti-vaccine".

Jonas Salk

Jonas Edward Salk (; October 28, 1914 – June 23, 1995) was an American medical researcher and virologist. He discovered and developed one of the first successful polio vaccines. Born in New York City, he attended New York University School of Medicine, later choosing to do medical research instead of becoming a practicing physician. In 1939, after earning his medical degree, Salk began an internship as a physician scientist at Mount Sinai Hospital. Two years later he was granted a fellowship at the University of Michigan, where he would study flu viruses with his mentor Thomas Francis, Jr.Until 1955, when the Salk vaccine was introduced, polio was considered one of the most frightening public health problems in the world. In the postwar United States, annual epidemics were increasingly devastating. The 1952 U.S. epidemic was the worst outbreak in the nation's history. Of nearly 58,000 cases reported that year, 3,145 people died and 21,269 were left with mild to disabling paralysis, with most of its victims being children. The "public reaction was to a plague", said historian William L. O'Neill. "Citizens of urban areas were to be terrified every summer when this frightful visitor returned." According to a 2009 PBS documentary, "Apart from the atomic bomb, America's greatest fear was polio." As a result, scientists were in a frantic race to find a way to prevent or cure the disease.

In 1947, Salk accepted an appointment to the University of Pittsburgh School of Medicine. In 1948, he undertook a project funded by the National Foundation for Infantile Paralysis, the organization that would fund the development of a vaccine, to determine the number of different types of polio virus. Salk saw an opportunity to extend this project towards developing a vaccine against polio, and, together with the skilled research team he assembled, devoted himself to this work for the next seven years. The field trial set up to test the Salk vaccine was, according to O'Neill, "the most elaborate program of its kind in history, involving 20,000 physicians and public health officers, 64,000 school personnel, and 220,000 volunteers." Over 1,800,000 school children took part in the trial. When news of the vaccine's success was made public on April 12, 1955, Salk was hailed as a "miracle worker" and the day almost became a national holiday. Around the world, an immediate rush to vaccinate began, with countries including Canada, Sweden, Denmark, Norway, West Germany, the Netherlands, Switzerland, and Belgium planning to begin polio immunization campaigns using Salk's vaccine.

Salk campaigned for mandatory vaccination, claiming that public health should be considered a "moral commitment." His sole focus had been to develop a safe and effective vaccine as rapidly as possible, with no interest in personal profit. As such, there is no patent for the vaccine. In 1960, he founded the Salk Institute for Biological Studies in La Jolla, California, which is today a center for medical and scientific research. He continued to conduct research and publish books, including Man Unfolding (1972), The Survival of the Wisest (1973), World Population and Human Values: A New Reality (1981), and Anatomy of Reality: Merging of Intuition and Reason (1983). Salk's last years were spent searching for a vaccine against HIV. His personal papers are stored at the University of California, San Diego Library.

MMR vaccine

The MMR vaccine is a vaccine against measles, mumps, and rubella (German measles). The first dose is generally given to children around 9 to 15 months of age, with a second dose at 15 months to 6 years of age, with at least 4 weeks between the doses. After two doses 97% of people are protected against measles, 88% against mumps, and at least 97% against rubella. The vaccine is also recommended in those who do not have evidence of immunity, those with well controlled HIV/AIDS, and within 72 hours of exposure to measles among those who are incompletely immunized. It is given by injection.The MMR vaccine is widely used around the world; with over 500 million doses having been given in over 100 countries as of 2001. Measles resulted in 2.6 million deaths per year before immunization became common. This has decreased to 122,000 deaths per year as of 2012, mostly in low income countries. Through vaccination, as of 2018, rates of measles in North and South America are very low. Rates of disease have been seen to increase in populations who go unvaccinated. Between 2000 and 2016, vaccination decreased measles deaths by a further 84%.Side effects of immunization are generally mild and go away without any specific treatment. These may include fever, and pain or redness at the injection site. Severe allergic reactions occur in about one in a million people. The MMR vaccine is not recommended during pregnancy, however, may be given while breastfeeding. The vaccine is safe to give at the same time as other vaccines. Being recently immunized does not increase the risk of passing measles, mumps, or rubella on to others. Vaccination does not increase the risk of autism. The MMR vaccine is a mixture of live weakened viruses of the three diseases.The MMR vaccine was developed by Maurice Hilleman. It was licensed for use by Merck in 1971. Stand alone measles, mumps, and rubella vaccines had been previously licensed in 1963, 1967, and 1969 respectively. Recommendations for a second dose were introduced in 1989. The MMRV vaccine which also covers chickenpox may be used instead. An MR vaccine, without coverage for mumps, is also occasionally used.

