A bivalent COVID-19 mRNA vaccine elicited broad immune responses and protection against Omicron subvariants infection
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.
Authors
- Douglas J. Mahoney (ORCID: https://orcid.org/0000-0002-0642-992X)
- Philip Samaan
- Reuben Samson (ORCID: https://orcid.org/0009-0005-8965-3212)
- Yilin Tan (ORCID: https://orcid.org/0000-0003-2958-978X)
- Jun Liu (ORCID: https://orcid.org/0000-0001-5040-8344)
- Danyel Evseev (ORCID: https://orcid.org/0000-0002-0371-4987)
- Jennifer Yang (ORCID: https://orcid.org/0000-0002-9968-5673)
- Alexandra Kurtesi (ORCID: https://orcid.org/0000-0002-4122-7899)
- Kristofor K. Ellestad (ORCID: https://orcid.org/0000-0001-9350-4977)
- Mario Ostrowski (ORCID: https://orcid.org/0000-0002-7369-1936)
- Cini Mathew John (ORCID: https://orcid.org/0000-0001-5404-6176)
- Eric G. Marcusson (ORCID: https://orcid.org/0000-0002-0504-8674)
- Suji Udayakumar (ORCID: https://orcid.org/0000-0001-8115-3735)
- Queenie Hu (ORCID: https://orcid.org/0000-0003-4272-5053)
- Kyle Potts (ORCID: https://orcid.org/0000-0002-4991-6402)
- Anne‐Claude Gingras (ORCID: https://orcid.org/0000-0002-6090-4437)
- Freda Qi (ORCID: https://orcid.org/0000-0002-2859-3667)
- Patrick Budylowski
- Natalia Martín‐Orozco
- Frans Budiman
- Ellaine Riczly Tohan
- Li Wang (ORCID: https://orcid.org/0000-0001-9580-2476)
- Yue Fan
- Yisen Wang (ORCID: https://orcid.org/0000-0002-0181-2137)
- Xinan Liu (ORCID: https://orcid.org/0000-0002-0497-6962)
- H. Menon
Institutions
- Mount Sinai Hospital (CA)
- St. Michael's Hospital (CA)
- Providence Health Care (CA)
- University of Calgary (CA)
- University of Toronto (CA)
- Providence College (US)
- Lunenfeld-Tanenbaum Research Institute (CA)
- Alberta Children's Hospital (CA)
- Sinai Health System (CA)
- Zhejiang Medicine (China) (CN)
Publication Details
- Journal
- npj Vaccines
- Published
- 2025-01-09
- DOI
- https://doi.org/10.1038/s41541-025-01062-8
- Citations
- 4
- Primary Topic
- SARS-CoV-2 and COVID-19 Research
- Type
- article
- Field-Weighted Citation Impact
- 5.58
Funders
- Chinese Academy of Sciences
- Canadian Institutes of Health Research