Kumar Sanjeev, Jain Shilpi, Wali Bushra, Zarnitsyna Veronika I, Joshi Devyani, Ellis Madison L, Lai Lilin, Malik Ansa A, McPherson Tarrant O, Godbole Sucheta, Patel Anamika, Linderman Susanne, Solis Daniel, Sahoo Malaya K, Bechnak Kareem, Paredes Isabel, Tanios Ralph, Kazzi Bahaa, Dib Serena M, Litvack Matthew B, Wimalasena Sonia T, Hicks Heather, Tamin Azaibi, Bowen Nicole E, Atherton Lydia, Paden Clinton, Harcourt Jennifer L, Wentworth David E, Ciric Caroline, West Richard H, Rostad Christina A, Teng I-Ting, Wang Danyi, Ortlund Eric A, Menachery Vineet D, Edupuganti Sri, Kwong Peter D, Rouphael Nadine, Pinsky Benjamin A, Douek Daniel C, Moreno Alberto, Wrammert Jens, Suthar Mehul S
Center for Childhood Infections and Vaccines, Children's Healthcare of Atlanta, Division of Infectious Diseases, Department of Pediatrics, Emory University School of Medicine, Atlanta, GA 30322, USA.
Emory Vaccine Center, Emory University, Atlanta, GA 30329, USA.
Sci Transl Med. 2025 Sep 3;17(814):eadu8067. doi: 10.1126/scitranslmed.adu8067.
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.
