Assay/Measuring HIV-1 and SIV Antibody Neutralization

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DESCRIPTION (provided by applicant): Recent strides in HIV-1 vaccine research have begun to define the roles of cellular and humoral immune responses and have renewed optimism that an effective prophylactic vaccine can be developed (Ho and Huang, 2002). It is anticipated that several vaccine candidates will be ready for large-scale evaluations in humans in the near future (2-5 years). In all likelihood, the development of a highly efficacious vaccine will be an iterative process in which lessons learned from early vaccine trials improve future generation vaccines. The evaluation of early candidates should help further clarify the protective roles of humoral (B-cell antibody) and cellular (cytotoxic T-cell) immune responses, and possibly identify other critical surrogate markers of protection. Once gleaned, this information can be directed toward the development of more potent and directed immunogens and delivery systems. At present, the HIV vaccine field is inadequately equipped to conduct the comprehensive analyses necessary to support ongoing and future vaccine efforts. In general, assays currently available to evaluate HIV-specific immune responses were developed for small research investigations and are not suited for the high volume sample testing necessary to support high throughput screening of potential immunogens, or large clinical efficacy trials. Such studies will require rapid, sensitive, and reliable assays with high-throughput testing capability. Furthermore, such systems must be amenable to pre-clinical investigations conducted in primate model systems, i.e. SIV/macaque. Recently, ViroLogic developed a novel cell-based infectivity assay that is capable of three distinct applications, (a) measuring the susceptibility of HIV-1 to entry inhibitor drugs, (b) determining co-receptor tropism and (c) detecting antibody neutralization. This SBIR-AT phase I proposal is focused on the further development of the antibody neutralization application. We intend to expand and enhance the capability of the neutralization assay, compile a large diverse specimen library comprised of functional HIV-1 envelope genes, and establish standard virus panels for the routine characterization of antibody responses.