Selected Grantee Publications
- Clear All
- 5 results found
- Vaccines/Therapeutics
- Imaging
- 2021
Dynamics and Origin of Rebound Viremia in SHIV-Infected Infant Macaques Following Interruption of Long-Term ART
Obregon-Perko et al., JCI Insight. 2021.
https://pubmed.ncbi.nlm.nih.gov/34699383/
Animal models that recapitulate human COVID-19 disease are critical for understanding SARS-CoV-2 viral and immune dynamics, mechanisms of disease, and testing of vaccines and therapeutics. A group of male pigtail macaques (PTMs) were euthanized either 6- or 21-days after SARS-CoV-2 viral challenge and demonstrated mild-to-moderate COVID-19 disease. Pulmonary infiltrates were dominated by T cells, virus-targeting T cells were predominantly CD4+, increases in circulating inflammatory and coagulation markers, pulmonary pathologic lesions, and the development of neutralizing antibodies were observed. Collectively, the data suggests PTMs are a valuable model to study COVID-19 pathogenesis and may be useful for testing vaccines and therapeutics. Supported by ORIP (P51OD011104) and NIAID.
Innate Immunity Stimulation via CpG Oligodeoxynucleotides Ameliorates Alzheimer’s Disease Pathology in Aged Squirrel Monkeys
Patel et al., Brain: A Journal of Neurology. 2021.
https://pubmed.ncbi.nlm.nih.gov/34128045/
Alzheimer's disease is the only illness among the top 10 causes of death for which there is no disease-modifying therapy. The authors have shown in transgenic Alzheimer's disease mouse models that harnessing innate immunity via TLR9 agonist CpG oligodeoxynucleotides (ODNs) modulates age-related defects associated with immune cells and safely reduces amyloid plaques, oligomeric amyloid-β, tau pathology, and cerebral amyloid angiopathy (CAA). They used a nonhuman primate model for sporadic Alzheimer's disease pathology that develops extensive CAA-elderly squirrel monkeys. They demonstrate that long-term use of Class B CpG ODN 2006 induces a favorable degree of innate immunity stimulation. CpG ODN 2006 has been well established in numerous human trials for a variety of diseases. This evidence together with their earlier research validates the beneficial therapeutic outcomes and safety of this innovative immunomodulatory approach. Supported by ORIP (P40OD010938), NINDS, NIA, and NCI.
Neutralizing Antibody Vaccine for Pandemic and Pre-Emergent Coronaviruses
Saunders et al., Nature. 2021.
https://doi.org/10.1038/s41586-021-03594-0
SARS-CoV-2 is a new member of the betacoronavirus (beta-CoV) genus, which also includes two common mild beta-CoVs and the life-threatening SARS-CoV-1 and MERS-CoV. Vaccines that elicit protective immunity against SARS-CoV-2 and beta-CoVs that circulate in animals could prevent future pandemics. Researchers designed a novel 24-mer SARS-CoV-2 receptor binding domain-sortase A conjugated nanoparticle vaccine (RBD-scNP). Investigators demonstrated that the immunization of macaques with RBD-scNP, and adjuvanted with 3M-052 and alum, elicits cross-neutralizing antibody responses against bat coronaviruses, SARS-CoV, and multiple SARS-CoV-2 variants of concern. This pioneering approach serves as a multimeric protein platform for the further development of generalized anti-beta-CoV vaccines. Supported by ORIP (U42OD021458), NIAID, and NCI.
A Pulsatile Release Platform Based on Photo-Induced Imine-Crosslinking Hydrogel Promotes Scarless Wound Healing
Zhang et al., Nature Communications. 2021.
https://pubmed.ncbi.nlm.nih.gov/33723267/
Skin wound healing is a dynamic and interactive process involving the collaborative efforts of growth factors, extracellular matrix (ECM), and different tissue and cell lineages. Although accumulating studies with a range of different model systems have increased our understanding of the cellular and molecular basis underlying skin scar formation, they have not been effectively translated to therapy. Development of effective therapeutic approaches for skin scar management is urgently needed. In this study, team of investigators devise a water-oil-water double emulsion strategy to encapsulate proteins within a photo-crosslinkable poly-lactic-co-glycolic acid (PLGA) shell, which can produce microcapsules with pulsatile drug release kinetics after administration. The results show that pulsatile release of the TGF-β inhibitor can accelerate skin wound closure while suppressing scarring in murine skin wounds and large animal preclinical models, suggesting that it could be an effective approach to achieve scarless wound healing in skin. Supported by ORIP (R01OD023700).
Acoustofluidic Rotational Tweezing Enables High-Speed Contactless Morphological Phenotyping of Zebrafish Larvae
Chen et al., Nature Communications. 2021.
https://pubmed.ncbi.nlm.nih.gov/33602914/
These authors demonstrate an acoustofluidic rotational tweezing platform that enables contactless, high-speed, 3D multispectral imaging and digital reconstruction of zebrafish larvae for quantitative phenotypic analysis. The acoustic-induced polarized vortex streaming achieves contactless and rapid (~1 s/rotation) rotation of zebrafish larvae enabling multispectral imaging of the zebrafish body and internal organs. They developed a 3D reconstruction pipeline that yields accurate 3D models based on the multi-view images for quantitative evaluation. With its contactless nature and advantages in speed and automation, the acoustofluidic rotational tweezing system has the potential to be a valuable asset for developmental biology and pre-clinical drug development in pharmacology. Supported by ORIP (R43OD024963), NCI, and NIGMS.