Byrne Joanne, Gu Lili, Garcia-Leon Alejandro, Gaillard Colette Marie, Saini Gurvin, Alalwan Dana, Tomás-Cortázar Julen, Kenny Grace, Donohue Sean, Reynolds Bearach, O'Gorman Tessa, Landay Alan, Doran Peter, Stemler Jannik, Koehler Philipp, Cox Rebecca Jane, Olesen Ole F, Lelievre Jean-Daniel, O'Broin Cathal, Savinelli Stefano, Feeney Eoin R, O'Halloran Jane A, Cotter Aoife, Horgan Mary, Kelly Christine, Sadlier Corrina, de Barra Eoghan, Cornely Oliver A, Gautier Virginie, Mallon Patrick Wg
Centre for Experimental Pathogen Host Research (CEPHR), University College Dublin, Dublin, Ireland.
Department of Infectious Diseases, St Vincent's University Hospital, Dublin, Ireland.
Front Immunol. 2024 Sep 17;15:1445653. doi: 10.3389/fimmu.2024.1445653. eCollection 2024.
A clear immune correlate of protection from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has not been defined. We explored antibody, B-cell, and T-cell responses to the third-dose vaccine and relationship to incident SARS-CoV-2 infection.
Adults in a prospective cohort provided blood samples at day 0, day 14, and 10 months after the third-dose SARS-CoV-2 vaccine. Participants self-reported incident SARS-CoV-2 infection. Plasma anti-SARS-CoV-2 receptor-binding domain (RBD) and spike-subunit-1 and spike-subunit-2 antibodies were measured. A sub-study assessed SARS-CoV-2-specific plasma and memory B-cell and memory T-cell responses in peripheral blood mononuclear cells by enzyme-linked immunospot. Comparative analysis between participants who developed incident infection and uninfected participants utilised non-parametric t-tests, Kaplan-Meier survival analysis, and Cox proportional hazard ratios.
Of the 132 participants, 47 (36%) reported incident SARS-CoV-2 infection at a median 16.5 (16.25-21) weeks after the third-dose vaccination. RBD titres and B-cell responses, but not T-cell responses, increased after the third-dose vaccine. Whereas no significant difference in day 14 antibody titres or T-cell responses was observed between participants with and without incident SARS-CoV-2 infection, RBD memory B-cell frequencies were significantly higher in those who did not develop infection [10.0% (4.5%-16.0%) versus 4.9% (1.6%-9.3%), p = 0.01]. RBD titres and memory B-cell frequencies remained significantly higher at 10 months than day 0 levels (p < 0.01).
Robust antibody and B-cell responses persisted at 10 months following the third-dose vaccination. Higher memory B-cell frequencies, rather than antibody titres or T-cell responses, predicted protection from subsequent infection, identifying memory B cells as a correlate of protection.
尚未明确针对严重急性呼吸综合征冠状病毒2（SARS-CoV-2）感染的明确免疫保护相关指标。我们探讨了对第三剂疫苗的抗体、B细胞和T细胞反应以及与SARS-CoV-2感染事件的关系。
前瞻性队列中的成年人在接种第三剂SARS-CoV-2疫苗后的第0天、第14天和第10个月提供血样。参与者自行报告SARS-CoV-2感染事件。检测血浆中抗SARS-CoV-2受体结合域（RBD）、刺突蛋白亚基1和刺突蛋白亚基2抗体。一项子研究通过酶联免疫斑点法评估外周血单个核细胞中SARS-CoV-2特异性血浆、记忆B细胞和记忆T细胞反应。对发生感染事件的参与者和未感染参与者进行比较分析，采用非参数t检验、Kaplan-Meier生存分析和Cox比例风险比。
在132名参与者中，47名（36%）报告在接种第三剂疫苗后的中位16.5（16.25 - 21）周发生SARS-CoV-2感染事件。第三剂疫苗接种后，RBD滴度和B细胞反应增加，但T细胞反应未增加。在发生和未发生SARS-CoV-2感染事件的参与者之间，第14天的抗体滴度或T细胞反应没有显著差异，但未发生感染的参与者中RBD记忆B细胞频率显著更高[10.0%（4.5% - 16.0%）对4.9%（1.6% - 9.3%），p = 0.01]。RBD滴度和记忆B细胞频率在10个月时仍显著高于第0天的水平（p < 0.01）。
第三剂疫苗接种后10个月，抗体和B细胞反应依然强劲。较高的记忆B细胞频率而非抗体滴度或T细胞反应预测了对后续感染的保护作用，表明记忆B细胞是保护相关指标。
