GMMA as adjuvant and carrier for mucosal delivery of group A streptococcus glycoconjugate vaccine

Group A streptococcus (GAS) infection is usually initiated by colonization of mucosal sites such as the pharynx, followed by invasion and systemic dissemination. Development of a vaccine that can prevent colonization is enticing as it would prevent subsequent infections and all associated autoimmune sequalae such as rheumatic heart disease (RHD). In this study we investigated the mucosal adjuvanticity of GMMA when used as a carrier protein for GAS carbohydrate (GAC) conjugate vaccine (GAC-GMMA). Mice were immunized sublingually or intranasally with GAC-GMMA or GAC-CRM₁₉₇, in the presence or absence of cholera toxin B subunit (CTB). The anti-GAC systemic and mucosal immune responses were evaluated and compared. Our results showed that, in addition to being a good carrier, GMMA is also a good mucosal adjuvant and mediated the induction of substantial levels of serum IgG median titer: 1,050-3,200) and of mucosal IgA (512-2,560) in the mouth, (640) in the nose, (768-1,024) in the intestines and (1,024-1,280) in the vagina. The induced response was similar or better than the response induced by the GAC-CRM₁₉₇ conjugate administered in combination with the mucosal adjuvant CTB. Furthermore, mucosal delivery of GAC-GMMA and GAC-CRM₁₉₇ induced IL-17 and IFNγ secretion by immune spleen cells, which are known to mediate neutrophils recruitment and nitric oxide production by macrophages necessary for controlling infections at mucosal surfaces. We demonstrated that GMMA could work both as a carrier and adjuvant for the mucosal delivery of GAC and mediates induction of both systemic and mucosal immune responses against GAS.