Laboratory of Mucosal Immunology, VIB Center for Inflammation Research, 9000 Ghent, Belgium.
Department of Internal Medicine and Pediatrics, Faculty of Medicine and Health Sciences, Ghent University, 9000 Ghent, Belgium.
Sci Transl Med. 2024 Oct 23;16(770):eadn2364. doi: 10.1126/scitranslmed.adn2364.
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.
为了预防呼吸道病毒感染并因此限制病毒传播，疫苗需要促进黏膜免疫。目前使用的信使 RNA（mRNA）COVID-19 疫苗诱导黏膜免疫的程度仍未得到充分描述。我们评估了 183 名个体的黏膜中和抗体反应。参与者在初次腺病毒载体或 mRNA COVID-19 疫苗接种后和 mRNA 加强疫苗接种后几个时间点进行采样。我们的研究结果表明，mRNA 加强剂的重复接种促进了鼻分泌物中严重急性呼吸综合征冠状病毒 2（SARS-CoV-2）中和抗体的产生。鼻中和血清 IgG 和 IgA 同种型的中和抗体滴度相互关联。我们在一种小鼠模型中研究了这些黏膜抗体的来源，其中小鼠接受了针对 SARS-CoV-2 的重复 mRNA 疫苗接种。这些实验表明，产生中和抗体的细胞存在于脾脏和骨髓中，尽管检测到黏膜抗体，但没有证据表明它们归巢到呼吸道黏膜。血清转移实验证实，循环抗体能够迁移到呼吸道黏膜。总之，这些结果表明，特别是在重复接种后，目前使用的 COVID-19 mRNA 疫苗可以引发黏膜中和抗体，并且疫苗接种也可能刺激先前 SARS-CoV-2 感染诱导的黏膜免疫。此外，循环抗体向呼吸道黏膜的迁移可能是一种主要机制。这些发现推进了我们对 mRNA 疫苗诱导免疫的理解，并对设计抗击呼吸道感染的疫苗策略具有重要意义。
