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From Wikipedia, the free encyclopedia

A vaccine is a biological preparation that improves 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. The agent stimulates the body's immune system to recognize the agent as foreign, destroy it, and "remember" it, so that the immune system can more easily recognize and destroy any of these microorganisms that it later encounters.

Vaccines can be prophylactic (e.g. to prevent or ameliorate the effects of a future infection by any natural or "wild" pathogen), or therapeutic (e.g. vaccines against cancer are also being investigated; see cancer vaccine).

The term vaccine derives from Edward Jenner's 1796 use of the term cow pox (Latin variolæ vaccinæ, adapted from the Latin vaccīn-us, from vacca cow), which, when administered to humans, provided them protection against smallpox.

Contents

History

Sometime during the 1770s Edward Jenner heard a milkmaid boast that she would never have the often-fatal or disfiguring disease smallpox, because she 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, inoculated an 8-year-old boy with it, and six weeks later variolated the boy's arm with smallpox, afterwards observing that the boy did not catch smallpox.[1][2] Further experimentation demonstrated the efficacy of the procedure on an infant.[2] Since vaccination with cowpox was much safer than smallpox inoculation,[3] the latter, though still widely practiced in England, was banned in 1840.[4] Louis Pasteur generalized Jenner's idea by developing what he called a rabies vaccine (now termed an antitoxin), and in the 19th century vaccines were considered a matter of national prestige, and compulsory vaccination laws were passed.[1]

The 20th 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. As vaccines became more common, many people began taking them for granted. However, vaccines remained elusive for many important diseases, including malaria and HIV.[1]

Types

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 currently in use.[5] These represent different strategies used to try to reduce risk of illness, while retaining the ability to induce a beneficial immune response.

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Killed

Vaccines containing killed microorganisms – these are previously virulent micro-organisms which have been killed with chemicals or heat. Examples are the Influenza (flu), cholera, bubonic plague, polio, hepatitis A, and Rabies vaccines.

Attenuated

Some vaccines contain live, attenuated microorganisms. Many of these are live viri that have been cultivated under conditions that disable their virulent properties, or which use closely-related but less dangerous organisms to produce a broad immune response, however some are bacterial in nature. They typically provoke more durable immunological responses and are the preferred type for healthy adults. Examples include the viral diseases yellow fever, measles, rubella, and mumps 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 immunogenicity to the vaccine.

Toxoid

Toxoids – these are inactivated toxic compounds in cases where these (rather than the micro-organism itself) cause illness. Examples of toxoid-based vaccines include tetanus and diphtheria. 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), 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.

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

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.[6]
  • 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
  • DNA vaccination – in recent years a new type of vaccine called DNA vaccination, created from an infectious agent's DNA, has been developed. It works by insertion (and expression, 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 advantage of DNA vaccines is that they are very easy to produce and store. As of 2006, DNA vaccination is still experimental.
  • 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[7].

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.[8] A multivalent or polyvalent vaccine is designed to immunize against two or more strains of the same microorganism, or against two or more microorganisms.[9] In certain cases a monovalent vaccine may be preferable for rapidly developing a strong immune response.[10]

Developing immunity

The immune system recognizes vaccine agents as foreign, destroys them, and "remembers" them. When the virulent version of an agent comes along 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) by 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 2 viruses in the vaccine.[11] 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.[12]

Vaccines have contributed to the eradication of smallpox, one of the most contagious and deadly diseases known to man. 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 four countries (Afghanistan, India, Nigeria and Pakistan).[1] The difficulty of reaching all children as well as cultural misunderstandings, however, have caused the anticipated eradication date to be missed several times.

Schedule

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

In order to provide 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: hepatitis A, hepatitis B, polio, mumps, measles, rubella, diphtheria, pertussis, tetanus, HiB, chickenpox, rotavirus, influenza, meningococcal disease and pneumonia. The 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 at 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 currently recommended in the U.S. and UK for ages 11–25. 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.

