Attenuated vaccine

An attenuated vaccine (or a live attenuated vaccine, LAV) 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 pathogen (inactivated vaccine).

Attenuated vaccines stimulate a strong and effective immune response that is long-lasting.[3] In comparison to inactivated vaccines, attenuated vaccines produce a stronger and more durable immune response with a quick immunity onset.[4][5][6] They are generally avoided in patients with severe immunodeficiencies.[7] Attenuated vaccines function by encouraging the body to create antibodies and memory immune cells in response to the specific pathogen which the vaccine protects against.[8] Common examples of live attenuated vaccines are measles, mumps, rubella, yellow fever, and some influenza vaccines.[3]

Development

Attenuated viruses

Viruses may be attenuated using the principles of evolution via serial passage of the virus through a foreign host species, such as:[9][10]

The initial virus population is applied to a foreign host. Through natural genetic variability or induced mutation, a small percentage of the viral particles should have the capacity to infect the new host.[10][11] These strains will continue to evolve within the new host and the virus will gradually lose its efficacy in the original host, due to lack of selection pressure.[10][11] 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 subject that is to receive the vaccine.[11] This makes it easier for the host 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".[11]

Viruses may also be attenuated via reverse genetics.[12] Attenuation by genetics is also used in the production of oncolytic viruses.[13]

Attenuated bacteria

Bacteria is typically attenuated by passage, similar to the method used in viruses.[14] Gene knockout guided by reverse genetics is also used.[15]

Administration

Attenuated vaccines can be administered in a variety of ways:

Oral vaccines or subcutaneous/intramuscular injection are for individuals older than 12 months. Live attenuated vaccines, with the exception of the rotavirus vaccine given at 6 weeks, is not indicated for infants younger than 9 months.[19]

Mechanism

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.[8] The cells and molecules can either prevent or reduce infection by killing infected cells or by producing interleukins.[8] The specific effectors evoked can be different based on the vaccine.[8] Live attenuated vaccines tend to help with the production of CD8+ cytotoxic T lymphocytes and T-dependent antibody responses.[8] A vaccine is only effective for as long as the body maintains a population of these cells.[8]

Attenuated vaccines are “weakened” version of pathogens (virus or bacteria). They are modified so that it cannot cause harm or disease in the body but are still able to activate the immune system.[20] This type of vaccine works by activating both the cellular and humoral immune responses of the adaptive immune system. When a person receives an oral or injection of the vaccine, B cells, which help make antibodies, are activated in two ways: T cell-dependent and T-cell independent.[21]

In T-cell dependent activation of B cells, B cells first recognize and present the antigen on MHCII receptors. T-cells can then recognize this presentation and bind to the B cell, resulting in clonal proliferation. This also helps IgM and plasma cells production as well as immunoglobulin switching. On the other hand, T-cell independent activation of B cells is due to non-protein antigens. This can lead to production of IgM antibodies. Being able to produce a B-cell response as well as memory killer T cells is a key feature of attenuated virus vaccines that help induce a potent immunity.[21]

Safety

Live-attenuated vaccines are safe and stimulate a strong and effective immune response that is long-lasting.[3] Given pathogens are attenuated, it is extremely rare for pathogens to revert to their pathogenic form and subsequently cause disease.[22] Additionally, within the five WHO-recommended live attenuated vaccines (tuberculosis, oral polio, measles, rotavirus, and yellow fever), severe adverse reactions are extremely rare.[22]

Individuals with severely compromised immune systems (e.g., HIV-infection, chemotherapy, immunosuppressive therapy, lymphoma, leukemia, combined immunodeficiencies) typically should not receive live-attenuated vaccines as they may not be able to produce an adequate and safe immune response.[3][22][23][24] Household contacts of immunodeficient individuals are still able to receive most attenuated vaccines since there is no increased risk of infection transmission, with the exception being the oral polio vaccine.[24]

As precaution, live-attenuated vaccines are not typically administered during pregnancy.[22][25] This is due to the risk of transmission of virus between mother and fetus.[25] In particular, the varicella and yellow fever vaccines have been shown to have adverse effects on fetuses and nursing babies.[25]

Some live attenuated vaccines have additional common, mild adverse effects due to their administration route.[25] For example, the live attenuated influenza vaccine is given nasally and is associated with nasal congestion.[25]

Compared to inactivated vaccines, live-attenuated vaccines are more prone to immunization errors as they must be kept under strict conditions during the cold chain and carefully prepared (e.g., during reconstitution).[3][22][23]

History

The history of vaccine development started with the creation of the smallpox vaccine by Edward Jenner in the late 18th century.[26] Jenner discovered that inoculating a human with an animal pox virus would grant immunity against smallpox, a disease considered to be one of the most devastating in human history.[27][28] Although the original smallpox vaccine is sometimes considered to be an attenuated vaccine due to its live nature, it was not strictly-speaking attenuated since it was not derived directly from smallpox. Instead, it was based on the related and milder cowpox disease.[29][30] The discovery that diseases could be artificially attenuated came in the late 19th century when Louis Pasteur was able to derive an attenuated strain of chicken cholera.[29] Pasteur applied this knowledge to develop an attenuated anthrax vaccine and demonstrating its effectiveness in a public experiment.[31] The first rabies vaccine was subsequently produced by Pasteur and Emile Roux by growing the virus in rabbits and drying the affected nervous tissue.[31]

The technique of cultivating a virus repeatedly in artificial media and isolating less virulent strains was pioneered in the early 20th century by Albert Calmette and Camille Guérin who developed an attenuated tuberculosis vaccine called the BCG vaccine.[26] This technique was later used by several teams when developing the vaccine for yellow fever, first by Sellards and Laigret, and then by Theiler and Smith.[26][29][32] The vaccine developed by Theiler and Smith proved to be hugely successful and helped establish recommended practices and regulations for many other vaccines. These include the growth of viruses in primary tissue culture (e.g., chick embryos), as opposed to animals, and the use of the seed stock system which uses the original attenuated viruses as opposed to derived viruses (done to reduce variance in vaccine development and decrease the chance of adverse effects).[29][32] The middle of the 20th century saw the work of many prominent virologists including Sabin, Hilleman, and Enders, and the introduction of several successful attenuated vaccines, such as those against polio, measles, mumps, and rubella.[33][34][35][36]

Advantages and disadvantages

Advantages

Disadvantages
  • In rare cases, particularly when there is inadequate vaccination of the population, natural mutations during viral replication, or interference by related viruses, can cause an attenuated virus to revert to its wild-type form or mutate to a new strain, potentially resulting in the new virus being infectious or pathogenic.[37][42]
  • Often not recommended for severely immunocompromised patients due to the risk of potential complications.[37][43][44]
  • Live strains typically require advanced maintenance, such as refrigeration and fresh media, making transport to remote areas difficult and costly.[37][45]

List of attenuated vaccines

Currently in-use

For many of the pathogens listed below there are many vaccines, the list below simply indicates that there are one (or more) attenuated vaccines for that particular pathogen, not that all vaccines for that pathogen are attenuated.

