抗体介导的抑制作用调节人类对流感疫苗接种的体液免疫反应。

Antibody-Mediated Suppression Regulates the Humoral Immune Response to Influenza Vaccination in Humans.

机构信息

Influenza Division, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia.

出版信息

J Infect Dis. 2024 Feb 14;229(2):310-321. doi: 10.1093/infdis/jiad493.

DOI:10.1093/infdis/jiad493

PMID:37981659

Abstract

BACKGROUND

Preexisting immunity, including memory B cells and preexisting antibodies, can modulate antibody responses to influenza in vivo to antigenically related antigens. We investigated whether preexisting hemagglutination inhibition (HAI) antibodies targeting the K163 epitope on the hemagglutinin (K163 antibodies) could affect antibody responses following vaccination with A/California/07/2009-like A(H1N1)pdm09 influenza viruses in humans.

METHODS

Pre- and postvaccination sera collected from 300 adults (birth years, 1961-1998) in 6 seasons (2010-2016) were analyzed by HAI assays with 2 reverse genetics viruses and A(H1N1) viruses circulated from 1977 to 2018. Antibody adsorption assays were used to verify the preexisting K163 antibody-mediated suppression effect.

RESULTS

Preexisting K163 antibody titers ≥80 affected HAI antibody responses following influenza vaccination containing A/California/07/2009-like antigens. At high K163 antibody concentrations (HAI antibody titers ≥160), all HAI antibody responses were suppressed. However, at moderate K163 antibody concentrations (HAI antibody titer, 80), only K163 epitope-specific antibody responses were suppressed, and novel HAI antibody responses targeting the non-K163 epitopes were induced by vaccination. Novel antibodies targeting non-K163 epitopes cross-reacted with newly emerging A(H1N1)pdm09 strains with a K163Q mutation rather than historic 1977-2007 A(H1N1) viruses.

CONCLUSIONS

K163 antibody-mediated suppression shapes antibody responses to A(H1N1)pdm09 vaccination. Understanding how preexisting antibodies suppress and redirect vaccine-induced antibody responses is of great importance to improve vaccine effectiveness.

摘要

背景

包括记忆 B 细胞和预先存在的抗体在内的预先存在的免疫可以调节体内针对具有抗原相关性的抗原的流感抗体反应。我们研究了针对血凝素（HA）上 K163 表位的预先存在的血凝抑制（HAI）抗体（K163 抗体）是否会影响接种 A/加利福尼亚/07/2009 样 A（H1N1）pdm09 流感病毒后的抗体反应。

方法

分析了 2010-2016 年 6 个季节（2010-2016 年）中 300 名成年人（出生年份为 1961-1998 年）的预接种和接种后血清，并用 2 种反向遗传学病毒和 1977-2018 年传播的 A（H1N1）病毒进行 HAI 检测。抗体吸附测定用于验证预先存在的 K163 抗体介导的抑制作用。

结果

预先存在的 K163 抗体滴度≥80 会影响含有 A/加利福尼亚/07/2009 样抗原的流感疫苗接种后的 HAI 抗体反应。在高 K163 抗体浓度（HAI 抗体滴度≥160）下，所有 HAI 抗体反应均受到抑制。然而，在中等 K163 抗体浓度（HAI 抗体滴度 80）下，仅 K163 表位特异性抗体反应受到抑制，并且通过疫苗接种诱导了针对非 K163 表位的新型 HAI 抗体反应。针对非 K163 表位的新型抗体与具有 K163Q 突变的新出现的 A（H1N1）pdm09 株而非历史上的 1977-2007 年 A（H1N1）病毒发生交叉反应。