Attenuated vaccine: Difference between revisions

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Vaccines function by encouraging the creation of cells, such as [[Cytotoxic T cell|CD8+]] and [[T helper cell|CD4+ T lymphocytes]], or molecules, such as [[Antibody|antibodies]], that are specific to the [[pathogen]].<ref name=":02">{{Cite book|url=https://www.worldcat.org/oclc/989157433|title=Plotkin's vaccines|others=Plotkin, Stanley A., 1932-, Orenstein, Walter A.,, Offit, Paul A.|year=2018|isbn=978-0-323-39302-7|edition=Seventh|location=Philadelphia, PA|oclc=989157433}}</ref> The cells and molecules can either prevent or reduce infection by killing infected cells or by producing [[interleukin]]s.<ref name=":02" /> The specific effectors evoked can be different based on the vaccine.<ref name=":02" /> Live attenuated vaccines tend to help with the production of CD8+ cytotoxic T lymphocytes and T-dependent antibody responses.<ref name=":02" /> A vaccine is only effective for as long as the body maintains a population of these cells {{citation needed|date=November 2020}}. Live attenuated vaccines can induce long-term, possibly lifelong, immunity without requiring multiple vaccine doses.<ref name=":2" /><ref name=":02" /> Live attenuated vaccines can also induce [[Cell-mediated immunity|cellular immune responses]], which do not rely solely on antibodies but also involve immune cells such as cytotoxic T cells or macrophages.<ref name=":2" />
Vaccines function by encouraging the creation of cells, such as [[Cytotoxic T cell|CD8+]] and [[T helper cell|CD4+ T lymphocytes]], or molecules, such as [[Antibody|antibodies]], that are specific to the [[pathogen]].<ref name=":02">{{Cite book|url=https://www.worldcat.org/oclc/989157433|title=Plotkin's vaccines|others=Plotkin, Stanley A., 1932-, Orenstein, Walter A.,, Offit, Paul A.|year=2018|isbn=978-0-323-39302-7|edition=Seventh|location=Philadelphia, PA|oclc=989157433}}</ref> The cells and molecules can either prevent or reduce infection by killing infected cells or by producing [[interleukin]]s.<ref name=":02" /> The specific effectors evoked can be different based on the vaccine.<ref name=":02" /> Live attenuated vaccines tend to help with the production of CD8+ cytotoxic T lymphocytes and T-dependent antibody responses.<ref name=":02" /> A vaccine is only effective for as long as the body maintains a population of these cells {{citation needed|date=November 2020}}. Live attenuated vaccines can induce long-term, possibly lifelong, immunity without requiring multiple vaccine doses.<ref name=":2" /><ref name=":02" /> Live attenuated vaccines can also induce [[Cell-mediated immunity|cellular immune responses]], which do not rely solely on antibodies but also involve immune cells such as cytotoxic T cells or macrophages.<ref name=":2" />


==Advantages==
==Advantages and Disadvantages==
*Activates all phases of the [[immune system]] (for instance [[IgA]] local [[antibodies]] are produced)<ref name="NCBI">{{cite journal|last1=Pasetti|first1=Marcela F|last2=Simon|first2=Jakub K.|last3=Sztein|first3=Marcelo B.|last4=Levine|first4=Myron M.|title=Immunology of Gut Mucosal Vaccines|volume=239|issue=1|pages=125–148|pmc=3298192|journal=Immunological Reviews|date=9 March 2012|pmid=21198669|doi=10.1111/j.1600-065X.2010.00970.x}}</ref>
*Provides more durable immunity; [[booster dose|boosters]] are required less frequently<ref>{{Cite web|url=https://www.vaccines.gov/basics/types/index.html|title=Vaccine Types {{!}} Vaccines.gov|website=www.vaccines.gov|access-date=2019-02-25}}</ref> {{citation needed|date=July 2015}}
*Low cost <ref>{{Cite journal|last=Minor|first=Philip D.|date=2015-05-01|title=Live attenuated vaccines: Historical successes and current challenges|journal=Virology|series=60th Anniversary Issue|volume=479-480|pages=379–392|doi=10.1016/j.virol.2015.03.032|pmid=25864107|issn=0042-6822|doi-access=free}}</ref>
*Quick immunity {{citation needed|date=July 2015}}
*Some are easy to transport and administer (for instance [[Polio vaccine|OPV]] for [[polio]] can be taken orally, rather than requiring a sterile injection by a trained healthworker, as the inactivated form IPV does)<ref>{{cite web|title=Polio and the Introduction of IPV for health workers (September 2014)|url=https://www.who.int/immunization/diseases/poliomyelitis/inactivated_polio_vaccine/Key_mess_FAQs.pdf|website=WHO.int|publisher=World Health Organization|access-date=20 July 2016|archiveurl=https://web.archive.org/web/20160720235631/http://www.who.int/immunization/diseases/poliomyelitis/inactivated_polio_vaccine/Key_mess_FAQs.pdf|archivedate=20 July 2016|date=1 September 2014}}</ref>
*Attenuated vaccines can have strong beneficial [[non-specific effect of vaccines|non-specific effects]]. That is effects which go beyond the specific protective effects against the targeted diseases.<ref name="Benn13">{{Cite journal|url = |title = A small jab – a big effect: nonspecific immunomodulation by vaccines|last1 = Benn|first1 = Christine S.|date = September 2013|journal = [[Trends in Immunology]]|doi = 10.1016/j.it.2013.04.004|pmid = 23680130|volume = 34|issue = 9|pages = 431–439|last2 = Netea|first2 = Mihai G.|last3 = Selin|first3 = Liisa K.|last4 = Aaby|first4 = Peter}}</ref>


