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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Nature Portfolio
2025-01-01
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| Series: | npj Vaccines |
| Online Access: | https://doi.org/10.1038/s41541-025-01062-8 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Jun Liu |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-88ac10ba59f847cbb08fa8c45d576f29 |
| institution | Kabale University |
| issn | 2059-0105 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | npj Vaccines |
| spelling | doaj-art-88ac10ba59f847cbb08fa8c45d576f292025-01-12T12:07:12ZengNature Portfolionpj Vaccines2059-01052025-01-0110111510.1038/s41541-025-01062-8A bivalent COVID-19 mRNA vaccine elicited broad immune responses and protection against Omicron subvariants infectionJun Liu0Li Wang1Alexandra Kurtesi2Patrick Budylowski3Kyle G. Potts4Haritha Menon5Yilin Tan6Philip Samaan7Xinan Liu8Yisen Wang9Queenie Hu10Reuben Samson11Freda Qi12Danyel Evseev13Cini John14Kristofor K. Ellestad15Yue Fan16Frans Budiman17Ellaine Riczly Tohan18Suji Udayakumar19Jennifer Yang20Eric G. Marcusson21Anne-Claude Gingras22Douglas J. Mahoney23Mario A. Ostrowski24Natalia Martin-Orozco25Providence Therapeutics Holdings, Inc.Everest MedicinesDepartment of Molecular Genetics, University of TorontoDepartment of Medicine, University of TorontoRiddell Center for Cancer Immunotherapy, Cumming School of Medicine, University of CalgaryProvidence Therapeutics Holdings, Inc.Providence Therapeutics Holdings, Inc.Department of Laboratory Medicine and Pathobiology, University of TorontoEverest MedicinesEverest MedicinesDepartment of Molecular Genetics, University of TorontoDepartment of Molecular Genetics, University of TorontoDepartment of Molecular Genetics, University of TorontoRiddell Center for Cancer Immunotherapy, Cumming School of Medicine, University of CalgaryRiddell Center for Cancer Immunotherapy, Cumming School of Medicine, University of CalgaryRiddell Center for Cancer Immunotherapy, Cumming School of Medicine, University of CalgaryEverest MedicinesDepartment of Medicine, University of TorontoDepartment of Medicine, University of TorontoDepartment of Medicine, University of TorontoEverest MedicinesProvidence Therapeutics Holdings, Inc.Department of Molecular Genetics, University of TorontoRiddell Center for Cancer Immunotherapy, Cumming School of Medicine, University of CalgaryDepartment of Medicine, University of TorontoProvidence Therapeutics Holdings, Inc.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.https://doi.org/10.1038/s41541-025-01062-8 |
| spellingShingle | 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 A bivalent COVID-19 mRNA vaccine elicited broad immune responses and protection against Omicron subvariants infection npj Vaccines |
| title | A bivalent COVID-19 mRNA vaccine elicited broad immune responses and protection against Omicron subvariants infection |
| title_full | A bivalent COVID-19 mRNA vaccine elicited broad immune responses and protection against Omicron subvariants infection |
| title_fullStr | A bivalent COVID-19 mRNA vaccine elicited broad immune responses and protection against Omicron subvariants infection |
| title_full_unstemmed | A bivalent COVID-19 mRNA vaccine elicited broad immune responses and protection against Omicron subvariants infection |
| title_short | A bivalent COVID-19 mRNA vaccine elicited broad immune responses and protection against Omicron subvariants infection |
| title_sort | bivalent covid 19 mrna vaccine elicited broad immune responses and protection against omicron subvariants infection |
| url | https://doi.org/10.1038/s41541-025-01062-8 |
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