Progress and prospects for herpesvirus vaccination using gB antigens.

The success of vaccines against varicella zoster virus (VZV) demonstrates the feasibility of high-level efficacy against clinical consequences of herpesvirus infection, but there is a need for new vaccines against others - in particular Epstein-Barr Virus (EBV), human cytomegalovirus (HCMV) and herpes simplex virus 1 and 2 (HSV). Herpesviruses use surface glycoproteins to trigger membrane fusion during cell invasion. Glycoprotein B (gB) is conserved across the family and acts as the fusogen. Vaccines based upon viral fusion proteins protect against many other viruses, and a gB-targeting HCMV vaccine achieved partial efficacy in clinical trials. This experience encourages development of improved gB-based antigens and formulations. There has recently been progress in stabilisation of the pre-fusion conformation of gB, which may be the more relevant structure with respect to immunological protection. Nonetheless gB-targeting vaccines have received less attention recently than vaccines against receptor-binding glycoproteins such as EBV gH/gL and gp350, and HCMV pentamer. We therefore seek to review current knowledge regarding gB as a vaccine antigen: understanding of herpesvirus gB structure and function, within the context of the wider process of herpesvirus entry into host cells; insights relevant to vaccine development from in vitro studies of antibody-gB interactions and effects; and the results from previous in vivo studies using gB-based vaccines. We conclude by critically appraising the potential for gB antigens to contribute to future herpesvirus vaccines, as compared to alternative or complementary approaches.