Evaluation of a novel bat orthoreovirus-based vaccine platform for the induction of mucosal immunity against SARS-CoV-2
While the pandemic phase fades out, effective SARS-CoV-2 vaccines remain vital to protect vulnerable groups in recurrent seasonal epidemics. Current vaccine modalities protect efficiently against severe disease and mortality, but vaccinees remain highly infectious upon breakthrough infection. Vaccines that establish local immunity in the respiratory tract to efficiently limit or prevent breakthrough infections may therefore further reduce the individual risk of severe complications but may also help to mitigate outbreak dynamics on population level. Mucosal immunity in the respiratory tract in form of secretory IgA and tissue-resident memory T cells have been shown to be crucial for an immediate and efficient immune control of other viral respiratory pathogens such as Influenza A and the Respiratory Syncytial Virus.
The project aims at developing a novel mucosal vaccine platform based on a Pteropine orthoreovirus (PRV). Bat-borne PRV show a broad species tropism and sporadically cause a self-limiting Influenza-like disease in humans. PRV is a promising mucosal vaccine platform due to its respiratory characteristic and a low seroprevalence in the human population. Using a reverse genetics system, the doctoral student will produce replication-deficient and attenuated PRV vectors for the mucosal delivery of SARS-CoV-2 antigens. The cellular tropism and distribution will be assessed in vivo by mucosal administration of a reporter PRV vector. First proof-of-concept immunizations will be conducted with vaccines delivering Spike protein as an established antigen that induces humoral and cellular immunity. We will also produce and test PRV-based vaccines that primarily aim at inducing strong, mucosal T cell immunity (Nucleocapsid, Membrane, NSPs), since it is increasingly recognized as a correlate of protection independent of antigenic variations in the Spike protein.
