Sheehan Jared, Trauth Amber J, Hagensee Michael E, Ramsay Alistair J
Department of Microbiology, Immunology, and Parasitology, Louisiana State University Health Sciences Center, New Orleans, LA 70112, USA.
Stanley S. Scott Cancer, Louisiana State University Health Sciences Center, New Orleans, LA 70112, USA.
Pathogens. 2025 Jan 8;14(1):44. doi: 10.3390/pathogens14010044.
Vaccination of COVID-19-convalescent individuals may generate 'hybrid' immunity of enhanced magnitude, durability, and cross-reactive breadth. Our primary goal was to characterize hybrid antibody (Ab) responses in a patient cohort infected with ancestral Wuhan-Hu-1 virus and vaccinated between 6 and 10 months later with the Wuhan-Hu-1-based BNT162b2 mRNA vaccine. We were particularly interested in determining the efficacy of neutralizing Ab responses against subsequently emergent SARS-CoV-2 variants. Sera collected at 3-monthly intervals over a period of 12 months were analyzed by ELISA for SARS-CoV-2 RBD-specific Ab responses, and also for neutralizing Ab activity using pseudovirus-based neutralization assays. We found that convalescent RBD-reactive IgG and IgA Ab responses did not decline significantly through 9 months post-diagnosis. These responses improved significantly following vaccination and remained elevated through at least 12-months. SARS-CoV-2 neutralizing Ab activity was detected in convalescent sera through 9 months post-diagnosis, although it trended downwards from 3 months. Neutralizing Ab activity against the Wuhan-Hu-1 strain was significantly improved by vaccination, to levels that persisted through the end of the study. However, sera collected from vaccinated convalescent subjects also had significant neutralization activity against Delta B.1.617.2 and Omicron variants that persisted for at least 2-3 months, unlike sera from unvaccinated convalescent controls. Thus, vaccination of Wuhan-Hu-1-convalescent individuals with the BNT162b2 vaccine improved and sustained protective neutralizing Ab activity against SARS-CoV-2, including cross-reactive neutralizing activity against variants that emerged months later.
新冠康复者接种疫苗可能会产生增强的强度、持久性和交叉反应广度的“混合”免疫力。我们的主要目标是在一组感染了原始武汉-胡-1病毒并在6至10个月后接种基于武汉-胡-1的BNT162b2 mRNA疫苗的患者队列中，对混合抗体（Ab）反应进行特征描述。我们特别感兴趣的是确定针对随后出现的SARS-CoV-2变体的中和抗体反应的效力。在12个月的时间里，每隔3个月收集一次血清，通过酶联免疫吸附测定（ELISA）分析针对SARS-CoV-2受体结合域（RBD）的特异性抗体反应，并使用基于假病毒的中和试验分析中和抗体活性。我们发现，康复者的RBD反应性IgG和IgA抗体反应在诊断后9个月内没有显著下降。接种疫苗后，这些反应显著改善，并至少在12个月内保持升高。在诊断后9个月内，康复者血清中检测到SARS-CoV-2中和抗体活性，尽管从3个月起呈下降趋势。接种疫苗后，针对武汉-胡-1毒株的中和抗体活性显著提高，并在研究结束时一直保持在该水平。然而，与未接种疫苗的康复对照者的血清不同，从接种疫苗的康复受试者中收集的血清对Delta B.1.617.2和奥密克戎变体也有显著的中和活性，且至少持续2至3个月。因此，用BNT162b2疫苗为感染武汉-胡-1的康复者接种疫苗，可改善并维持针对SARS-CoV-2的保护性中和抗体活性，包括对数月后出现的变体的交叉反应性中和活性。
