Vaccine Protection against Simian Immunodeficiency Virus by Recombinant Strains of Herpes Simplex Virus

An effective vaccine for AIDS may require development of novel vectors capable of eliciting long-lasting immune responses. Here we report the development and use of replication-competent and replication-defective strains of recombinant herpes simplex virus (HSV) that express envelope and Nef antigens of simian immu-nodeficiency virus (SIV). The HSV recombinants induced antienvelope antibody responses that persisted at relatively stable levels for months after the last administration. Two of seven rhesus monkeys vaccinated with recombinant HSV were solidly protected, and another showed a sustained reduction in viral load following rectal challenge with pathogenic SIVmac239 at 22 weeks following the last vaccine administration. HSV vectors thus show great promise for being able to elicit persistent immune responses and to provide durable protection against AIDS. Preclinical vaccine testing for AIDS has relied principally on simian immunodeficiency virus (SIV) in macaque monkeys. Vaccine protection against pathogenic, difficult to neutralize strains of SIV, which could be considered representative of field strains of human immunodeficiency virus type 1 (HIV-1), has proven very difficult to achieve. Consequently, most studies have used a homologous strain of SIV for challenge 2 to 4 weeks after the last vaccine boost. Even with these optimized conditions, solid vaccine efficacies of even 50 % have seldo