vaccine resistance

{{Short description|Adaptation of pathogens to reduce the protection of vaccines}}

{{also|Breakthrough infection}}

{{Distinguish|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).{{cn|date=July 2023}}

Some of the causes advanced for less frequent emergence of resistance are{{Cite journal|last1=Kennedy|first1=David A.|last2=Read|first2=Andrew F.|date=2017-03-29|title=Why does drug resistance readily evolve but vaccine resistance does not?|journal=Proceedings of the Royal Society B: Biological Sciences|language=en|volume=284|issue=1851|pages=20162562|doi=10.1098/rspb.2016.2562|issn=0962-8452|pmc=5378080|pmid=28356449}}{{Cite journal|last1=Kennedy|first1=David A.|last2=Read|first2=Andrew F.|date=2018-12-18|title=Why the evolution of vaccine resistance is less of a concern than the evolution of drug resistance|journal=Proceedings of the National Academy of Sciences|volume=115|issue=51|pages=12878–12886|doi=10.1073/pnas.1717159115|pmc=6304978|pmid=30559199|bibcode=2018PNAS..11512878K |doi-access=free}} 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.{{Cite journal|last=McLean|first=Angela Ruth|date=1995-09-22|title=Vaccination, evolution and changes in the efficacy of vaccines: a theoretical framework|url=https://royalsocietypublishing.org/doi/10.1098/rspb.1995.0164|journal=Proceedings of the Royal Society of London. Series B: Biological Sciences|volume=261|issue=1362|pages=389–393|doi=10.1098/rspb.1995.0164|pmid=8587880|bibcode=1995RSPSB.261..389M|s2cid=24978821|url-access=subscription}}{{Cite journal|last=Mclean|first=A. R|date=1998-01-01|title=Vaccines and their impact on the control of disease|journal=British Medical Bulletin|volume=54|issue=3|pages=545–556|doi=10.1093/oxfordjournals.bmb.a011709|pmid=10326283|issn=0007-1420|doi-access=free}}

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.{{Cite journal|last1=Graham|first1=Andrea L.|last2=Allen|first2=Judith E.|last3=Read|first3=Andrew F.|date=2005-11-10|title=Evolutionary Causes and Consequences of Immunopathology|url=https://www.annualreviews.org/doi/10.1146/annurev.ecolsys.36.102003.152622|journal=Annual Review of Ecology, Evolution, and Systematics|volume=36|issue=1|pages=373–397|doi=10.1146/annurev.ecolsys.36.102003.152622|issn=1543-592X|url-access=subscription}}

