Abstract
The SARS-CoV-2 Omicron subvariant BA.5 rapidly spread worldwide and replaced BA.1/BA.2 in many countries, becoming globally dominant. BA.5 has unique amino acid substitutions in the spike protein that both mediate immune escape from neutralizing antibodies produced by immunizations and increase ACE2 receptor binding affinity. In a comprehensive, long-term (up to 9 months post primary vaccination), experimental vaccination study using male Syrian hamsters, we evaluate neutralizing antibody responses and efficacy against BA.5 challenge after primary vaccination with Ad26.COV2.S (Janssen) or BNT162b2 (Pfizer/BioNTech) followed by a homologous or heterologous booster with mRNA-1273 (Moderna) or NVX-CoV2373 (Novavax). Notably, one high or low dose of Ad26.COV2.S provides more durable immunity than two primary doses of BNT162b2, and the NVX-CoV2373 booster provides the strongest augmentation of immunity, reduction in BA.5 viral replication, and disease. Our data demonstrate the immunogenicity and efficacy of different prime/boost vaccine regimens against BA.5 infection in an immune-competent model and provide new insights regarding COVID-19 vaccine strategies.
| Original language | English |
|---|---|
| Article number | 4260 |
| Journal | Nature Communications |
| Volume | 14 |
| Issue number | 1 |
| DOIs | |
| State | Published - Dec 2023 |
Bibliographical note
Publisher Copyright:© 2023, The Author(s).
Funding
This project has been funded in whole or in part with Federal funds from the National Institute of Allergy and Infectious Diseases, National Institutes of Health, Department of Health and Human Services, under Contract No. 75N93021C00016 and grant R24 AI120942 (to S.C.W.), and by the Sealy and Smith Foundation (to SCW). During part of the study R.R.G.M. received a grant from Fundação de Amparo à Pesquisa do Estado de São Paulo—FAPESP (2019/27803-2), W.M.S. is supported by a Global Virus Network fellowship. We thank the in vivo NIH-SAVE group for their thoughtful insights during the study, Nehad Saada, Allan McConnell and Patricia A. Valdes for technical assistance. We acknowledge the Anatomic Pathology Laboratory at University of Texas Medical Branch for tissue sectioning. The authors acknowledge Mimi Guebre-Xabier, Nita Patel, Gale Smith, and Greg Glenn at Novavax, Inc. for providing NVX-CoV2373 vaccine and Sayda M. Elbashir and Darin Edwards at Moderna, Inc. for providing the preclinical version of mRNA-1273 vaccine. This project has been funded in whole or in part with Federal funds from the National Institute of Allergy and Infectious Diseases, National Institutes of Health, Department of Health and Human Services, under Contract No. 75N93021C00016 and grant R24 AI120942 (to S.C.W.), and by the Sealy and Smith Foundation (to SCW). During part of the study R.R.G.M. received a grant from Fundação de Amparo à Pesquisa do Estado de São Paulo—FAPESP (2019/27803-2), W.M.S. is supported by a Global Virus Network fellowship. We thank the in vivo NIH-SAVE group for their thoughtful insights during the study, Nehad Saada, Allan McConnell and Patricia A. Valdes for technical assistance. We acknowledge the Anatomic Pathology Laboratory at University of Texas Medical Branch for tissue sectioning. The authors acknowledge Mimi Guebre-Xabier, Nita Patel, Gale Smith, and Greg Glenn at Novavax, Inc. for providing NVX-CoV2373 vaccine and Sayda M. Elbashir and Darin Edwards at Moderna, Inc. for providing the preclinical version of mRNA-1273 vaccine.
| Funders | Funder number |
|---|---|
| NIH-SAVE | |
| National Institutes of Health (NIH) | |
| U.S. Department of Health and Human Services | 75N93021C00016, R24 AI120942 |
| National Institute of Allergy and Infectious Diseases | |
| Sealy and Smith Foundation | |
| Fundação de Amparo à Pesquisa do Estado de São Paulo | 2019/27803-2 |
ASJC Scopus subject areas
- General Chemistry
- General Biochemistry, Genetics and Molecular Biology
- General Physics and Astronomy