==Disadvantages==
=== Advantages ===

*In extremely rare cases, natural mutations can cause a reversion to virulence.<ref name=Shimizu_2004>{{cite journal |vauthors=Shimizu H, Thorley B, Paladin FJ |title=Circulation of type 1 vaccine-derived poliovirus in the Philippines in 2001 |journal=J. Virol. |volume=78 |issue=24 |pages=13512–21 |date=December 2004 |pmid=15564462 |pmc=533948 |doi=10.1128/JVI.78.24.13512-13521.2004 |display-authors=etal}}</ref> In this case, the virus can revert to wild type or develop into an entirely new strain.
* Accurately imitate natural infections.<ref name=":4">{{Citation|last=Yadav|first=Dinesh K.|title=Vaccines|date=2014|url=https://linkinghub.elsevier.com/retrieve/pii/B9780124160026000262|work=Animal Biotechnology|pages=491–508|publisher=Elsevier|language=en|doi=10.1016/b978-0-12-416002-6.00026-2|isbn=978-0-12-416002-6|access-date=2020-11-09|last2=Yadav|first2=Neelam|last3=Khurana|first3=Satyendra Mohan Paul}}</ref><ref name=":03">{{Cite journal|last=Vetter|first=Volker|last2=Denizer|first2=Gülhan|last3=Friedland|first3=Leonard R.|last4=Krishnan|first4=Jyothsna|last5=Shapiro|first5=Marla|date=2018-02-17|title=Understanding modern-day vaccines: what you need to know|url=https://doi.org/10.1080/07853890.2017.1407035|journal=Annals of Medicine|volume=50|issue=2|pages=110–120|doi=10.1080/07853890.2017.1407035|issn=0785-3890|pmid=29172780}}</ref>
*Live vaccines are not usually recommended for [[Immunodeficiency|immunocompromised]] patients due to the risk of potentially severe complications.<ref name="MMWR2011">{{cite news | first = Andrew T. | last = Kroger |author2=Ciro V. Sumaya |author3=Larry K. Pickering |author4=William L. Atkinson | title = General Recommendations on Immunization: Recommendations of the Advisory Committee on Immunization Practices (ACIP) | date = 2011-01-28 | publisher = [[Centers for Disease Control and Prevention]] | url = https://www.cdc.gov/mmwr/preview/mmwrhtml/rr6002a1.htm?s_cid=rr6002a1_e | work = Morbidity and Mortality Weekly Report (MMWR) | access-date = 2011-03-11}}</ref>
* Are effective at evoking both strong [[antibody]] and [[Cell-mediated immunity|cell-mediated]] immune reactions.<ref name=":4" /><ref name=":03" /><ref name=":5">{{Cite journal|last=Gil|first=Carmen|last2=Latasa|first2=Cristina|last3=García-Ona|first3=Enrique|last4=Lázaro|first4=Isidro|last5=Labairu|first5=Javier|last6=Echeverz|first6=Maite|last7=Burgui|first7=Saioa|last8=García|first8=Begoña|last9=Lasa|first9=Iñigo|last10=Solano|first10=Cristina|date=2020|title=A DIVA vaccine strain lacking RpoS and the secondary messenger c-di-GMP for protection against salmonellosis in pigs|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6954585/|journal=Veterinary Research|volume=51|doi=10.1186/s13567-019-0730-3|issn=0928-4249|pmc=6954585|pmid=31924274}}</ref>