Effectiveness

Vaccines do not guarantee complete protection from a disease.[13] Sometimes this is because the host's immune system simply does not respond adequately or at all. This may be due to a lowered immunity in general (diabetes, steroid use, HIV infection, age) or because the host's immune system does not have a B cell capable of generating antibodies to that antigen.

Even if the host develops antibodies, the human immune system is not perfect and in any case the immune system might still not be able to defeat the infection.

Adjuvants are typically used to boost immune response. Most often aluminium adjuvants are used, but adjuvants like squalene are also used in some vaccines and more vaccines with squalene and phosphate adjuvants are being tested. Larger doses are used in some cases for older people (50-75 years and up), whose immune response to a given vaccine is not as strong.[14]

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 other diseases)
  • the strain of vaccine (some vaccinations are for different strains of the disease) [2]
  • whether one kept to the timetable for the vaccinations (see Vaccination schedule)
  • some individuals are "non-responders" to certain vaccines, meaning that they do not generate antibodies even after being vaccinated correctly
  • other factors such as ethnicity, age, or genetic predisposition

When a vaccinated individual does develop the disease vaccinated against, the disease is likely to be milder than without vaccination.[citation needed]

The following are important considerations in the effectiveness of a vaccination program:[citation needed]

  1. careful modelling to anticipate the impact 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 and
  3. maintaining high immunization rates, even when a disease has become rare.

In 1958 there were 763,094 cases of measles and 552 deaths in the United States.[15][16] With the help of new vaccines, the number of cases dropped to fewer than 150 per year (median of 56).[16] In early 2008, there were 64 suspected cases of measles. 54 out of 64 infections were associated with importation from another country, although only 13% were actually acquired outside of the United States; 63 of these 64 individuals either had never been vaccinated against measles, or were uncertain whether they had been vaccinated.[16]

Controversy

James Gillray, The Cow-Pock—or—the Wonderful Effects of the New Inoculation! (1802)

Opposition to vaccination, from a wide array of vaccine critics, has existed since the earliest vaccination campaigns.[17] Although the benefits of preventing suffering and death from serious infectious diseases greatly outweigh the risks of rare adverse effects following immunization,[18][19] disputes have arisen over the morality, ethics, effectiveness, and safety of vaccination. Some vaccination critics say that vaccines are ineffective against disease[20] or that vaccine safety studies are inadequate.[19][20] Some religious groups do not allow vaccination,[21] and some political groups oppose mandatory vaccination on the grounds of individual liberty.[17]

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.[22]

Most vaccine development to date has relied on "push" funding by government, universities and non-profit organizations.[23] Many vaccines have been highly cost effective and beneficial for public health.[22] The number of vaccines actually administered has risen dramatically in recent decades. This increase, particularly in the number of different vaccines administered to children before entry into schools[24] may be due to government mandates and support, rather than economic incentive.[citation needed]

Many researchers and policymakers are calling for a different approach, using "pull" mechanisms to motivate industry. Mechanisms such as prizes, tax credits, or advance market commitments could ensure a financial return to firms that successfully developed an HIV vaccine. If the policy were well-designed, it might also ensure people have access to a vaccine if and when it is developed.[citation needed]

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 on the development of new vaccines as well as the protection of secrecy.[25]

Production

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)[26]. Bacteria are grown in bioreactors (e.g., Haemophilus influenzae type b). Alternatively, 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.[27] Combination vaccines are harder to develop and produce, because of potential incompatibilities and interactions among the antigens and other ingredients involved.[28]

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 productivitity and few 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.[28]

Excipients

Beside the active vaccine itself, the following excipients are commonly present in vaccine preparations:[29]

  • 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 kill unwanted viruses and 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 preservative that is added to vials of vaccine that contain more than one dose to prevent contamination and growth of potentially harmful bacteria.

