include cytomegalovirus, Herpesvirus varicellae (varicella-zoster virus), and Epstein-Barr virus. All have the capacity for persistence in the human host (Nahmias and Josey, 1982).
HSV-1 and HSV-2 are complex viruses containing a large, double-stranded DNA genome coding for about 50 viral proteins. About half of HSV-1 and HSV-2 sequences are homologous. There has been some progress recently towards identifying the genes responsible for latency and carcinogenicity (Roizman et al., 1984).
Of particular importance to the prospects for immunization are the surface glycoproteins of the HSV-1 and HSV-2 viral envelopes. Herpes simplex viruses carry five major surface glycoproteins—designated gB, gC, gD, gE, and gG. Some of these glycoproteins (e.g., gD, gB, and gC) are known to induce high level neutralizing antibodies in naturally infected individuals, and are thought to be potential candidates for subunit vaccines. Genes coding for gD have been cloned and expressed in mammalian cell lines (Lasky et al., 1984).
The immunology of HSV infections has been reviewed recently by Shore and Nahmias (1981). In primary HSV infections, humoral antibodies can be detected within 1 to 3 weeks and assays of cellular immunity in vitro have demonstrated a cell-mediated response after a similar period.
It is not clear which of these responses leads to curtailment of primary infection in normal individuals. HSV infections in immunocompromised hosts tend to be severe and chronic.
Recurrence of latent HSV infection takes place in spite of the presence of circulating antibodies, probably because of the factors responsible for latency, about which very little is known. Hence, it probably will be necessary to stimulate immunity prior to exposure to achieve protection.
Vaccines containing viral glycoprotein surface antigens, prepared in chick embryo culture, have been shown to be effective in stimulating immunity and preventing disease in experimentally infected animals (Hilleman et al., 1981). Trials in humans are discussed below.
Estimates for the disease burden are based on information from Nahmias and Josey (1982), and the National Institute of Allergy and Infectious Diseases (1980, 1983); on advice from Bryson (personal communication, 1983), Cates (personal communication, 1983), Corey (personal communication, 1984), Guinan (personal communication, 1984), Johnson (personal communication, 1983), Nahmias (personal communication, 1984), and Whitley (personal communication, 1984); and on the specific references cited. The Morbidity Categories referred to below are defined in Chapter 4 and Table I.9.