Protective immunity against ocular herpes infection and disease induced by highly immunogenic self-adjuvanting glycoprotein D lipopeptide vaccines

Abstract

Purpose: An important phase in the development of an ocular herpes simplex virus type 1 (HSV-1) subunit vaccine is the identification of an efficient, safe, and adjuvant-free antigen delivery system capable of inducing and sustaining long-term memory T-cell protective immunity. This study was conducted to test the hypothesis that immunization with self-adjuvanting lipopeptide bearing HSV-1 glycoprotein D (gD) T-cell epitopes would elicit long-term HSV-specific T cells and decrease infection, disease, or both in a ocular herpes mouse model.

Methods: Five immunodominant CD4(+) T-cell peptide epitopes (gD(1-29), gD(49-82), gD(146-179), gD(228-257), and gD(332-358)), recently identified from HSV-1 gD, were covalently linked to a palmitic acid moiety (lipopeptides) and delivered subcutaneously in adjuvant-free saline. The primary and memory T cells induced by these molecularly defined lipopeptides and their protective efficacy were assessed, in terms of virus replication in the eye, ocular disease, and survival.

Results: Three gD lipopeptides, that drive dendritic cell maturation in vitro, induced long-term, virus-specific, IFN-gamma-producing CD4(+) Th(1) responses, associated with a reduction in ocular herpes infection and disease. Immunization with a cocktail of these three highly immunogenic Th(1) lipopeptides increased survival, lowered the peak of ocular virus titer, and cleared the ocular disease.

Conclusions: Vaccination with a mixture self-adjuvanting lipopeptides containing novel HSV-1 immunodominant gD T-cell epitopes protected mice from ocular herpes infection and disease. The strength of protective immunity induced by these lipopeptides together with their safety provide a molecularly defined vaccine formulation that could combat ocular herpes infection and disease in humans.