Long-term humoral immune responses against SARS-CoV-2 in healthy individuals and patients with primary immunodeficienciess

尽管接受了重症监护治疗，SARS-CoV-2感染仍可保持少症状或最终死亡。因此，一个人是否对第二次感染SARS-CoV2产生了终身保护，以及哪些机制有助于这种保护，这一问题是非常相关的，特别是在当前争夺最好的疫苗的背景下。尽管记忆B细胞在SARS-CoV-2感染过程中发生的冠状病毒诱导的疾病(新冠肺炎)的恢复期或疫苗接种后起主要作用，但到目前为止，对SARS-CoV-2特异性记忆B细胞的发育还没有详细的研究。在这种背景下，记忆B细胞识别哪些病毒抗原，记忆B细胞可以被检测到多长时间，以及记忆B细胞的抗原特异性如何与针对SARS-CoV-2的血清抗体和记忆T细胞反应的特异性相关尚不清楚。为了解决这些问题，我们从弗莱堡大学医院的工作人员中建立了800多人的队列，其中约10%--正如我们所能表明的--接触过SARS-CoV-2病毒。此外，在与其他欧洲中心的合作下，我们能够创建一个由10名患有明确免疫缺陷综合征的患者组成的小队列，这些患者在COVID19中幸存下来。在这个队列中，我们将分析SARS-CoV-2反应性记忆B细胞在一年时间内的亚群、特异性、频率和寿命。在免疫缺陷患者的队列中，我们计划调查病毒特异性B细胞和T细胞的形成和亚群特征，以应对冠状病毒感染，以及与具有免疫能力的供者的潜在差异。一旦针对SARS-CoV-2的疫苗可用，我们计划对接种疫苗的个人进行这些研究，并将结果与研究SARS-CoV-2感染的康复者获得的数据进行比较。我们希望我们的方法能够确定感染和疫苗接种在多大程度上导致了持久的B细胞记忆，可以预防因再次感染SARS-CoV-2而导致的新冠肺炎。这与记忆性T细胞反应的发展是如何关联的，并了解哪些参数与强烈的记忆反应最相关。这种方法将使我们能够为PAD/CVID患者开发合适的疫苗接种策略，并调查他们随着时间的推移的免疫反应。

SARS-CoV-2 infections can remain oligosymptomatic or end fatally despite of intensive care treatment. Therefore, the question whether one develops a lifelong protection against a second infection by SARS-CoV2 and which mechanisms contribute to the protection is highly relevant, especially also in the context of the current race for the best vaccine. So far, the development of SARS-CoV-2 specific memory B cells has not been studied in detail although memory B cells contribute essentially after convalescence or after vaccination against the coronavirus-induced disease (Covid-19) which develops in the course of SARS-CoV-2 infections. In this context, it is unclear which viral antigens are recognized by memory B cells, how long memory B cells can be detected and how the antigen specificity of memory B cells correlates with the specificity of serum antibodies and memory T cell responses directed against SARS-CoV-2. To approach these questions, we have established a cohort of more than 800 persons from the staff of the University Hospital Freiburg, of which - as we have been able show - about 10% have been exposed to SARS-CoV-2. In addition, in collaboration with other European centers we were able to create a small cohort of 10 patients with defined immunodeficiency syndromes, who have survived COVID19. In this cohorts we will analyze the subsets, specificity, frequency and longevity of SARS-CoV-2 reactive memory B cells over the time period of one year. In the cohort of immunodeficient patients we plan to investigate the formation and subset characteristics of virus-specific B- and T-cells in response to coronavirus infection as well as potential differences to immunocompetent donors. Once vaccinations against SARS-CoV-2 are available, we plan to carry out these studies with vaccinated individuals and compare the results with the data obtained from studying convalescents from SARS-CoV-2 infections. We hope that our approach will allow to determine the extent to which infections and vaccinations lead to a long-lasting B cell memory which can protect against Covid-19 resulting from re-infection with SARS-CoV-2., how this correlates with the development of a memory T cell response and to understand, which parameters correlate the best with a strong memory response.This approach will hopefully allow us to develop suitable strategies for vaccination against SARS-CoV-2 for PAD/CVID patients and survey their immune response over time.