MMR vaccine and autism

Claims of a link between the MMR vaccine and autism have been extensively investigated and found to be false. The link was first suggested in the early 1990s and came to public notice largely as a result of the 1998 Lancet MMR autism fraud, characterised as "perhaps the most damaging medical hoax of the last 100 years". The fraudulent research paper authored by Andrew Wakefield and published in The Lancet claimed to link the vaccine to colitis and autism spectrum disorders. The paper was retracted in 2010 but is still cited by anti-vaccinationists.The claims in the paper were widely reported, leading to a sharp drop in vaccination rates in the UK and Ireland. Promotion of the claimed link, which continues in anti-vaccination propaganda despite being refuted, has led to an increase in the incidence of measles and mumps, resulting in deaths and serious permanent injuries. Following the initial claims in 1998, multiple large epidemiological studies were undertaken. Reviews of the evidence by the Centers for Disease Control and Prevention, the American Academy of Pediatrics, the Institute of Medicine of the US National Academy of Sciences, the UK National Health Service, and the Cochrane Library all found no link between the MMR vaccine and autism. Physicians, medical journals, and editors have described Wakefield's actions as fraudulent and tied them to epidemics and deaths.An investigation by journalist Brian Deer found that Andrew Wakefield, the author of the original research paper linking the vaccine to autism, had multiple undeclared conflicts of interest, had manipulated evidence, and had broken other ethical codes. The Lancet paper was partially retracted in 2004 and fully retracted in 2010, when Lancet's editor-in-chief Richard Horton described it as "utterly false" and said that the journal had been deceived. Wakefield was found guilty by the General Medical Council of serious professional misconduct in May 2010 and was struck off the Medical Register, meaning he could no longer practise as a doctor in the UK. In 2011, Deer provided further information on Wakefield's improper research practices to the British Medical Journal, which in a signed editorial described the original paper as fraudulent. The scientific consensus is that there is no link between the MMR vaccine and autism and that the vaccine's benefits greatly outweigh its risks.

Measles

Measles is a highly contagious infectious disease caused by the measles virus. Symptoms usually develop 10–12 days after exposure to an infected person and last 7–10 days. Initial symptoms typically include fever, often greater than 40 °C (104.0 °F), cough, runny nose, and inflamed eyes. Small white spots known as Koplik's spots may form inside the mouth two or three days after the start of symptoms. A red, flat rash which usually starts on the face and then spreads to the rest of the body typically begins three to five days after the start of symptoms. Common complications include diarrhea (in 8% of cases), middle ear infection (7%), and pneumonia (6%). Less commonly seizures, blindness, or inflammation of the brain may occur. Other names include morbilli, rubeola, red measles, and English measles. Rubella, which is sometimes called German measles, and roseola are different diseases caused by unrelated viruses.Measles is an airborne disease which spreads easily through the coughs and sneezes of infected people. It may also be spread through contact with saliva or nasal secretions. Nine out of ten people who are not immune and share living space with an infected person will be infected . People are infectious to others from four days before to four days after the start of the rash. Most people do not get the disease more than once. Testing for the measles virus in suspected cases is important for public health efforts.The measles vaccine is effective at preventing the disease, and is often delivered in combination with other vaccines. Vaccination resulted in a 75% decrease in deaths from measles between 2000 and 2013, with about 85% of children worldwide being currently vaccinated. Once a person has become infected, no specific treatment is available, but supportive care may improve outcomes. This may include oral rehydration solution (slightly sweet and salty fluids), healthy food, and medications to control the fever. Antibiotics may be used if a secondary bacterial infection such as bacterial pneumonia occurs. Vitamin A supplementation is also recommended in the developing world.Measles affects about 20 million people a year, primarily in the developing areas of Africa and Asia. It is one of the leading vaccine-preventable disease causes of death. In 1980, 2.6 million people died of it, and in 1990, 545,000 died; by 2014, global vaccination programs had reduced the number of deaths from measles to 73,000. Rates of disease and deaths, however, increased in 2017 due to a decrease in immunization. The risk of death among those infected is about 0.2%, but may be up to 10% in people with malnutrition. Most of those who die from the infection are less than five years old. Measles is not believed to affect other animals.

