Programs and Activities Highlights
- Nonhuman Primate Resources Fact Sheet
ORIP revised its fact sheet on Nonhuman Primate Resources. ORIP reviewed the fact sheet for accuracy and added information on two resources: the Biospecimens Query System of the National Primate Research Centers Consortium and the Primate Pathology Image Database. This is one of several fact sheets that serve as valuable resources for potential investigators to learn about ORIP resources and programs.
- Swine Models Fact Sheet
ORIP created a new fact sheet on Swine Models. Swine have become valuable models for cardiovascular diseases, diabetes, heart and lung transplantation, and xenotransplantation. This fact sheet lists valuable ORIP-supported resources and initiatives in a concise and comprehensive manner. This is one of several fact sheets that serve as valuable resources for potential investigators to learn about ORIP resources and programs.
- National Primate Research Centers Directors Biannual Meeting
The National Primate Research Centers (NPRCs) Directors Meeting was held in spring 2024. During this meeting, the Directors and other NPRC staff provided information and updates on their centers. The NPRC Program complements and enables the missions of NIH institutes and centers by providing the animals, facilities, expertise, and resources for nonhuman primate research in specific disease areas.
- 2024 U42 Specific-Pathogen-Free Macaque Colonies Steering Committee Meeting
ORIP scheduled and organized the annual meeting of the U42 Specific-Pathogen-Free (SPF) Macaque Steering Committee held May 8, 2024. Attendees included U42 SPF macaque colony principal investigators, other key people associated with the U42 SPF colonies, and OAR and NIH staff. Information presented during the meeting will help ORIP make future recommendations and budget justifications for new initiatives and programs.
- Rodent Resource Fact Sheet
ORIP revised its fact sheet on rodent resources. ORIP reviewed the fact sheet for accuracy and added artificial intelligence–based mouse genetic discovery as a resource. This fact sheet is one of several fact sheets that serve as valuable resources for potential investigators to learn about ORIP resources and programs.
Read more in the archive.
ORIP-Supported Research Highlights
- Single-Component Multilayered Self-Assembling Protein Nanoparticles Presenting Glycan-Trimmed Uncleaved Prefusion Optimized Envelope Trimers as HIV-1 Vaccine Candidates
Researchers are interested in engineering protein nanoparticles to mimic virus-like particles for an HIV-1 vaccine. In this study, researchers explored a strategy that combines HIV envelope glycoprotein (Env) stabilization, nanoparticle display, and glycan trimming. They designed a panel of constructs for biochemical, biophysical, and structural characterization. Using female mice, female rabbits, and rhesus macaques of both sexes, they demonstrated that glycan trimming increases the frequency of vaccine responders and steers antibody responses away from immunodominant glycan holes and glycan patches. This work offers a potential strategy for overcoming the challenges posed by the Env glycan shield in vaccine development.
- Surgical Protocol for Partial Heart Transplantation in Growing Piglets
Researchers are interested in using partial heart transplantation (i.e., only the part of the heart containing the necessary heart valve is transplanted) to deliver growing heart valve implants. This novel technique allows partial heart transplants to grow, similar to the valves in heart transplants. More work is needed, however, to understand the underlying biological mechanisms of this approach and achieve progress in clinical care. In the current study, the authors present a surgical protocol for partial heart transplantation in growing piglets (sex not specified). This model will enable other researchers to seek fundamental knowledge about the nature of partial heart transplants.
- CD8+ T Cell Targeting of Tumor Antigens Presented by HLA-E
Researchers have hypothesized that human leukocyte antigen-E (HLA-E)–positive cancer cells could be targeted by HLA-E–restricted CD8+ T cells. In this study, the authors assessed whether major histocompatibility complex E (MHC-E) expression by cancer cells can be targeted for MHC-E–restricted T-cell control. Using male rhesus macaques, they found that a cytomegalovirus can be used as a vector to generate specific immune cells that can target cancer cells. The authors conclude that targeting HLA-E with restricted specific CD8+ T cells could offer a new approach for immunotherapy of prostate cancer. Overall, this study supports the concept of a cancer vaccine.
- Potent Antibody-Dependent Cellular Cytotoxicity of a V2-Specific Antibody Is Not Sufficient for Protection of Macaques Against SIV Challenge
Antibody-dependent cellular cytotoxicity (ADCC) has been correlated with decreased risk of HIV acquisition. Researchers tested the ability of PGT145, an antibody that neutralizes genetically diverse HIV-1 isolates, to protect male and female rhesus macaques against simian immunodeficiency virus (SIV) via ADCC activity. They found that a single amino acid substitution in the V2 core epitope of the SIV envelope increases PGT145 binding and confers sensitivity to neutralization. Peak and chronic phase viral loads were lower, and time to peak viremia was delayed. They concluded that ADCC is insufficient for protection by this antibody, but increasing the affinity of antibody binding could confer partial protection.
- Consistent Survival in Consecutive Cases of Life-Supporting Porcine Kidney Xenotransplantation Using 10GE Source Pigs
Xenotransplantation offers potential for addressing organ donor shortages, and the U.S. Food and Drug Administration recently issued guidance on a regulatory path forward. Researchers have performed studies in this area, but concerns have been expressed about safe clinical translation of their results (e.g., survival, preclinical procurement, immunosuppression, clinical standards of care). In this study, the authors report consistent survival in consecutive cases of kidney xenotransplantation from pigs (male and female) to baboons (male and female). The authors propose that their findings serve as proof of concept for prevention of xenograft rejection in recipients of genetically modified porcine kidneys. This work offers insights for immunosuppression regimens for first-in-human clinical trials.
Read more in the archive.
