Vaccine resistance

See also: Breakthrough infection

Not to be confused with vaccine hesitancy.

Vaccine resistance is the evolutionary adaptation of pathogens to infect and spread through vaccinated individuals, analogous to antimicrobial resistance. It concerns both human and animal vaccines. Although the emergence of a number of vaccine resistant pathogens has been well documented, this phenomenon is nevertheless much more rare and less of a concern than antimicrobial resistance.

Vaccine resistance may be considered a special case of immune evasion, from the immunity conferred by the vaccine. Since the immunity conferred by a vaccine may be different from that induced by infection by the pathogen, the immune evasion may also be easier (in case of an inefficient vaccine) or more difficult (would be the case of the universal flu vaccine). We speak of vaccine resistance only if the immune evasion is a result of evolutionary adaptation of the pathogen (and not a feature of the pathogen that it had before any evolutionary adaptation to the vaccine) and the adaptation is driven by the selective pressure induced by the vaccine (this would not be the case of an immune evasion that is the result of genetic drift that would be present even without vaccinating the population).^{[ citation needed ]}

Some of the causes advanced for less frequent emergence of resistance are ^{[1] [2]} that

• vaccines are mostly used for prophylaxis, that is before infection occurs, and usually act to suppress the pathogen before the host becomes infectious
• most vaccines target multiple antigenic sites of the pathogen
• different hosts may produce different immune responses to the same pathogen

For diseases that confer long lasting immunity after exposure, typically childhood diseases, it was argued that a vaccine may provide the same immune response as natural infection, so it is expected that there should be no vaccine resistance. ^{[3] [4]}

If vaccine resistance emerges the vaccine may retain some level of protection against serious infection, possibly by modifying the immune response of the host away from immunopathology. ^[5]

The best known cases of vaccine resistance are for the following diseases

• animal diseases
  • Marek's disease where actually more virulent strains emerged after vaccination ^{[6] [7]} because the vaccine did not protect against infection and transmission, only against serious forms of the disease
  • Yersinia ruckeri ^{[8] [9]} because a single mutation was sufficient to generate vaccine resistance
  • avian metapneumovirus ^{[10] [11] [12] [13]}
• human diseases
  • Streptococcus pneumoniae ^{[14] [15]} because recombination with another serotype not targeted by the vaccine
  • hepatitis B virus ^{[16] [17] [18] [19]} because the vaccine targeted a single site formed by 9 amino acids
  • Bordetella pertussis ^{[20] [21] [22] [23]} because not all serotypes were targeted and later because acellular vaccines targeted only a few antigens

Other less documented cases are for avian influenza, ^[24] avian reovirus, ^[25] Corynebacterium diphtheriae , ^[26] feline calicivirus, ^[27] H. influenzae , ^[28] infectious bursal disease virus, ^[29] Neisseria meningitidis , ^[30] Newcastle disease virus, ^[31] and porcine circovirus type 2. ^[32]

