Programs and Activities Highlights
- Site Visit to Emory National Primate Research Center
The ORIP and DPCPSI Directors participated in a site visit to the Emory National Primate Research Center (ENPRC) in March 2024. They viewed the facilities and procedures at ENPRC to improve communications, understanding, and trust between partners. They also reinforced the team approach between ENPRC and NIH to addressing challenges.
- Notice of Extension of the Expiration Date for PAR-21-167: Development of Animal Models and Related Biological Materials for Research (R21 Clinical Trial Not Allowed)
The purpose of this notice is to extend the expiration date for PAR-21-167, Development of Animal Models and Related Biological Materials for Research (R21 Clinical Trial Not Allowed). With the addition/extension by two application due dates, PAR-21-167 now expires on January 8, 2025. NIH standard due dates are applied to this notice.
- Discussion Regarding Conventional Nonhuman Primates
ORIP convened a meeting among the California National Primate Research Center (CNPRC), Biomedical Advanced Research and Development Authority, Centers for Disease Control and Prevention, U.S. Department of Defense, U.S. Food and Drug Administration, and NIH collaborators in February 2024 to discuss CNPRC's availability of conventional NHPs for biomedical research.
- Limited Competition: Specific-Pathogen-Free Macaque Colonies to Support HIV/AIDS Research (U42 Clinical Trial Not Allowed); PAR-24-129
The purpose of this notice of funding opportunity is to provide continuing support for specific-pathogen-free (SPF) macaque colonies previously funded under the auspices of PAR-21-089 and PAR-18-669 that support HIV research. Breeding colonies are essential to sustain appropriate SPF macaques for research related to HIV. Pedigree SPF macaques are free of certain viruses, which may confound the results of HIV-related investigations or present a risk to the personnel who care for the animals. The SPF macaques are genetically characterized for major histocompatibility complex class I types, which have large effects on macaque immune responses to simian immunodeficiency virus.
- Sex as a Biological Variable Policy for Studies Using Nonhuman Primates in Neuroscience Research
The NIH Office of Research on Women’s Health developed the NIH Policy on Sex as a Biological Variable (SABV), which builds on the importance of sex in biology, health, and disease, as well as the need for research to consider sex to be relevant for all people. In January 2024, NIH convened a virtual workshop to provide the neuroscience research community an opportunity to discuss challenges and potential solutions for applying the SABV policy fairly and consistently to nonhuman primate (NHP) studies. An ORIP staff member presented at the workshop as an invited panelist to provide ORIP's perspective on the NHP shortage, best utilization of existing resources, and issues regarding NHP use in neuroscience research.
Read more in the archive.
ORIP-Supported Research Highlights
- Pigs in Transplantation Research and Their Potential as Sources of Organs in Clinical Xenotransplantation
The pig has now gained importance as a potential source of organs for clinical xenotransplantation. When an organ from a wild-type (i.e., genetically unmodified) pig is transplanted into an immunosuppressed nonhuman primate, a vigorous host immune response causes hyperacute rejection (within minutes or hours). This response has been largely overcome by (1) extensive gene editing of the organ-source pig and (2) the administration to the recipient of novel immunosuppressive therapy based on blockade of the CD40/CD154 T-cell costimulation pathway. The combination of gene editing and novel immunosuppressive therapy has extended life-supporting pig kidney graft survival to greater than 1 year and of pig heart survival to up to 9 months. This review briefly describes the techniques of gene editing, the potential risks of transfer of porcine endogenous retroviruses with the organ, and the need for breeding and housing of donor pigs under biosecure conditions.
- Trade-Offs Shaping Transmission of Sylvatic Dengue and Zika Viruses in Monkey Hosts
Mosquito-borne dengue (DENV) and Zika (ZIKV) viruses originated in Old World sylvatic (forest) cycles involving monkeys and canopy-living Aedes mosquitoes. Both viruses spilled over into human transmission and were translocated to the Americas, opening a path for spillback into neotropical sylvatic cycles. This article reports that the trade-offs that shape within-host dynamics and transmission of these viruses are lacking, hampering efforts to predict spillover and spillback. The data revealed evidence of an immunologically mediated trade‑off between duration and magnitude of virus replication, as higher-peak ZIKV titers are associated with shorter durations of viremia, and higher natural killer cell levels are associated with lower peak ZIKV titers and lower anti-DENV-2 antibody levels. Furthermore, patterns of transmission of each virus from a neotropical monkey suggest that ZIKV has greater potential than DENV-2 to establish a sylvatic transmission cycle in the Americas.
- TGF-Β Blockade Drives a Transitional Effector Phenotype in T Cells Reversing SIV Latency and Decreasing SIV Reservoirs In Vivo
Interruption of antiretroviral therapy leads to rapid rebound of viremia due to the establishment of a persistent viral reservoir early after infection. Using a treatment regimen similar to the one tested in clinical trials, the authors show how galunisertib affects immune cell function, increases simian immunodeficiency virus (SIV) reactivation, and reduces the viral reservoir in female rhesus macaques. Their findings reveal a galunisertib-driven shift toward an effector phenotype in T and natural killer cells. Taken together, this work demonstrates that galunisertib, a clinical-stage TGF-β inhibitor, reverses SIV latency and decreases SIV reservoirs by driving T cells toward an effector phenotype, enhancing immune responses in vivo in the absence of toxicity.
- Lymphoid Tissues Contribute to Plasma Viral Clonotypes Early After Antiretroviral Therapy Interruption in SIV-Infected Rhesus Macaques
Researchers are interested in better understanding the sources, timing, and mechanisms of HIV rebound that occurs after interruption of antiretroviral therapy (ART). Using rhesus macaques (sex not specified), investigators tracked barcoded simian immunodeficiency virus (SIV) clonotypes over time and among tissues. Among the tissues studied, mesenteric lymph nodes, inguinal lymph nodes, and spleen contained viral barcodes detected in plasma. Additionally, the authors reported that CD4+ T cells harbored the most viral RNA after ART interruption. These tissues are likely to contribute to viral reactivation and rebound after ART interruption, but further studies are needed to evaluate the relative potential contributions from other tissues and organs.
- IL-21-IgFc Immunotherapy Alters Transcriptional Landscape of Lymph Node Cells Leading to Enhanced Flu Vaccine Response in Aging and SIV Infection
Aging is associated with increased risk of seasonal flu disease burden and serious flu-related complications, particularly for people with HIV. In this study, investigators aimed to elucidate the immunomodulation following flu vaccination in aging male and female rhesus macaques infected with simian immunodeficiency virus (SIV). Their results suggest that IL-21 treatment at the time of flu vaccination modulates the inductive lymph node germinal center activity to reverse SIV-associated immune dysfunction. The authors identified IL-21 as a potential candidate molecule for immunotherapy to enhance flu vaccine responses in affected populations. Further studies could examine the overall benefit of IL-21 immunotherapy on mucosal lung immunity and protection against infection.
Read more in the archive.
