Predominance of a Drifted Influenza A (H3N2) Clade and Its Association with Age-Specific Influenza Vaccine Effectiveness Variations, Influenza Season 2018–2019

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.

Moderately Low Effectiveness of the Influenza Quadrivalent Vaccine: Potential Mismatch between Circulating Strains and Vaccine Strains

“…The findings of our study align with similar studies that have investigated the genetic diversity and relatedness of influenza virus strains [41,42]. Similarly, a study by [43] found that the majority of H3N2 viruses circulating during the 2012-2013 season in the United States were antigenically similar to the vaccine strain. However, as we observed in our study, the presence of divergent clades of H3N2 viruses, has also been documented [43,44].…”

“…Similarly, a study by [43] found that the majority of H3N2 viruses circulating during the 2012-2013 season in the United States were antigenically similar to the vaccine strain. However, as we observed in our study, the presence of divergent clades of H3N2 viruses, has also been documented [43,44]. In this study, we observed a homogeneous pattern of the A/H3 virus circulation, whereas A/H1 sequences clustered into different phylogenetic groups.…”

Diversity in the Circulation of Influenza A(H3N2) Viruses in the Northern Hemisphere in the 2018–19 Season

“…Such disparity between circulating viruses and the vaccine strain could have resulted in low immunity of populations against clade-3C.3a viruses, allowing significant spread of clade-3C.3a viruses in Israel, Asia, USA, and some countries in Europe, leading to reduced vaccine effectiveness (VE). Indeed, in Israel, we found a very low VE against A(H3N2) influenza virus in the winter of 2018–19 among infants, children, and young adults though, among adults aged ≥45 years, we found higher VE which could be due to previous exposure to clade-3C.3a viruses a few years earlier [ 31 ]. Similar findings were also found in Europe and in the USA, where clade-3C.3a viruses had circulated at high levels in recent years [ 32 , 33 ].…”

Vaccination and Vaccine Effectiveness: A Commentary of Special Issue Editors

“…A review conducted on immunization protocols of IAC in Western countries demonstrated substantially different approaches that should be corrected [ 21 ]. Glatman-Freedman et al analyzed the variation in the vaccine effectiveness (VE) of influenza vaccination in Israel during the 2018/2019 season according to different clades of influenza A (H3N2) virus [ 22 ], and Barbara et al observed a substantial increase of vaccination adherence among HCWs of the Catholic UH of Rome, Italy, due to evidence-based promoting strategies [ 23 ]. Panatto and colleagues, through a case-control test negative design, analyzed the VE of influenza vaccination during the 2018/2019 season in two Italian regions [ 24 ].…”