NEUTRALIZING ANTIBODIES IN SERA FROM MACAQUES IMMUNIZED WITH ATTENUATED SIMIAN IMMUNODEFICIENCY VIRUS

Infection with attenuated simian immunodeficiency virus (SIV) in rhesu s macaques has been shown to raise antibodies capable of neutralizing an animal challenge stock of primary SIVmac251 in CEMx174 cells that c orrelate with resistance to infection after experimental challenge wit h this virulent virus (M. S.Wyand, K. H. Manson, M. Garcia-Moll, D. C. Montefiori, and R. C. Desrosiers, J. Virol. 70:3724-3733, 1996). Here we show that these neutralizing antibodies are not detected in human and rhesus peripheral blood mononuclear cells (PBMC), In addition, neu tralization of primary SIVmac251 in human and rhesus PBMC was rarely d etected with plasma samples from a similar group of animals that had b een infected either with SIVmac239 Delta nef for 1.5 years or with SIV mac239 Delta 3 for 3.2 years, although low-level neutralization was de tected in CEMx174 cells. Potent neutralization was detected in CEMx174 cells when the latter plasma samples were assessed with laboratory-ad apted SIVmac251. In contrast to primary SIVmac251, laboratory-adapted SIVmac251 did not replicate in human and rhesus PBMC despite its abili ty to utilize CCR5, Bonzo/STRL33, and BOB/gpr15 as coreceptors for vir us entry. These results illustrate the importance of virus passage his tory and the choice of indicator cells for making assessments of neutr alizing antibodies to lentiviruses such as SIV. They also demonstrate that primary SIVmac251 is less sensitive to neutralization in human an d rhesus PBMC than it is in established cell lines, Results obtained i n PBMC did not support a role for neutralizing antibodies as a mechani sm of protection in animals immunized with attenuated SIV and challeng ed with primary SIVmac251.