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. 2016 Oct 1;214(7):1010-9.
doi: 10.1093/infdis/jiw181. Epub 2016 May 6.

Enhanced Genetic Characterization of Influenza A(H3N2) Viruses and Vaccine Effectiveness by Genetic Group, 2014-2015

Brendan Flannery  1 , Richard K Zimmerman  2 , Larisa V Gubareva  1 , Rebecca J Garten  1 , Jessie R Chung  3 , Mary Patricia Nowalk  2 , Michael L Jackson  4 , Lisa A Jackson  4 , Arnold S Monto  5 , Suzanne E Ohmit  5 , Edward A Belongia  6 , Huong Q McLean  6 , Manjusha Gaglani  7 , Pedro A Piedra  8 , Vasiliy P Mishin  1 , Anton P Chesnokov  1 , Sarah Spencer  3 , Swathi N Thaker  1 , John R Barnes  1 , Angie Foust  1 , Wendy Sessions  1 , Xiyan Xu  1 , Jacqueline Katz  1 , Alicia M Fry  1
Affiliations

Enhanced Genetic Characterization of Influenza A(H3N2) Viruses and Vaccine Effectiveness by Genetic Group, 2014-2015

Brendan Flannery et al. J Infect Dis. .

Erratum in

  • Erratum.
    [No authors listed] [No authors listed] J Infect Dis. 2017 Jun 1;215(11):1774. doi: 10.1093/infdis/jix220. J Infect Dis. 2017. PMID: 28863447 Free PMC article. No abstract available.

Abstract

Background: During the 2014-2015 US influenza season, expanded genetic characterization of circulating influenza A(H3N2) viruses was used to assess the impact of the genetic variability of influenza A(H3N2) viruses on influenza vaccine effectiveness (VE).

Methods: A novel pyrosequencing assay was used to determine genetic group, based on hemagglutinin (HA) gene sequences, of influenza A(H3N2) viruses from patients enrolled at US Influenza Vaccine Effectiveness Network sites. VE was estimated using a test-negative design comparing vaccination among patients infected with influenza A(H3N2) viruses and uninfected patients.

Results: Among 9710 enrollees, 1868 (19%) tested positive for influenza A(H3N2) virus; genetic characterization of 1397 viruses showed that 1134 (81%) belonged to 1 HA genetic group (3C.2a) of antigenically drifted influenza A(H3N2) viruses. Effectiveness of 2014-2015 influenza vaccination varied by influenza A(H3N2) virus genetic group from 1% (95% confidence interval [CI], -14% to 14%) against illness caused by antigenically drifted influenza A(H3N2) virus group 3C.2a viruses versus 44% (95% CI, 16%-63%) against illness caused by vaccine-like influenza A(H3N2) virus group 3C.3b viruses.

Conclusions: Effectiveness of 2014-2015 influenza vaccination varied by genetic group of influenza A(H3N2) virus. Changes in HA genes related to antigenic drift were associated with reduced VE.

Keywords: genetic characterization; influenza; influenza vaccine; pyrosequencing; vaccine effectiveness.

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Figures

Figure 1.
Figure 1.
Phylogenetic tree based on hemagglutinin (HA) genes of influenza A(H3N2) viruses collected during March 2014–April 2015 and analyzed at the Centers for Disease Control and Prevention (Atlanta, GA). Phylogenetic tree is based on genetic differences as compared to the A/Texas/50/2012 consensus sequence. Amino acid substitutions delineating major branches are shown. Date of collection follows names of viruses from US public health laboratories participating in US virologic surveillance (normal font) and from patients enrolled at US Influenza Vaccine Effectiveness Network sites (bold font).
Figure 2.
Figure 2.
Numbers of polymerase chain reaction (PCR)–confirmed infections with influenza A(H3N2) viruses by genetic group and percentage influenza virus positivity among patients with medically-attended acute respiratory illness, by week of symptom onset, US Influenza Vaccine Effectiveness Network, 10 November 2014–10 April 2015.
Figure 3.
Figure 3.
Geographic distribution of genetic groups of influenza A(H3N2) viruses in the United States and from patients enrolled in the US Influenza Vaccine Effectiveness Network study. A, Viruses from influenza A(H3N2) virus–positive patients enrolled from 10 November 2014 through 10 April 2015 (n = 1397). Pie charts present the proportional distribution of hemagglutinin (HA) genetic group, based on the number of genetically characterized influenza A(H3N2) viruses from patients enrolled at each study site. B, Viruses identified by US public health laboratories from 10 November 2014 through 10 April 2015 and submitted to the Centers for Disease Control and Prevention for genetic characterization (n = 1633). Pie charts present the proportional distribution of HA genetic group, based on the number of genetically characterized influenza A(H3N2) viruses from each state or territory.
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