Intranasal Cry1Ac Protoxin is an Effective Mucosal and Systemic Carrier and Adjuvant of Streptococcus pneumoniae Polysaccharides in Mice

Abstract

Streptococcus pneumoniae is a major respiratory pathogen in infants, children and the elderly. Available parenteral anti-pneumococcal vaccines based on type-specific capsular polysaccharides (CPSs) are useful in adults but do not elicit protective immunity in infants and young children. To enhance their immunogenicity, pneumococcal CPSs conjugated to proteins are being developed. Mucosal vaccines may induce mucosal and systemic immune responses, but their development has been hampered by the lack of effective, inexpensive innocuous mucosal adjuvants or immunogenic vaccine carriers. We have demonstrated that the recombinant Cry1Ac protoxin from Bacillus thuringiensis is highly immunogenic and has mucosal and systemic adjuvant effects on proteins coadministered in mice. In this work, we evaluated Cry1Ac as a carrier and adjuvant of S. pneumoniae CPS for the induction of mucosal and systemic antibody responses after intranasal and intraperitoneal immunization in mice. Our results demonstrate that intranasal application of pneumococcal polysaccharides either coadministered or conjugated with Cry1Ac induces higher systemic and mucosal specific antibody responses than those elicited by pneumococcal polysaccharides alone. Adjuvant effects of Cry1Ac on polysaccharides may be appropriate for vaccine design.