Dose-Dependent Efficacy of a Riboflavin and Ultraviolet Light-Inactivated Whole-Virion SARS-CoV-2 Vaccine in a...

Background: A novel platform to produce whole-virion vaccines using riboflavin and ultraviolet (UV) light for photochemical inactivation has been developed. We previously reported on the potential for this platform to produce a safe and effective inactivated whole-virion SARS-CoV-2 vaccine. Feasibility studies used a hamster infection challenge model to explore the effects of route of administration and adjuvants on immune responses elicited by the vaccine candidate. Here, we utilized the same animal model to evaluate the dose response to the vaccine candidate in combination with the adjuvant CpG1018. Methods: A pilot batch of the vaccine candidate was produced at a contract development and manufacturing organization (CDMO) for use in this study. A two-dose intramuscular regimen at three antigen concentrations formulated with CpG1018 adjuvant was assessed against a live SARS-CoV-2 (USA-WA-1/2020) challenge. Results: The vaccine elicited dose-dependent neutralizing antibody responses, with peak PRNT₅₀ titers exceeding 1:5120. Vaccination significantly reduced lung viral burden and mitigated pulmonary pathology compared to controls. Antibodies persisted up to 154 days post-vaccination and neutralized Delta and Omicron (Jn.1) variants but showed limited activity against XBB.1.5. Flow cytometry revealed enhanced CD4⁺ Th1-biased responses in higher-dose groups. Conclusions: These findings demonstrate the protective efficacy of the SolaVAX SARS-CoV-2 vaccine candidate and support further evaluation of this vaccine production platform.