Formulation Attributes Impact Immune Profile of an Oral and Thermostable COVID-19 Subunit Vaccine.

While approved vaccines for COVID-19 provide protection against severe disease and death, they have limited efficacy in the prevention of infection and virus transmission. Mucosal immunity is preferred over systemic immunity to provide protection at the point of entry against pathogens such as SARS-CoV-2. VaxForm has developed an oral vaccine delivery platform that elicits mucosal and systemic immune responses by targeting immune cells in the gut through C-type lectin receptors. The technology consists of microencapsulating the vaccine with an enteric polymer, which also results in enhanced thermostability. This article describes the formulation development and in vivo testing of a novel protein-based oral COVID-19 vaccine using this technology. Results demonstrate successful induction of immune response in mice and showed that the particle size of the vaccines following administration can impact the ratio of mucosal to systemic response. Immunogenicity and thermostability of liquid suspension and dry powder versions of the vaccine were compared in mice. The liquid suspension vaccine showed excellent heat resistance by maintaining immunogenicity after 14 days of storage at 60 °C. While further investigation is needed to determine correlates of protection and duration of response for mucosal immunity, this study demonstrates the vaccine's potential as a COVID-19 booster to enhance mucosal protection in humans and improve global access by lowering the cost of production, removing cold-chain requirements, and allowing self-administration.