| Autor: |
Mohit Verma, Shiho Tanaka, Lise Zakin, Kyle Dinkins, Adrian Rice, Wendy Higashide, Elizabeth R Gabitzsch, Peter A. Sieling, Emily A. Voigt, C. Anders Olson, Peter Battisti, Jeffrey T. Safrit, Corey Casper, Brett Morimoto, Sierra Reed, Patricia Spilman, Shivani Mody, Patrick Soon-Shiong, Sam Beaver |
| Rok vydání: |
2021 |
| Předmět: |
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| DOI: |
10.1101/2021.11.29.470440 |
| Popis: |
We assessed if immune responses are enhanced in CD-1 mice by heterologous vaccination with two different nucleic acid-based COVID-19 vaccines: a next-generation human adenovirus serotype 5 (hAd5)-vectored dual-antigen spike (S) and nucleocapsid (N) vaccine (AdS+N) and a self-amplifying and -adjuvanted S RNA vaccine (SASA S) delivered by a nano-lipid carrier. The AdS+N vaccine encodes S modified with a fusion motif to increase cell-surface expression. The N antigen is modified with an Enhanced T-cell Stimulation Domain (N-ETSD) to direct N to the endosomal/lysosomal compartment and increase MHC class I and II stimulation potential. The S sequence in the SASA S vaccine comprises the D614G mutation, two prolines to stabilize S in the prefusion conformation, and 3 glutamines in the furin cleavage region to increase cross-reactivity across variants. CD-1 mice received vaccination by homologous and heterologous prime > boost combinations. Humoral responses to S were the highest with any regimen including the SASA S vaccine, and IgG bound to wild type and Delta (B.1.617.2) variant S1 at similar levels. An AdS+N boost of an SASA S prime particularly enhanced both CD4+ and CD8+ T-cell responses to both wild type and Delta S peptides relative to all other vaccine regimens. Sera from mice receiving SASA S homologous or heterologous vaccination were found to be highly neutralizing of all pseudovirus strains tested: Wuhan, Beta, Delta, and Omicron strain. The findings here support the clinical testing of heterologous vaccination by an SASA S > AdS+N regimen to provide increased protection against emerging SARS-CoV-2 variants. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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