Predominance of a Drifted Influenza A (H3N2) Clade and its Association with Age-specific Influenza Vaccine Effectiveness Variations, Influenza Season 2018-2019.

Aharona Glatman-Freedman,Itay Omer,Rakefet Pando,Lital Keinan-Boker,Ella Mendelson,Yaron Drori,Hanna Sefty,Alina Rosenberg,Ital Nemet,Michal Mandelboim

doi:10.3390/vaccines8010078

Abstract

Background: Influenza A (H3N2) clade 3C.3a was the predominant influenza virus in Israel throughout the 2018-2019 season, constituting a drift from the influenza A (H3N2) vaccine. We estimated the end-of season vaccine effectiveness (VE) by age, among community patients with influenza-like illness (ILI), considering the hemagglutinin (HA) gene mutations and amino acid substitutions of influenza A (H3N2) viruses detected. Methods: Nose-throat samples were analyzed for the presence of influenza virus, type/subtype, and HA gene sequence. HA gene sequences and amino acid substitutions were compared to the influenza A/Singapore/INFIMH-16-0019/2016 (H3N2)-like 2018-2019 vaccine virus, and a phylogenetic tree was generated. Influenza VE against influenza A (H3N2) was estimated using the test-negative design. VE was estimated by age group and by 15 year moving age intervals. Results: In total, 90% of the influenza A (H3N2) viruses belonged to the 3C.3a clade, constituting a unique situation in the northern hemisphere. Adjusted all-age influenza A (H3N2) VE was −3.5% (95% CI: −51.2 to 29.1). Although adjusted VEs were very low among infants, children, and young adults, a VE of 45% (95% CI: −19.2 to 74.6) was estimated among adults aged ≥45 years old. Conclusions: The higher VE point estimates among older adults may be related to previous exposure to similar influenza viruses.

Highlights

In recent years, influenza A (H3N2) viruses have presented a significant challenge for vaccine selection
A total of 54 (90%) viruses belonged to the 3C.3a clade, which differed from the 3C.2a1 subclade of the influenza A/Singapore/INFIMH-16-0019/2016 (H3N2)-like virus included in the 2018-2019 influenza vaccine
The 3C.3a influenza A (H3N2) viruses differed from influenza A (H3N2) viruses that circulated in most locations in the northern hemisphere, especially in the early and middle parts of the season [16], and had poor antigenic reaction with antibodies elicited by the 2018–2019 influenza A (H3N2) vaccine virus [1]

Summary

Introduction

Influenza A (H3N2) viruses have presented a significant challenge for vaccine selection. Vaccines 2020, 8, 78 drift, with the emergence of clade 3C.2a during the 2014–2015 season [3], as well as genetic divergence of the 3C.2a A (H3N2) clade into several subclades circulating concurrently, starting from the 2016–2017 season [4] This rapid process of diversification has raised our concern regarding the ability to select an influenza A (H3N2) vaccine virus that matches the circulating influenza A (H3N2) viruses in all or most countries located in a single hemisphere. We estimated the end-of season vaccine effectiveness (VE) by age, among community patients with influenza-like illness (ILI), considering the hemagglutinin (HA) gene mutations and amino acid substitutions of influenza A (H3N2) viruses detected. Adjusted influenza A (H3N2) VE estimates for specific age groups demonstrated that the vaccine was not effective among children and adults

Methods

Results

Conclusion