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HIV-1 and its simian counterpart SIV have been exquisitely tailored by evolution to evade host immunity. By virtue of specific adaptations that thwart individual innate or adaptive immune mechanisms, and an overall replication strategy that provides for rapid establishment of a large, systemic viral population, capable of dynamic adaptation to almost all immune selection pressures, these viruses, once established, almost invariably stay one step ahead of the host's immune system, and in the vast majority of infected individuals, replicate indefinitely. Although many vaccine approaches tested to date have been able to enhance the magnitude of the immune responses to HIV//SIV infection, most of these responses, whether cellular or humoral, have largely failed to be both effectively antiviral and targeted to prevent the emergence of fully functional escape variants. Recent advances, however, have provided strong evidence that the initial stages of infection following mucosal transmission of these viruses are more vulnerable to immune intervention, and have led to the development of vaccine strategies that elicit responses able to effectively intervene in these early stages of infection, either preventing acquisition of infection or establishing early, stringent, and durable control. Here, we place HIV//AIDS vaccine development in the context of the basic immunobiology of HIV and SIV, review the evidence for their vulnerability to immune responses immediately after mucosal transmission, and discuss how this newly recognized vulnerability might be exploited for the development of an effective HIV//AIDS vaccine. [ABSTRACT FROM AUTHOR]

The development of an HIV vaccine is proving to be an unprecedented challenge. The difficulty in creating this vaccine arises from the enormous genetic variation of the virus and the unusual importance of cytotoxic T lymphocytes (CTL) in controlling its spread. Whereas traditional vaccine strategies are unlikely to confer safe and effective HIV protection, novel strategies for eliciting CTL have provided sub- stantial clinical benefits in nonhuman primate model systems. These vaccine strategies, including plasmid DNA and live recombinant vectors, are cunently being evaluated in human clinical trials. [ABSTRACT FROM AUTHOR]