LIVE ATTENUATED SIMIAN IMMUNODEFICIENCY VIRUS PREVENTS SUPERINFECTIONBY CLONED SIVMAC251 IN CYNOMOLGUS MONKEYS

The ability of a live attenuated simian immunodeficiency virus (SIV) t o protect against challenge with cloned SIVmac251/BK28 was evaluated i n four cynomolgus macaques. The intravenous infection of the C8 varian t of the SIVmac251/32H vi rus, carrying an in-frame 12 bp deletion in the nef gene, did not affect the CD4(+) and CD8(+) cell counts, and a persistent infection associated with an extremely low virus burden in peripheral blood mononuclear cells (PBMCs) was established, After 40 w eeks, these monkeys were challenged intravenously with a 50 MID50 dose of SIVmac251/BK28 virus grown on macaque cells, Four naive monkeys we re infected as controls, Monkeys were monitored for 62 weeks following challenge, Attempts to rescue virus from either PBMCs or bone marrow from the C8-vaccinated monkeys were unsuccessful, but in two cases vir us was re-isolated from lymph node cells, The presence of the SIV prov irus with the C8 variant genotype maintaining its original nef deletio n was shown by differential PCR in PBMCs, lymph nodes and bone marrow, Furthermore, in contrast to the control monkeys, the vaccinated monke ys showed normal levels for CD4(+) and CD8(+) cells, minimal lymphoid hyperplasia and no clinical signs of infection, Our results confirm th at vaccination with live attenuated virus can confer protection. This appears to be dependent on the ability of the CS variant to establish a persistent but attenuated infection which is necessary for inducing an immune response, as suggested by the persistence of a strong immune B cell memory and by the over-expression of interleukin (IL)-2, inter feron-gamma and IL-15 mRNAs in PBMCs of CS-vaccinated monkeys but not in those of control monkeys.