Live, attenuated SIV vaccines have elicited the best protective immunity against SIV challenge of the available vaccines against SIV. This may be due to the continued expression of viral proteins from the persisting viral genome in the infected monkeys, the expression of all the SIV proteins from endogenous pathways, or other aspects of the immune response to the live, attenuated virus. Because of the safety concerns about the potential use of a live, attenuated vaccine against HIV, it is important to determine the critical mechanisms for induction of protective immunity against SIV. In this application we propose to, first, test whether effective protective immunity can be induced against SIV by the use of herpesvirus vectors that can persist in the host. Second, we will determine whether replication is necessary for induction of immunity against SIV by using replication-defective herpesvirus vectors as compared with replication-competent viruses. In addition, replication-defective SIV strains will be constructed to determine if this form of mutant virus will induce effective immunity against SIV. Finally, we will determine whether expression of all the SIV proteins through endogenous pathways is needed for protective immunity. We will construct herpesvirus vectors that express SIV gp120 or gp120 plus gag proteins to determine whether expression of SIV proteins in addition to envelope protein lead to a more effective immune response protecting against SIV infection.
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