Neutralizing antibodies in sera from macaques immunized with attenuated simian immunodeficiency virus

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.