Multi-antigenic human cytomegalovirus mRNA vaccines that elicit potent humoral and cell-mediated immunity

Abstract

A cytomegalovirus (CMV) vaccine that is effective at preventing congenital infection and reducing CMV disease in transplant patients remains a high priority as no approved vaccines exist. While the precise correlates of protection are unknown, neutralizing antibodies and antigen-specific T cells have been implicated in controlling infection. We demonstrate that the immunization of mice and nonhuman primates (NHPs) with lipid nanoparticles (LNP) encapsulating modified mRNA encoding CMV glycoproteins gB and pentameric complex (PC) elicit potent and durable neutralizing antibody titers. Since the protective correlates in pregnant women and transplant recipients may differ, we developed an additional mRNA vaccine expressing the immunodominant CMV T cell antigen pp65. Administration of pp65 vaccine with PC and gB elicited robust multi-antigenic T cell responses in mice. Our data demonstrate that mRNA/LNP is a versatile platform that enables the development of vaccination strategies that could prevent CMV infection and consequent disease in different target populations.

Keywords: Cytogam; Cytomegalovirus; Neutralizing antibodies; Pentameric complex; mRNA vaccine.