Lu Xiuhua, Liu Feng, Tzeng Wen-Pin, Zheng Xiao-Yu, Tumpey Terrence M, York Ian A, Kondor Rebecca J, Levine Min Z
Influenza Division, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia, USA.
Open Forum Infect Dis. 2025 Jul 25;12(8):ofaf440. doi: 10.1093/ofid/ofaf440. eCollection 2025 Aug.
Understanding hemagglutination inhibition antibody immunodominance (HAI-Ab-ID) is key to forecasting influenza virus antigenic drift and improving vaccine strain selection. We explored epitope-specific HAI-Ab-IDs in adults immunized with A/California/07/2009-like (CA/09) vaccine and A(H1N1)pdm09 viral evolutions.
Sera from adults (N = 300; birth year, 1961-1998) collected from 2010 to 2016 were analyzed in HAI assays. To determine epitope-specific HAI-Ab-IDs, 4 reverse genetics (RG) viruses were generated: RG-wt possessing CA/09 wild type hemagglutinin and 3 RG mutants containing K163Q, K130 deletion, or D127N/N129T mutations. To analyze cross-reactive or strain-specific HAI-Ab-IDs, 10 historical 1977-2007 A(H1N1) viruses were used. Antibody adsorption assays were used to verify the specificity of HAI-Ab-IDs. Publicly available sequences of A(H1N1)pdm09 viruses from GISAID (Global Initiative on Sharing All Influenza Data; n = 100 277, 2010-2024) were analyzed for viral evolution.
Four HAI-Ab-IDs targeting the epitopes possessing K163, D127 + N129 + K130, K130, or D127 + N129 were detected in >50% donors during 2010 to 2016. Three HAI-Ab-IDs (K163-Ab-IDs, D127/N129/K130-Ab-IDs, and K130-Ab-IDs) cross-inhibited some 1977-2007 viruses. Conversely, D127/N129-Ab-ID showed no cross-inhibition with historical 1977-2007 viruses. Low proportions of K130-Ab-IDs were presented mainly in prevaccination sera. Shifts of cross-reactive HAI-Ab-IDs to strain-specific D127/N129-Ab-ID occurred between 2010 and 2016. The HAI-Ab-IDs exerted immune selection pressures on hemagglutinin (4 positions: D127, N129, K130, and K163). So far, 3 escape mutations became fixed in the 2013-2014 season (K163Q), 2020-2021 season (N129D), and 2022-2023 season (K130N).
HAI-Ab-IDs were common phenomena in adults from 2010 to 2016. Preexisting HAI-Ab-IDs drove viral and antibody evolutions by HAI-Ab-mediated immune selection and suppression. Monitoring viral and HAI-Ab-ID evolution is of great importance to improve vaccine effectiveness.
了解血凝抑制抗体免疫优势（HAI-Ab-ID）是预测流感病毒抗原漂移和改进疫苗株选择的关键。我们探究了接种A/加利福尼亚/07/2009样（CA/09）疫苗的成年人中的表位特异性HAI-Ab-ID以及A（H1N1）pdm09病毒的进化情况。
对2010年至2016年收集的成年人（N = 300；出生年份，1961 - 1998年）血清进行血凝抑制试验分析。为确定表位特异性HAI-Ab-ID，构建了4种反向遗传学（RG）病毒：具有CA/09野生型血凝素的RG-wt以及3种含有K163Q、K130缺失或D127N/N129T突变的RG突变体。为分析交叉反应性或毒株特异性HAI-Ab-ID，使用了10种1977 - 2007年的历史A（H1N1）病毒。采用抗体吸附试验验证HAI-Ab-ID的特异性。对来自全球共享流感数据倡议组织（GISAID；n = 100277，2010 - 2024年）的A（H1N1）pdm09病毒公开可用序列进行病毒进化分析。
在2010年至2016年期间，超过50%的供体中检测到针对具有K163、D127 + N129 + K130、K130或D127 + N129表位的4种HAI-Ab-ID。3种HAI-Ab-ID（K163-Ab-ID、D127/N129/K130-Ab-ID和K130-Ab-ID）交叉抑制了一些1977 - 2007年的病毒。相反，D127/N129-Ab-ID与1977 - 2007年的历史病毒无交叉抑制。低比例的K130-Ab-ID主要出现在接种前血清中。2010年至2016年期间，交叉反应性HAI-Ab-ID向毒株特异性D127/N129-Ab-ID发生了转变。HAI-Ab-ID对血凝素（4个位点：D127、N129、K130和K163）施加了免疫选择压力。到目前为止，3种逃逸突变在2013 - 2014季（K163Q）、2020 - 2021季（N129D）和2022 - 2023季（K130N）中固定下来。
HAI-Ab-ID在2010年至2016年的成年人中是常见现象。预先存在的HAI-Ab-ID通过HAI-Ab介导的免疫选择和抑制推动病毒和抗体的进化。监测病毒和HAI-Ab-ID的进化对于提高疫苗效力至关重要。
