Antigen Presenting Cell Targetted, Adjuvant free Mucosal Vaccine Induces Protection against Pneumococcal Infection

Abstract Protein-based subunit vaccines require adjuvants to increase their immunogenicity. However, there is lack of FDA-approved mucosal adjuvant. We have previously shown that targeting antigens to antigen presenting cells increases their immunogenicity. Specifically, Streptococcus pneumoniae (Sp) protective antigen (PspA) fused to a single-chain bivalent-anti human Fc-gamma-receptor-I (hFcgRI) antibody, when introduced into mice, generates protection against Sp. To further enhance the immunogenicity of the anti-hFcgRI-PspA fusion protein, we have incorporated an additional hFcgRI-binding moiety, with the resultant trivalent-anti-hFcgRI inducing better protection compared to the bivalent anti-hFcgRI-based vaccine. This improved vaccine requires fewer immunizations to confer over 90% protection, significantly higher than that of bivalent-anti-hFcgRI-PspA (less than 60%). The trivalent- anti-hFcgRI-PspA also induces significantly higher levels of Sp-specific antibodies. In addition, we observed elevated levels of mucosal IgA responses in trivalent-anti-hFcgRI-PspA-immunized mice compared to that of bivalent anti-hFcgRI-PspA. Both trivalent-anti-hFcgRI-PspA and bivalent anti-hFcgRI-PspA enhanced antigen presentation in FcgRI-dependent manner. We have further observed that trivalent-anti-hFcgRI-PspA induces recruitment of innate immune cells in the nasopharyngeal lymphoid tissue upon intranasal immunization, which is a hallmark of adjuvant activity. Thus, our study suggests that anti-hFcgRI-PspA compensates for the lack of adjuvant by inducing adjuvant effects, and can be utilized as a mucosal vaccine platform.