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{{Cite journal|last=Witter|first=R. L.|date=1997|title=Increased Virulence of Marek's Disease Virus Field Isolates|url=https://www.jstor.org/stable/1592455|journal=Avian Diseases|volume=41|issue=1|pages=149–163|doi=10.2307/1592455|jstor=1592455|pmid=9087332|issn=0005-2086|url-access=subscription}}{{Cite journal|last1=Read|first1=Andrew F.|last2=Baigent|first2=Susan J.|last3=Powers|first3=Claire|last4=Kgosana|first4=Lydia B.|last5=Blackwell|first5=Luke|last6=Smith|first6=Lorraine P.|last7=Kennedy|first7=David A.|last8=Walkden-Brown|first8=Stephen W.|last9=Nair|first9=Venugopal K.|date=2015-07-27|title=Imperfect Vaccination Can Enhance the Transmission of Highly Virulent Pathogens|journal=PLOS Biology|language=en|volume=13|issue=7|pages=e1002198|doi=10.1371/journal.pbio.1002198|issn=1545-7885|pmc=4516275|pmid=26214839 |doi-access=free }} because the vaccine did not protect against infection and transmission, only against serious forms of the disease
• Yersinia ruckeri{{Cite journal|date=2003-01-01|title=Recovery of a New Biogroup of Yersinia ruckeri from Diseased Rainbow Trout (Oncorhynchus mykiss, Walbaum)|url=https://www.sciencedirect.com/science/article/abs/pii/S0723202004701691|journal=Systematic and Applied Microbiology|language=en|volume=26|issue=1|pages=127–131|doi=10.1078/072320203322337416|issn=0723-2020|last1=Austin|first1=D.A.|last2=Robertson|first2=P.A.W.|last3=Austin|first3=B.|pmid=12747420|url-access=subscription}}{{Cite journal|title=Independent Emergence of Yersinia ruckeri Biotype 2 in the United States and Europe|journal=Applied and Environmental Microbiology|year=2011|language=en|doi=10.1128/aem.02997-10|pmc=3126439|pmid=21441334|last1=Welch|first1=Timothy J.|last2=Verner-Jeffreys|first2=David W.|last3=Dalsgaard|first3=Inger|last4=Wiklund|first4=Thomas|last5=Evenhuis|first5=Jason P.|last6=Garcia Cabrera|first6=Jose A.|last7=Hinshaw|first7=Jeffrey M.|last8=Drennan|first8=John D.|last9=Lapatra|first9=Scott E.|volume=77|issue=10|pages=3493–3499|bibcode=2011ApEnM..77.3493W}} because a single mutation was sufficient to generate vaccine resistance
• avian metapneumovirus{{Cite journal|last1=Banet-Noach|first1=Caroline|last2=Simanov|first2=Lubov|last3=Laham-Karam|first3=Nihay|last4=Perk|first4=Shimon|last5=Bacharach|first5=Eran|date=2009|title=Longitudinal Survey of Avian Metapneumoviruses in Poultry in Israel: Infiltration of Field Strains into Vaccinated Flocks|url=https://www.jstor.org/stable/25599093|journal=Avian Diseases|volume=53|issue=2|pages=184–189|doi=10.1637/8466-090408-Reg.1|jstor=25599093|pmid=19630222|s2cid=21433553|issn=0005-2086|url-access=subscription}}{{Cite journal|date=2010-01-22|title=Field avian Metapneumovirus evolution avoiding vaccine induced immunity|url=https://www.sciencedirect.com/science/article/pii/S0264410X09017320|journal=Vaccine|language=en|volume=28|issue=4|pages=916–921|doi=10.1016/j.vaccine.2009.10.149|issn=0264-410X|last1=Catelli|first1=Elena|last2=Lupini|first2=Caterina|last3=Cecchinato|first3=Mattia|last4=Ricchizzi|first4=Enrico|last5=Brown|first5=Paul|last6=Naylor|first6=Clive J.|pmid=19931381|url-access=subscription}}{{Cite journal|date=2010-11-20|title=Avian metapneumovirus (AMPV) attachment protein involvement in probable virus evolution concurrent with mass live vaccine introduction|url=https://www.sciencedirect.com/science/article/pii/S0378113510001951|journal=Veterinary Microbiology|language=en|volume=146|issue=1–2|pages=24–34|doi=10.1016/j.vetmic.2010.04.014|issn=0378-1135|last1=Cecchinato|first1=Mattia|last2=Catelli|first2=Elena|last3=Lupini|first3=Caterina|last4=Ricchizzi|first4=Enrico|last5=Clubbe|first5=Jayne|last6=Battilani|first6=Mara|last7=Naylor|first7=Clive J.|pmid=20447777|url-access=subscription}}{{Cite journal|last1=Naylor|first1=Clive J.|last2=Ling|first2=Roger|last3=Edworthy|first3=Nicole|last4=Savage|first4=Carol E.|last5=Easton|first5=Andrew J.YR 2007|title=Avian metapneumovirus SH gene end and G protein mutations influence the level of protection of live-vaccine candidates|journal=Journal of General Virology|year=2007|volume=88|issue=6|pages=1767–1775|doi=10.1099/vir.0.82755-0|pmid=17485538|issn=1465-2099|doi-access=free}}
• human diseases
