Inactivated Rabies Virus Vectored Sars-Cov-2 Vaccine Prevents Disease In A Syrian Hamster Model

Author summaryWe have developed an inactivated rabies virus vectored vaccine platform that has been used to develop a vaccine against SARS-CoV-2 (CORAVAX). CORAVAX induced high levels of neutralizing antibodies against SARS-CoV-2. Here we show that vaccinated hamsters, the best animal model for Covid-19, were protected against viral replication, indicating that this vaccine can stop transmission. CORAVAX also prevented lung disease. Rabies virus vaccines have been used in more than 100 million people worldwide, are safe and used in children and pregnant women. Therefore, it is anticipated that CORAVAX will generate robust immune responses against SARS-CoV-2 in humans that may also mimic the long-term protection seen in rabies vaccines.Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an emergent coronavirus that has caused a worldwide pandemic. Although human disease is often asymptomatic, some develop severe illnesses such as pneumonia, respiratory failure, and death. There is an urgent need for a vaccine to prevent its rapid spread as asymptomatic infections accounting for up to 40% of transmission events. Here we further evaluated an inactivated rabies vectored SARS-CoV-2 S1 vaccine CORAVAX in a Syrian hamster model. CORAVAX adjuvanted with MPLA-AddaVax, a TRL4 agonist, induced high levels of neutralizing antibodies and generated a strong Th1-biased immune response. Vaccinated hamsters were protected from weight loss and viral replication in the lungs and nasal turbinates three days after challenge with SARS-CoV-2. CORAVAX also prevented lung disease, as indicated by the significant reduction in lung pathology. This study highlights CORAVAX as a safe, immunogenic, and efficacious vaccine that warrants further assessment in human trials.