Neutralizing Antibodies in Sera from Macaques Immunized with Attenuated Simian Immunodeficiency Virus |
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| Authors: | Alphonse J Langlois Ronald C Desrosiers Mark G Lewis Vineet N KewalRamani Dan R Littman Ji Ying Zhou Kelledy Manson Michael S Wyand Dani P Bolognesi and David C Montefiori |
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| Affiliation: | Department of Surgery, Duke University Medical Center, Durham, North Carolina1.; New England Regional Primate Research Center, Harvard Medical School, Southborough,2. and GTC Mason Laboratories, Worcester,5. Massachusetts; Henry M. Jackson Research Foundation, Rockville, Maryland3.; and Division of Molecular Pathogenesis, Skirball Institute of Biomolecular Medicine, New York University Medical Center, New York, New York4. |
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| Abstract: | Infection with attenuated simian immunodeficiency virus (SIV) in rhesus macaques has been shown to raise antibodies capable of neutralizing an animal challenge stock of primary SIVmac251 in CEMx174 cells that correlate with resistance to infection after experimental challenge with 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, neutralization of primary SIVmac251 in human and rhesus PBMC was rarely detected with plasma samples from a similar group of animals that had been infected either with SIVmac239Δnef for 1.5 years or with SIVmac239Δ3 for 3.2 years, although low-level neutralization was detected in CEMx174 cells. Potent neutralization was detected in CEMx174 cells when the latter plasma samples were assessed with laboratory-adapted SIVmac251. In contrast to primary SIVmac251, laboratory-adapted SIVmac251 did not replicate in human and rhesus PBMC despite its ability to utilize CCR5, Bonzo/STRL33, and BOB/gpr15 as coreceptors for virus entry. These results illustrate the importance of virus passage history and the choice of indicator cells for making assessments of neutralizing antibodies to lentiviruses such as SIV. They also demonstrate that primary SIVmac251 is less sensitive to neutralization in human and rhesus PBMC than it is in established cell lines. Results obtained in PBMC did not support a role for neutralizing antibodies as a mechanism of protection in animals immunized with attenuated SIV and challenged with primary SIVmac251. |
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