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Poor Immunogenicity, Not Vaccine Strain Egg Adaptation, May Explain the Low H3N2 Influenza Vaccine Effectiveness in 2012–2013

BACKGROUND: Influenza vaccination aims to prevent infection by influenza virus and reduce associated morbidity and mortality; however, vaccine effectiveness (VE) can be modest, especially for subtype A(H3N2). Low VE has been attributed to mismatches between the vaccine and circulating influenza stra...

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Autores principales: Cobey, Sarah, Gouma, Sigrid, Parkhouse, Kaela, Chambers, Benjamin S, Ertl, Hildegund C, Schmader, Kenneth E, Halpin, Rebecca A, Lin, Xudong, Stockwell, Timothy B, Das, Suman R, Landon, Emily, Tesic, Vera, Youngster, Ilan, Pinsky, Benjamin A, Wentworth, David E, Hensley, Scott E, Grad, Yonatan H
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6051447/
https://www.ncbi.nlm.nih.gov/pubmed/29471464
http://dx.doi.org/10.1093/cid/ciy097
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author Cobey, Sarah
Gouma, Sigrid
Parkhouse, Kaela
Chambers, Benjamin S
Ertl, Hildegund C
Schmader, Kenneth E
Halpin, Rebecca A
Lin, Xudong
Stockwell, Timothy B
Das, Suman R
Landon, Emily
Tesic, Vera
Youngster, Ilan
Pinsky, Benjamin A
Wentworth, David E
Hensley, Scott E
Grad, Yonatan H
author_facet Cobey, Sarah
Gouma, Sigrid
Parkhouse, Kaela
Chambers, Benjamin S
Ertl, Hildegund C
Schmader, Kenneth E
Halpin, Rebecca A
Lin, Xudong
Stockwell, Timothy B
Das, Suman R
Landon, Emily
Tesic, Vera
Youngster, Ilan
Pinsky, Benjamin A
Wentworth, David E
Hensley, Scott E
Grad, Yonatan H
author_sort Cobey, Sarah
collection PubMed
description BACKGROUND: Influenza vaccination aims to prevent infection by influenza virus and reduce associated morbidity and mortality; however, vaccine effectiveness (VE) can be modest, especially for subtype A(H3N2). Low VE has been attributed to mismatches between the vaccine and circulating influenza strains and to the vaccine’s elicitation of protective immunity in only a subset of the population. The low H3N2 VE in the 2012–2013 season was attributed to egg-adaptive mutations that created antigenic mismatch between the actual vaccine strain (IVR-165) and both the intended vaccine strain (A/Victoria/361/2011) and the predominant circulating strains (clades 3C.2 and 3C.3). METHODS: We investigated the basis of low VE in 2012–2013 by determining whether vaccinated and unvaccinated individuals were infected by different viral strains and by assessing the serologic responses to IVR-165, A/Victoria/361/2011, and 3C.2 and 3C.3 strains in an adult cohort before and after vaccination. RESULTS: We found no significant genetic differences between the strains that infected vaccinated and unvaccinated individuals. Vaccination increased titers to A/Victoria/361/2011 and 3C.2 and 3C.3 representative strains as much as to IVR-165. These results are consistent with the hypothesis that vaccination boosted cross-reactive immune responses instead of specific responses against unique vaccine epitopes. Only approximately one-third of the cohort achieved a ≥4-fold increase in titer. CONCLUSIONS: In contrast to analyses based on ferret studies, low H3N2 VE in 2012–2013 in adults does not appear to be due to egg adaptation of the vaccine strain. Instead, low VE might have been caused by low vaccine immunogenicity in a subset of the population.
