XBB.1.5 COVID-19疫苗引发了对祖先和XBB.1.5 SARS-CoV-2刺突蛋白的持久抗体反应

IF 14.6 1区医学 Q1 CELL BIOLOGY

Science Translational Medicine Pub Date : 2025-09-03 DOI:10.1126/scitranslmed.adu8067

Sanjeev Kumar, Shilpi Jain, Bushra Wali, Veronika I. Zarnitsyna, Devyani Joshi, Madison L. Ellis, Lilin Lai, Ansa A. Malik, Tarrant O. McPherson, Sucheta Godbole, Anamika Patel, Susanne Linderman, Daniel Solis, Malaya K. Sahoo, Kareem Bechnak, Isabel Paredes, Ralph Tanios, Bahaa Kazzi, Serena M. Dib, Matthew B. Litvack, Sonia T. Wimalasena, Heather Hicks, Azaibi Tamin, Nicole E. Bowen, Lydia Atherton, Clinton Paden, Jennifer L. Harcourt, David E. Wentworth, Caroline Ciric, Richard H. West, Christina A. Rostad, I-Ting Teng, Danyi Wang, Eric A. Orlund, Vineet D. Menachery, Sri Edupuganti, Peter D. Kwong, Nadine Rouphael, Benjamin A. Pinsky, Daniel C. Douek, Alberto Moreno, Jens Wrammert, Mehul S. Suthar

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引用次数: 0

摘要

不同的SARS-CoV-2变体的迅速出现导致2023-2024年将COVID-19 mRNA疫苗更新为含有XBB.1.5 SARS-CoV-2刺突抗原的单价版本。为了确定免疫后抗体反应的持久性和广度，我们分析了24个人在单次XBB.1.5 mRNA疫苗接种前后长达6个月的抗体和记忆B细胞。通过活病毒中和试验，我们发现XBB.1.5疫苗提高了对祖先SARS-CoV-2毒株（WA1）、BA.5毒株和XBB.1.5 Omicron变体的抗体中和活性的大小和广度。持久的WA1和XBB.1.5 IgG刺突蛋白结合抗体被诱导，估计半衰期分别为703和531天（在第120天）。与WA1刺突蛋白相比，接种后抗XBB.1.5刺突蛋白的IgG1和IgG4结合抗体增加较多。通过血清消耗和记忆B细胞分析发现，高比例的抗体对WA1和XBB.1.5菌株都有交叉反应，并且这种交叉反应是持久的。最后，我们评估了这些抗体对更现代的循环Omicron菌株的中和活性，并观察到接种后6个月与XBB.1.5相比，对KP.2和KP.3的交叉反应性降低。这些数据表明，与先前的WA1或二价疫苗相比，XBB.1.5 COVID-19疫苗促进了更持久的结合和中和抗体。然而，具有刺突蛋白突变的分散的Omicron变体能够逃避这些中和抗体，这强调了定期考虑COVID-19疫苗重新配制的必要性。

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The XBB.1.5 COVID-19 vaccine elicits a durable antibody response to ancestral and XBB.1.5 SARS-CoV-2 spike proteins

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The XBB.1.5 COVID-19 vaccine elicits a durable antibody response to ancestral and XBB.1.5 SARS-CoV-2 spike proteins

The rapid emergence of divergent SARS-CoV-2 variants led to a 2023–2024 update of the COVID-19 mRNA vaccine to a monovalent version containing the XBB.1.5 SARS-CoV-2 spike antigen. To determine the durability and breadth of the antibody responses after immunization, we analyzed antibodies and memory B cells from 24 individuals before and after a single XBB.1.5 mRNA vaccine dose for up to 6 months. Using a live virus neutralization assay, we found that the XBB.1.5 vaccine improved the magnitude and breadth of antibody neutralizing activity against the ancestral SARS-CoV-2 strain (WA1), BA.5 strain, and XBB.1.5 Omicron variants. Durable WA1 and XBB.1.5 IgG spike protein binding antibodies were induced with an estimated half-life of 703 and 531 days (at day 120), respectively. There was a greater increase of IgG1 and IgG4 binding antibodies against the XBB.1.5 spike protein compared with the WA1 spike protein postvaccination. A high proportion of antibodies were cross-reactive against both WA1 and XBB.1.5 strains, as determined by serum depletion and memory B cell analysis, and this cross-reactivity was durable. Last, we evaluated the neutralizing activity of these antibodies against more contemporary circulating Omicron strains and observed reduced cross-reactivity to KP.2 and KP.3 compared with XBB.1.5 6 months after vaccination. These data show that the XBB.1.5 COVID-19 vaccine promotes more durable binding and neutralizing antibodies than prior ancestral WA1 or bivalent vaccines. However, divergent Omicron variants with mutations in the spike protein were able to evade these neutralizing antibodies, emphasizing the need for periodic consideration of COVID-19 vaccine reformulation.

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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.