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Published on: April 22, 2010
Neutralizing antibodies in sera from macaques immunized with attenuated simian immunodeficiency virus
A J Langlois1, R C Desrosiers, M G Lewis
1Department of Surgery, Duke University Medical Center, Durham, North Carolina, USA.
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 SIVmac239Deltanef for 1.5 years or with SIVmac239Delta3 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.
Insights
Neutralizing antibodies against simian immunodeficiency virus (SIV) were detected in cell lines but not in peripheral blood mononuclear cells (PBMC). This suggests neutralizing antibodies may not be the primary mechanism of protection against SIV infection in vivo.
Area of Science:
- Virology
- Immunology
- Infectious Diseases
Background:
- Previous studies showed attenuated simian immunodeficiency virus (SIV) infection in rhesus macaques induces neutralizing antibodies correlating with protection against virulent SIVmac251 challenge.
- These antibodies were detected using the CEMx174 cell line.
- The role of neutralizing antibodies in protection against SIV infection requires further investigation, particularly in relevant cell types.
Purpose of the Study:
- To investigate the presence and activity of neutralizing antibodies against SIV in human and rhesus peripheral blood mononuclear cells (PBMC).
- To compare the neutralization capacity of antibodies against primary SIVmac251 and laboratory-adapted SIVmac251 in different cell types.
- To assess the relevance of neutralizing antibodies as a mechanism of protection in SIV-immunized and challenged animals.
Main Methods:
- Assessed neutralizing antibodies in plasma samples from SIV-infected rhesus macaques.
- Tested neutralization of primary SIVmac251 and laboratory-adapted SIVmac251 in human and rhesus PBMC, and CEMx174 cells.
- Evaluated virus replication and coreceptor usage (CCR5, Bonzo/STRL33, BOB/gpr15) in PBMC.
Main Results:
- Neutralizing antibodies detected in CEMx174 cells were not found in human and rhesus PBMC.
- Primary SIVmac251 neutralization was rarely detected in PBMC, but low-level neutralization occurred in CEMx174 cells.
- Laboratory-adapted SIVmac251 showed potent neutralization in CEMx174 cells but did not replicate in PBMC.
Conclusions:
- Virus passage history and indicator cell choice significantly impact assessments of lentiviral neutralizing antibodies.
- Primary SIVmac251 is less sensitive to neutralization in PBMC compared to established cell lines.
- Results do not support a role for neutralizing antibodies as the primary mechanism of protection in SIV-immunized macaques challenged with primary SIVmac251.
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