• Streptococcus pneumoniae{{Cite journal|last1=Weinberger|first1=Daniel M|last2=Malley|first2=Richard|last3=Lipsitch|first3=Marc|date=December 2011|title=Serotype replacement in disease after pneumococcal vaccination|url=http://dx.doi.org/10.1016/S0140-6736(10)62225-8|journal=The Lancet|volume=378|issue=9807|pages=1962–1973|doi=10.1016/s0140-6736(10)62225-8|issn=0140-6736|pmc=3256741|pmid=21492929}}{{Cite journal|last1=Brueggemann|first1=Angela B.|last2=Pai|first2=Rekha|last3=Crook|first3=Derrick W.|last4=Beall|first4=Bernard|date=2007-11-16|title=Vaccine Escape Recombinants Emerge after Pneumococcal Vaccination in the United States|journal=PLOS Pathogens|language=en|volume=3|issue=11|pages=e168|doi=10.1371/journal.ppat.0030168|issn=1553-7374|pmc=2077903|pmid=18020702 |doi-access=free }} because recombination with another serotype not targeted by the vaccine
• hepatitis B virus{{Cite journal|last1=Carman|first1=W.F.|last2=Karayiannis|first2=P.|last3=Waters|first3=J.|last4=Thomas|first4=H.C.|last5=Zanetti|first5=A.R.|last6=Manzillo|first6=G.|last7=Zuckerman|first7=A.J.|date=August 1990|title=Vaccine-induced escape mutant of hepatitis B virus|url=http://dx.doi.org/10.1016/0140-6736(90)91874-A|journal=The Lancet|volume=336|issue=8711|pages=325–329|doi=10.1016/0140-6736(90)91874-a|pmid=1697396|s2cid=45479217|issn=0140-6736|url-access=subscription}}{{Cite journal|last1=Zanetti|first1=A.R.|last2=Tanzi|first2=E.|last3=Manzillo|first3=G.|last4=Maio|first4=G.|last5=Sbreglia|first5=C.|last6=Caporaso|first6=N.|last7=Thomas|first7=Howard|last8=Zuckerman|first8=ArieJ.|title=Hepatitis B Variant in Europe|date=November 1988|url=http://dx.doi.org/10.1016/S0140-6736(88)90541-7|journal=The Lancet|volume=332|issue=8620|pages=1132–1133|doi=10.1016/s0140-6736(88)90541-7|pmid=2460710|s2cid=2638727|issn=0140-6736|url-access=subscription}}{{Cite journal|last1=Romanò|first1=Luisa|last2=Paladini|first2=Sara|last3=Galli|first3=Cristina|last4=Raimondo|first4=Giovanni|last5=Pollicino|first5=Teresa|last6=Zanetti|first6=Alessandro R.|date=2015-01-01|title=Hepatitis B vaccination|url=https://doi.org/10.4161/hv.34306|journal=Human Vaccines & Immunotherapeutics|volume=11|issue=1|pages=53–57|doi=10.4161/hv.34306|issn=2164-5515|pmc=4514213|pmid=25483515}}{{Cite journal|last1=Sheldon|first1=J.|last2=Soriano|first2=V.|date=2008-02-04|title=Hepatitis B virus escape mutants induced by antiviral therapy|journal=Journal of Antimicrobial Chemotherapy|volume=61|issue=4|pages=766–768|doi=10.1093/jac/dkn014|pmid=18218641|issn=0305-7453|doi-access=free}} because the vaccine targeted a single site formed by 9 amino acids
• Bordetella pertussis{{Cite journal|last1=Mooi|first1=F. R.|last2=van Oirschot|first2=H.|last3=Heuvelman|first3=K.|last4=van der Heide|first4=H. G.|last5=Gaastra|first5=W.|last6=Willems|first6=R. J.|date=February 1998|title=Polymorphism in the Bordetella pertussis virulence factors P.69/pertactin and pertussis toxin in The Netherlands: temporal trends and evidence for vaccine-driven evolution|journal=Infection and Immunity|volume=66|issue=2|pages=670–675|doi=10.1128/IAI.66.2.670-675.1998|issn=0019-9567|pmid=9453625|pmc=107955}}{{Cite journal|last1=Kallonen|first1=Teemu|last2=He|first2=Qiushui|date=2009-07-01|title=Bordetella pertussis strain variation and evolution postvaccination|url=https://doi.org/10.1586/erv.09.46|journal=Expert Review of Vaccines|volume=8|issue=7|pages=863–875|doi=10.1586/erv.09.46|pmid=19538113|s2cid=22946846|issn=1476-0584|url-access=subscription}}{{Cite journal|last1=Hegerle|first1=Nicolas|last2=Guiso|first2=Nicole|date=2014-09-01|title=Bordetella pertussis and pertactin-deficient clinical isolates: lessons for pertussis vaccines|url=https://doi.org/10.1586/14760584.2014.932254|journal=Expert Review of Vaccines|volume=13|issue=9|pages=1135–1146|doi=10.1586/14760584.2014.932254|pmid=24953157|s2cid=21534501|issn=1476-0584|url-access=subscription}}{{Cite journal|date=2015-11-17|title=Pertactin negative Bordetella pertussis demonstrates higher fitness under vaccine selection pressure in a mixed infection model|url=https://www.sciencedirect.com/science/article/pii/S0264410X15013407|journal=Vaccine|language=en|volume=33|issue=46|pages=6277–6281|doi=10.1016/j.vaccine.2015.09.064|issn=0264-410X|last1=Safarchi|first1=Azadeh|last2=Octavia|first2=Sophie|last3=Luu|first3=Laurence Don Wai|last4=Tay|first4=Chin Yen|last5=Sintchenko|first5=Vitali|last6=Wood|first6=Nicholas|last7=Marshall|first7=Helen|last8=McIntyre|first8=Peter|last9=Lan|first9=Ruiting|pmid=26432908|url-access=subscription}} because not all serotypes were targeted and later because acellular vaccines targeted only a few antigens

