Intranasal immunisation of mice with a streptococcal peptide-based vaccine.

Abstract

The comparative roles of systemic and local responses in immune protection after group A streptococcal (GAS) infection are not fully understood. After parenteral immunisation of mice with M protein type-specific and conserved region peptides, there is an induction of serum bactericidal antibodies (Abs). In humans, type-specific immunity to GAS infection is long lasting, and Abs to the conserved region of M protein increase with age and immune status. Opsonic serum Abs may only form part of the protective response as there is also evidence for a protective role for secretory IgA (sIgA). Passive transfer of M protein-specific human sIgA significantly inhibited streptococcal infection in mice1. Intranasal (i.n.) immunisation with conserved peptides linked to cholera toxin subunit B (CTB) resulted in a significant reduction in pharyngeal colonisation of mice following homologous and heterologous GAS challenge2–4. These data suggest that mucosal protective responses may be directed to non-type specific regions of the M protein, however there was a failure to demonstrate the presence of M protein peptide-specific sIgA. We are further investigating the role of an M protein peptide-based mucosal vaccine to prevent infection and rheumatic fever. Mucosal immunisation has the advantage of inducing immune responses effective at preventing attachment/colonisation in the throat (a site of natural infection), and then triggering systemic immunity important for eliminating any invading bacteria. Work in our laboratory has focussed on a 20 amino acid epitope, p145 (LRRDLDASREAKKQVEKALE) within the conserved C-repeat region of the M protein. Abs to p145 raised after subcutaneous (s.c.) immunisation of mice could effectively opsonise and direct killing of a number of field isolates and reference strains5.