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spelling pubmed-60514472018-07-23 Poor Immunogenicity, Not Vaccine Strain Egg Adaptation, May Explain the Low H3N2 Influenza Vaccine Effectiveness in 2012–2013 Cobey, Sarah Gouma, Sigrid Parkhouse, Kaela Chambers, Benjamin S Ertl, Hildegund C Schmader, Kenneth E Halpin, Rebecca A Lin, Xudong Stockwell, Timothy B Das, Suman R Landon, Emily Tesic, Vera Youngster, Ilan Pinsky, Benjamin A Wentworth, David E Hensley, Scott E Grad, Yonatan H Clin Infect Dis Articles and Commentary BACKGROUND: Influenza vaccination aims to prevent infection by influenza virus and reduce associated morbidity and mortality; however, vaccine effectiveness (VE) can be modest, especially for subtype A(H3N2). Low VE has been attributed to mismatches between the vaccine and circulating influenza strains and to the vaccine’s elicitation of protective immunity in only a subset of the population. The low H3N2 VE in the 2012–2013 season was attributed to egg-adaptive mutations that created antigenic mismatch between the actual vaccine strain (IVR-165) and both the intended vaccine strain (A/Victoria/361/2011) and the predominant circulating strains (clades 3C.2 and 3C.3). METHODS: We investigated the basis of low VE in 2012–2013 by determining whether vaccinated and unvaccinated individuals were infected by different viral strains and by assessing the serologic responses to IVR-165, A/Victoria/361/2011, and 3C.2 and 3C.3 strains in an adult cohort before and after vaccination. RESULTS: We found no significant genetic differences between the strains that infected vaccinated and unvaccinated individuals. Vaccination increased titers to A/Victoria/361/2011 and 3C.2 and 3C.3 representative strains as much as to IVR-165. These results are consistent with the hypothesis that vaccination boosted cross-reactive immune responses instead of specific responses against unique vaccine epitopes. Only approximately one-third of the cohort achieved a ≥4-fold increase in titer. CONCLUSIONS: In contrast to analyses based on ferret studies, low H3N2 VE in 2012–2013 in adults does not appear to be due to egg adaptation of the vaccine strain. Instead, low VE might have been caused by low vaccine immunogenicity in a subset of the population. Oxford University Press 2018-08-01 2018-02-20 /pmc/articles/PMC6051447/ /pubmed/29471464 http://dx.doi.org/10.1093/cid/ciy097 Text en © The Author(s) 2018. Published by Oxford University Press for the Infectious Diseases Society of America. http://creativecommons.org/licenses/by/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Articles and Commentary
Cobey, Sarah
Gouma, Sigrid
Parkhouse, Kaela
Chambers, Benjamin S
Ertl, Hildegund C
Schmader, Kenneth E
Halpin, Rebecca A
Lin, Xudong
Stockwell, Timothy B
Das, Suman R
Landon, Emily
Tesic, Vera
Youngster, Ilan
Pinsky, Benjamin A
Wentworth, David E
Hensley, Scott E
Grad, Yonatan H
Poor Immunogenicity, Not Vaccine Strain Egg Adaptation, May Explain the Low H3N2 Influenza Vaccine Effectiveness in 2012–2013
title Poor Immunogenicity, Not Vaccine Strain Egg Adaptation, May Explain the Low H3N2 Influenza Vaccine Effectiveness in 2012–2013
title_full Poor Immunogenicity, Not Vaccine Strain Egg Adaptation, May Explain the Low H3N2 Influenza Vaccine Effectiveness in 2012–2013
title_fullStr Poor Immunogenicity, Not Vaccine Strain Egg Adaptation, May Explain the Low H3N2 Influenza Vaccine Effectiveness in 2012–2013
title_full_unstemmed Poor Immunogenicity, Not Vaccine Strain Egg Adaptation, May Explain the Low H3N2 Influenza Vaccine Effectiveness in 2012–2013
title_short Poor Immunogenicity, Not Vaccine Strain Egg Adaptation, May Explain the Low H3N2 Influenza Vaccine Effectiveness in 2012–2013
title_sort poor immunogenicity, not vaccine strain egg adaptation, may explain the low h3n2 influenza vaccine effectiveness in 2012–2013
topic Articles and Commentary
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6051447/
https://www.ncbi.nlm.nih.gov/pubmed/29471464
http://dx.doi.org/10.1093/cid/ciy097
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