SARS-CoV-2 XBB.1.5 mRNA 强化疫苗可产生有限的黏膜免疫力

IF 15.8 1区医学 Q1 CELL BIOLOGY

Science Translational Medicine Pub Date : 2024-10-23 DOI:10.1126/scitranslmed.adp8920

Ninaad Lasrado, Marjorie Rowe, Katherine McMahan, Nicole P. Hachmann, Jessica Miller, Catherine Jacob-Dolan, Jinyan Liu, Brookelynne Verrette, Kristin A. Gotthardt, Darren M. Ty, Juliana Pereira, Camille R. Mazurek, Amelia Hoyt, Ai-ris Y. Collier, Dan H. Barouch

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引用次数: 0

摘要

目前的 COVID-19 疫苗能有效预防严重疾病，但对获得性感染的保护却微乎其微。肌肉注射 COVID-19 疫苗可诱导强大的血清中和抗体 (NAbs)，但其增强粘膜免疫反应的能力仍有待确定。本研究表明，XBB.1.5信使核糖核酸（mRNA）增强剂可提高人类对多种严重急性呼吸系统综合征冠状病毒2（SARS-CoV-2）变种（包括主要的循环变种JN.1）的血清中和能力。与此相反，我们发现 XBB.1.5 mRNA 增强剂不会增强粘膜 NAbs 或粘膜 IgA 反应，尽管急性 SARS-CoV-2 XBB 感染会大大增加粘膜抗体反应。这些数据表明，目前的XBB.1.5 mRNA增强剂能显著增强外周抗体反应，但不能有力地增强粘膜抗体反应。我们的数据突显了人类外周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预防呼吸道病毒感染的重要性。

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SARS-CoV-2 XBB.1.5 mRNA booster vaccination elicits limited mucosal immunity

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.

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来源期刊

Science Translational Medicine CELL BIOLOGY-MEDICINE, RESEARCH & EXPERIMENTAL

CiteScore

26.70

自引率

1.20%

发文量

309

审稿时长

1.7 months

期刊介绍： Science Translational Medicine is an online journal that focuses on publishing research at the intersection of science, engineering, and medicine. The goal of the journal is to promote human health by providing a platform for researchers from various disciplines to communicate their latest advancements in biomedical, translational, and clinical research. The journal aims to address the slow translation of scientific knowledge into effective treatments and health measures. It publishes articles that fill the knowledge gaps between preclinical research and medical applications, with a focus on accelerating the translation of knowledge into new ways of preventing, diagnosing, and treating human diseases. The scope of Science Translational Medicine includes various areas such as cardiovascular disease, immunology/vaccines, metabolism/diabetes/obesity, neuroscience/neurology/psychiatry, cancer, infectious diseases, policy, behavior, bioengineering, chemical genomics/drug discovery, imaging, applied physical sciences, medical nanotechnology, drug delivery, biomarkers, gene therapy/regenerative medicine, toxicology and pharmacokinetics, data mining, cell culture, animal and human studies, medical informatics, and other interdisciplinary approaches to medicine. The target audience of the journal includes researchers and management in academia, government, and the biotechnology and pharmaceutical industries. It is also relevant to physician scientists, regulators, policy makers, investors, business developers, and funding agencies.