Other less documented cases are for avian influenza,{{Cite journal|title=Effect of Vaccine Use in the Evolution of Mexican Lineage H5N2 Avian Influenza Virus|journal=Journal of Virology|year=2004|language=en|doi=10.1128/jvi.78.15.8372-8381.2004|pmc=446090|pmid=15254209|last1=Lee|first1=Chang-Won|last2=Senne|first2=Dennis A.|last3=Suarez|first3=David L.|volume=78|issue=15|pages=8372–8381}} avian reovirus,{{Cite journal|last1=Lu|first1=Huaguang|last2=Tang|first2=Yi|last3=Dunn|first3=Patricia A.|last4=Wallner-Pendleton|first4=Eva A.|last5=Lin|first5=Lin|last6=Knoll|first6=Eric A.|date=2015-10-15|title=Isolation and molecular characterization of newly emerging avian reovirus variants and novel strains in Pennsylvania, USA, 2011–2014|journal=Scientific Reports|language=en|volume=5|issue=1|pages=14727|doi=10.1038/srep14727|issn=2045-2322|pmc=4606735|pmid=26469681|bibcode=2015NatSR...514727L}} Corynebacterium diphtheriae,{{Cite journal|last1=Soubeyrand|first1=Benoit|last2=Plotkin|first2=Stanley A.|date=June 2002|title=Antitoxin vaccines and pathogen virulence|url=https://www.nature.com/articles/417609b|journal=Nature|language=en|volume=417|issue=6889|pages=609–610|doi=10.1038/417609b|pmid=12050654|s2cid=4408258|issn=1476-4687|url-access=subscription}} feline calicivirus,{{Cite journal|date=2006-10-05|title=The challenge for the next generation of feline calicivirus vaccines|url=https://www.sciencedirect.com/science/article/pii/S0378113506001386|journal=Veterinary Microbiology|language=en|volume=117|issue=1|pages=14–18|doi=10.1016/j.vetmic.2006.04.004|issn=0378-1135|last1=Radford|first1=Alan D.|last2=Dawson|first2=Susan|last3=Coyne|first3=Karen P.|last4=Porter|first4=Carol J.|last5=Gaskell|first5=Rosalind M.|pmid=16698199|url-access=subscription}} H. influenzae,{{Cite journal|last1=Ribeiro|first1=Guilherme S.|last2=Reis|first2=Joice N.|last3=Cordeiro|first3=Soraia M.|last4=Lima|first4=Josilene B. T.|last5=Gouveia|first5=Edilane L.|last6=Petersen|first6=Maya|last7=Salgado|first7=Kátia|last8=Silva|first8=Hagamenon R.|last9=Zanella|first9=Rosemeire Cobo|last10=Almeida|first10=Samanta C. Grassi|last11=Brandileone|first11=Maria Cristina|date=January 2003|title=Prevention ofHaemophilus influenzaeType b (Hib) Meningitis and Emergence of Serotype Replacement with Type a Strains after Introduction of Hib Immunization in Brazil|journal=The Journal of Infectious Diseases|volume=187|issue=1|pages=109–116|doi=10.1086/345863|pmid=12508153|issn=0022-1899|doi-access=free}} infectious bursal disease virus,{{Cite journal|last=Berg|first=Thierry P. Van Den|date=2000-06-01|title=Acute infectious bursal disease in poultry: A review|url=https://doi.org/10.1080/03079450050045431|journal=Avian Pathology|volume=29|issue=3|pages=175–194|doi=10.1080/03079450050045431|issn=0307-9457|pmid=19184804|s2cid=23178744|url-access=subscription}} Neisseria meningitidis,{{Cite journal|last1=Kertesz|first1=Daniel A.|last2=Coulthart|first2=Michael B.|last3=Ryan|first3=J. Alan|last4=Johnson|first4=Wendy M.|last5=Ashton|first5=Fraser E.|date=June 1998|title=Serogroup B, Electrophoretic Type 15 Neisseria meningitidis in Canada|journal=The Journal of Infectious Diseases|volume=177|issue=6|pages=1754–1757|doi=10.1086/517439|pmid=9607865|issn=0022-1899|doi-access=free}} Newcastle disease virus,{{Cite journal|last1=Boven|first1=Michiel van|last2=Bouma|first2=Annemarie|last3=Fabri|first3=Teun H. F.|last4=Katsma|first4=Elly|last5=Hartog|first5=Leo|last6=Koch|first6=Guus|date=2008-02-01|title=Herd immunity to Newcastle disease virus in poultry by vaccination|url=https://doi.org/10.1080/03079450701772391|journal=Avian Pathology|volume=37|issue=1|pages=1–5|doi=10.1080/03079450701772391|issn=0307-9457|pmc=2556191|pmid=18202943}} and porcine circovirus type 2.{{Cite journal|last1=Franzo|first1=Giovanni|last2=Tucciarone|first2=Claudia Maria|last3=Cecchinato|first3=Mattia|last4=Drigo|first4=Michele|date=2016-12-19|title=Porcine circovirus type 2 (PCV2) evolution before and after the vaccination introduction: A large scale epidemiological study|journal=Scientific Reports|language=en|volume=6|issue=1|pages=39458|doi=10.1038/srep39458|issn=2045-2322|pmc=5171922|pmid=27991573|bibcode=2016NatSR...639458F}}