Selected Grantee Publications
- Clear All
- 295 results found
- Down Syndrome
- Immunology
Antimicrobial Prophylaxis Does Not Improve Post-Surgical Outcomes in SIV/SHIV–Uninfected or SIV/SHIV–Infected Macaques (Macaca mulatta and Macaca fascicularis) Based on a Retrospective Analysis
Moats et al., PLOS One. 2022.
https://www.doi.org/10.1371/journal.pone.0266616
Some institutions routinely administer antimicrobial prophylaxis to nonhuman primates prior to surgery to prevent surgical site infections. In this study, the investigators assessed the influence of antimicrobial prophylaxis on complication rates in macaques of both sexes receiving peripheral lymph node (PLN) and laparoscopic biopsies. After PLN biopsies, no significant differences were observed between animals that received antimicrobial prophylaxis and those that did not. After laparoscopic biopsies, complication rates were greater in animals that received antimicrobial prophylaxis. Because of these findings, the authors recommend eliminating the use of unnecessary antibiotics in research animals. Supported by ORIP (U42OD023038, P51OD011092).
Early Post-Vaccination Gene Signatures Correlate With the Magnitude and Function of Vaccine-Induced HIV Envelope–Specific Plasma Antibodies in Infant Rhesus Macaques
Vijayan et al., Frontiers in Immunology. 2022.
https://www.doi.org/10.3389/fimmu.2022.840976
An effective vaccine is needed to reduce HIV infections, particularly among younger people. The initiation of an HIV vaccine regimen in early life could allow the development of mature HIV‑specific antibody responses that protect against infection. The investigators compared the effects of two vaccine regimens in infant rhesus macaques (sex not specified). Both vaccines induced a rapid innate response, indicated by elevated inflammatory plasma cytokines and altered gene expression. By performing a network analysis, the investigators identified differentially expressed genes associated with B cell activation. These findings suggest that vaccine-induced immunity can be optimized by modulating specific antibody and T cell responses. Supported by ORIP (P51OD011107), NCI, NIAID, and NIDCR.
Obesity Alters Pathology and Treatment Response in Inflammatory Disease
Bapat et al., Nature. 2022.
https://www.doi.org/10.1038/s41586-022-04536-0
Obesity and metabolic disease have been shown to affect immunotherapeutic outcomes. By studying classical type 2 T helper cells (TH2) in lean and obese male mouse models for atopic dermatitis, investigators found that the biologic therapies protected lean mice but exacerbated disease in obese mice. RNA sequencing and genome analyses revealed decreased activity of nuclear receptor peroxisome proliferator-activated receptor-γ (PPARγ) in TH2 cells in obese mice when compared to lean mice, indicating that PPARγ is required to prevent aberrant non-TH2 inflammation. Understanding the effects of obesity on immunological disease could inform a potential precision medicine approach to target obesity-induced immune dysregulation. Supported by ORIP (S10OD023689), NIAID, NCI, NIDDK, and NIGMS.
Common and Divergent Features of T Cells From Blood, Gut, and Genital Tract of Antiretroviral Therapy–Treated HIV+ Women
Xie et al., Journal of Immunology. 2022.
https://www.doi.org/10.4049/jimmunol.2101102
T cells residing in mucosal tissues play important roles in homeostasis and defense against microbial pathogens, but how organ system environments affect the properties of resident T cells is relatively unknown. Researchers phenotyped T cells in the gut and reproductive tract using blood and tissue samples from women with HIV who have achieved viral suppression via antiretroviral therapy. The T cells exhibited differing expression of CD69 and CD103 markers, whereas resident memory CD8+ T cells from the female reproductive tract expressed PD1 preferentially. Additionally, CXCR4+ T inflammatory mucosal cells expressed multiple chemokine receptors differentially. These results suggest that T cells take on distinct properties in different mucosal sites, which allows them to tailor activities to their surrounding milieu. This study offers important insights for reproductive medicine in women. Supported by ORIP (S10OD018040), NHLBI, NIAID, and NIDDK.
A Potent Myeloid Response Is Rapidly Activated in the Lungs of Premature Rhesus Macaques Exposed to Intra-Uterine Inflammation
Jackson et al., Mucosal Immunology. 2022.
https://www.doi.org/10.1038/s41385-022-00495-x
Up to 40% of preterm births are associated with histological chorioamnionitis (HCA), which can lead to neonatal mortality, sepsis, respiratory disease, and neurodevelopmental problem. Researchers used rhesus macaques to comprehensively describe HCA-induced fetal mucosal immune responses and delineate the individual roles of IL-1β and TNFα in HCA-induced fetal pathology. Their data indicate that the fetal innate immune system can mount a rapid, multifaceted pulmonary immune response to in utero exposure to inflammation. Taken together, this work provides mechanistic insights into the association between HCA and the postnatal lung morbidities of the premature infant and highlights the therapeutic potential of inflammatory blockade in the fetus. Supported by ORIP (P51OD011107), NIEHS, NIDDK, NHLBI, and NICHD.
