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Our earlier reports demonstrated that Cynomolgus macaques vaccinated with either inactivated partially purified simian immunodeficiency virus (SIV), fixed SIV-infected C8166 (a human T lymphoblastoid cell line) cells, or fixed uninfected C8166 cells can be protected against a challenge infection with the 32H isolate of SIVmac 251 (grown in C8166) (Stott, E. J., W. L. Chan, K. H. G. Mills, M. Page, F. Taffs, M. Cranage, P. Greenway, and P. Kitchin. 1990. Lancet. 336:1538; Stott, E. J., P. A. Kitchin, M. Page, B. Flanagan, L. F. Taffs, W. L. Chan, K. H. G. Mills, P. Silvera, and A. Rodgers. 1991. Nature [Lond.]. 353:393). Protection is correlated with the levels of antibody response to cellular antigens in the human cells from which the virus immunogen was grown. However, the mechanism of protection is unclear. We report here the analysis of sera from these protected monkeys and demonstrate that there is positive correlation of protection with antibody response to the HLA class I molecule.