Bacterial vaccines

Viral vaccines

Bacterial vaccines

Viral vaccines

References
  1. Badgett, Marty R.; Auer, Alexandra; Carmichael, Leland E.; Parrish, Colin R.; Bull, James J. (October 2002). "Evolutionary Dynamics of Viral Attenuation". Journal of Virology. 76 (20): 10524–10529. doi:10.1128/JVI.76.20.10524-10529.2002. ISSN 0022-538X. 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. "Vaccine Types | Vaccines". www.vaccines.gov. Retrieved 16 November 2020.
  4. 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 (1): 3. doi:10.1186/s13567-019-0730-3. ISSN 0928-4249. PMC 6954585. PMID 31924274.
  5. Tretyakova, Irina; Lukashevich, Igor S.; Glass, Pamela; Wang, Eryu; Weaver, Scott; Pushko, Peter (4 February 2013). "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.
  6. Zou, Jing; Xie, Xuping; Luo, Huanle; Shan, Chao; Muruato, Antonio E.; Weaver, Scott C.; Wang, Tian; Shi, Pei-Yong (7 September 2018). "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.
  7. "ACIP Altered Immunocompetence Guidelines for Immunizations | CDC". www.cdc.gov. 19 September 2023. Retrieved 26 September 2023.
  8. 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)
  9. Jordan, Ingo; Sandig, Volker (11 April 2014). "Matrix and Backstage: Cellular Substrates for Viral Vaccines". Viruses. 6 (4): 1672–1700. doi:10.3390/v6041672. ISSN 1999-4915. PMC 4014716. PMID 24732259.
  10. 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.
  11. 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.
  12. Nogales, Aitor; Martínez-Sobrido, Luis (22 December 2016). "Reverse Genetics Approaches for the Development of Influenza Vaccines". International Journal of Molecular Sciences. 18 (1): 20. doi:10.3390/ijms18010020. ISSN 1422-0067. PMC 5297655. PMID 28025504.
  13. Gentry GA (1992). "Viral thymidine kinases and their relatives". Pharmacology & Therapeutics. 54 (3): 319–55. doi:10.1016/0163-7258(92)90006-L. PMID 1334563.
  14. "Immunology and Vaccine-Preventable Diseases" (PDF). CDC.
  15. Xiong, Kun; Zhu, Chunyue; Chen, Zhijin; Zheng, Chunping; Tan, Yong; Rao, Xiancai; Cong, Yanguang (24 April 2017). "Vi Capsular Polysaccharide Produced by Recombinant Salmonella enterica Serovar Paratyphi A Confers Immunoprotection against Infection by Salmonella enterica Serovar Typhi". Frontiers in Cellular and Infection Microbiology. 7: 135. doi:10.3389/fcimb.2017.00135. PMC 5401900. PMID 28484685.
  16. Herzog, Christian (2014). "Influence of parenteral administration routes and additional factors on vaccine safety and immunogenicity: a review of recent literature". Expert Review of Vaccines. 13 (3): 399–415. doi:10.1586/14760584.2014.883285. ISSN 1476-0584. PMID 24512188. S2CID 46577849.
  17. Gasparini, R.; Amicizia, D.; Lai, P. L.; Panatto, D. (2011). "Live attenuated influenza vaccine--a review". Journal of Preventive Medicine and Hygiene. 52 (3): 95–101. ISSN 1121-2233. PMID 22010534.
  18. Morrow, W. John W. (2012). Vaccinology : Principles and Practice. Sheikh, Nadeem A., Schmidt, Clint S., Davies, D. Huw. Hoboken: John Wiley & Sons. ISBN 978-1-118-34533-7. OCLC 795120561.
  19. "Your Child's Immunizations: Rotavirus Vaccine (RV) (for Parents) - Nemours KidsHealth". kidshealth.org. Retrieved 15 September 2022.
  20. Policy (OIDP), Office of Infectious Disease and HIV/AIDS (26 April 2021). "Vaccine Types". HHS.gov. Retrieved 15 September 2022. {{cite web}}: |last= has generic name (help)