Antibody-Peptide Epitope Conjugates for Personalized Cancer Therapy
Zhang et al., Cancer Research. 2022.
https://pubmed.ncbi.nlm.nih.gov/34965933/
Antibody-peptide epitope conjugates (APEC) are a new class of modified antibody-drug conjugates that redirect T cell viral immunity against tumor cells. Investigators developed an experimental pipeline to create patient-specific APECs and identified new preclinical therapies for ovarian carcinoma. Based on functional assessment of viral peptide antigen responses to common viruses like cytomegalovirus in ovarian cancer patients, a library of 192 APECs with distinct protease cleavage sequences was created using the anti-epithelial cell adhesion molecule (EpCAM) antibody. The streamlined and systemic approach includes assessing APEC function in vivo using a new zebrafish xenograft platform that facilitates high-resolution single-cell imaging to assess therapy responses and then validating top candidates using traditional mouse xenograft studies and primary patient samples. This study develops a high-throughput preclinical platform to identify patient-specific antibody-peptide epitope conjugates that target cancer cells and demonstrates the potential of this immunotherapy approach for treating ovarian carcinoma. Supported by ORIP (R24OD016761).
Inflammatory Blockade Prevents Injury to the Developing Pulmonary Gas Exchange Surface in Preterm Primates
Toth et al., Science Translational Medicine. 2022.
https://www.doi.org/10.1126/scitranslmed.abl8574
Chorioamnionitis, an inflammatory condition affecting the placenta and fluid surrounding the developing fetus, affects 25% to 40% of preterm births. Investigators used a prenatal rhesus macaque model to assess how fetal inflammation could affect lung development. They found that inflammatory injury directly disrupted the developing gas exchange surface of the primate lung, with extensive damage to alveolar structure. Blockade of the inflammatory cytokines IL-1β and TNFα ameliorated LPS-induced inflammatory lung injury by blunting stromal responses to inflammation and modulating innate immune activation in myeloid cells. These data provide new insight into key mechanisms of developmental lung injury and highlight targeted inflammatory blockade as a potential therapeutic approach to ameliorate lung injury in the neonatal population. Supported by ORIP (P51OD011107), NIAID, NHLBI, NICHD, and NIEHS.
Presence of Natural Killer B Cells in Simian Immunodeficiency Virus–Infected Colon That Have Properties and Functions Similar to Those of Natural Killer Cells and B Cells but Are a Distinct Cell Population
Cogswell et al., mSphere. 2022.
https://www.doi.org/10.1128/jvi.00235-22
HIV infection of the gut is associated with increased mucosal inflammation, and the role of natural killer B (NKB) cells in this process requires further investigation. In this study, the researchers used rhesus and cynomolgus macaque models to characterize the function and characteristics of NKB cells in response to simian immunodeficiency virus (SIV) infection. They reported that NKB cells can kill target cells, proliferate, and express several inflammatory cytokines. The properties of NKB cells could provide insight into the inflammation observed in the gut during SIV infection, and the individual contributions of each cytokine and receptor–ligand interaction could be explored in a future study. Supported by ORIP (P51OD011106), NIAID, and NIGMS.
Using the Autofluorescence Finder on the Sony ID7000TM Spectral Cell Analyzer to Identify and Unmix Multiple Highly Autofluorescent Murine Lung Populations
Wanner et al., Frontiers in Bioengineering and Biotechnology. 2022.
https://www.doi.org/10.3389/fbioe.2022.827987
The investigators explored a new imaging approach to detect faint fluorescent signals that are masked in the background of cell types that emit high‑intensity autofluorescence (AF) signals in a flow cytometry panel. Using a novel AF finder tool on the Sony ID7000™ spectral cell analyzer, the investigators studied multiple AF subsets in complex and heterogeneous murine lung single-cell suspensions. Major immune and lung tissue resident cells in a murine model of asthma were easily identified in a multicolor panel using AF subtraction. The findings demonstrate the practicality of the AF finder tool, particularly when analyzing samples with multiple AF populations of varying intensities, to reduce fluorescence background and increase signal resolution in spectral flow cytometry. Supported by ORIP (S10OD025207) and NHLBI.
Phagocytosis by an HIV Antibody Is Associated with Reduced Viremia Irrespective of Enhanced Complement Lysis
Spencer et al., Nature Communications. 2022.
https://doi.org/10.1038/s41467-022-28250-7
Researchers used the bNAb 10E8v4 targeting the HIV Env protein to examine the role of antibody-mediated effector and complement (C′) activity when 10E8v4 was administered prophylactically to rhesus monkeys challenged with simian-human immunodeficiency virus (SHIV). With sub-protective dosing, the researchers found a 78–88% reduction in post-acute viremia that was associated with 10E8v4–mediated phagocytosis. These results suggest that effector functions inherent to unmodified 10E8v4 contribute to therapeutic efficacy against SHIV, while C′ functions do not contribute to efficacy in this context. This research informs the design of bNAb modifications for improving the protective efficacy of this therapeutic approach against HIV. Supported by ORIP (P51OD011092, U42OD023038) and NIAID.