Attenuated vaccine

An attenuated vaccine is a vaccine created by reducing the virulence of a pathogen, but still keeping it viable (or "live").[1] Attenuation takes an infectious agent and alters it so that it becomes harmless or less virulent. These vaccines contrast to those produced by "killing" the virus (inactivated vaccine).

Examples

Examples of "live" (example attenuated) vaccines include:

Development

Viruses may be attenuated via passage of the virus through a foreign host, such as:

  • Tissue culture
  • Embryonated eggs
  • Live animals

The initial virus population is applied to a foreign host. One or more of these will possess a mutation that enables it to infect the new host. These mutations will spread, as the mutations allow the virus to grow well in the new host; the result is a population that is significantly different from the initial population, and thus will not grow well in the original host when it is re-introduced (hence is "attenuated"). This process is known as "passage" in which the virus becomes so well adapted to the foreign host that it is no longer harmful to the vaccinated subject. This makes it easier for the host's immune system to eliminate the agent and create the immunological memory cells which will likely protect the patient if they are infected with a similar version of the virus in "the wild".

Administration

In an attenuated vaccine, live virus particles with very low virulence are administered. They will reproduce, but very slowly. Since they do reproduce and continue to present antigen beyond the initial vaccination, boosters are required less often. These vaccines are produced by growing the virus in tissue cultures that will select for less virulent strains, or by mutagenesis or targeted deletions in genes required for virulence. There is a small risk of reversion to virulence; this risk is smaller in vaccines with deletions. Attenuated vaccines also cannot be used by immunocompromised individuals.

Advantages
  • Activates all phases of the immune system (for instance IgA local antibodies are produced)[4]
  • Provides more durable immunity; boosters are required less frequently[5]
  • Low cost [6]
  • Quick immunity
  • Some are easy to transport/administer (for instance OPV for polio can be taken orally, rather than requiring a sterile injection by a trained healthworker, as the inactivated form IPV does)[7]
  • Vaccines have strong beneficial non-specific effects. That is effects which go beyond the specific protective effects against the targeted diseases.[8]

Disadvantages
  • Secondary mutation can cause a reversion to virulence.[9] In this case, the virus can mutate back to the wild type virus or mutate further.
  • Can cause severe complications in immunocompromised patients.[10]
  • Some can be difficult to transport due to requirement to maintain conditions (e.g. temperature)

References
  1. Badgett MR, Auer A, Carmichael LE, Parrish CR, Bull JJ (October 2002). "Evolutionary dynamics of viral attenuation". J. Virol. 76 (20): 10524–9. doi:10.1128/JVI.76.20.10524-10529.2002. PMC 136581. PMID 12239331.
  2. "Immunization". Archived from the original on 7 March 2009. Retrieved 2009-03-10.
  3. Levine, Myron M.; Ferreccio, Catterine; Black, Robert E.; Lagos, Rosanna; Martin, Oriana San; Blackwelder, William C. (July 15, 2007). "Ty21a Live Oral Typhoid Vaccine and Prevention of Paratyphoid Fever Caused by Salmonella enterica Serovar Paratyphi B". Clinical Infectious Diseases. 45 (Supplement 1): S24–S28. doi:10.1086/518141. ISSN 1058-4838. PMID 17582564.
  4. Pasetti, Marcela F; Simon, Jakub K.; Sztein, Marcelo B.; Levine, Myron M. (9 March 2012). "Immunology of Gut Mucosal Vaccines". Immunological Reviews. 239 (1): 125–148. doi:10.1111/j.1600-065X.2010.00970.x. PMC 3298192. PMID 21198669.
  5. "Vaccine Types | Vaccines.gov". www.vaccines.gov. Retrieved 2019-02-25.
  6. Minor, Philip D. (2015-05-01). "Live attenuated vaccines: Historical successes and current challenges". Virology. 60th Anniversary Issue. 479-480: 379–392. doi:10.1016/j.virol.2015.03.032. ISSN 0042-6822.
  7. "Polio and the Introduction of IPV for health workers (September 2014)" (PDF). WHO.int. World Health Organization. 1 September 2014. Archived from the original (PDF) on 20 July 2016. Retrieved 20 July 2016.
  8. Benn, Christine S.; Netea, Mihai G.; Selin, Liisa K.; Aaby, Peter (September 2013). "A small jab – a big effect: nonspecific immunomodulation by vaccines". Trends in Immunology. 34 (9): 431–439. doi:10.1016/j.it.2013.04.004. PMID 23680130.
  9. Shimizu H, Thorley B, Paladin FJ, et al. (December 2004). "Circulation of type 1 vaccine-derived poliovirus in the Philippines in 2001". J. Virol. 78 (24): 13512–21. doi:10.1128/JVI.78.24.13512-13521.2004. PMC 533948. PMID 15564462.
  10. Kroger, Andrew T.; Ciro V. Sumaya; Larry K. Pickering; William L. Atkinson (2011-01-28). "General Recommendations on Immunization: Recommendations of the Advisory Committee on Immunization Practices (ACIP)". Morbidity and Mortality Weekly Report (MMWR). Centers for Disease Control and Prevention. Retrieved 2011-03-11.
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