Immunogenicity of a Group A Streptococcal peptide vaccine conjugated to CRM197 (53.12)

Abstract

Abstract Group A Streptococcus (GAS) causes several disease manifestations and remains a huge medical burden in developing and developed countries, therefore there is an imminent need for a prophylactic vaccine. One focal point of vaccine development for GAS has been the M protein, an alpha-helical coiled-coil surface protein. An epitope derived from the C-terminal region of the M protein, J8, has been shown to be highly immunogenic and to generate opsonophagocytic killing (OPK) activity and protection in mice. Here we evaluated the use of an alternative protein carrier, CRM197, a molecularly detoxified version of diphtheria toxoid (DT), by conjugating J8 to CRM197 and immunizing C3H and Balb/c mice with this vaccine on AAHSA (Amorphous Aluminum Hydroxyphosphate Sulfate Adjuvant). J8-specific ELISA and whole bacteria immunofluorescence (IFA) were used to evaluate immunogenicity. Functional antibody activity was evaluated by opsonophagocytosis (OPK) and protection from a GAS intranasal challenge. J8 conjugated to CRM197 induced high antibody responses to J8; these specific antibodies recognized the epitope on the surface of the bacteria by IFA and demonstrated functional activity in an OPK assay. Additionally, J8-CRM197 immunized mice demonstrated significantly greater survival than adjuvant control immunized mice. This study showed that CRM197 is a suitable carrier protein for J8 peptide conjugation in C3H and Balb/c mice.