Highly scalable prefusion-stabilized RSV F vaccine with enhanced immunogenicity and robust protection.

ABSTRACT: Stabilizing the RSV F protein in its prefusion conformation is crucial for effective vaccine development but has remained a significant challenge. Traditional stabilization methods, such as disulfide bonds and cavity-filling mutations, have been labor-intensive and have often resulted in suboptimal expression levels. Here, we report the design of an RSV prefusion F (preF) antigen using a proline-scanning strategy, incorporating seven proline substitutions to achieve stabilization. The resulting variant, preF7P, is structurally and biochemically validated to maintain the correct prefusion state. PreF7P demonstrates superior immunogenicity with a 1.8-fold increase in neutralizing antibody titers when compared to DS-cav2, and provides protection from clinical disease against both RSV A and B

SUBMITTER: Huang Q 

PROVIDER: S-EPMC12370985 | biostudies-literature | 2025 Aug

REPOSITORIES: biostudies-literature