Co-immunization with spike and nucleocapsid based DNA vaccines for long-term protective immunity against SARS-CoV-2 Omicron
The continuing evolution of SARS-CoV-2 variants challenges the durability of existing spike (S)-based COVID-19 vaccines. We hypothesized that vaccines composed of both S and nucleocapsid (N) antigens would increase the durability of protection by strengthening and broadening cellular immunity compared with S-based vaccines. To test this, we examined the immunogenicity and efficacy of wild-type SARS-CoV-2 S- and N-based DNA vaccines administered individually or together to K18-hACE2 mice. S, N, and S + N vaccines all elicited polyfunctional CD4<sup>+</sup> and CD8<sup>+</sup> T cell responses and provided short-term cross-protection against Beta and Omicron BA.2 variants, but only co-immunization with S + N vaccines provided long-term protection against Omicron BA.2. Depletion of CD4<sup>+</sup> and CD8<sup>+</sup> T cells reduced the long-term efficacy, demonstrating a crucial role for T cells in the durability of protection. These findings underscore the potential to enhance long-lived protection against SARS-CoV-2 variants by combining S and N antigens in next-generation COVID-19 vaccines.
Authors
- Shailendra Kumar Verma (ORCID: https://orcid.org/0000-0001-9142-3022)
- Paolla Beatriz Almeida Pinto
- Kantinan Chuensirikulchai (ORCID: https://orcid.org/0009-0002-1141-6485)
- Hsueh-Han Lu (ORCID: https://orcid.org/0000-0002-0832-9607)
- Kristen Valentine (ORCID: https://orcid.org/0000-0003-0662-3076)
- Julia Timis
- Annie Elong Ngono (ORCID: https://orcid.org/0000-0002-6741-3518)
- Erin Maule
- Qin Hui Li (ORCID: https://orcid.org/0000-0002-2792-9018)
- Sujan Shresta (ORCID: https://orcid.org/0000-0003-2906-8474)
- Fernanda Ana‐Sosa‐Batiz
- Sara Landeras-Bueno (ORCID: https://orcid.org/0000-0003-2143-2569)
- Erica Ollmann Saphire (ORCID: https://orcid.org/0000-0002-1206-7451)
- Kathryn M. Hastie (ORCID: https://orcid.org/0000-0002-3406-1210)
- Rúbens Prince dos Santos Alves (ORCID: https://orcid.org/0000-0001-5538-6025)
- Kenneth Kim (ORCID: https://orcid.org/0000-0002-5993-4575)
- Ada M. B. Alves (ORCID: https://orcid.org/0000-0002-5487-4032)
- Michael N. Nguyen (ORCID: https://orcid.org/0000-0002-4184-7078)
Institutions
- La Jolla Institute for Immunology (US)
- Universidad Cardenal Herrera CEU (ES)
- University of California San Diego (US)
- Chiang Mai University (TH)
- Fundação Oswaldo Cruz (BR)
Publication Details
- Journal
- npj Vaccines
- Published
- 2024-12-19
- DOI
- https://doi.org/10.1038/s41541-024-01043-3
- Citations
- 4
- Primary Topic
- SARS-CoV-2 and COVID-19 Research
- Type
- article
- Field-Weighted Citation Impact
- 1.56
Funders
- Division of Intramural Research, National Institute of Allergy and Infectious Diseases
- GHR Foundation
- Coordenação de Aperfeiçoamento de Pessoal de Nível Superior
- National Institutes of Health