To prevent infection by respiratory viruses and consequently limit virus circulation, vaccines need to promote mucosal immunity. The extent to which the currently used messenger RNA (mRNA)–based COVID-19 vaccines induce mucosal immunity remains poorly characterized. We evaluated mucosal neutralizing antibody responses in a cohort of 183 individuals. Participants were sampled at several time points after primary adenovirus vector–based or mRNA-based COVID-19 vaccination and after mRNA-based booster vaccinations. Our findings revealed that repeated vaccination with mRNA boosters promoted severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) neutralizing antibodies in nasal secretions. Nasal and serum neutralizing antibody titers of both IgG and IgA isotypes correlated to one another. We investigated the source of these mucosal antibodies in a mouse model wherein mice received repeated mRNA vaccines for SARS-CoV-2. These experiments indicated that neutralizing antibody–producing cells reside in the spleen and bone marrow, whereas no proof of tissue homing to the respiratory mucosa was observed, despite the detection of mucosal antibodies. Serum transfer experiments confirmed that circulating antibodies were able to migrate to the respiratory mucosa. Collectively, these results demonstrate that, especially upon repeated vaccination, the currently used COVID-19 mRNA vaccines can elicit mucosal neutralizing antibodies and that vaccination might also stimulate mucosal immunity induced by previous SARS-CoV-2 infection. Moreover, migration of circulating antibodies to the respiratory mucosa might be a main mechanism. These findings advance our understanding of mRNA vaccine–induced immunity and have implications for the design of vaccine strategies to combat respiratory infections.

中文翻译：

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基于 COVID-19 mRNA 的重复疫苗接种有助于 SARS-CoV-2 中和粘膜中的抗体反应


为了防止呼吸道病毒感染，从而限制病毒传播，疫苗需要促进粘膜免疫。目前使用的基于信使 RNA （mRNA） 的 COVID-19 疫苗诱导粘膜免疫的程度仍然难以表征。我们在 183 名个体的队列中评估了粘膜中和抗体反应。参与者在基于腺病毒载体或基于 mRNA 的 COVID-19 初级疫苗接种后和基于 mRNA 的加强疫苗接种后的多个时间点进行采样。我们的研究结果表明，重复接种 mRNA 加强剂可促进严重急性呼吸系统综合症冠状病毒 2 （SARS-CoV-2） 中和鼻腔分泌物中的抗体。IgG 和 IgA 同种型的鼻腔和血清中和抗体滴度彼此相关。我们在小鼠模型中研究了这些粘膜抗体的来源，其中小鼠接受了重复的 SARS-CoV-2 mRNA 疫苗。这些实验表明，产生中和抗体的细胞存在于脾脏和骨髓中，而尽管检测到粘膜抗体，但没有观察到组织归巢到呼吸道粘膜的证据。血清转移实验证实，循环抗体能够迁移到呼吸道粘膜。总的来说，这些结果表明，尤其是在重复接种疫苗后，目前使用的 COVID-19 mRNA 疫苗可以引发粘膜中和抗体，并且接种疫苗还可能刺激先前 SARS-CoV-2 感染诱导的粘膜免疫。此外，循环抗体向呼吸道粘膜的迁移可能是一个主要机制。 这些发现促进了我们对 mRNA 疫苗诱导免疫的理解，并对设计对抗呼吸道感染的疫苗策略具有重要意义。