Immune Response to Synthetic Herpes Simplex Virus Peptides:The Feasibility of a Synthetic Vaccine

Abstract

Synthetic peptides which are selected from immunogenic proteins offer an approach to the development of a Vaccine with optimal properties. The strategy used for the design of such a synthetic Vaccine includes:(1) the identification of regions in the protein molecule which act as determinants for B cells as well as for T cells; (2) the chemical synthesis of identified antigenic determinants; and (3) the attachment of the synthetic peptides to suitable carriers which allow optimal presentation of the peptide antigen. For our studies we have chosen glycoprotein D(gD) of the herpes simplex virus (HSV). This antigen appears to be the major target of the immune response to HSV (PAOLETTI et al. 1984; CHAN 1983; LASKY et al. 1984; LONG et al. 1984; SPEAR 1984) and therefore represents a logical choice for a subunit Vaccine against an HSV infection. We will describe the localization and chemical synthesis as well as the physicochemical and immunological characterizaton of a major antigenic site of HSV gD. Synthetic peptides comprising this antigenic site are recognized by HSV type-common and type-specific antibodies, as well as by HSV-primed T cells, and immunization with these molecules induces both a B cell and a T cell response. Most important is the finding that a Single injection of these peptides can confer long-term protection against a lethal HSV infection, but only when the peptides are incorporated into liposomes. The exact nature of this immune and protective response will be the subject of this paper.