IL-21 and IFNα Therapy Rescues Terminally Differentiated NK Cells and Limits SIV Reservoir in ART-Treated Macaques
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Nonpathogenic simian immunodeficiency virus (SIV) infections in natural hosts, such as vervet monkeys, are characterized by a lack of gut microbial translocation, robust secondary lymphoid natural killer cell responses, and limited SIV dissemination in lymph node B-cell follicles. Using antiretroviral therapy-treated, SIV-infected rhesus monkeys—a pathogenic model—researchers showed that interleukin-21 and interferon alpha therapy generate terminally differentiated blood natural killer cells with potent human leukocyte antigen-E-restricted activity in response to SIV envelope peptides.
Tract Pathogen-Mediated Inflammation Through Development of Multimodal Treatment Regimen and Its Impact on SIV Acquisition in Rhesus Macaques
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In addition to being premier HIV models, rhesus macaques are models for other infectious diseases and colitis, where background colon health and inflammation may confound results. Starting with the standard specific-pathogen-free (SPF) model, researchers established a gastrointestinal pathogen-free (GPF) colony via multimodal therapy (enrofloxacin, azithromycin, fenbendazole, and paromomycin) to eliminate common endemic pathogens (EPs).
Postpubertal Spermatogonial Stem Cell Transplantation Restores Functional Sperm Production in Rhesus Monkeys Irradiated Before and After Puberty
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Cancer treatment of prepubertal patients impacts future fertility due to the abolition of spermatogonial stem cells (SSCs). Prepubertal rhesus monkeys (n=6) were unilaterally castrated, and the remaining testes irradiated twice to insure loss of SSCs; the animals were treated with a vehicle or GnRH antagonist for 8 weeks (n=3/treatment). The cryopreserved prepubertal testicular tissue was allergenically transplanted into the intact testes of the monkeys after puberty. Recovery of viable donor epididymal sperm was observed in half the monkeys.
MRI Characteristics of Japanese Macaque Encephalomyelitis (JME): