Nonhuman Primate Models for HIV/AIDS Vaccine Development

Abstract

The development of HIV vaccines has been hampered by the lack of an animal model that can accurately predict vaccine efficacy. Chimpanzees can be infected with HIV-1 but are not practical for research. However, several species of macaques are susceptible to the Simian Immunodeficiency Viruses (SIV) that causes a disease in macaques that closely mimics HIV in humans. Thus, macaque-SIV models of HIV infection have become a critical foundation for AIDS vaccine development. Here, we examine the multiple variables and considerations that must be taken into account to use this NHP model effectively. These include the species and subspecies of macaques, virus strain, dose and route of administration and macaque genetics including Major Histocompatibility Complex molecules that affect immune responses and other virus restriction factors. We illustrate how these NHP models can be used to carry out studies of immune responses in mucosal and other tissues than could not easily be performed on human volunteers. Futhermore macaques are an ideal model system to optimize adjuvants, test vaccine platforms, and identify correlates of protection that can advance the HIV vaccine field. We also illustrate techniques used to identify different macaque lymphocyte populations and review some poxvirus vaccine candidates that are in various stages of clinical trials. Understanding how to effectively use this valuable model will greatly increase the likelihood of finding a successful vaccine for HIV.

Adjuvanting a Simian Immunodeficiency Virus Vaccine with Toll-Like Receptor Ligands Encapsulated in Nanoparticles Induces Persistent Antibody Responses and Enhanced Protection in TRIM5α Restrictive Macaques

“…Animals carrying either restrictive or permissive TRIM5␣ alleles were equally distributed in the treatment groups used in the study, as shown in Table S1. Mamu-A*001 ϩ , Mamu-B*008 Ϫ , and Mamu-B*017 Ϫ animals were also equally distributed among the treatment groups, even though these alleles have not previously been associated with resistance to the acquisition of the SIVsmE660 strain (30). The presence of restrictive TRIM5␣ alleles was not associated with protection in unvaccinated animals (Fig.…”

“…Env-specific IgG-, IgA-, and IgM-secreting B cells in wells from an ELISPOT assay plate for animals immunized with protein-NP at days 0, 4, and 7 after the first boost immunization in the study are shown. immunity induced by vaccinations, the animals were intravaginally challenged with repeated exposures to low doses of a heterologous SIVsmE660 swarm (30)(31)(32). RMs were challenged once weekly for up to 12 exposures with SIVsmE660 (20,000 50% tissue culture infective doses [TCID 50 ] or 0.5 to 1 50% animal infective doses [AID 50 ]).…”

“…Survival curves were compared using a log-rank (Mantel-Cox) test, and a P value of Ͻ0.05 was considered significant. (30,32). Animals carrying either restrictive or permissive TRIM5␣ alleles were equally distributed in the treatment groups used in the study, as shown in Table S1.…”

High‐resolution quantitative proteome analysis reveals substantial differences between phagosomes of RAW 264.7 and bone marrow derived macrophages

“…1A). Moreover, we performed fluorogenic assays to measure pH, proteolysis, and oxidative capacity of phagosomes in real time 17, 18, 19 and identified a significant faster phagosome acidification in BMDMs (Fig. 1B), which is possibly due to the faster phagocytosis compared to RAW 264.7 cells.…”

SIVmac Infection of Macaques, Immunopathogenesis of

“…Similar to the SIVmac lineage discovery at the NEPRC, another lineage called SIVb670/H4/H9 group was isolated after unintended transmission of the virus from sooty mangabeys to rhesus macaques in a leprosy-related experiment at the Tulane National Primate Research Center (TNPRC) (Voevodin and Marx 2009). This group of viruses includes SIVsmE660 that is moderately sensitive to neutralization, in contrast to the highly neutralization-resistant SIVmac239 clone (Voevodin and Marx 2009;Pancino et al 2011;Sui et al 2013). …”