  21. Sompayrac, Lauren (2019). How the immune system works (Sixth ed.). Hoboken, NJ. ISBN 978-1-119-54212-4. OCLC 1083261548.{{cite book}}: CS1 maint: location missing publisher (link)
  22. "MODULE 2 – Live attenuated vaccines (LAV) - WHO Vaccine Safety Basics". vaccine-safety-training.org. Retrieved 16 November 2020.
  23. Yadav, Dinesh K.; Yadav, Neelam; Khurana, Satyendra Mohan Paul (1 January 2014), Verma, Ashish S.; Singh, Anchal (eds.), "Chapter 26 - Vaccines: Present Status and Applications", Animal Biotechnology, San Diego: Academic Press, pp. 491–508, doi:10.1016/b978-0-12-416002-6.00026-2, ISBN 978-0-12-416002-6, S2CID 83112999, retrieved 16 November 2020
  24. Sobh, Ali; Bonilla, Francisco A. (November 2016). "Vaccination in Primary Immunodeficiency Disorders". The Journal of Allergy and Clinical Immunology: In Practice. 4 (6): 1066–1075. doi:10.1016/j.jaip.2016.09.012. PMID 27836056.
  25. Su, John R.; Duffy, Jonathan; Shimabukuro, Tom T. (2019), "Vaccine Safety", Vaccinations, Elsevier, pp. 1–24, doi:10.1016/b978-0-323-55435-0.00001-x, ISBN 978-0-323-55435-0, S2CID 239378645, retrieved 17 November 2020
  26. Plotkin, Stanley (26 August 2014). "History of vaccination". Proceedings of the National Academy of Sciences of the United States of America. 111 (34): 12283–12287. Bibcode:2014PNAS..11112283P. doi:10.1073/pnas.1400472111. ISSN 1091-6490. PMC 4151719. PMID 25136134.
  27. Eyler, John M. (October 2003). "Smallpox in history: the birth, death, and impact of a dread disease". Journal of Laboratory and Clinical Medicine. 142 (4): 216–220. doi:10.1016/s0022-2143(03)00102-1. ISSN 0022-2143. PMID 14625526.
  28. Thèves, Catherine; Crubézy, Eric; Biagini, Philippe (15 September 2016), Drancourt; Raoult (eds.), "History of Smallpox and Its Spread in Human Populations", Paleomicrobiology of Humans, American Society of Microbiology, vol. 4, no. 4, pp. 161–172, doi:10.1128/microbiolspec.poh-0004-2014, ISBN 978-1-55581-916-3, PMID 27726788, retrieved 14 November 2020
  29. Galinski, Mark S.; Sra, Kuldip; Haynes, John I.; Naspinski, Jennifer (2015), Nunnally, Brian K.; Turula, Vincent E.; Sitrin, Robert D. (eds.), "Live Attenuated Viral Vaccines", Vaccine Analysis: Strategies, Principles, and Control, Berlin, Heidelberg: Springer, pp. 1–44, doi:10.1007/978-3-662-45024-6_1, ISBN 978-3-662-45024-6, retrieved 14 November 2020
  30. Minor, Philip D. (1 May 2015). "Live attenuated vaccines: Historical successes and current challenges". Virology. 479–480: 379–392. doi:10.1016/j.virol.2015.03.032. ISSN 0042-6822. PMID 25864107.
  31. Schwartz, M. (7 July 2008). "The life and works of Louis Pasteur". Journal of Applied Microbiology. 91 (4): 597–601. doi:10.1046/j.1365-2672.2001.01495.x. ISSN 1364-5072. PMID 11576293. S2CID 39020116.
  32. Frierson, J. Gordon (June 2010). "The Yellow Fever Vaccine: A History". The Yale Journal of Biology and Medicine. 83 (2): 77–85. ISSN 0044-0086. PMC 2892770. PMID 20589188.
  33. Shampo, Marc A.; Kyle, Robert A.; Steensma, David P. (July 2011). "Albert Sabin—Conqueror of Poliomyelitis". Mayo Clinic Proceedings. 86 (7): e44. doi:10.4065/mcp.2011.0345. ISSN 0025-6196. PMC 3127575. PMID 21719614.
  34. Newman, Laura (30 April 2005). "Maurice Hilleman". BMJ: British Medical Journal. 330 (7498): 1028. doi:10.1136/bmj.330.7498.1028. ISSN 0959-8138. PMC 557162.
