A bivalent COVID-19 mRNA vaccine elicited broad immune responses and protection against Omicron subvariants infection

A bivalent COVID-19 mRNA vaccine elicited broad immune responses and protection against Omicron subvariants infection

Abstract Continuously emerging SARS-CoV-2 Omicron subvariants pose a threat thwarting the effectiveness of approved COVID-19 vaccines. Especially, the protection breadth and degree of these vaccines against antigenically distant Omicron subvariants is unclear. Here, we report the immunogenicity and...

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Main Authors: Jun Liu, Li Wang, Alexandra Kurtesi, Patrick Budylowski, Kyle G. Potts, Haritha Menon, Yilin Tan, Philip Samaan, Xinan Liu, Yisen Wang, Queenie Hu, Reuben Samson, Freda Qi, Danyel Evseev, Cini John, Kristofor K. Ellestad, Yue Fan, Frans Budiman, Ellaine Riczly Tohan, Suji Udayakumar, Jennifer Yang, Eric G. Marcusson, Anne-Claude Gingras, Douglas J. Mahoney, Mario A. Ostrowski, Natalia Martin-Orozco
Format: Article
Language:English
Published: Nature Portfolio 2025-01-01
Series:npj Vaccines
Online Access:https://doi.org/10.1038/s41541-025-01062-8
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Summary:Abstract Continuously emerging SARS-CoV-2 Omicron subvariants pose a threat thwarting the effectiveness of approved COVID-19 vaccines. Especially, the protection breadth and degree of these vaccines against antigenically distant Omicron subvariants is unclear. Here, we report the immunogenicity and efficacy of a bivalent mRNA vaccine, PTX-COVID19-M1.2 (M1.2), which encodes native spike proteins from Wuhan-Hu-1 (D614G) and Omicron BA.2.12.1, in mouse and hamster models. Both primary series and booster vaccination using M1.2 elicited potent and broad nAbs against Wuhan-Hu-1 (D614G) and some Omicron subvariants. Strong spike-specific T cell responses against Wuhan-Hu-1 and Omicron subvariants, including JN.1, were also induced. Vaccination with M1.2 protected animals from Wuhan-Hu-1 and multiple Omicron subvariants challenges. Interestingly, protection against XBB.1.5 lung infection did not correlate with nAb levels. These results indicate that M1.2 generated a broadly protective immune response against antigenically distant Omicron subvariants, and spike-specific T cells probably contributed to the breadth of the protection.
ISSN:2059-0105

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