Comparative Evaluation of Simian,Simian–Human,and Human Immunodeficiency Virus Infections in the Pigtail Macaque ( Macaca nemestrina ) Model

Abstract

The global impact of HIV/AIDS intensifies the need for a preventive vaccine and nonhuman primate models can help provide critical insights into effective immunity. Pigtail macaques (Macaca nemestrina) are increasingly studied as a nonhuman primate model for AIDS. We compared the virologic and immunologic characteristics of HIV-1, SIV, and SHIV infection of naive pigtail macaques across a series of preclinical HIV vaccine studies. SIV_mac251 and SIV_mac239 infection of naive pigtail macaques resulted in a gradual decline in peripheral CD4⁺ T cells in the setting of high levels of viremia, approximating most closely human infection of HIV-1. In contrast, the CXCR4-utilizing SHIV_mn229 virus resulted in rapid depletion of CD4⁺ T cells and minimal generation of humoral or cellular immune responses, similar to that observed with SHIV_89.6P infection of rhesus macaques. Infection with the CCR5-utilizing, rhesus macaque passaged, SHIV_SF162P3 resulted in some overall CD4⁺ T cell decline, however, three of eight macaques naturally control SHIV_SF162P3 viremia to very low levels in the setting of robust adaptive immunity. Despite attempts at infecting pigtail macaques with HIV-1 strains passaged in juvenile pigtail macaques in vivo or in PBMC isolated from pigtail macaquesin vitro, only lower nonsustained levels of viral replication were observed. Our results provide a series of virologic models with which to evaluate potential AIDS vaccines in pigtail macaques.