NVX-CoV2373 ancestral and NVX-CoV2540 BA.5 protein nanoparticle vaccines protect against Omicron BA.5 variant in Syrian hamsters

SUMMARY The emergence of SARS-CoV-2 variants with greater transmissibility or immune evasion properties has jeopardized the existing vaccine and antibody-based countermeasures. Here, we evaluated the efficacy of boosting with the protein nanoparticle NVX-CoV2373 or NVX-CoV2540 vaccines containing ancestral or BA.5 S proteins, respectively, in mRNA-immunized pre-immune hamsters, against challenge with the Omicron BA.5 variant of SARS-CoV-2. Serum antibody binding and neutralization titers were quantified before challenge, and viral loads were measured 3 days after challenge. Compared to an mRNA vaccine boost, NVX-CoV2373 or NVX-CoV2540 induced higher serum antibody binding responses against ancestral Wuhan-1 or BA.5 spike proteins, and greater neutralization of Omicron BA.1 and BA.5 variants. One and three months after vaccine boosting, hamsters were challenged with the Omicron BA.5 variant. NVX-CoV2373 and NVX-CoV2540 boosted hamsters showed reduced viral infection in the nasal washes, nasal turbinates, and lungs compared to unvaccinated animals. Also, NVX-CoV2540 BA.5 boosted animals had fewer breakthrough infections than NVX-CoV2373 or mRNA-vaccinated hamsters. Thus, immunity induced by NVX-CoV2373 or NVX-CoV2540 boosting can protect against the Omicron BA.5 variant in the Syrian hamster model. IMPORTANCE As SARS-CoV-2 variants continue to emergence, the efficacy of prior and updated COVID-19 vaccines need to be tested. Here, we tested the efficacy of two nanoparticle protein-based vaccines in pre-immune hamsters against a challenge with the BA.5 Omicron variant of SARS-CoV-2. Compared to an mRNA vaccine boost, the nanoparticle vaccine NVX-CoV2373 and NVX-CoV2540 induced higher serum antibody binding and neutralization responses against ancestral Wuhan-1 or BA.5 variants. One and three months after the last immunization, hamsters were challenged with the Omicron BA.5 variant. NVX-CoV2373 and NVX-CoV2540 boosted hamsters showed reduced viral infection in the nasal washes, nasal turbinates, and lungs compared to unvaccinated animals. Animals that received the homologous vaccine, NVX-CoV2540, had fewer breakthrough infections than NVX-CoV2373 or mRNA-vaccinated hamsters. Together, our data shows that the BA.5 nanoparticle vaccine is effective and that it is important to update the COVID-19 vaccine to match currently circulating strains of SARS-CoV-2.