Role of preservatives

Many vaccines need preservatives to prevent serious adverse effects such as the Staphylococcus infection that, in one 1928 incident, killed 12 of 21 children inoculated with a diphtheria vaccine that lacked a preservative.[30] Several preservatives are available, including thiomersal, phenoxyethanol, and formaldehyde. Thiomersal is more effective against bacteria, has 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.[31] Although controversial claims have been made that thiomersal contributes to autism, no convincing scientific evidence supports these claims.[32][33][34]

Delivery systems

Woman receiving rubella vaccination, Brazil, 2008.

There are several new delivery systems in development, which will hopefully make vaccines more efficient to deliver. Possible methods include liposomes and ISCOM (immune stimulating complex).[35]

The latest developments in vaccine delivery technologies have resulted in oral vaccines. A polio vaccine was developed and tested by volunteer vaccinations with no formal training; the results were very positive in that the ease of the vaccines increased dramatically. With an oral vaccine, there is no risk of blood contamination. Oral vaccines are likely to be solid which have proven to be more stable and less likely to freeze; this 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, will decrease costs of vaccines. Finally, a microneedle approach, which is still in stages of development, seems to be the vaccine of the future, the microneedle, which is "pointed projections fabricated into arrays that can create vaccine delivery pathways through the skin".[36]

Plasmids

The use of plasmids has been validated in preclinical studies as a protective vaccine strategy for cancer and infectious diseases. However, the crossover application into human studies has been met with poor results based on the inability 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.[37]

Use in nonhumans

Vaccinations of animals are used both to prevent their contracting diseases and to prevent transmission of disease to humans[38]. 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.

Trends

Vaccine development has several trends:[39]

  • Until recently, most vaccines were aimed at infants and children, but adolescents and adults are increasingly being targeted.[39][40]
  • Combinations of vaccines are becoming more common; vaccines containing five or more components are used in many parts of the world.[39]
  • New methods of administering vaccines are being developed, such as skin patches, aerosols via inhalation devices, and eating genetically engineered plants.[39]
  • Vaccines are being designed to stimulate innate immune responses, as well as adaptive.[39]
  • Attempts are being made to develop vaccines to help cure chronic infections, as opposed to preventing disease.[39]
  • Vaccines are being developed to defend against bioterrorist attacks such as anthrax, plague, and smallpox.[39]

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.[41] For example, the experimental vaccine CYT006-AngQb has been investigated as a possible treatment for high blood pressure.[42] Factors that have impact on the trends of vaccine development include progress in translatory medicine, demographics, regulatory science, political, cultural, and social responses.[43]