References

1. Kennedy, David A.; Read, Andrew F. (2017-03-29). "Why does drug resistance readily evolve but vaccine resistance does not?". Proceedings of the Royal Society B: Biological Sciences. 284 (1851): 20162562. doi:10.1098/rspb.2016.2562. ISSN   0962-8452. PMC   5378080 . PMID   28356449.
2. Kennedy, David A.; Read, Andrew F. (2018-12-18). "Why the evolution of vaccine resistance is less of a concern than the evolution of drug resistance". Proceedings of the National Academy of Sciences. 115 (51): 12878–12886. Bibcode:2018PNAS..11512878K. doi: 10.1073/pnas.1717159115 . PMC   6304978 . PMID   30559199.
3. McLean, Angela Ruth (1995-09-22). "Vaccination, evolution and changes in the efficacy of vaccines: a theoretical framework" . Proceedings of the Royal Society of London. Series B: Biological Sciences. 261 (1362): 389–393. Bibcode:1995RSPSB.261..389M. doi:10.1098/rspb.1995.0164. PMID   8587880. S2CID   24978821.
4. Mclean, A. R (1998-01-01). "Vaccines and their impact on the control of disease". British Medical Bulletin. 54 (3): 545–556. doi: 10.1093/oxfordjournals.bmb.a011709 . ISSN   0007-1420. PMID   10326283.
5. Graham, Andrea L.; Allen, Judith E.; Read, Andrew F. (2005-11-10). "Evolutionary Causes and Consequences of Immunopathology" . Annual Review of Ecology, Evolution, and Systematics. 36 (1): 373–397. doi:10.1146/annurev.ecolsys.36.102003.152622. ISSN   1543-592X.
6. Witter, R. L. (1997). "Increased Virulence of Marek's Disease Virus Field Isolates" . Avian Diseases. 41 (1): 149–163. doi:10.2307/1592455. ISSN   0005-2086. JSTOR   1592455. PMID   9087332.
7. Read, Andrew F.; Baigent, Susan J.; Powers, Claire; Kgosana, Lydia B.; Blackwell, Luke; Smith, Lorraine P.; Kennedy, David A.; Walkden-Brown, Stephen W.; Nair, Venugopal K. (2015-07-27). "Imperfect Vaccination Can Enhance the Transmission of Highly Virulent Pathogens". PLOS Biology. 13 (7): e1002198. doi: 10.1371/journal.pbio.1002198 . ISSN   1545-7885. PMC   4516275 . PMID   26214839.
8. Austin, D.A.; Robertson, P.A.W.; Austin, B. (2003-01-01). "Recovery of a New Biogroup of Yersinia ruckeri from Diseased Rainbow Trout (Oncorhynchus mykiss, Walbaum)" . Systematic and Applied Microbiology. 26 (1): 127–131. doi:10.1078/072320203322337416. ISSN   0723-2020. PMID   12747420.
9. Welch, Timothy J.; Verner-Jeffreys, David W.; Dalsgaard, Inger; Wiklund, Thomas; Evenhuis, Jason P.; Garcia Cabrera, Jose A.; Hinshaw, Jeffrey M.; Drennan, John D.; Lapatra, Scott E. (2011). "Independent Emergence of Yersinia ruckeri Biotype 2 in the United States and Europe". Applied and Environmental Microbiology. 77 (10): 3493–3499. Bibcode:2011ApEnM..77.3493W. doi:10.1128/aem.02997-10. PMC   3126439 . PMID   21441334.
10. Banet-Noach, Caroline; Simanov, Lubov; Laham-Karam, Nihay; Perk, Shimon; Bacharach, Eran (2009). "Longitudinal Survey of Avian Metapneumoviruses in Poultry in Israel: Infiltration of Field Strains into Vaccinated Flocks" . Avian Diseases. 53 (2): 184–189. doi:10.1637/8466-090408-Reg.1. ISSN   0005-2086. JSTOR   25599093. PMID   19630222. S2CID   21433553.
11. Catelli, Elena; Lupini, Caterina; Cecchinato, Mattia; Ricchizzi, Enrico; Brown, Paul; Naylor, Clive J. (2010-01-22). "Field avian Metapneumovirus evolution avoiding vaccine induced immunity" . Vaccine. 28 (4): 916–921. doi:10.1016/j.vaccine.2009.10.149. ISSN   0264-410X. PMID   19931381.
