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

• Published in: npj vaccines Vol. 10; no. 1; pp. 4 - 15
• Main Authors: Liu, Jun, Wang, Li, Kurtesi, Alexandra, Budylowski, Patrick, Potts, Kyle G., Menon, Haritha, Tan, Yilin, Samaan, Philip, Liu, Xinan, Wang, Yisen, Hu, Queenie, Samson, Reuben, Qi, Freda, Evseev, Danyel, John, Cini, Ellestad, Kristofor K., Fan, Yue, Budiman, Frans, Tohan, Ellaine Riczly, Udayakumar, Suji, Yang, Jennifer, Marcusson, Eric G., Gingras, Anne-Claude, Mahoney, Douglas J., Ostrowski, Mario A., Martin-Orozco, Natalia
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 10.01.2025; Nature Publishing Group; Nature Portfolio
• Subjects: 631/326/590/2293; 631/61/24/590/2293; Biomedical and Life Sciences; Biomedicine; Clinical trials; COVID-19; COVID-19 vaccines; Disease transmission; Drug dosages; Human subjects; Immune response; Immunogenicity; Immunology; Infections; Infectious Diseases; Lymphocytes; Medical Microbiology; mRNA vaccines; Mutation; Protected animals; Public Health; Severe acute respiratory syndrome coronavirus 2; Vaccine; Vaccines; Viral infections; Virology
• ISSN: 2059-0105; 2059-0105
• DOI: 10.1038/s41541-025-01062-8

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.