See also

References

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  5. ^ The Main Types of Vaccines
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  7. ^ Meri S, Jördens M, Jarva H. Microbial complement inhibitors as vaccines. Vaccine. 2008 Dec 30;26 Suppl 8:I113-7. Review.PMID: 19388175
  8. ^ Monovalent at Dorland's Medical Dictionary
  9. ^ Polyvalent vaccine at Dorlands Medical Dictionary
  10. ^ "Questions and answers on monovalent oral polio vaccine type 1 (mOPV1) “Issued jointly by WHO and UNICEF”". http://www.pediatriconcall.com/fordoctor/medical_original_articles/oral_polio_vaccine.asp. 
  11. ^ Sutter RW, Cochi SL, Melnick JL (1999). "Live attenuated polio vaccines". in Plotkin SA, Orenstein WA (eds.). Vaccines. Philadelphia: W. B. Saunders. pp. 364–408. 
  12. ^ 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): 3179–3188. doi:10.1016/S0264-410X(01)00020-2. PMID 11312014. 
  13. ^ Grammatikos AP, Mantadakis E, Falagas ME. Meta-analyses on pediatric infections and vaccines. Infect Dis Clin North Am. 2009; 23(2):431-57.PMID 19393917
  14. ^ "Adapting Vaccines For Our Aging Immune Systems". http://www.npr.org/templates/story/story.php?storyId=123406640. 
  15. ^ 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. http://www.journals.uchicago.edu/doi/full/10.1086/377693. 
  16. ^ a b c "Measles--United States, January 1-April 25, 2008". MMWR Morb. Mortal. Wkly. Rep. 57 (18): 494–8. May 2008. PMID 18463608. http://www.cdc.gov/mmwr/preview/mmwrhtml/mm5718a5.htm. 
  17. ^ a b Wolfe R, Sharp L (2002). "Anti-vaccinationists past and present". BMJ 325 (7361): 430–2. doi:10.1136/bmj.325.7361.430. PMID 12193361. http://bmj.bmjjournals.com/cgi/content/full/325/7361/430. 
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  19. ^ a b Demicheli V, Jefferson T, Rivetti A, Price D (2005). "Vaccines for measles, mumps and rubella in children". Cochrane Database Syst Rev 19 (4). doi:10.1002/14651858.CD004407.pub2. PMID 16235361. Lay summary – Cochrane press release (PDF) (2005-10-19). 
  20. ^ a b Halvorsen R (2007). The Truth about Vaccines. Gibson Square. ISBN 9781903933923. 
  21. ^ Sinal SH, Cabinum-Foeller E, Socolar R (2008). "Religion and medical neglect". South Med J 101 (7): 703–6. doi:10.1097/SMJ.0b013e31817997c9 (inactive 2008-10-26). PMID 18580731. 
  22. ^ a b Goodman, Jesse L. (2005-05-04). "Statement of Jesse L. Goodman, M.D., M.P.H. Director, Center for Biologics, Evaluation and Research Before the Committee on Energy and Commerce United States House of Representatives". http://www.fda.gov/ola/2005/influenza0504.html. Retrieved 2008-06-15. 
  23. ^ Olesen OF, Lonnroth A, Mulligan B (2009). "Human vaccine research in the European Union". Vaccine 27 (5): 640–5. doi:10.1016/j.vaccine.2008.11.064. PMID 19059446. 
  24. ^ Ihara T. The strategy for prevention of measles and rubella prevalence with measles-rubella (MR) vaccine in Japan. Vaccine. 2009 Mar 5. [Epub ahead of print]PMID: 19366578
  25. ^ 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. 
  26. ^ The Washington Post: Three ways to make a vaccine
  27. ^ 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. 
  28. ^ 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. 
  29. ^ CDC. "Ingredients of Vaccines - Fact Sheet". http://www.cdc.gov/vaccines/vac-gen/additives.htm. Retrieved december 20, 2009. 
  30. ^ "Thimerosal in vaccines". Center for Biologics Evaluation and Research, U.S. Food and Drug Administration. 2007-09-06. http://www.fda.gov/BiologicsBloodVaccines/SafetyAvailability/VaccineSafety/UCM096228. Retrieved 2007-10-01. 
  31. ^ 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. 
  32. ^ Boseley, Sarah (Tuesday 2 February 2010 16.29 GMT). "Lancet retracts 'utterly false' MMR paper". Guardian.co.uk. http://www.guardian.co.uk/society/2010/feb/02/lancet-retracts-mmr-paper. Retrieved 2 February 2010. 
  33. ^ Wang, Shirley (February 2, 2010). "Lancet Retracts Study Tying Vaccine to Autism". Wall Street Journal. http://online.wsj.com/article/SB10001424052748704022804575041212437364420.html?mod=WSJ_hp_mostpop_emailed. Retrieved 2 February 2010. 
  34. ^ Offit PA (2007). "Thimerosal and vaccines—a cautionary tale". N Engl J Med 357 (13): 1278–9. doi:10.1056/NEJMp078187. PMID 17898096. http://content.nejm.org/cgi/content/full/357/13/1278. 
  35. ^ 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. 
  36. ^ 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. 
  37. ^ Lowe et al. (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. http://www.horizonpress.com/pla. 
  38. ^ Patel JR, Heldens JG. Immunoprophylaxis against important virus disease of horses, farm animals and birds. Vaccine. 2009 Mar 13;27(12):1797-1810. Review. PMID: 19402200
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  40. ^ Carlson B (2008). "Adults now drive growth of vaccine market". Genet Eng Biotechnol News 28 (11): 22–3. http://www.genengnews.com/articles/chitem.aspx?aid=2490. 
  41. ^ 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. 
  42. ^ Samuelsson O, Herlitz H (2008). "Vaccination against high blood pressure: a new strategy". Lancet 371 (9615): 788–9. doi:10.1016/S0140-6736(08)60355-4. PMID 18328909. 
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External links


