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188 Whole-Killed-Particle Vaccines in SIV Model Systems
L. E. Henderson*, E. Chertova, R. C. Sowder II, J. W. Bess, Jr., J. Lifson, and L. O. Arthur
AIDS Vaccine Program, SAIC Frederick, MD, USA
Mild oxidizing agents such as Aldrithiol-2 (AT-2) inactivate infectious retroviruses by oxidizing core proteins and without concomitant modification of surface envelope proteins. Noninfectious virion particles prepared by this methodology still retain native and functional surface proteins, including gp120, TM, and HLA class I and class II. Methods have been developed to analyze the amount and composition of functional surface proteins on virion particles. In collaborations with Dr. J. Hoxie (for SIV Mac) and Dr. R. Benveniste (for SIV Mne), strains of SIVs have been identified that incorporate "high" (6(12 gag proteins per gp120) and "low" (50(60 gag proteins per gp120) amounts of env proteins. These strains can be produced from cells that are either plus or minus for HLA II and inactivated by the action of AT-2. Thus, it is now possible to prepare and analyze noninfectious whole-killed-particles of SIV with defined amounts and compositions of native surface proteins. These highly defined whole-killed-particles can be used as immunogens and tested in the appropriate macaque model for their ability to elicit protective immunological responses against pathogenic strains of SIV. Initial studies have shown that whole-killed-particles of SIV Mne (E11S) (a strain with high levels of gp120) can elicit a protective response against a homologous challenge. To extend these studies, rhesus macaques have been immunized with whole-killed-particles prepared from a strain of SIV Mac (donated by J. Hoxie) that retains high amounts of gp120. The immunization protocol includes animals injected with the immunogen alone in buffered saline and others where the site of injection is prepared by a CpG adjuvant before injection of the immunogen. These animals will be challenged with a pathogenic SIV Mac and the results will be presented. A rational plan to explore and test variables in the design vaccines utilizing the highly defined whole-killed-particles will be discussed.
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