  35. Katz, S. L. (2009). "John F. Enders and Measles Virus Vaccine—a Reminiscence". Measles. Current Topics in Microbiology and Immunology. Vol. 329. pp. 3–11. doi:10.1007/978-3-540-70523-9_1. ISBN 978-3-540-70522-2. ISSN 0070-217X. PMID 19198559. S2CID 2884917.
  36. Plotkin, Stanley A. (1 November 2006). "The History of Rubella and Rubella Vaccination Leading to Elimination". Clinical Infectious Diseases. 43 (Supplement_3): S164–S168. doi:10.1086/505950. ISSN 1058-4838. PMID 16998777.
  37. 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, S2CID 83112999, retrieved 9 November 2020
  38. Vetter, Volker; Denizer, Gülhan; Friedland, Leonard R.; Krishnan, Jyothsna; Shapiro, Marla (17 February 2018). "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. S2CID 25514266.
  39. Minor, Philip D. (May 2015). "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.
  40. Mak, Tak W.; Saunders, Mary E. (1 January 2006), 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 14 November 2020
  41. 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.
  42. 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.
  43. Kroger, Andrew T.; Ciro V. Sumaya; Larry K. Pickering; William L. Atkinson (28 January 2011). "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 11 March 2011.
  44. Cheuk, Daniel KL; Chiang, Alan KS; Lee, Tsz Leung; Chan, Godfrey CF; Ha, Shau Yin (16 March 2011). "Vaccines for prophylaxis of viral infections in patients with hematological malignancies". Cochrane Database of Systematic Reviews (3): CD006505. doi:10.1002/14651858.cd006505.pub2. ISSN 1465-1858. PMID 21412895.
  45. Levine, Myron M. (30 December 2011). ""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. PMID 22486974.
  46. Donegan, Sarah; Bellamy, Richard; Gamble, Carrol L (15 April 2009). "Vaccines for preventing anthrax". Cochrane Database of Systematic Reviews. 2009 (2): CD006403. doi:10.1002/14651858.cd006403.pub2. ISSN 1465-1858. PMC 6532564. PMID 19370633.
  47. Harris, Jason B (15 November 2018). "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.
  48. Verma, Shailendra Kumar; Tuteja, Urmil (14 December 2016). "Plague Vaccine Development: Current Research and Future Trends". Frontiers in Immunology. 7: 602. doi:10.3389/fimmu.2016.00602. ISSN 1664-3224. PMC 5155008. PMID 28018363.
  49. Odey, Friday; Okomo, Uduak; Oyo-Ita, Angela (5 December 2018). "Vaccines for preventing invasive salmonella infections in people with sickle cell disease". Cochrane Database of Systematic Reviews. 12 (4): CD006975. doi:10.1002/14651858.cd006975.pub4. ISSN 1465-1858. PMC 6517230. PMID 30521695.
  50. Schrager, Lewis K.; Harris, Rebecca C.; Vekemans, Johan (24 February 2019). "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.
  51. Meiring, James E; Giubilini, Alberto; Savulescu, Julian; Pitzer, Virginia E; Pollard, Andrew J (1 November 2019). "Generating the Evidence for Typhoid Vaccine Introduction: Considerations for Global Disease Burden Estimates and Vaccine Testing Through Human Challenge". Clinical Infectious Diseases. 69 (Suppl 5): S402–S407. doi:10.1093/cid/ciz630. ISSN 1058-4838. PMC 6792111. PMID 31612941.
  52. Jefferson, Tom; Rivetti, Alessandro; Di Pietrantonj, Carlo; Demicheli, Vittorio (1 February 2018). "Vaccines for preventing influenza in healthy children". Cochrane Database of Systematic Reviews. 2018 (2): CD004879. doi:10.1002/14651858.cd004879.pub5. ISSN 1465-1858. PMC 6491174. PMID 29388195.