*Live strains typically require advanced maintenance, such as refrigeration and fresh media, making transport to remote areas difficult and costly.
* Can elicit long-lasting or life-long immunity.<ref name=":4" /><ref name=":03" /><ref name=":6">{{Cite journal|last=Tretyakova|first=Irina|last2=Lukashevich|first2=Igor S.|last3=Glass|first3=Pamela|last4=Wang|first4=Eryu|last5=Weaver|first5=Scott|last6=Pushko|first6=Peter|date=2013-02-04|title=Novel Vaccine against Venezuelan Equine Encephalitis Combines Advantages of DNA Immunization and a Live Attenuated Vaccine|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3556218/|journal=Vaccine|volume=31|issue=7|pages=1019–1025|doi=10.1016/j.vaccine.2012.12.050|issn=0264-410X|pmc=3556218|pmid=23287629}}</ref>
* Often only one or two doses are required. <ref name=":4" /><ref name=":03" /><ref name=":7">{{Cite journal|last=Zou|first=Jing|last2=Xie|first2=Xuping|last3=Luo|first3=Huanle|last4=Shan|first4=Chao|last5=Muruato|first5=Antonio E.|last6=Weaver|first6=Scott C.|last7=Wang|first7=Tian|last8=Shi|first8=Pei-Yong|date=2018-09-07|title=A single-dose plasmid-launched live-attenuated Zika vaccine induces protective immunity|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6197676/|journal=EBioMedicine|volume=36|pages=92–102|doi=10.1016/j.ebiom.2018.08.056|issn=2352-3964|pmc=6197676|pmid=30201444}}</ref>
* Quick immunity onset.<ref name=":5" /><ref name=":6" /><ref name=":7" />
* Cost-effective (compared to some other health interventions).<ref>{{Cite journal|last=Minor|first=Philip D.|date=2015-05|title=Live attenuated vaccines: Historical successes and current challenges|url=https://pubmed.ncbi.nlm.nih.gov/25864107/|journal=Virology|volume=479-480|pages=379–392|doi=10.1016/j.virol.2015.03.032|issn=1096-0341|pmid=25864107}}</ref><ref>{{Citation|last=Mak|first=Tak W.|title=23 - Vaccines and Clinical Immunization|date=2006-01-01|url=http://www.sciencedirect.com/science/article/pii/B9780120884513500259|work=The Immune Response|pages=695–749|editor-last=Mak|editor-first=Tak W.|place=Burlington|publisher=Academic Press|language=en|isbn=978-0-12-088451-3|access-date=2020-11-14|last2=Saunders|first2=Mary E.|editor2-last=Saunders|editor2-first=Mary E.}}</ref>
* Can have strong beneficial [[Non-specific effect of vaccines|non-specific effects]].<ref name="Benn132">{{Cite journal|last1=Benn|first1=Christine S.|last2=Netea|first2=Mihai G.|last3=Selin|first3=Liisa K.|last4=Aaby|first4=Peter|date=September 2013|title=A small jab – a big effect: nonspecific immunomodulation by vaccines|url=|journal=[[Trends in Immunology]]|volume=34|issue=9|pages=431–439|doi=10.1016/j.it.2013.04.004|pmid=23680130}}</ref>

