Reis Laise Rodrigues, Silva-Moraes Vanessa, Teixeira-Carvalho Andréa, Ross Ted M
Florida Research and Innovation Center, Cleveland Clinic, Port Saint Lucie, FL, United States.
Integrated Research Group in Biomarkers, René Rachou Institute-FIOCRUZ, Belo Horizonte, Brazil.
Front Immunol. 2024 Nov 20;15:1481910. doi: 10.3389/fimmu.2024.1481910. eCollection 2024.
This investigation elucidated the differences in humoral and H1N1 HA-specific memory B-cells response in participants exhibiting distinct immune response patterns prior to and after vaccination with Fluzone, the quadrivalent split-inactivated seasonal influenza virus vaccine. Participants were categorized into persistent non-responders and persistent responders based on their hemagglutination-inhibition (HAI) antibody titers to the H1N1 component from each vaccine administered between the 2019-2020 to 2023-2024 seasons. Persistent responders had higher fold change in H1N1 HA-specific CD21 expressing B-cells, plasmablasts, and plasma cells. A significant increase in H1N1 HA-specific transitional B-cells in persistent non-responders was observed. The frequency and fold change of H1N1-specific IgM-expressing memory B-cells was higher in persistent non-responders. Dimensionality reduction analysis also demonstrated higher IgM expression for persistent non-responders than persistent responders. Furthermore, persistent non-responders had a significant fold change increase in IgA tissue-like memory, IgG exhausted tissue-like memory, and double negative (DN) activated memory cells. In contrast, persistent responders had increased frequency of IgG-activated memory B-cells, IgG resting B-cells and DN resting B-cells. Correlation analysis revealed a positive correlation between HAI titers and DN memory B-cells and a negative correlation between HAI titers and IgG-expressing memory B-cells in persistent non-responders. Conversely, persistent responders had a positive correlation between HAI titers and IgA resting memory B-cells and a negative correlation between IgG memory B-cells and DN memory B-cells. Overall, this study provided valuable insights into the differential immune memory B-cell responses following influenza virus vaccination and paves the way for future research to further unravel the complexities of vaccine-induced memory B-cells and ultimately improve vaccination strategies against influenza virus infection.
本研究阐明了在接种四价裂解灭活季节性流感病毒疫苗Fluzone前后表现出不同免疫反应模式的参与者中，体液免疫和H1N1 HA特异性记忆B细胞反应的差异。根据2019 - 2020年至2023 - 2024年期间接种的每种疫苗中H1N1成分的血凝抑制（HAI）抗体滴度，将参与者分为持续无反应者和持续反应者。持续反应者在H1N1 HA特异性表达CD21的B细胞、浆母细胞和浆细胞中具有更高的倍数变化。在持续无反应者中观察到H1N1 HA特异性过渡性B细胞显著增加。持续无反应者中表达H1N1特异性IgM的记忆B细胞的频率和倍数变化更高。降维分析还表明，持续无反应者的IgM表达高于持续反应者。此外，持续无反应者在IgA组织样记忆、IgG耗竭组织样记忆和双阴性（DN）活化记忆细胞中具有显著的倍数变化增加。相比之下，持续反应者中IgG活化记忆B细胞、IgG静息B细胞和DN静息B细胞的频率增加。相关性分析显示，在持续无反应者中，HAI滴度与DN记忆B细胞呈正相关，与表达IgG的记忆B细胞呈负相关。相反，持续反应者中HAI滴度与IgA静息记忆B细胞呈正相关，IgG记忆B细胞与DN记忆B细胞呈负相关。总体而言，本研究为流感病毒疫苗接种后不同的免疫记忆B细胞反应提供了有价值的见解，并为未来进一步揭示疫苗诱导的记忆B细胞的复杂性并最终改善针对流感病毒感染的疫苗接种策略的研究铺平了道路。