Mumps

Mumps is a viral disease caused by the mumps virus. Initial signs and symptoms often include fever, muscle pain, headache, poor appetite, and feeling generally unwell. This is then usually followed by painful swelling of one or both parotid salivary glands. Symptoms typically occur 16 to 18 days after exposure and resolve after seven to ten days. Symptoms are often more severe in adults than in children. About a third of people have mild or no symptoms. Complications may include meningitis (15 percent), pancreatitis (four percent), inflammation of the heart, permanent deafness, and testicular inflammation which uncommonly results in infertility. Women may develop ovarian swelling but this does not increase the risk of infertility.Mumps is highly contagious and spreads rapidly among people living in close quarters. The virus is transmitted by respiratory droplets or direct contact with an infected person. Only humans get and spread the disease. People are infectious from about seven days before the start of symptoms to about eight days after. Once an infection has run its course, a person is typically immune for life. Reinfection is possible but the ensuing infection tends to be mild. Diagnosis is usually suspected due to parotid swelling and can be confirmed by isolating the virus on a swab of the parotid duct. Testing for IgM antibodies in the blood is simple and may be useful; however, it can be falsely negative in those who have been immunized.Mumps is preventable by two doses of the mumps vaccine. Most of the developed world includes it in their immunization programs, often in combination with measles, rubella, and varicella vaccine. Countries that have low immunization rates may see an increase in cases among older age groups and thus worse outcomes. There is no specific treatment. Efforts involve controlling symptoms with pain medication such as paracetamol (acetaminophen). Intravenous immunoglobulin may be useful in certain complications. Hospitalization may be required if meningitis or pancreatitis develops. About one in ten thousand people who are infected die.Without immunization about 0.1 percent to one percent of the population are affected per year. Widespread vaccination has resulted in a more than 90 percent decline in rates of disease. Mumps is more common in the developing world where vaccination is less common. Outbreaks, however, may still occur in a vaccinated population. Before the introduction of a vaccine, mumps was a common childhood disease worldwide. Larger outbreaks of disease would typically occur every two to five years. Children between the ages of five and nine were most commonly affected. Among immunized populations often those in their early 20s are affected. Around the equator it often occurs all year round while in the more northerly and southerly regions of the world it is more common in the winter and spring. Painful swelling of the parotid glands and testicles was described by Hippocrates in the 5th century BCE.

Polio vaccine

Polio vaccines are vaccines used to prevent poliomyelitis (polio). Two types are used: an inactivated poliovirus given by injection (IPV) and a weakened poliovirus given by mouth (OPV). The World Health Organization recommends all children be fully vaccinated against polio. The two vaccines have eliminated polio from most of the world, and reduced the number of cases reported each year from an estimated 350,000 in 1988 to 22 in 2017.The inactivated polio vaccines are very safe. Mild redness or pain may occur at the site of injection. Oral polio vaccines cause about three cases of vaccine-associated paralytic poliomyelitis per million doses given. This compares with 5,000 cases per million who are paralysed following a polio infection. Both are generally safe to give during pregnancy and in those who have HIV/AIDS but are otherwise well.The first polio vaccine was the inactivated polio vaccine. It was developed by Jonas Salk and came into use in 1955. The oral polio vaccine was developed by Albert Sabin and came into commercial use in 1961. They are on the World Health Organization's List of Essential Medicines, the most effective and safe medicines needed in a health system. The wholesale cost in the developing world is about US$0.25 per dose for the oral form as of 2014. In the United States, it costs between $25 and $50 for the inactivated form.

Poliomyelitis

Poliomyelitis, often called polio or infantile paralysis, is an infectious disease caused by the poliovirus. In about 0.5 percent of cases there is muscle weakness resulting in an inability to move. This can occur over a few hours to a few days. The weakness most often involves the legs but may less commonly involve the muscles of the head, neck and diaphragm. Many people fully recover. In those with muscle weakness about 2 to 5 percent of children and 15 to 30 percent of adults die. Another 25 percent of people have minor symptoms such as fever and a sore throat and up to 5 percent have headache, neck stiffness and pains in the arms and legs. These people are usually back to normal within one or two weeks. In up to 70 percent of infections there are no symptoms. Years after recovery post-polio syndrome may occur, with a slow development of muscle weakness similar to that which the person had during the initial infection.Poliovirus is usually spread from person to person through infected fecal matter entering the mouth. It may also be spread by food or water containing human feces and less commonly from infected saliva. Those who are infected may spread the disease for up to six weeks even if no symptoms are present. The disease may be diagnosed by finding the virus in the feces or detecting antibodies against it in the blood. The disease only occurs naturally in humans.The disease is preventable with the polio vaccine; however, multiple doses are required for it to be effective. The US Centers for Disease Control and Prevention recommends polio vaccination boosters for travelers and those who live in countries where the disease is occurring. Once infected there is no specific treatment. In 2016, there were 37 cases of wild polio and 5 cases of vaccine-derived polio. This is down from 350,000 wild cases in 1988. In 2014 the disease was only spreading between people in Afghanistan, Nigeria, and Pakistan. In 2015 Nigeria had stopped the spread of wild poliovirus but it reoccurred in 2016.Poliomyelitis has existed for thousands of years, with depictions of the disease in ancient art. The disease was first recognized as a distinct condition by the English physician Michael Underwood in 1789 and the virus that causes it was first identified in 1908 by the Austrian immunologist Karl Landsteiner. Major outbreaks started to occur in the late 19th century in Europe and the United States. In the 20th century it became one of the most worrying childhood diseases in these areas. The first polio vaccine was developed in the 1950s by Jonas Salk. In 2013 the World Health Organization hoped that vaccination efforts and early detection of cases would result in global eradication of the disease by 2018.

Smallpox

Smallpox was an infectious disease caused by one of two virus variants, variola major and variola minor. The last naturally occurring case was diagnosed in October 1977 and the World Health Organization (WHO) certified the global eradication of the disease in 1980. The risk of death following contracting the disease was about 30%, with higher rates among babies. Often those who survived had extensive scarring of their skin and some were left blind.The initial symptoms of the disease included fever and vomiting. This was followed by formation of sores in the mouth and a skin rash. Over a number of days the skin rash turned into characteristic fluid filled bumps with a dent in the center. The bumps then scabbed over and fell off leaving scars. The disease used to spread between people or via contaminated objects. Prevention was by the smallpox vaccine. Once the disease had developed certain antiviral medication may have helped.The origin of smallpox is unknown. The earliest evidence of the disease dates back to the 3rd century BCE in Egyptian mummies. The disease historically occurred in outbreaks. In 18th-century Europe it is estimated 400,000 people per year died from the disease, and one-third of the cases resulted in blindness. These deaths included those of four reigning monarchs and a queen consort. In the 20th century it is estimated that smallpox resulted in 300–500 million deaths. As recently as 1967, 15 million cases occurred a year.Edward Jenner discovered in 1798 that vaccination could prevent smallpox. In 1967, the WHO intensified efforts to eliminate the disease. Smallpox is one of two infectious diseases to have been eradicated, the other being rinderpest in 2011. The term "smallpox" was first used in Britain in the 15th century to distinguish the disease from syphilis, which was then known as the "great pox". Other historical names for the disease include pox, speckled monster, and red plague.

Smallpox vaccine

Smallpox vaccine, the first successful vaccine to be developed, was introduced by Edward Jenner in 1796. He followed up his observation that milkmaids who had previously caught cowpox did not later catch smallpox by showing that inoculated cowpox protected against inoculated smallpox.

Typhoid fever

Typhoid fever, also known simply as typhoid, is a bacterial infection due to Salmonella typhi that causes symptoms. Symptoms may vary from mild to severe and usually begin six to thirty days after exposure. Often there is a gradual onset of a high fever over several days; weakness, abdominal pain, constipation, headaches, and mild vomiting also commonly occur. Some people develop a skin rash with rose colored spots. In severe cases there may be confusion. Without treatment, symptoms may last weeks or months. Diarrhea is uncommon. Other people may carry the bacterium without being affected; however, they are still able to spread the disease to others. Typhoid fever is a type of enteric fever, along with paratyphoid fever.The cause is the bacterium Salmonella Typhi, also known as Salmonella enterica serotype Typhi, growing in the intestines and blood. Typhoid is spread by eating or drinking food or water contaminated with the feces of an infected person. Risk factors include poor sanitation and poor hygiene. Those who travel in the developing world are also at risk. Only humans can be infected. Symptoms are similar to those of many other infectious diseases. Diagnosis is by either culturing the bacteria or detecting the bacterium's DNA in the blood, stool, or bone marrow. Culturing the bacterium can be difficult. Bone marrow testing is the most accurate.A typhoid vaccine can prevent about 40% to 90% of cases during the first two years. The vaccine may have some effect for up to seven years. It is recommended for those at high risk or people traveling to areas where the disease is common. Other efforts to prevent the disease include providing clean drinking water, good sanitation, and handwashing. Until it has been confirmed that an individual's infection is cleared, the individual should not prepare food for others. The disease is treated with antibiotics such as azithromycin, fluoroquinolones or third generation cephalosporins. Resistance to these antibiotics has been developing, which has made treatment of the disease more difficult.In 2015, there were 12.5 million new cases worldwide. The disease is most common in India. Children are most commonly affected. Rates of disease decreased in the developed world in the 1940s as a result of improved sanitation and use of antibiotics to treat the disease. Each year in the United States, about 400 cases are reported and it is estimated that the disease occurs in about 6,000 people. In 2015, it resulted in about 149,000 deaths worldwide – down from 181,000 in 1990 (about 0.3% of the global total). The risk of death may be as high as 20% without treatment. With treatment, it is between 1 and 4%. Typhus is a different disease. However, the name typhoid means "resembling typhus" due to the similarity in symptoms.

Vaccination

Vaccination is the administration of antigenic material (a vaccine) to stimulate an individual's immune system to develop adaptive immunity to a pathogen. Vaccines can prevent or ameliorate infectious disease. When a sufficiently large percentage of a population has been vaccinated, herd immunity results. The effectiveness of vaccination has been widely studied and verified. Vaccination is the most effective method of preventing infectious diseases; widespread immunity due to vaccination is largely responsible for the worldwide eradication of smallpox and the elimination of diseases such as polio, measles, and tetanus from much of the world.

Smallpox was most likely the first disease people tried to prevent by inoculation and was the first disease for which a vaccine was produced. The smallpox vaccine was invented in 1796 by English physician Edward Jenner and although at least six people had used the same principles years earlier he was the first to publish evidence that it was effective and to provide advice on its production. Louis Pasteur furthered the concept through his work in microbiology. The immunization was called vaccination because it was derived from a virus affecting cows (Latin: vacca 'cow'). Smallpox was a contagious and deadly disease, causing the deaths of 20–60% of infected adults and over 80% of infected children. When smallpox was finally eradicated in 1979, it had already killed an estimated 300–500 million people in the 20th century.

In common speech, vaccination and immunization have a similar meaning. This distinguishes it from inoculation, which uses unweakened live pathogens, although in common usage either can refer to an immunization. Vaccination efforts have been met with some controversy on scientific, ethical, political, medical safety, and religious grounds. In rare cases, vaccinations can injure people. In the United States, people may receive compensation for those injuries under the National Vaccine Injury Compensation Program. Early success brought widespread acceptance, and mass vaccination campaigns have greatly reduced the incidence of many diseases in numerous geographic regions.

Vaccine hesitancy

Vaccine hesitancy, a reluctance or refusal to vaccinate or have one's children vaccinated, has been identified by the World Health Organization as one of the top ten global health threats of 2019. Hesitancy results from public debates around the medical, ethical and legal issues related to vaccines. Hesitancy and debates have occurred since the invention of vaccination, and indeed pre-date the coining of the terms "vaccine" and "vaccination" by nearly 80 years.

Despite overwhelming scientific consensus that vaccines are safe and effective, unsubstantiated scares regarding their safety still occur, resulting in outbreaks and deaths from vaccine-preventable diseases. For example, the belief that vaccines cause autism has been widely disproven by scientific evidence, yet still leads some parents to delay or avoid vaccinating their children. The specific hypotheses raised by anti-vaccination advocates change over time, but the proposed cause always remains the same: vaccines.Falling immunisation rates due to vaccine hesitancy have led to outbreaks of preventable disease, notably measles and pertussis. This has led in turn to pressure for mandatory vaccination, including California Senate Bill 277 and Australia's No Jab No Pay, which has been strenuously opposed by anti-vaccination activists. Both vaccine mandates and opposition to them date back at least a century; such opposition may be based on anti-vaccine sentiment or concern that mandatory vaccination violates civil liberties or reduces public trust in vaccination.

Whooping cough

Whooping cough (also known as pertussis or 100-day cough) is a highly contagious bacterial disease. Initially, symptoms are usually similar to those of the common cold with a runny nose, fever, and mild cough. This is followed by weeks of severe coughing fits. Following a fit of coughing, a high-pitched whoop sound or gasp may occur as the person breathes in. The coughing may last for 10 or more weeks, hence the phrase "100-day cough". A person may cough so hard that they vomit, break ribs, or become very tired from the effort. Children less than one year old may have little or no cough and instead have periods where they do not breathe. The time between infection and the onset of symptoms is usually seven to ten days. Disease may occur in those who have been vaccinated, but symptoms are typically milder.Pertussis is caused by the bacterium Bordetella pertussis. It is an airborne disease which spreads easily through the coughs and sneezes of an infected person. People are infectious from the start of symptoms until about three weeks into the coughing fits. Those treated with antibiotics are no longer infectious after five days. Diagnosis is by collecting a sample from the back of the nose and throat. This sample can then be tested by either culture or by polymerase chain reaction.Prevention is mainly by vaccination with the pertussis vaccine. Initial immunization is recommended between six and eight weeks of age, with four doses to be given in the first two years of life. Protection from pertussis decreases over time, so additional doses of vaccine are often recommended for older children and adults. Antibiotics may be used to prevent the disease in those who have been exposed and are at risk of severe disease. In those with the disease, antibiotics are useful if started within three weeks of the initial symptoms, but otherwise have little effect in most people. In pregnant women and children less than one year old, antibiotics are recommended within six weeks of symptom onset. Antibiotics used include erythromycin, azithromycin, clarithromycin, or trimethoprim/sulfamethoxazole. Evidence to support interventions for the cough, other than antibiotics, is poor. About 50% of infected children less than a year old require hospitalization and nearly 0.5% (1 in 200) die.An estimated 16.3 million people worldwide were infected in 2015. Most cases occur in the developing world, and people of all ages may be affected. In 2015, pertussis resulted in 58,700 deaths – down from 138,000 deaths in 1990. Outbreaks of the disease were first described in the 16th century. The bacterium that causes the infection was discovered in 1906. The pertussis vaccine became available in the 1940s.

This page is based on a Wikipedia article written by authors (here).
Text is available under the CC BY-SA 3.0 license; additional terms may apply.
Images, videos and audio are available under their respective licenses.