使用免疫动物血清对过去十年推荐的季节性流感 H3N2 疫苗进行回顾性免疫原性分析。

Retrospective immunogenicity analysis of seasonal flu H3N2 vaccines recommended in the past ten years using immunized animal sera.

机构信息

Division of HIV/AIDS and Sex-Transmitted Virus Vaccines, Institute for Biological Product Control, National Institutes for Food and Drug Control (NIFDC), No. 31 Huatuo Street, Daxing District, Beijing, 102629, China; Shanghai Institute of Biological Products Co. LTD, 350 Anshun Road, Changning District, Shanghai, 200051, China.

出版信息

EBioMedicine. 2022 Dec;86:104350. doi: 10.1016/j.ebiom.2022.104350. Epub 2022 Nov 17.

DOI:10.1016/j.ebiom.2022.104350

PMID:36403423

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9678686/

Abstract

BACKGROUND

Influenza A (H3N2) virus (A/H3N2) has complex antigenic evolution, resulting in frequent vaccine strain updates. We aimed to evaluate the protective effect of the vaccine strains on the circulating strains from past ten years and provide a basis for finding a broader and more efficient A/H3N2 vaccine strain.

METHODS

Eighty-four representative circulating A/H3N2 strains were selected from 65,791 deposited sequences in 2011-2020 and pseudotyped viruses were constructed with the VSV vector. We immunized guinea pigs with DNA vaccine containing the A/H3N2 components of the vaccine strains from 2011 to 2021 and tested neutralizing antibody against the pseudotyped viruses. We used a hierarchical clustering method to classify the eighty-four representative strains into different antigenic clusters. We also immunized animals with monovalent vaccine stock of the vaccine strains for the 2020-2021 and 2021-2022 seasons and tested neutralizing antibody against the pseudotyped viruses.

FINDINGS

The vaccine strains PE/09, VI/11 and TE/12 induced higher levels of neutralizing antibody against representative strains circulating in recommended year and the year immediately prior whereas vaccine strains HK/14, HK/19 and CA/20 induced poor neutralization against all representative strains. The representative strains were divided into five antigenic clusters (AgV), which were not identical to gene clades. The AgV5 strains were most difficult to be protected among the five clusters. Compared with single-dose immunization, three doses of monovalent vaccine stock (HK/19 or CA/20) could induce stronger and broader neutralizing antibodies against strains in each of the antigenic clusters.

INTERPRETATION

The protective effect of vaccine strains indicated that the accurate selection of A/H3N2 vaccine strains must remain a top priority. By increasing the frequency of immunization, stronger and broader neutralizing antibodies against strains in all antigenic clusters were induced, which provides direction for a new immunization strategy.

FUNDING

This work was supported by a grant from National Key R&D Program of China (No. 2021YFC2301700).

摘要

背景

甲型流感病毒（H3N2）（A/H3N2）具有复杂的抗原进化，导致疫苗株频繁更新。我们旨在评估过去十年中疫苗株对流行株的保护作用，并为寻找更广泛、更有效的 A/H3N2 疫苗株提供依据。

方法

从 2011 年至 2020 年的 65791 个存储序列中选择 84 株具有代表性的循环 A/H3N2 株，并使用 VSV 载体构建假病毒。我们用含有 2011 年至 2021 年疫苗株成分的 DNA 疫苗免疫豚鼠，并检测针对假病毒的中和抗体。我们采用层次聚类方法将 84 株代表性毒株分为不同的抗原簇。我们还用 2020-2021 年和 2021-2022 年季节的单价疫苗株免疫动物，并检测针对假病毒的中和抗体。

结果

疫苗株 PE/09、VI/11 和 TE/12 诱导针对当年和前一年流行株的中和抗体水平较高，而疫苗株 HK/14、HK/19 和 CA/20 对所有代表性毒株的中和作用较差。代表性毒株分为 5 个抗原簇（AgV），与基因进化枝不一致。在这 5 个簇中，AgV5 株最难保护。与单剂量免疫相比，单价疫苗株（HK/19 或 CA/20）三剂免疫可诱导针对各抗原簇中株更强、更广泛的中和抗体。