  53. Yun, Sang-Im; Lee, Young-Min (1 February 2014). "Japanese encephalitis". Human Vaccines & Immunotherapeutics. 10 (2): 263–279. doi:10.4161/hv.26902. ISSN 2164-5515. PMC 4185882. PMID 24161909.
  54. Griffin, Diane E. (1 March 2018). "Measles Vaccine". Viral Immunology. 31 (2): 86–95. doi:10.1089/vim.2017.0143. ISSN 0882-8245. PMC 5863094. PMID 29256824.
  55. 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.
  56. "Observed Rate of Vaccine Reactions – Measles, Mumps and Rubella Vaccines" (PDF). World Health Organization Information Sheet. May 2014.
  57. Di Pietrantonj, Carlo; Rivetti, Alessandro; Marchione, Pasquale; Debalini, Maria Grazia; Demicheli, Vittorio (20 April 2020). "Vaccines for measles, mumps, rubella, and varicella in children". The Cochrane Database of Systematic Reviews. 4 (4): CD004407. doi:10.1002/14651858.CD004407.pub4. ISSN 1469-493X. PMC 7169657. PMID 32309885.
  58. Bandyopadhyay, Ananda S.; Garon, Julie; Seib, Katherine; Orenstein, Walter A. (2015). "Polio vaccination: past, present and future". Future Microbiology. 10 (5): 791–808. doi:10.2217/fmb.15.19. ISSN 1746-0921. PMID 25824845.
  59. Bruijning-Verhagen, Patricia; Groome, Michelle (July 2017). "Rotavirus Vaccine: Current Use and Future Considerations". The Pediatric Infectious Disease Journal. 36 (7): 676–678. doi:10.1097/INF.0000000000001594. ISSN 1532-0987. PMID 28383393. S2CID 41278475.
  60. Lambert, Nathaniel; Strebel, Peter; Orenstein, Walter; Icenogle, Joseph; Poland, Gregory A. (6 June 2015). "Rubella". Lancet. 385 (9984): 2297–2307. doi:10.1016/S0140-6736(14)60539-0. ISSN 0140-6736. PMC 4514442. PMID 25576992.
  61. Voigt, Emily A.; Kennedy, Richard B.; Poland, Gregory A. (September 2016). "Defending against smallpox: a focus on vaccines". Expert Review of Vaccines. 15 (9): 1197–1211. doi:10.1080/14760584.2016.1175305. ISSN 1744-8395. PMC 5003177. PMID 27049653.
  62. Marin, Mona; Marti, Melanie; Kambhampati, Anita; Jeram, Stanley M.; Seward, Jane F. (1 March 2016). "Global Varicella Vaccine Effectiveness: A Meta-analysis". Pediatrics. 137 (3): e20153741. doi:10.1542/peds.2015-3741. ISSN 1098-4275. PMID 26908671. S2CID 25263970.
  63. Monath, Thomas P.; Vasconcelos, Pedro F. C. (March 2015). "Yellow fever". Journal of Clinical Virology. 64: 160–173. doi:10.1016/j.jcv.2014.08.030. ISSN 1873-5967. PMID 25453327. S2CID 5124080.
  64. Schmader, Kenneth (7 August 2018). "Herpes Zoster". Annals of Internal Medicine. 169 (3): ITC19–ITC31. doi:10.7326/AITC201808070. ISSN 1539-3704. PMID 30083718. S2CID 51926613.
  65. Mirhoseini, Ali; Amani, Jafar; Nazarian, Shahram (April 2018). "Review on pathogenicity mechanism of enterotoxigenic Escherichia coli and vaccines against it". Microbial Pathogenesis. 117: 162–169. doi:10.1016/j.micpath.2018.02.032. ISSN 1096-1208. PMID 29474827.
  66. Kubinski, Mareike; Beicht, Jana; Gerlach, Thomas; Volz, Asisa; Sutter, Gerd; Rimmelzwaan, Guus F. (12 August 2020). "Tick-Borne Encephalitis Virus: A Quest for Better Vaccines against a Virus on the Rise". Vaccines. 8 (3): 451. doi:10.3390/vaccines8030451. ISSN 2076-393X. PMC 7564546. PMID 32806696.
  67. "Safety and Immunogenicity of COVI-VAC, a Live Attenuated Vaccine Against COVID-19". ClinicalTrials.gov. United States National Library of Medicine. Retrieved 8 June 2021.
This article is issued from Wikipedia. The text is licensed under Creative Commons - Attribution - Sharealike. Additional terms may apply for the media files.