Nonhuman primate models for the evaluation of HIV-1 preventive vaccine strategies

Abstract

Purpose of review Nonhuman primate (NHP) models of AIDS are powerful systems for evaluating HIV vaccine approaches in vivo. Authentic features of HIV-1 transmission, dissemination, target cell tropism, and pathogenesis, and aspects of anti-HIV-1 immune responses, can be recapitulated in NHPs provided the appropriate specific model parameters are considered. Here, we discuss key model parameter options and their implications for HIV-1 vaccine evaluation. Recent findings With the availability of several different NHP host species/subspecies, different challenge viruses and challenge stock production methods, and various challenge routes and schema, multiple NHP models of AIDS exist for HIV vaccine evaluation. The recent development of multiple new challenge viruses, including chimeric simian-human immunodeficiency viruses (SHIVs) and simian immunodeficiency virus (SIV) clones, improved characterization of challenge stocks and production methods, and increased insight into specific challenge parameters have resulted in an increase in the number of available models and a better understanding of the implications of specific study design choices. Summary Recent progress and technical developments promise new insights into basic disease mechanisms and improved models for better preclinical evaluation of interventions to prevent HIV transmission.

Treatment with native heterodimeric IL-15 increases cytotoxic lymphocytes and reduces SHIV RNA in lymph nodes

“…HIV infection in humans and SIV/SHIV infection in macaques lead to the establishment of long-term viral reservoirs able to persist despite antiretroviral therapy (ART) and give rise to recrudescent infection when treatment is interrupted. Although long-lived latently infected CD4 + T cells have been identified as an important contributor to this viral reservoir, it has also been shown, in both HIV infected humans and SIV infected macaques, that cells actively producing virus can persist in privileged anatomic locations including B cell follicles within secondary lymphoid tissues [ 35 – 44 ]. Similar to HIV infected elite controllers, macaques infected with SIV that suppress viremia to low or undetectable levels continue to harbor virus infected cells within the follicles [ 41 , 42 ].…”

Derivation of simian tropic HIV-1 infectious clone reveals virus adaptation to a new host

“…This is in part because HIV-1 is highly specific for humans and does not generally infect or cause disease in other species. Thus, far, infection of macaques with simian immunodeficiency viruses (SIV) or SHIVs (SIV expressing HIV-1 Env proteins) have been the most widely used models for AIDS research and have yielded important advances; for example, in vaccine evaluation (1). Nevertheless, differences between HIV-1 and SIVs in immunologic and drug targets limit the utility of these models.…”

What Is the Predictive Value of Animal Models for Vaccine Efficacy in Humans?

“…In these studies, NHPs were infected via systemic (intravenous) or mucosal (intravaginal, intrarectal) routes with either a single high-dose challenge or by repeat administration of small doses (for mucosal challenge). The level of virus replication and disease outcome varied significantly (Sharma et al 2015;Del Prete et al 2016;Lopker et al 2016).…”