Differential Influence of Age on the Relationship between Genetic Mismatch and A(H1N1)pdm09 Vaccine Effectiveness.

Lirong Cao,Jingzhi Lou,Hong Zheng,Shi Zhao,Renee Chan,Benny Zee,Paul Chan,Maggie Wang,Zigui Chen,Marc Chong

doi:10.3390/v13040619

Lirong Cao, Jingzhi Lou + Show 8 more

Open Access

https://doi.org/10.3390/v13040619

Copy DOI

Journal: Viruses	Publication Date: Apr 4, 2021
Citations: 4	License type: CC BY 4.0

Affiliation: Chinese University of Hong Kong

Abstract

Assessment of influenza vaccine effectiveness (VE) and identification of relevant influencing factors are the current priorities for optimizing vaccines to reduce the impacts of influenza. To date, how the difference between epidemic strains and vaccine strains at genetic scale affects age-specific vaccine performance remains ambiguous. This study investigated the association between genetic mismatch on hemagglutinin and neuraminidase genes and A(H1N1)pdm09 VE in different age groups with a novel computational approach. We found significant linear relationships between VE and genetic mismatch in children, young adults, and middle-aged adults. In the children’s group, each 3-key amino acid mutation was associated with an average of 10% decrease in vaccine effectiveness in a given epidemic season, and genetic mismatch exerted no influence on VE for the elderly group. We demonstrated that present vaccines were most effective for children, while protection for the elderly was reduced and indifferent to vaccine component updates. Modeling such relationships is practical to inform timely evaluation of VE in different groups of populations during mass vaccination and may inform age-specific vaccination regimens.

Highlights

Since the emergence of the pandemic H1N1 influenza in early 2009, the swine-originA(H1N1)pdm09 virus has replaced the seasonal H1N1 subtype and become one of the four major circulating viruses underlying seasonal influenza epidemics [1]
Protein sequences of human influenza A(H1N1)pdm09 virus were retrieved from the global initiative on sharing all influenza data (GISAID) [18], with sampling dates ranging from 1 January 2009 to 31 December 2019
effective mutation distance (EMD) was defined by the Hamming distance on the effective mutations (EMs) underlying seasonal influenza epidemics [20,21,22], which could be interpreted as the amino acid substitutions that contributed to the viral escape from herd immunity

Summary

Introduction

A(H1N1)pdm virus has replaced the seasonal H1N1 subtype and become one of the four major circulating viruses underlying seasonal influenza epidemics [1]. The new subtype is introduced as one of the components in the trivalent or quadrivalent seasonal influenza vaccines [3]. The current VE exhibits high season-to-season variations, mostly due to the genetic mismatch of the circulating strains and the vaccine virus [6]. Apart from survey-based VE studies, the hemagglutination inhibition (HI) test is a standard method to evaluate the antigenic distance [7]. Studies based on antigenic distance showed that past vaccinations might have a negative or positive interference on current vaccine efficacy depending on the antigenic relatedness among the previous vaccine virus, current vaccine virus and the circulating strains [9,10,11]. Sequence-based methods were proposed to estimate the VE using various genetic mismatch summary statistics [12,13]

Methods

Results

Conclusion