The general goal of this program is to use herpesvirus recombinants as vectors for the expression of SIV proteins to provide safe, effective vaccines against AIDS viruses. Our hypothesis is that herpesviruses can be genetically modified to provide safe viral vectors for AIDS vaccines that possess some of the some biological properties as AIDS viruses First, herpes viruses can persist in the host and periodically reactive, providing periodic responses in mouse model systems. Even replication-defective herpes strains seem to induce durable immune responses in mouse model systems. Second, herpes viruses activate a strong cellular immune response without the risk of killing T cells. Thus, our hope is that the herpesvirus recombinant vectors can induce a robust cellular response against AIDS virus antigens that is continually activated and eliminate any HIV or SIV infected cell soon after infection. The goal of the first project, entitled """"""""Herpes Simplex Virus as an AIDS Vaccine Vector,"""""""" is to use herpes simplex virus type 2 as a vaccine vector to express SIV env and gag proteins using replication-defective and replication competent strains of HSV-2 and rev-independent SIV gag and env genes. The goal of the second project, entitled """"""""Construction of Rhesus Rhadinovirus Vaccine Vectors,"""""""" is to construct and analyze replication-competent strains of rhesus monkey rhadinovirus (RRV) that express SIV antigens at high levels. The goal of the third project, entitled """"""""Herpesvirus Vectors as Vaccines in Rhesus Monkeys,"""""""" is to utilize the recombinants constructed in Projects 1 and 2 for vaccine/challenge experiments in rhesus monkeys. Humoral and cellular immune response against SIV and herpesviral antigens will be measured. projection against various forms of SIV challenge will be measured. Through these studies we hope to construct prototype vaccines against SIV which can be translated into vaccines against HIV. The common approaches for construction of recombinant vectors in herpesviruses and the ability to compare recombinants in a common rhesus monkey model provide unifying themes for this program.
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