IN-VIVO RESISTANCE TO SIMIAN IMMUNODEFICIENCY VIRUS SUPERINFECTION DEPENDS ON ATTENUATED VIRUS DOSE

Infection of macaques with attenuated simian immunodeficiency virus (S IV) induces potent superinfection resistance that may be applicable to the development of an AIDS vaccine but little information exists conc erning the conditions necessary for the induction of this vaccine effe ct. We report that only a high dose of attenuated SIVmac protected mac aques against intravenous challenge with more virulent virus 15 weeks after primary infection. Three of four animals given 2000-20 000 TCID5 0 of SIVmacC8, a molecular clone of SIVmac251(32H) with a 12 bp deleti on in the nef gene, essentially resisted superinfection with uncloned SIVmac, In two animals challenge virus was never detected by PCR and i n one animal challenge virus was detected on one occasion only. Althou gh animals given 2-200 TCID50 of attenuated virus were superinfected t hey were spared from the loss of CD4 cells seen in infected naive cont rols, Protection from superinfection did not correlate with immune res ponses, including the levels of virus-specific antibodies or virus-neu tralizing activity measured on the day of challenge; although, after s uperinfection challenge, Nef-specific CTL responses were detected only in animals infected with high doses of attenuated SIV, Unexpectedly, cell-associated virus loads 2 weeks after inoculation were significant ly lower in animals infected with a high dose of attenuated SIV compar ed to those in animals infected with a low dose. Our results suggest t hat the early dynamics of infection with attenuated virus influence su perinfection resistance.