Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02115, USA.
Sci Transl Med. 2024 Oct 23;16(770):eadp8920. doi: 10.1126/scitranslmed.adp8920.
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.
目前的 COVID-19 疫苗能为重症疾病提供强大保护，但对感染的预防作用微乎其微。肌肉内接种的 COVID-19 疫苗能诱导出强大的血清中和抗体（NAb），但其增强黏膜免疫应答的能力仍有待确定。在这项研究中，我们表明，XBB.1.5 mRNA 加强针会导致人类对多种严重急性呼吸综合征冠状病毒 2（SARS-CoV-2）变种的血清中和作用增强，包括主要流行的 JN.1 变种。相比之下，我们发现 XBB.1.5 mRNA 加强针并没有增强黏膜 NAb 或黏膜 IgA 反应，尽管急性 SARS-CoV-2 XBB 感染会大大增强黏膜抗体反应。这些数据表明，目前的 XBB.1.5 mRNA 加强针能显著增强外周抗体反应，但不能强烈增强黏膜抗体反应。我们的数据突显了人类外周和黏膜免疫系统之间的分离，并强调了开发新一代疫苗以增强黏膜免疫来预防呼吸道病毒感染的重要性。
