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Genetic and antigenic typing of seasonal influenza virus breakthrough cases from a 2008-2009 vaccine efficacy trial

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Abstract
Estimations of the effectiveness of vaccines against seasonal influenza virus are guided by comparisons of the antigenicities between influenza virus isolates from clinical breakthrough cases with strains included in a vaccine. This study examined whether the prediction of antigenicity using a sequence analysis of the hemagglutinin (HA) gene-encoded HA1 domain is a simpler alternative to using the conventional hemagglutination inhibition (HI) assay, which requires influenza virus culturing. Specimens were taken from breakthrough cases that occurred in a trivalent influenza virus vaccine efficacy trial involving >43,000 participants during the 2008-2009 season. A total of 498 influenza viruses were successfully subtyped as A(H3N2) (380 viruses), A(H1N1) (29 viruses), B(Yamagata) (23 viruses), and B(Victoria) (66 viruses) from 603 PCR- or culture-confirmed specimens. Unlike the B strains, most A(H3N2) (377 viruses) and all A(H1N1) viruses were classified as homologous to the respective vaccine strains based on their HA1 domain nucleic acid sequence. HI titers relative to the respective vaccine strains and PCR subtyping were determined for 48% (182/380) of A(H3N2) and 86% (25/29) of A(H1N1) viruses. Eighty-four percent of the A(H3N2) and A(H1N1) viruses classified as homologous by sequence were matched to the respective vaccine strains by HI testing. However, these homologous A(H3N2) and A(H1N1) viruses displayed a wide range of relative HI titers. Therefore, although PCR is a sensitive diagnostic method for confirming influenza virus cases, HA1 sequence analysis appeared to be of limited value in accurately predicting antigenicity; hence, it may be inappropriate to classify clinical specimens as homologous or heterologous to the vaccine strain for estimating vaccine efficacy in a prospective clinical trial.
Keywords
SURVEILLANCE, SEQUENCES, DYNAMICS, CANADA, VARIANTS, EVOLUTION, HEMAGGLUTININ, GROUP STRAINS, AMINO-ACID SUBSTITUTIONS, A/H3N2 VIRUSES

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Citation

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Chicago
Durviaux, Serge, John Treanor, Jiri Beran, Xavier Duval, Meral Esen, Gregory Feldman, Sharon E Frey, et al. 2014. “Genetic and Antigenic Typing of Seasonal Influenza Virus Breakthrough Cases from a 2008-2009 Vaccine Efficacy Trial.” Clinical and Vaccine Immunology 21 (3): 271–279.
APA
Durviaux, S., Treanor, J., Beran, J., Duval, X., Esen, M., Feldman, G., Frey, S. E., et al. (2014). Genetic and antigenic typing of seasonal influenza virus breakthrough cases from a 2008-2009 vaccine efficacy trial. CLINICAL AND VACCINE IMMUNOLOGY, 21(3), 271–279.
Vancouver
1.
Durviaux S, Treanor J, Beran J, Duval X, Esen M, Feldman G, et al. Genetic and antigenic typing of seasonal influenza virus breakthrough cases from a 2008-2009 vaccine efficacy trial. CLINICAL AND VACCINE IMMUNOLOGY. 2014;21(3):271–9.
MLA
Durviaux, Serge, John Treanor, Jiri Beran, et al. “Genetic and Antigenic Typing of Seasonal Influenza Virus Breakthrough Cases from a 2008-2009 Vaccine Efficacy Trial.” CLINICAL AND VACCINE IMMUNOLOGY 21.3 (2014): 271–279. Print.
@article{4345334,
  abstract     = {Estimations of the effectiveness of vaccines against seasonal influenza virus are guided by comparisons of the antigenicities between influenza virus isolates from clinical breakthrough cases with strains included in a vaccine. This study examined whether the prediction of antigenicity using a sequence analysis of the hemagglutinin (HA) gene-encoded HA1 domain is a simpler alternative to using the conventional hemagglutination inhibition (HI) assay, which requires influenza virus culturing. Specimens were taken from breakthrough cases that occurred in a trivalent influenza virus vaccine efficacy trial involving {\textrangle}43,000 participants during the 2008-2009 season. A total of 498 influenza viruses were successfully subtyped as A(H3N2) (380 viruses), A(H1N1) (29 viruses), B(Yamagata) (23 viruses), and B(Victoria) (66 viruses) from 603 PCR- or culture-confirmed specimens. Unlike the B strains, most A(H3N2) (377 viruses) and all A(H1N1) viruses were classified as homologous to the respective vaccine strains based on their HA1 domain nucleic acid sequence. HI titers relative to the respective vaccine strains and PCR subtyping were determined for 48\% (182/380) of A(H3N2) and 86\% (25/29) of A(H1N1) viruses. Eighty-four percent of the A(H3N2) and A(H1N1) viruses classified as homologous by sequence were matched to the respective vaccine strains by HI testing. However, these homologous A(H3N2) and A(H1N1) viruses displayed a wide range of relative HI titers. Therefore, although PCR is a sensitive diagnostic method for confirming influenza virus cases, HA1 sequence analysis appeared to be of limited value in accurately predicting antigenicity; hence, it may be inappropriate to classify clinical specimens as homologous or heterologous to the vaccine strain for estimating vaccine efficacy in a prospective clinical trial.},
  author       = {Durviaux, Serge and Treanor, John and Beran, Jiri and Duval, Xavier and Esen, Meral and Feldman, Gregory and Frey, Sharon E and Launay, Odile and Leroux-Roels, Geert and McElhaney, Janet E and Nowakowski, Andrzej and Ruiz-Palacios, Guillermo M and van Essen, Gerrit A and Oostvogels, Lidia and Devaster, Jeanne-Marie and Walravens, Karl},
  issn         = {1556-6811},
  journal      = {CLINICAL AND VACCINE IMMUNOLOGY},
  keyword      = {SURVEILLANCE,SEQUENCES,DYNAMICS,CANADA,VARIANTS,EVOLUTION,HEMAGGLUTININ,GROUP STRAINS,AMINO-ACID SUBSTITUTIONS,A/H3N2 VIRUSES},
  language     = {eng},
  number       = {3},
  pages        = {271--279},
  title        = {Genetic and antigenic typing of seasonal influenza virus breakthrough cases from a 2008-2009 vaccine efficacy trial},
  url          = {http://dx.doi.org/10.1128/CVI.00544-13},
  volume       = {21},
  year         = {2014},
}

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