Vaccine

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A modern kit to vaccinate against smallpox

A vaccine is a medication, usually made from something that is or was alive, that gives immunity to a particular bacterial or viral disease. The term comes from the Latin vaccīn-us (from vacca, meaning cow); in 1796 Edward Jenner used cows infected with cowpox (variolae vaccinae) to protect people against smallpox.[1]

History[change | edit source]

In the 1770s, Edward Jenner realised that people who had already had cowpox (a disease that is related to smallpox) usually did not get smallpox. He inoculated a boy with cowpox to test this. Then he infected the boy with smallpox. The boy did not get sick because he had already had cowpox. Because cowpox inoculation made fewer people sick than smallpox inoculation, England made smallpox inoculation illegal in 1840. In 1853, they made another law that every child had to be vaccinated.

In the 19th century Louis Pasteur made a rabies vaccine. In the 20th century vaccines were introduced against diphtheria, measles, mumps, and rubella. In the 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[change | edit source]

A vaccine often contains something like a germ that has been weakened or killed or the germ's toxins. Some vaccines are synthetic vaccines that are made in a laboratory.

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

Developing immunity[change | edit source]

Vaccines can be prophylactic (e.g. to make the effects of a future infection by any natural pathogen less dangerous or stop them completely), 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[change | edit source]

Vaccines do not guarantee complete protection from a disease.[3] 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) [4]
  • whether one kept to the timetable for the vaccinations (see Vaccination schedule). Vaccines usually do not produce permanent effects, so they might need many different vaccinations on a schedule.
  • some individuals are "non-responders" to certain vaccines, meaning that their immune systems do not create 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.[5]

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

Controversy in not using vaccines[change | edit source]

Opposition to using vaccines has existed since the earliest time.[6] 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,[7][8] disputes have arisen over the morality, ethics, effectiveness, safety of using vaccines[9] or that vaccine safety studies are inadequate.[8][9] Some religious groups do not allow uses of vaccines, [10] and some political groups oppose mandatory vaccination on the grounds of individual liberty.[6] In response a study says- "Vaccine refusal not only increases the individual risk of disease but also increases the risk for the whole community.[11]

In a study of parents of children aged between six months and six years of age it was found that only “13% of parents who reported following an alternative vaccination schedule, most refused only certain vaccines (53%) and/or delayed some vaccines until the child was older (55%). Only 17% reported refusing all vaccines.”(Dempsey). Now knowing that there are more people delaying vaccination as opposed to completely skipping vaccination, we can see that there are arguably more people realizing the need for these vaccinations. As discussed earlier, there are people who are concerned about the safety of the vaccinations being given, thus the reason for so many people choosing to delay certain vaccinations until their child is older. The main reasons for concerns of safety seem to be linked to concerns regarding a child’s fragile immune system. This concern is based upon reports that some live viral vaccines, such as those containing attenuated measles virus, can decrease protective immune response to the varicella vaccine and that it can cause excess invasive bacterial infections in developing countries. It should be known that the current vaccines have not been shown to cause immunosuppression in healthy children (Chatterjee).

Principle 18 of the Yogyakarta Principles also affirm the protection from unethical or involuntary treatments including vaccines[12]

Economics of development and patents[change | edit source]

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.[13]

Most vaccine development to date has relied on governments, universities and non-profit organizations.[14] Many vaccines have been highly cost effective and beneficial for public health.[13] 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[15] 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.[16]

Stages in production of vaccines[change | edit source]

  • 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).[17] 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.[18] Combination vaccines are harder to develop and produce, because of potential incompatibilities and interactions among the antigens and other ingredients involved.[19]

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.[19]

Additional components in vaccines[change | edit source]

In vaccine preparations beside the active vaccine itself, the following components are commonly present :[20]

  • 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.[21] Although controversial claims have been made that thiomersal contributes to autism, no convincing scientific evidence supports these claims.[22] 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.[23]

Delivery systems[change | edit source]

A child is vaccinated against poliomyelitis. This vaccine can be given orally, such as a few drops of liquid on a piece of sugar.

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).[24] 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".[25]

Use in veterinary medicine[change | edit source]

Vaccinations of animals are used both to prevent their contracting diseases and to prevent transmission of disease to humans.[26] 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[change | edit source]

  • Nowadays, vaccines were aimed at infants, children, as well as at adolescents and adults.[27][28]
  • Combinations of vaccines are becoming more common; vaccines containing five or more components are used in many parts of the world.[27]
  • New methods of administering vaccines are being developed, such as skin patches, aerosols via inhalation devices, and eating genetically engineered plants.[27]
  • Vaccines are being designed to stimulate innate and adaptive immune responses.[27]
  • Attempts are being made to develop vaccines to help cure chronic infections, as opposed to preventing disease.[27]
  • Appreciation for sex and pregnancy differences in vaccine responses "might change the strategies used by public health officials".[29]

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.[30] For example, the experimental vaccine CYT006-AngQb has been investigated as a possible treatment for high blood pressure.[31]

References[change | edit source]

  1. 1.0 1.1 1.2 Stern AM, Markel H (2005). "The history of vaccines and immunization: familiar patterns, new challenges". Health Aff 24 (3): 611–21. doi:10.1377/hlthaff.24.3.611. PMID 15886151. http://content.healthaffairs.org/cgi/content/full/24/3/611.
  2. The Main Types of Vaccines
  3. . PMID 19393917.
  4. http://bmj.bmjjournals.com/cgi/content/full/319/7206/352
  5. "Adapting Vaccines For Our Aging Immune Systems". http://www.npr.org/templates/story/story.php?storyId=123406640.
  6. 6.0 6.1 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.
  7. Bonhoeffer J, Heininger U (2007). "Adverse events following immunization: perception and evidence". Curr Opin Infect Dis 20 (3): 237–46. doi:10.1097/QCO.0b013e32811ebfb0. PMID 17471032.
  8. 8.0 8.1 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).
  9. 9.0 9.1 Halvorsen R (2007). The Truth about Vaccines. Gibson Square. ISBN 9781903933923.
  10. 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.
  11. 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
  12. Yogyakarta Principles, Principle 18. Protection from Medical Abuse,(d)
  13. 13.0 13.1 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.
  14. 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.
  15. . PMID 19366578.
  16. 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.
  17. The Washington Post: Three ways to make a vaccine
  18. 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.
  19. 19.0 19.1 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.
  20. CDC. "Ingredients of Vaccines - Fact Sheet". http://www.cdc.gov/vaccines/vac-gen/additives.htm. Retrieved December 20, 2009.
  21. 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.
  22. 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.
  23. "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.
  24. 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.
  25. 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.
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  28. 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.
  29. 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.
  30. 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.
  31. 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.