Insights into the antigenic advancement of influenza A(H3N2) viruses, 2011–2018

Abstract

Influenza A(H3N2) viruses evade human immunity primarily by acquiring antigenic changes in the haemagglutinin (HA). HA receptor-binding features of contemporary A(H3N2) viruses hinder traditional antigenic characterization using haemagglutination inhibition and promote selection of HA mutants. Thus, alternative approaches are needed to reliably assess antigenic relatedness between circulating viruses and vaccines. We developed a high content imaging-based neutralization test (HINT) to reduce antigenic mischaracterization resulting from virus adaptation to cell culture. Ferret reference antisera were raised using clinical specimens containing viruses representing recent vaccine strains. Analysis of viruses circulating during 2011–2018 showed that gain of an N158-linked glycosylation in HA was a molecular determinant of antigenic distancing between A/Hong Kong/4801/2014-like (clade 3C.2a) and A/Texas/50/2012-like viruses (clade 3C.1), while multiple evolutionary HA F193S substitution were linked to antigenic distancing from A/Switzerland/97152963/2013-like (clade 3C.3a) and further antigenic distancing from A/Texas/50/2012-like viruses. Additionally, a few viruses carrying HA T135K and/or I192T showed reduced neutralization by A/Hong Kong/4801/2014-like antiserum. Notably, this technique elucidated the antigenic characteristics of clinical specimens, enabling direct characterization of viruses produced in vivo , and eliminating in vitro culture, which rapidly alters the genotype/phenotype. HINT is a valuable new antigenic analysis tool for vaccine strain selection.

Interim estimates of 2019/20 vaccine effectiveness during early-season co-circulation of influenza A and B viruses, Canada, February 2020

“…Effectiveness of the 2019/20 clade 3C.3a vaccine against predominant 3C.2a1b viruses is higher than observed for the 2018/19 clade 3C.2a1 vaccine against late-season A(H3N2) viruses overall (17%) or in clade-specific analyses against co-circulating 3C.2a1b (27%) or 3C.3a (−32%) viruses [25]. Antibody induced to clade 3C.3a may be more cross-reactive than that of antibody induced to clade 3C.2a [26,27], and recent parallel substitutions shared between 3C.3a and 3C.2a1b/T135K viruses (e.g. A138S, F193S) may further contribute.…”

Antigenic assessment of the H3N2 component of the 2019-2020 Northern Hemisphere influenza vaccine

“…3N2 influenza viruses include many subclades with different genetic and antigenic properties 1 . Antigenically distinct 3c2.A and 3c3.A H3N2 viruses emerged during the 2014-2015 season 2 , which led to a major vaccine mismatch and low vaccine effectiveness 3,4 .…”

A comprehensive influenza reporter virus panel for high-throughput deep profiling of neutralizing antibodies

“…Recent attempted improvements of the WHO-recommended ELISA-based MN assay protocol( 67–69 ) underscore the need for the development of more reliable assays. Although the use of R3 viruses offers further advancements in the assay throughput, safety, and precision, this approach has its own limitations.…”