Simple English

A vaccine is a medication, usually of biological origin, which improves immunity to a particular disease. The term derives from the Latin vaccīn-us (from vacca cow); in 1796 Edward Jenner used cows infected with cowpox (variolae vaccinae) to protect people against smallpox.[1]

Contents

History

In the 19th century Louis Pasteur developed a rabies vaccine. In the 20th century vaccines were introduced against diphtheria, measles, mumps, and rubella. In 1950s the polio vaccine was developed. However, vaccines still do not exist for many important diseases, including malaria and HIV.[1]Compulsory vaccination laws were passed.[1]

Types of vaccines

A vaccine typically contains an agent that resembles a disease-causing microorganism in weakened or killed forms or its toxins. While the majority of vaccines are dead, inactivated or attenuated organisms, purified products derived from them, some vaccines are synthetic vaccines. The latter are composed mainly or wholly of synthetic peptides, carbohydrates or antigens.

There are several types of vaccines currently in use. [2]

  • Dead vaccines contain killed, but previously virulent, microorganisms which have been destroyed by chemicals or heat: influenza vaccine, cholera vaccine, bubonic plague vaccine, polio vaccine , hepatitis A vaccine, and rabies vaccine.
  • Attenuated vaccines contain live microorganisms that have been cultivated under conditions that disable their virulent properties, or which use closely related but less dangerous organisms to produce a immune response. They typically provoke more durable immunological responses than killed vaccines and are the preferred type for healthy adults. Examples include yellow fever, measles, rubella, and mumps and typhoid. The live Mycobacterium tuberculosis vaccine contains a virulently modified strain called "BCG".
  • Toxoid vaccines are made from inactivated toxic compounds that cause illness rather than the micro-organism. Examples include tetanus and diphtheria. Although Crotalus atrox toxoid is used to vaccinate dogs against rattlesnake bites.
  • Subunit vaccines contain Protein subunits. Rather than introduce an attenuated microorganism 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, 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.
  • Conjugate vaccines derive from the fact that certain bacteria have poorly immunogenic polysaccharide outer coats. By linking these outer coats to proteins (e.g. toxins), the immune system begins to recognize the polysaccharide as if it were a protein antigen. The example is Haemophilus influenzae type B vaccine.
  • Some vaccines are in development:
      • Dendritic cell vaccines combine dendritic cells with antigens. These vaccines have shown some positive preliminary results for treating brain tumors.[3]
      • Recombinant vaccine combines the physiology of one microorganism and the DNA of the other. Immunity can be created against diseases that have complex infection processes
      • DNA vaccination created from an infectious agent's DNA. It works by insertion (and expression, triggering immune system recognition) of viral or bacterial DNA into human or animal cells. Some cells of the immune system will mount an attack against these proteins and cells expressing them. One advantage of DNA vaccines is that they are very easy to produce and store.
      • T-cell receptor peptide vaccines are under development for Valley Fever, stomatitis, and atopic dermatitis. These peptides have been shown to modulate cytokine production and improve cell mediated immunity.
  • Valence of vaccines

Vaccines may be monovalent or multivalent. A monovalent vaccine is designed to immunize against a single antigen or single microorganism.[4] A multivalent vaccine is designed to immunize against two or more strains of the same microorganism, or against two or more microorganisms. [5] In certain cases a monovalent vaccine may be preferable for rapidly developing a strong immune response.[6] When two or more vaccines are mixed together in the same formulation, they can interfere as in 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 2 viruses in the vaccine.[7] 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.[8]

Developing immunity

Vaccines can be prophylactic (e.g. to prevent or ameliorate the effects of a future infection by any natural pathogen), or therapeutic (e.g. vaccines against cancer). The agent in the vaccine stimulates the body's immune system to recognize the agent as foreign, destroy it, and "remember" it. Then the immune system can more easily recognize and destroy any of the microorganisms that it later encounters. When the virulent version of an agent comes along 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) by recognizing and destroying infected cells before that agent can multiply to vast numbers.

Effectiveness of vaccines

Vaccines do not guarantee complete protection from a disease.[9] Sometimes, this is because the host's immune system simply does not respond adequately or at all. This may be due to a lowered immunity in general (diabetes, steroid use, HIV infection, age) or because the host's immune system does not have a B cell capable of generating antibodies to that antigen. Even if the host develops antibodies, the immune system might still not be able to defeat the infection.

The efficacy is dependent on a number of factors:

  • the disease itself (for some diseases vaccination performs better than for other diseases)
  • the strain of vaccine (some vaccinations are for different strains of the disease) [1]
  • whether one kept to the timetable for the vaccinations (see Vaccination schedule). Vaccines usually do not produce ever-lasting effect, so they need repeated administration on vaccination schedule.
  • some individuals are "non-responders" to certain vaccines, meaning that they do not generate antibodies even after being vaccinated correctly
  • other factors such as ethnicity, age, or genetic predisposition. Larger doses are used in some cases for older people (50–75 years and up), whose immune response to a given vaccine is not as strong.[10]

Adjuvants usually boost immune response. They include aluminium adjuvants, squalene, squalene and phosphate adjuvants.

Controversy in using vaccines

Opposition to using vaccines has existed since the earliest time.[11] Although the benefits of using vaccines in preventing suffering and death from infectious diseases greatly outweigh the risks of rare adverse effects following administration of vaccines,[12][13] disputes have arisen over the morality, ethics, effectiveness, safety of using vaccines and their effectiveness[14] or that vaccine safety studies are inadequate.[13][14] Some religious groups do not allow uses of vaccines, [15] and some political groups oppose mandatory vaccination on the grounds of individual liberty.[11] In response, concern has been raised about the medical risks of vaccines, increased rates of life-threatening infections.[16]

Economics of development and patents

One challenge in vaccine development is economic. The diseases most demanding a vaccine, 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, the financial and other risks are great.[17]

Most vaccine development to date has relied on governments, universities and non-profit organizations.[18] Many vaccines have been highly cost effective and beneficial for public health.[17] The number of vaccines actually administered has risen dramatically in recent decades. This increase, particularly in the number of different vaccines administered to children before entry into schools[19] may be due to government mandates and support, rather than economic incentive.

The filing of patents on vaccine development processes can 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 on the development of new vaccines as well as the protection of secrecy.[20]

Stages in production of vaccines

  • In first stage, the antigen itself is generated. Viruses are grown 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).[21] Bacteria are grown in bioreactors (e.g., Haemophilus influenzae type b). A recombinant protein derived from the viruses or bacteria can also be generated in yeast, bacteria, or cell cultures.
  • The antigen 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.[22] Combination vaccines are harder to develop and produce, because of potential incompatibilities and interactions among the antigens and other ingredients involved.[23]

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 productivitity and few 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.[23]

Additional components in vaccines

In vaccine preparations beside the active vaccine itself, the following components are commonly present :[24]

  • Aluminum salts or gels are added as adjuvants 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 or to kill unwanted viruses and 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 preservative is added to vials of vaccine that contain more than one dose to prevent contamination and growth of potentially harmful bacteria.

Preservatives in vaccines, such as thiomersal, phenoxyethanol, and formaldehyde, prevent serious adverse effects. Thiomersal is more effective against bacteria, has better shelf life, and improves vaccine stability, potency, and safety, but in the U.S., the European Union, and a few other rich countries, it is no longer used as a preservative in childhood vaccines, as a precautionary measure due to its mercury content.[25] Although controversial claims have been made that thiomersal contributes to autism, no convincing scientific evidence supports these claims.[26] Absence of any preservative in vaccine may result in adverse effects, such as Staphylococcus infection that, in one 1928 incident, killed 12 of 21 children inoculated with a diphtheria vaccine that lacked a preservative.[27]

Delivery systems

There are several new delivery systems in development, which will hopefully make vaccines more efficient to deliver. Possible methods include liposomes and ISCOM (immune stimulating complex).[28] New delivery technologies have resulted in oral vaccines, as a polio vaccine. With an oral vaccine, there is no risk of blood contamination. Solid oral vaccines have proven to be more stable and less likely to freeze; this 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, will decrease costs of vaccines. Finally, a micro needle approach seems to be the vaccine of the future. The microneedle, which is "pointed projections fabricated into arrays that can create vaccine delivery pathways through the skin".[29]

Use in veterinary medicine

Vaccinations of animals are used both to prevent their contracting diseases and to prevent transmission of disease to humans.[30] 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.

Several trends in vaccine development

[31]

  • Nowadays, vaccines were aimed at infants, children, as well as at adolescents and adults. [31][32]
  • Combinations of vaccines are becoming more common; vaccines containing five or more components are used in many parts of the world.[31]
  • New methods of administering vaccines are being developed, such as skin patches, aerosols via inhalation devices, and eating genetically engineered plants.[31]
  • Vaccines are being designed to stimulate innate and adaptive immune responses.[31]
  • Attempts are being made to develop vaccines to help cure chronic infections, as opposed to preventing disease.[31]
  • Appreciation for sex and pregnancy differences in vaccine responses "might change the strategies used by public health officials".[33]

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.[34] For example, the experimental vaccine CYT006-AngQb has been investigated as a possible treatment for high blood pressure.[35]

