Intranasal Administration Is an Effective Mucosal Vaccine Delivery Route for Self‐Adjuvanting Lipid Core Peptides Targeting the Group A Streptococcal M Protein

Abstract

We investigated the lipid core peptide (LCP) system for mucosal vaccine delivery against infection with group A streptococcus (GAS)--the causative pathogen of rheumatic fever and rheumatic heart disease. An LCP vaccine formulation containing 2 different peptide epitopes of the antiphagocytic M protein of GAS--a conformational epitope from the carboxyterminal conserved C-repeat region and an aminoterminal serotypic epitope--was intranasally administered to mice with cholera toxin B subunit or without additional adjuvant. Our data demonstrate that the LCP vaccine formulation induced the elicitation of antigen-specific systemic immunoglobulin G responses when administered with or without cholera toxin B subunit, whereas cholera toxin B subunit was required for the induction of antigen-specific mucosal immunoglobulin A responses. Immune serum samples from vaccinated mice were capable of opsonization of a homologous GAS strain, as well as opsonization of a heterologous GAS strain. Furthermore, mice were protected from GAS challenge following immunization with the LCP vaccine formulation, even in the absence of additional adjuvant. These data support the potential of the LCP system in the development of a self-adjuvanting, synthetic, peptide-based mucosal GAS vaccine for the prevention of diseases caused by GAS.