12. Cecchinato, Mattia; Catelli, Elena; Lupini, Caterina; Ricchizzi, Enrico; Clubbe, Jayne; Battilani, Mara; Naylor, Clive J. (2010-11-20). "Avian metapneumovirus (AMPV) attachment protein involvement in probable virus evolution concurrent with mass live vaccine introduction" . Veterinary Microbiology. 146 (1–2): 24–34. doi:10.1016/j.vetmic.2010.04.014. ISSN   0378-1135. PMID   20447777.
13. Naylor, Clive J.; Ling, Roger; Edworthy, Nicole; Savage, Carol E.; Easton, Andrew J.YR 2007 (2007). "Avian metapneumovirus SH gene end and G protein mutations influence the level of protection of live-vaccine candidates". Journal of General Virology. 88 (6): 1767–1775. doi: 10.1099/vir.0.82755-0 . ISSN   1465-2099. PMID   17485538.
14. Weinberger, Daniel M; Malley, Richard; Lipsitch, Marc (December 2011). "Serotype replacement in disease after pneumococcal vaccination". The Lancet. 378 (9807): 1962–1973. doi:10.1016/s0140-6736(10)62225-8. ISSN   0140-6736. PMC   3256741 . PMID   21492929.
15. Brueggemann, Angela B.; Pai, Rekha; Crook, Derrick W.; Beall, Bernard (2007-11-16). "Vaccine Escape Recombinants Emerge after Pneumococcal Vaccination in the United States". PLOS Pathogens. 3 (11): e168. doi: 10.1371/journal.ppat.0030168 . ISSN   1553-7374. PMC   2077903 . PMID   18020702.
16. Carman, W.F.; Karayiannis, P.; Waters, J.; Thomas, H.C.; Zanetti, A.R.; Manzillo, G.; Zuckerman, A.J. (August 1990). "Vaccine-induced escape mutant of hepatitis B virus" . The Lancet. 336 (8711): 325–329. doi:10.1016/0140-6736(90)91874-a. ISSN   0140-6736. PMID   1697396. S2CID   45479217.
17. Zanetti, A.R.; Tanzi, E.; Manzillo, G.; Maio, G.; Sbreglia, C.; Caporaso, N.; Thomas, Howard; Zuckerman, ArieJ. (November 1988). "Hepatitis B Variant in Europe" . The Lancet. 332 (8620): 1132–1133. doi:10.1016/s0140-6736(88)90541-7. ISSN   0140-6736. PMID   2460710. S2CID   2638727.
18. Romanò, Luisa; Paladini, Sara; Galli, Cristina; Raimondo, Giovanni; Pollicino, Teresa; Zanetti, Alessandro R. (2015-01-01). "Hepatitis B vaccination". Human Vaccines & Immunotherapeutics. 11 (1): 53–57. doi:10.4161/hv.34306. ISSN   2164-5515. PMC   4514213 . PMID   25483515.
19. Sheldon, J.; Soriano, V. (2008-02-04). "Hepatitis B virus escape mutants induced by antiviral therapy". Journal of Antimicrobial Chemotherapy. 61 (4): 766–768. doi: 10.1093/jac/dkn014 . ISSN   0305-7453. PMID   18218641.
20. Mooi, F. R.; van Oirschot, H.; Heuvelman, K.; van der Heide, H. G.; Gaastra, W.; Willems, R. J. (February 1998). "Polymorphism in the Bordetella pertussis virulence factors P.69/pertactin and pertussis toxin in The Netherlands: temporal trends and evidence for vaccine-driven evolution". Infection and Immunity. 66 (2): 670–675. doi:10.1128/IAI.66.2.670-675.1998. ISSN   0019-9567. PMC   107955 . PMID   9453625.
21. Kallonen, Teemu; He, Qiushui (2009-07-01). "Bordetella pertussis strain variation and evolution postvaccination" . Expert Review of Vaccines. 8 (7): 863–875. doi:10.1586/erv.09.46. ISSN   1476-0584. PMID   19538113. S2CID   22946846.
22. Hegerle, Nicolas; Guiso, Nicole (2014-09-01). "Bordetella pertussis and pertactin-deficient clinical isolates: lessons for pertussis vaccines" . Expert Review of Vaccines. 13 (9): 1135–1146. doi:10.1586/14760584.2014.932254. ISSN   1476-0584. PMID   24953157. S2CID   21534501.