*

=== Disadvantages ===

* In extremely rare cases natural [[Mutation|mutations]] can cause a virus to revert to its [[Wild type|wild-type]] form or mutate to a new [[Strain (biology)|strain]], potentially resulting in the new virus being infectious, pathogenic, or dangerous.<ref name=":4" /><ref name="Shimizu_20042">{{cite journal|display-authors=etal|vauthors=Shimizu H, Thorley B, Paladin FJ|date=December 2004|title=Circulation of type 1 vaccine-derived poliovirus in the Philippines in 2001|journal=J. Virol.|volume=78|issue=24|pages=13512–21|doi=10.1128/JVI.78.24.13512-13521.2004|pmc=533948|pmid=15564462}}</ref>
* Often not recommended for [[Immunodeficiency|immunocompromised]] patients due to the risk of potentially severe complications.<ref name=":4" /><ref name="MMWR20112">{{cite news|last=Kroger|first=Andrew T.|author2=Ciro V. Sumaya|author3=Larry K. Pickering|author4=William L. Atkinson|date=2011-01-28|title=General Recommendations on Immunization: Recommendations of the Advisory Committee on Immunization Practices (ACIP)|work=Morbidity and Mortality Weekly Report (MMWR)|publisher=[[Centers for Disease Control and Prevention]]|url=https://www.cdc.gov/mmwr/preview/mmwrhtml/rr6002a1.htm?s_cid=rr6002a1_e|accessdate=2011-03-11}}</ref><ref>{{Cite journal|last=Cheuk|first=Daniel KL|last2=Chiang|first2=Alan KS|last3=Lee|first3=Tsz Leung|last4=Chan|first4=Godfrey CF|last5=Ha|first5=Shau Yin|date=2011-03-16|title=Vaccines for prophylaxis of viral infections in patients with hematological malignancies|url=https://doi.org//10.1002/14651858.CD006505.pub2|journal=Cochrane Database of Systematic Reviews|doi=10.1002/14651858.cd006505.pub2|issn=1465-1858}}</ref>
* Live strains typically require advanced maintenance, such as refrigeration and fresh media, making transport to remote areas difficult and costly.<ref name=":4" /><ref>{{Cite journal|last=Levine|first=Myron M.|date=2011-12-30|title=“IDEAL” vaccines for resource poor settings|url=http://www.sciencedirect.com/science/article/pii/S0264410X1101886X|journal=Vaccine|series=Smallpox Eradication after 30 Years: Lessons, Legacies and Innovations|language=en|volume=29|pages=D116–D125|doi=10.1016/j.vaccine.2011.11.090|issn=0264-410X}}</ref>


== List of attenuated vaccines ==
== List of attenuated vaccines ==

Revision as of 22:45, 14 November 2020

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.[2] These vaccines contrast to those produced by "killing" the virus (inactivated vaccine).

Development

Viruses may be attenuated via passage of the virus through a foreign host, such as:[3][4]

The initial virus population is applied to a foreign host. Through natural genetic variability or induced mutation, a small percent of the viral particles should have the capacity to infect the new host.[4][5] These strains will continue to evolve within the new host and the virus will gradually lose its efficacy in the original due to lack of selection pressure.[4][5] 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.[5] 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".[5]

Viruses may also be attenuated via reverse genetics.

Mechanism

Live attenuated vaccines are administered via a viral transport media containing the relevant viral particles. The media may be given orally, injected via a hypodermic needle or by inhalation with the method often dependent upon the source phage's virulence factors.

Vaccines function by encouraging the creation of cells, such as CD8+ and CD4+ T lymphocytes, or molecules, such as antibodies, that are specific to the pathogen.[6] The cells and molecules can either prevent or reduce infection by killing infected cells or by producing interleukins.[6] The specific effectors evoked can be different based on the vaccine.[6] Live attenuated vaccines tend to help with the production of CD8+ cytotoxic T lymphocytes and T-dependent antibody responses.[6] A vaccine is only effective for as long as the body maintains a population of these cells [citation needed]. Live attenuated vaccines can induce long-term, possibly lifelong, immunity without requiring multiple vaccine doses.[5][6] Live attenuated vaccines can also induce cellular immune responses, which do not rely solely on antibodies but also involve immune cells such as cytotoxic T cells or macrophages.[5]

Advantages and Disadvantages

Advantages

Disadvantages

  • In extremely rare cases natural mutations can cause a virus to revert to its wild-type form or mutate to a new strain, potentially resulting in the new virus being infectious, pathogenic, or dangerous.[7][15]
  • Often not recommended for immunocompromised patients due to the risk of potentially severe complications.[7][16][17]
  • Live strains typically require advanced maintenance, such as refrigeration and fresh media, making transport to remote areas difficult and costly.[7][18]

