Immunological and structural evaluation of the intranasally administrated CVB1 whole-virus and VLP vaccines.

Abstract

Coxsackievirus B1 (CVB1) is a common cause of acute and chronic myocarditis, cardiomyopathy, and meningitis. CVBs replicate in mucosal membranes. Therefore, vaccines inducing robust mucosal immune responses are needed. We investigated the immunogenicity of virus-like particles (VLP) and inactivated virus vaccines for CVB1, administered to mice either subcutaneously or intranasally, formulated with and without commercial and an experimental adjuvant. In this study, epigallocatechin-3-gallate (EGCG) was used both as a potential adjuvant and as an inactivating agent. EGCG adjuvanted CVB1-VLP enhanced immunogenicity via the parenteral route, but not intranasally. EGCG-adjuvanted and non-adjuvanted CVB1-VLPs triggered an immune response after intranasal administration, although the response remained weak. Intranasal administration of formalin-inactivated virus elicited robust CVB1-specific humoral, cellular, and mucosal immune responses, but after EGCG-inactivation, the mucosal antibody response was lower than after formalin-inactivation. To identify the link between structure and mucosal immunogenicity, we solved the structures of CVB1-VLP and formalin-inactivated CVB1 virus at resolutions ranging from 2.15 to 4.1 Å. The structural difference between VLP and formalin-inactivated CVB1 was the presence of the genome and cross-linked amino acid residues in the formalin-inactivated virus. Formalin-inactivated CVB1 vaccine shows promise for mucosal immunizations and the structural data supports the development of next-generation VLP-vaccines in the future.