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<p>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.</p>

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

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年1月10日

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  • 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

摘要

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.