List of attenuated vaccines

Currently in-use

Bacterial vaccines

Viral vaccines

In development

Bacterial vaccines

Viral vaccines

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. ^ Pulendran, Bali; Ahmed, Rafi (June 2011). "Immunological mechanisms of vaccination". Nature Immunology. 12 (6): 509–517. doi:10.1038/ni.2039. ISSN 1529-2908. PMC 3253344. PMID 21739679.
  3. ^ Jordan, Ingo; Sandig, Volker (2014-04-11). "Matrix and Backstage: Cellular Substrates for Viral Vaccines". Viruses. 6 (4): 1672–1700. doi:10.3390/v6041672. ISSN 1999-4915. PMC 4014716. PMID 24732259.{{cite journal}}: CS1 maint: unflagged free DOI (link)
  4. ^ a b c Nunnally, Brian K.; Turula, Vincent E.; Sitrin, Robert D., eds. (2015). Vaccine Analysis: Strategies, Principles, and Control. doi:10.1007/978-3-662-45024-6. ISBN 978-3-662-45023-9. S2CID 39542692.
  5. ^ a b c d e f Hanley, Kathryn A. (December 2011). "The double-edged sword: How evolution can make or break a live-attenuated virus vaccine". Evolution. 4 (4): 635–643. doi:10.1007/s12052-011-0365-y. ISSN 1936-6426. PMC 3314307. PMID 22468165.
  6. ^ a b c d e Plotkin's vaccines. Plotkin, Stanley A., 1932-, Orenstein, Walter A.,, Offit, Paul A. (Seventh ed.). Philadelphia, PA. 2018. ISBN 978-0-323-39302-7. OCLC 989157433.{{cite book}}: CS1 maint: location missing publisher (link) CS1 maint: others (link)
  7. ^ a b c d e f g Yadav, Dinesh K.; Yadav, Neelam; Khurana, Satyendra Mohan Paul (2014), "Vaccines", Animal Biotechnology, Elsevier, pp. 491–508, doi:10.1016/b978-0-12-416002-6.00026-2, ISBN 978-0-12-416002-6, retrieved 2020-11-09
  8. ^ a b c d Vetter, Volker; Denizer, Gülhan; Friedland, Leonard R.; Krishnan, Jyothsna; Shapiro, Marla (2018-02-17). "Understanding modern-day vaccines: what you need to know". Annals of Medicine. 50 (2): 110–120. doi:10.1080/07853890.2017.1407035. ISSN 0785-3890. PMID 29172780.
  9. ^ a b Gil, Carmen; Latasa, Cristina; García-Ona, Enrique; Lázaro, Isidro; Labairu, Javier; Echeverz, Maite; Burgui, Saioa; García, Begoña; Lasa, Iñigo; Solano, Cristina (2020). "A DIVA vaccine strain lacking RpoS and the secondary messenger c-di-GMP for protection against salmonellosis in pigs". Veterinary Research. 51. doi:10.1186/s13567-019-0730-3. ISSN 0928-4249. PMC 6954585. PMID 31924274.{{cite journal}}: CS1 maint: unflagged free DOI (link)
  10. ^ a b Tretyakova, Irina; Lukashevich, Igor S.; Glass, Pamela; Wang, Eryu; Weaver, Scott; Pushko, Peter (2013-02-04). "Novel Vaccine against Venezuelan Equine Encephalitis Combines Advantages of DNA Immunization and a Live Attenuated Vaccine". Vaccine. 31 (7): 1019–1025. doi:10.1016/j.vaccine.2012.12.050. ISSN 0264-410X. PMC 3556218. PMID 23287629.
  11. ^ a b Zou, Jing; Xie, Xuping; Luo, Huanle; Shan, Chao; Muruato, Antonio E.; Weaver, Scott C.; Wang, Tian; Shi, Pei-Yong (2018-09-07). "A single-dose plasmid-launched live-attenuated Zika vaccine induces protective immunity". EBioMedicine. 36: 92–102. doi:10.1016/j.ebiom.2018.08.056. ISSN 2352-3964. PMC 6197676. PMID 30201444.
  12. ^ Minor, Philip D. (2015-05). "Live attenuated vaccines: Historical successes and current challenges". Virology. 479–480: 379–392. doi:10.1016/j.virol.2015.03.032. ISSN 1096-0341. PMID 25864107. {{cite journal}}: Check date values in: |date= (help)
  13. ^ Mak, Tak W.; Saunders, Mary E. (2006-01-01), Mak, Tak W.; Saunders, Mary E. (eds.), "23 - Vaccines and Clinical Immunization", The Immune Response, Burlington: Academic Press, pp. 695–749, ISBN 978-0-12-088451-3, retrieved 2020-11-14
  14. ^ 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.
  15. ^ 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.
  16. ^ 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.
