Immunogenicity and efficacy of an mRNA vaccine expressing a virus-like particle spike antigen against SARS-CoV-2
The COVID-19 pandemic spurred mRNA vaccine innovation, but new SARS-CoV-2 variants highlight the need for vaccines with improved potency and durability. This report presents a novel mRNA vaccine platform encoding virus-like particle antigens (mRNA-VLPs) that mimic native virus structures, aiming to boost antibody responses via enhanced B cell activation. In animal studies, mRNA-VLP vaccines generated stronger neutralizing antibody responses across multiple variants compared to conventional mRNA vaccines expressing native spike proteins. In non-human primates, these elevated antibodies lasted at least six months. An mRNA-VLP vaccine encoding the Omicron spike outperformed traditional mRNA vaccines in mice as both a monovalent and bivalent (with ancestral spike) formulation. In hamsters, even low doses of mRNA-VLP vaccine provided complete protection, similar to high doses of native spike mRNA vaccines. These results suggest the mRNA-VLP platform could significantly strengthen vaccine efficacy and breadth against evolving SARS-CoV-2 variants.
Authors
- Oliver J. Acton (ORCID: https://orcid.org/0000-0003-3928-2300)
- Joseph R. Francica (ORCID: https://orcid.org/0000-0003-1336-4682)
- Hawley C. Pruitt (ORCID: https://orcid.org/0000-0002-8189-5031)
- Tara Kenny
- Cheyne Kurokawa
- Johnathan D. Guest (ORCID: https://orcid.org/0000-0003-1521-5242)
- Phillip A. Swanson
- Vinita Puri (ORCID: https://orcid.org/0000-0001-9698-0047)
- Richard Roque (ORCID: https://orcid.org/0000-0003-0964-8455)
- Yíngyún Caì (ORCID: https://orcid.org/0000-0002-1101-0920)
- Seme Diallo (ORCID: https://orcid.org/0000-0002-7739-4349)
- Kuishu Ren (ORCID: https://orcid.org/0000-0002-9634-3256)
- Angela D. Pack (ORCID: https://orcid.org/0000-0002-7579-2343)
- Sarah Siddiqui (ORCID: https://orcid.org/0000-0001-8818-5078)
- Jason P. Laliberte (ORCID: https://orcid.org/0009-0006-7131-1369)
- Hibret A. Adissu (ORCID: https://orcid.org/0000-0003-3365-7466)
- Yueh–Ming Loo (ORCID: https://orcid.org/0000-0001-6294-7273)
- George Thom (ORCID: https://orcid.org/0000-0002-1029-3551)
- Michael R. Newton
- Mark T. Esser (ORCID: https://orcid.org/0000-0003-1689-3475)
- Wade Blair (ORCID: https://orcid.org/0000-0002-2672-5136)
- Yi Zhang (ORCID: https://orcid.org/0000-0002-8228-2560)
- Rakesh Choudhary (ORCID: https://orcid.org/0000-0001-9888-0939)
- Yihan Cheng (ORCID: https://orcid.org/0009-0005-7240-5749)
- Kim Rosenthal
- Daniel Flores
- Vanessa Cadevilla Peano
- Noel Janney
- Giune Padilla
Institutions
- AstraZeneca (United Kingdom) (GB)
- SUNY Upstate Medical University (US)
- AstraZeneca (South Korea) (KR)
- AstraZeneca (Australia) (AU)
- AstraZeneca (Switzerland) (CH)
- AstraZeneca (Poland) (PL)
- AstraZeneca (Finland) (FI)
- Intego (Germany) (DE)
- AstraZeneca (United States) (US)
Publication Details
- Journal
- npj Vaccines
- Published
- 2025-12-13
- DOI
- https://doi.org/10.1038/s41541-025-01303-w
- Citations
- 1
- Primary Topic
- SARS-CoV-2 and COVID-19 Research
- Type
- article
- Field-Weighted Citation Impact
- 1.40