23. Safarchi, Azadeh; Octavia, Sophie; Luu, Laurence Don Wai; Tay, Chin Yen; Sintchenko, Vitali; Wood, Nicholas; Marshall, Helen; McIntyre, Peter; Lan, Ruiting (2015-11-17). "Pertactin negative Bordetella pertussis demonstrates higher fitness under vaccine selection pressure in a mixed infection model" . Vaccine. 33 (46): 6277–6281. doi:10.1016/j.vaccine.2015.09.064. ISSN   0264-410X. PMID   26432908.
24. Lee, Chang-Won; Senne, Dennis A.; Suarez, David L. (2004). "Effect of Vaccine Use in the Evolution of Mexican Lineage H5N2 Avian Influenza Virus". Journal of Virology. 78 (15): 8372–8381. doi:10.1128/jvi.78.15.8372-8381.2004. PMC   446090 . PMID   15254209.
25. Lu, Huaguang; Tang, Yi; Dunn, Patricia A.; Wallner-Pendleton, Eva A.; Lin, Lin; Knoll, Eric A. (2015-10-15). "Isolation and molecular characterization of newly emerging avian reovirus variants and novel strains in Pennsylvania, USA, 2011–2014". Scientific Reports. 5 (1): 14727. Bibcode:2015NatSR...514727L. doi:10.1038/srep14727. ISSN   2045-2322. PMC   4606735 . PMID   26469681.
26. Soubeyrand, Benoit; Plotkin, Stanley A. (June 2002). "Antitoxin vaccines and pathogen virulence" . Nature. 417 (6889): 609–610. doi:10.1038/417609b. ISSN   1476-4687. PMID   12050654. S2CID   4408258.
27. Radford, Alan D.; Dawson, Susan; Coyne, Karen P.; Porter, Carol J.; Gaskell, Rosalind M. (2006-10-05). "The challenge for the next generation of feline calicivirus vaccines" . Veterinary Microbiology. 117 (1): 14–18. doi:10.1016/j.vetmic.2006.04.004. ISSN   0378-1135. PMID   16698199.
28. Ribeiro, Guilherme S.; Reis, Joice N.; Cordeiro, Soraia M.; Lima, Josilene B. T.; Gouveia, Edilane L.; Petersen, Maya; Salgado, Kátia; Silva, Hagamenon R.; Zanella, Rosemeire Cobo; Almeida, Samanta C. Grassi; Brandileone, Maria Cristina (January 2003). "Prevention ofHaemophilus influenzaeType b (Hib) Meningitis and Emergence of Serotype Replacement with Type a Strains after Introduction of Hib Immunization in Brazil". The Journal of Infectious Diseases. 187 (1): 109–116. doi: 10.1086/345863 . ISSN   0022-1899. PMID   12508153.
29. Berg, Thierry P. Van Den (2000-06-01). "Acute infectious bursal disease in poultry: A review" . Avian Pathology. 29 (3): 175–194. doi:10.1080/03079450050045431. ISSN   0307-9457. PMID   19184804. S2CID   23178744.
30. Kertesz, Daniel A.; Coulthart, Michael B.; Ryan, J. Alan; Johnson, Wendy M.; Ashton, Fraser E. (June 1998). "Serogroup B, Electrophoretic Type 15 Neisseria meningitidis in Canada". The Journal of Infectious Diseases. 177 (6): 1754–1757. doi: 10.1086/517439 . ISSN   0022-1899. PMID   9607865.
31. Boven, Michiel van; Bouma, Annemarie; Fabri, Teun H. F.; Katsma, Elly; Hartog, Leo; Koch, Guus (2008-02-01). "Herd immunity to Newcastle disease virus in poultry by vaccination". Avian Pathology. 37 (1): 1–5. doi:10.1080/03079450701772391. ISSN   0307-9457. PMC   2556191 . PMID   18202943.
32. Franzo, Giovanni; Tucciarone, Claudia Maria; Cecchinato, Mattia; Drigo, Michele (2016-12-19). "Porcine circovirus type 2 (PCV2) evolution before and after the vaccination introduction: A large scale epidemiological study". Scientific Reports. 6 (1): 39458. Bibcode:2016NatSR...639458F. doi:10.1038/srep39458. ISSN   2045-2322. PMC   5171922 . PMID   27991573.