  17. ^ Cheuk, Daniel KL; Chiang, Alan KS; Lee, Tsz Leung; Chan, Godfrey CF; Ha, Shau Yin (2011-03-16). "Vaccines for prophylaxis of viral infections in patients with hematological malignancies". Cochrane Database of Systematic Reviews. doi:10.1002/14651858.cd006505.pub2. ISSN 1465-1858.
  18. ^ Levine, Myron M. (2011-12-30). ""IDEAL" vaccines for resource poor settings". Vaccine. Smallpox Eradication after 30 Years: Lessons, Legacies and Innovations. 29: D116–D125. doi:10.1016/j.vaccine.2011.11.090. ISSN 0264-410X.
  19. ^ Donegan, Sarah; Bellamy, Richard; Gamble, Carrol L (2009-04-15). "Vaccines for preventing anthrax". Cochrane Database of Systematic Reviews. doi:10.1002/14651858.cd006403.pub2. ISSN 1465-1858. PMC 6532564. PMID 19370633.
  20. ^ Harris, Jason B (2018-11-15). "Cholera: Immunity and Prospects in Vaccine Development". The Journal of Infectious Diseases. 218 (Suppl 3): S141–S146. doi:10.1093/infdis/jiy414. ISSN 0022-1899. PMC 6188552. PMID 30184117.
  21. ^ Verma, Shailendra Kumar; Tuteja, Urmil (2016-12-14). "Plague Vaccine Development: Current Research and Future Trends". Frontiers in Immunology. 7. doi:10.3389/fimmu.2016.00602. ISSN 1664-3224. PMC 5155008. PMID 28018363.{{cite journal}}: CS1 maint: unflagged free DOI (link)
  22. ^ Odey, Friday; Okomo, Uduak; Oyo-Ita, Angela (2018-12-05). "Vaccines for preventing invasive salmonella infections in people with sickle cell disease". Cochrane Database of Systematic Reviews. doi:10.1002/14651858.cd006975.pub4. ISSN 1465-1858. PMC 6517230. PMID 30521695.
  23. ^ Schrager, Lewis K.; Harris, Rebecca C.; Vekemans, Johan (2019-02-24). "Research and development of new tuberculosis vaccines: a review". F1000Research. 7: 1732. doi:10.12688/f1000research.16521.2. ISSN 2046-1402. PMC 6305224. PMID 30613395.{{cite journal}}: CS1 maint: unflagged free DOI (link)
  24. ^ Meiring, James E; Giubilini, Alberto; Savulescu, Julian; Pitzer, Virginia E; Pollard, Andrew J (2019-11-01). "Generating the Evidence for Typhoid Vaccine Introduction: Considerations for Global Disease Burden Estimates and Vaccine Testing Through Human Challenge". Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America. 69 (Suppl 5): S402–S407. doi:10.1093/cid/ciz630. ISSN 1058-4838. PMC 6792111. PMID 31612941.
  25. ^ Jefferson, Tom; Rivetti, Alessandro; Di Pietrantonj, Carlo; Demicheli, Vittorio (2018-02-01). "Vaccines for preventing influenza in healthy children". Cochrane Database of Systematic Reviews. doi:10.1002/14651858.cd004879.pub5. ISSN 1465-1858. PMC 6491174. PMID 29388195.
  26. ^ Yun, Sang-Im; Lee, Young-Min (2014-02-01). "Japanese encephalitis". Human Vaccines & Immunotherapeutics. 10 (2): 263–279. doi:10.4161/hv.26902. ISSN 2164-5515. PMC 4185882. PMID 24161909.
  27. ^ Griffin, Diane E. (2018-03-01). "Measles Vaccine". Viral Immunology. 31 (2): 86–95. doi:10.1089/vim.2017.0143. ISSN 0882-8245. PMC 5863094. PMID 29256824.
  28. ^ Su, Shih-Bin; Chang, Hsiao-Liang; Chen, And Kow-Tong (5 March 2020). "Current Status of Mumps Virus Infection: Epidemiology, Pathogenesis, and Vaccine". International Journal of Environmental Research and Public Health. 17 (5): 1686. doi:10.3390/ijerph17051686. ISSN 1660-4601. PMC 7084951. PMID 32150969.{{cite journal}}: CS1 maint: unflagged free DOI (link)
  29. ^ "Observed Rate of Vaccine Reactions – Measles, Mumps and Rubella Vaccines" (PDF). World Health Organization Information Sheet. May 2014.
  30. ^ a b Di Pietrantonj, Carlo; Rivetti, Alessandro; Marchione, Pasquale; Debalini, Maria Grazia; Demicheli, Vittorio (April 20, 2020). "Vaccines for measles, mumps, rubella, and varicella in children". The Cochrane Database of Systematic Reviews. 4: CD004407. doi:10.1002/14651858.CD004407.pub4. ISSN 1469-493X. PMC 7169657. PMID 32309885.
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