PROTECTION FROM PATHOGENIC SIVMAC CHALLENGE FOLLOWING SHORT-TERM INFECTION WITH A NEF-DEFICIENT ATTENUATED VIRUS

Infection of rhesus macaques with attenuated SIVmac is, at present, th e only strategy which confers significant protection from challenge wi th wild-type SIVmac grown in monkey PBMC. However, initial results sug gest that the protective mechanism does not develop until late after ' 'vaccination'' (approx 10 months). As part of a European study using t he C8 variant of SIVmac(251-32H) (containing an in-frame 12-bp deletio n in the nef gene), we wished to determine (a) if protection could be achieved against challenge with a ''swarm'' of SIVmac(251-32H) produce d in monkey cells and (b) if protection could be demonstrated after a short period of infection with the attenuated virus. Eight Indian rhes us macaques were infected with C8 and four were challenged after 10 we eks with 50 MID(50) of an uncloned stock of SIVmac(251-32H) grown in r hesus cells, and the other four were challenged after 20 weeks. Four a nimals served as naive controls. Three of the four monkeys challenged at 10 weeks and three of those challenged at 20 weeks were protected f rom productive superinfection. From one monkey in each group it was, h owever, possible to demonstrate the presence of the wild-type provirus in monkey PBMC by diagnostic PCR and anamnestic immune response. Ther e was no apparent correlation between the levels of binding or neutral izing antibodies on the day of challenge and subsequent protection. Ap proximately 1 year after infection with the attenuated virus all monke ys were rechallenged with the heterologous SIVsm strain, first with 10 -20 MID(50) and then with 1000 MID(50). Although not all of the SIVsm- inoculated naive controls became productively infected, PCR analysis f ailed to reveal any evidence for infection of the ''immunized'' monkey s. (C) 1996 Academic Press, Inc.