Self-Adjuvanting Virus-Like Particles for Sublingual Vaccination against Group A Streptococcus Elicit Protective Immunity in Systemic and Mucosal Sites

Group A streptococcus (GAS) is an important pathogen, which infects primarily in oropharynx and induces mortality and morbidity. Here we introduced virus-like particle (VLP) to GAS vaccine via sublingual route to induced protective immunity. Peptide antigens from GAS M-surface protein can confer protection against infection; however, it still remains a challenge to adapt vaccine candidate peptides for immunogenic mucosal vaccines. In this study, a modular murine polyomavirus (MuPyV) VLP was engineered to display a GAS antigenic peptide, J8i. Heterologous modules containing one or two J8i antigen elements were integrated with the MuPyV-VLP, and produced using microbial protein expression, standard purification techniques and in vitro VLP assembly. Sublingual administration with VLP-J8i resulted in high level of IgG antibody in the serum with good balance of Th1 and Th2 immune response. Of note, sublingual vaccination with VLP-J8i induced high level of IgA antibody in saliva. Moreover, saliva isolated from mice immunized with VLP-J8i demonstrated protective immune response against GAS in vitro. This study shows that the potential of sublingual vaccination as a favorable mucosal vaccine formula for VLP-J8i which can potentially block horizontal transmission by eradicating pharyngeal colonization of GAS.