Previous investigations, which simulated the usual sequence of the humanHerpes simplex virus (HSV) infections, had shown that the oral infection of mice with HSV-1 caused only weak protection from genital infection with HSV-2, although the course of infection was attenuated and lethality diminished. This type of immunity can be conferred on persons who are exposed to measles, mumps, whooping cough, poliomyelitis, rabies, rubella (German measles), tetanus, chickenpox, and herpes zoster (shingles). Mortality rates, lesion scores and viral titers were significantly reduced in SKH-1 mice immunized with gD/GPI-0100 prior to cutaneous inoculation with HSV-1 and the protective effects were greater than those using the standard alum adjuvant. Immunization with HSV-2 dl5-29 reduced viral replication in the cornea, prevented ocular disease and reduced latent infection by the HSV-1 strain. On day 5 postinfection, virus replication in the eye was measured, and on day 30 postinfection, infiltration of the trigeminal ganglia (TG) by CD4, CD8, programmed death 1 (PD-1), and T cell immunoglobulin and mucin domain-containing protein 3 (Tim-3) was monitored by immunohistochemistry and quantitative real-time PCR (qRT-PCR). A guinea pig model, which displays a HSV-2 infection that closely resembles the pathogenesis and symptoms of the disease in humans, was employed for studying the impact of immunization on the establishment of latency and recurrent genital herpes. The virus titers in the vaginal secretions of the vaccinated mice significantly reduced with time, and the B2 : D2 gene vaccine decreased more than each individual vaccine alone.
Overall, these results indicate that viral replication is not necessary to elicit a potent and durable HSV-specific immune response and suggest that replication-deficient viruses may be effective in eliciting protection against viral pathogens. All the DNA vaccines failed to block the latent infection in sensory nerves.