Intranasal vaccination with SfbI or M protein-derived peptides conjugated to diphtheria toxoid confers protective immunity against a lethal challenge with Streptococcus pyogenes

We investigated whether intranasal immunisation with diphtheria toxoid (DT) conjugated polypeptides encompassing T and B cell epitopes of the SfbI protein (FNBR) or a conformational-constrained B cell epitope of the M1 protein (J8) was able to confer protection against lethal mucosal challenge with a heterologous Streptococcus pyogenes strain. To this end, BALB/c mice were immunised with the conjugates. Strong antigen-specific antibody responses were observed in both serum and mucosal secretions. Vaccinated mice were challenged 10 days after the last boost by the intranasal route. Animals receiving FNBR-DT co-administered with either the cholera toxin B subunit (CTB) or the TLR 2/6 agonist MALP-2 were efficiently protected against the virulent S. pyogenes strain (90% and 70% survival, respectively), whereas those immunised with J8-DT plus either CTB or MALP-2 showed intermediate levels of protection (60% and 40%, respectively). The obtained results indicate that in our experimental animal model peptide-based conjugate vaccines represent a valid alternative to protect against streptococcal infection.