Krause Robert G E, Moyo-Gwete Thandeka, Richardson Simone I, Makhado Zanele, Manamela Nelia P, Hermanus Tandile, Mkhize Nonhlanhla N, Keeton Roanne, Benede Ntombi, Mennen Mathilda, Skelem Sango, Karim Farina, Khan Khadija, Riou Catherine, Ntusi Ntobeko A B, Goga Ameena, Gray Glenda, Hanekom Willem, Garrett Nigel, Bekker Linda-Gail, Groll Andreas, Sigal Alex, Moore Penny L, Burgers Wendy A, Leslie Alasdair
Africa Health Research Institute, Durban, 4001, South Africa.
School of Laboratory Medicine and Medical Sciences, University of KwaZulu-Natal, Durban, 4001, South Africa.
NPJ Vaccines. 2023 Aug 12;8(1):119. doi: 10.1038/s41541-023-00724-9.
Neutralizing antibodies strongly correlate with protection for COVID-19 vaccines, but the corresponding memory B cells that form to protect against future infection are relatively understudied. Here we examine the effect of prior SARS-CoV-2 infection on the magnitude and phenotype of the memory B cell response to single dose Johnson and Johnson (Ad26.COV2.S) vaccination in South African health care workers. Participants were either naïve to SARS-CoV-2 or had been infected before vaccination. SARS-CoV-2-specific memory B-cells expand in response to Ad26.COV2.S and are maintained for the study duration (84 days) in all individuals. However, prior infection is associated with a greater frequency of these cells, a significant reduction in expression of the germinal center chemokine receptor CXCR5, and increased class switching. These B cell features correlated with neutralization and antibody-dependent cytotoxicity (ADCC) activity, and with the frequency of SARS-CoV-2 specific circulating T follicular helper cells (cTfh). Vaccination-induced effective neutralization of the D614G variant in both infected and naïve participants but boosted neutralizing antibodies against the Beta and Omicron variants only in participants with prior infection. In addition, the SARS-CoV-2 specific CD8+ T cell response correlated with increased memory B cell expression of the lung-homing receptor CXCR3, which was sustained in the previously infected group. Finally, although vaccination achieved equivalent B cell activation regardless of infection history, it was negatively impacted by age. These data show that phenotyping the response to vaccination can provide insight into the impact of prior infection on memory B cell homing, CSM, cTfh, and neutralization activity. These data can provide early signals to inform studies of vaccine boosting, durability, and co-morbidities.
中和抗体与新冠疫苗的保护作用密切相关，但针对未来感染形成的相应记忆B细胞的研究相对较少。在此，我们研究了既往感染严重急性呼吸综合征冠状病毒2（SARS-CoV-2）对南非医护人员单剂接种强生公司（Ad26.COV2.S）疫苗后记忆B细胞反应的强度和表型的影响。参与者要么未曾感染过SARS-CoV-2，要么在接种疫苗前已被感染。SARS-CoV-2特异性记忆B细胞会对Ad26.COV2.S产生反应并扩增，且在所有个体中在研究期间（84天）持续存在。然而，既往感染与这些细胞的频率更高、生发中心趋化因子受体CXCR5的表达显著降低以及类别转换增加有关。这些B细胞特征与中和及抗体依赖性细胞毒性（ADCC）活性相关，也与SARS-CoV-2特异性循环滤泡辅助性T细胞（cTfh）的频率相关。疫苗接种在感染和未感染的参与者中均诱导了对D614G变体的有效中和，但仅在既往感染的参与者中增强了针对贝塔和奥密克戎变体的中和抗体。此外，SARS-CoV-2特异性CD8+ T细胞反应与肺归巢受体CXCR3的记忆B细胞表达增加相关，这在既往感染组中持续存在。最后，尽管无论感染史如何，疫苗接种都能实现同等程度的B细胞激活，但它受到年龄的负面影响。这些数据表明，对疫苗接种反应进行表型分析可以深入了解既往感染对记忆B细胞归巢、类别转换记忆、cTfh和中和活性的影响。这些数据可以提供早期信号，为疫苗加强接种、持久性和合并症的研究提供参考。