References

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  2. The Main Types of Vaccines
  3. Kim W, Liau LM (2010). [Expression error: Unexpected < operator "Dendritic cell vaccines for brain tumors"]. Neurosurg Clin N Am 21 (1): 139–57. doi:10.1016/j.nec.2009.09.005. PMID 19944973. 
  4. Monovalent at Dorland's Medical Dictionary
  5. Polyvalent vaccine at Dorlands Medical Dictionary
  6. "Questions and answers on monovalent oral polio vaccine type 1 (mOPV1) “Issued jointly by WHO and UNICEF”". http://www.pediatriconcall.com/fordoctor/medical_original_articles/oral_polio_vaccine.asp. 
  7. Sutter RW, Cochi SL, Melnick JL (1999). "Live attenuated polio vaccines". In Plotkin SA, Orenstein WA (eds.). Vaccines. Philadelphia: W. B. Saunders. pp. 364–408. 
  8. Kanesa-thasan N, Sun W, Kim-Ahn G, et al. (2001). [Expression error: Unexpected < operator "Safety and immunogenicity of attenuated dengue virus vaccines (Aventis Pasteur) in human volunteers"]. Vaccine 19 (23–24): 3179–3188. doi:10.1016/S0264-410X(01)00020-2. PMID 11312014. 
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  10. "Adapting Vaccines For Our Aging Immune Systems". http://www.npr.org/templates/story/story.php?storyId=123406640. 
  11. 11.0 11.1 Wolfe R, Sharp L (2002). "Anti-vaccinationists past and present". BMJ 325 (7361): 430–2. doi:10.1136/bmj.325.7361.430. PMID 12193361. http://bmj.bmjjournals.com/cgi/content/full/325/7361/430. 
  12. Bonhoeffer J, Heininger U (2007). [Expression error: Unexpected < operator "Adverse events following immunization: perception and evidence"]. Curr Opin Infect Dis 20 (3): 237–46. doi:10.1097/QCO.0b013e32811ebfb0. PMID 17471032. 
  13. 13.0 13.1 Demicheli V, Jefferson T, Rivetti A, Price D (2005). [Expression error: Unexpected < operator "Vaccines for measles, mumps and rubella in children"]. Cochrane Database Syst Rev 19 (4). doi:10.1002/14651858.CD004407.pub2. PMID 16235361. Lay summary – Cochrane press release (PDF) (2005-10-19). 
  14. 14.0 14.1 Halvorsen R (2007). The Truth about Vaccines. Gibson Square. ISBN 9781903933923. 
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  16. Vaccine Refusal, Mandatory Immunization, and the Risks of Vaccine-Preventable Diseases by Saad B. Omer, M.B., B.S., Ph.D., M.P.H., Daniel A. Salmon, Ph.D., M.P.H., Walter A. Orenstein, M.D., M. Patricia deHart, Sc.D., and Neal Halsey, M.D. in the New England Journal of Medicine, Volume 360:1981-1988, May 7, 2009.http://content.nejm.org/cgi/content/full/360/19/1981
  17. 17.0 17.1 Goodman, Jesse L. (2005-05-04). "Statement of Jesse L. Goodman, M.D., M.P.H. Director, Center for Biologics, Evaluation and Research Before the Committee on Energy and Commerce United States House of Representatives". http://www.fda.gov/ola/2005/influenza0504.html. Retrieved 2008-06-15. 
  18. Olesen OF, Lonnroth A, Mulligan B (2009). [Expression error: Unexpected < operator "Human vaccine research in the European Union"]. Vaccine 27 (5): 640–5. doi:10.1016/j.vaccine.2008.11.064. PMID 19059446. 
  19. . PMID 19366578. 
  20. Hardman Reis T (2006). [Expression error: Unexpected < operator "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. 
  21. The Washington Post: Three ways to make a vaccine
  22. Muzumdar JM, Cline RR (2009). [Expression error: Unexpected < operator "Vaccine supply, demand, and policy: a primer"]. J Am Pharm Assoc 49 (4): e87–99. doi:10.1331/JAPhA.2009.09007. PMID 19589753. 
  23. 23.0 23.1 Bae K, Choi J, Jang Y, Ahn S, Hur B (2009). [Expression error: Unexpected < operator "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. 
  24. CDC. "Ingredients of Vaccines - Fact Sheet". http://www.cdc.gov/vaccines/vac-gen/additives.htm. Retrieved december 20, 2009. 
  25. Bigham M, Copes R (2005). [Expression error: Unexpected < operator "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. 
  26. Offit PA (2007). "Thimerosal and vaccines—a cautionary tale". N Engl J Med 357 (13): 1278–9. doi:10.1056/NEJMp078187. PMID 17898096. http://content.nejm.org/cgi/content/full/357/13/1278. 
  27. "Thimerosal in vaccines". Center for Biologics Evaluation and Research, U.S. Food and Drug Administration. 2007-09-06. http://www.fda.gov/BiologicsBloodVaccines/SafetyAvailability/VaccineSafety/UCM096228. Retrieved 2007-10-01. 
  28. Morein B, Hu KF, Abusugra I (2004). [Expression error: Unexpected < operator "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. 
  29. Giudice EL, Campbell JD (2006). [Expression error: Unexpected < operator "Needle-free vaccine delivery"]. Adv Drug Deliv Rev 58 (1): 68–89. doi:10.1016/j.addr.2005.12.003. PMID 16564111. 
  30. . PMID 19402200. 
  31. 31.0 31.1 31.2 31.3 31.4 31.5 Plotkin SA (2005). [Expression error: Unexpected < operator "Vaccines: past, present and future"]. Nat Med 11 (4 Suppl): S5–11. doi:10.1038/nm1209. PMID 15812490. 
  32. Carlson B (2008). "Adults now drive growth of vaccine market". Genet Eng Biotechnol News 28 (11): 22–3. http://www.genengnews.com/articles/chitem.aspx?aid=2490. 
  33. Klein SL, Jedlicka A, Pekosz A (May 2010). [Expression error: Unexpected < operator "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. 
  34. Spohn G, Bachmann MF (2008). [Expression error: Unexpected < operator "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. 
  35. Samuelsson O, Herlitz H (2008). [Expression error: Unexpected < operator "Vaccination against high blood pressure: a new strategy"]. Lancet 371 (9615): 788–9. doi:10.1016/S0140-6736(08)60355-4. PMID 18328909. 


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