Current COVID-19 vaccines provide robust protection against severe disease but minimal protection against acquisition of infection. Intramuscularly administered COVID-19 vaccines induce robust serum neutralizing antibodies (NAbs), but their ability to boost mucosal immune responses remains to be determined. In this study, we show that the XBB.1.5 messenger RNA (mRNA) boosters result in increased serum neutralization to multiple severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants in humans, including the dominant circulating variant JN.1. In contrast, we found that the XBB.1.5 mRNA booster did not augment mucosal NAbs or mucosal IgA responses, although acute SARS-CoV-2 XBB infection substantially increased mucosal antibody responses. These data demonstrate that current XBB.1.5 mRNA boosters substantially enhance peripheral antibody responses but do not robustly increase mucosal antibody responses. Our data highlight a separation between the peripheral and mucosal immune systems in humans and emphasize the importance of developing next-generation vaccines to augment mucosal immunity to protect against respiratory virus infections.

中文翻译：

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SARS-CoV-2 XBB.1.5 mRNA 加强疫苗接种引发有限的粘膜免疫


目前的 COVID-19 疫苗对重症提供了强有力的保护，但对感染的保护作用最低。肌肉注射 COVID-19 疫苗可诱导强大的血清中和抗体 （NAb），但它们增强粘膜免疫反应的能力仍有待确定。在这项研究中，我们表明 XBB.1.5 信使 RNA （mRNA） 增强剂导致血清对人类多种严重急性呼吸系统综合症冠状病毒 2 （SARS-CoV-2） 变体的中和作用增加，包括主要的循环变体 JN.1。相比之下，我们发现 XBB.1.5 mRNA 加强剂并没有增强粘膜 NAbs 或粘膜 IgA 反应，尽管急性 SARS-CoV-2 XBB 感染显着增加了粘膜抗体反应。这些数据表明，目前的 XBB.1.5 mRNA 加强剂显著增强了外周抗体反应，但并不能显著增加粘膜抗体反应。我们的数据强调了人类外周免疫系统和粘膜免疫系统之间的分离，并强调了开发下一代疫苗以增强粘膜免疫以防止呼吸道病毒感染的重要性。