INDUCTION OF VIGOROUS CYTOTOXIC T-LYMPHOCYTE RESPONSES BY LIVE ATTENUATED SIMIAN IMMUNODEFICIENCY VIRUS

Although live attenuated vaccine strains of simian immunodeficiency vi rus (Sn) have proven highly effective in protecting macaques against c hallenge with pathogenic SIV strains, little is known about the mechan isms of protective immunity induced by these vaccines, We examined cyt otoxic T-lymphocyte (CTL) responses against SIV in animals infected wi th SIVmac239 Delta nef (deficient in nef) or STVmac239 Delta 3 (defici ent in nef, vpr, and upstream sequences in U3), To enhance detection o f SN-specific CTL activity, we stimulated peripheral blood mononuclear cells with autologous B-lymphoblastoid cell lines which had been infe cted with recombinant vaccinia viruses expressing SIV proteins and sub sequently inactivated with psoralen and UV light. Animals chronically infected with SIV239 Delta nef or SN239 Delta 3 mounted vigorous CTL r esponses against the SIV Gag and Env proteins, This CTL activity was m ajor histocompatibility class restricted and mediated by CD8(+) T lymp hocytes, CTL responses persisted at relatively high levels for more th an 6 Sears after infection, Limiting dilution precursor frequency assa ys demonstrated that the frequency of SN-specific CTLs was as high as 234 CTL precursors per 100,000 cells, Animals acutely infected with SN 239 Delta nef developed CTL activity by day 14 after infection, coinci dent with decreases in viral load, Animals acutely infected with SIV23 9 Delta 3 developed CTL responses within 4 weeks of infection, Thus, v accination of juvenile or adult animals with SN239 Delta nef or SN239 Delta 3 results in the induction of a vigorous CTL response which aris es early in the course of infection and persists for gears after a sin gle inoculation of virus.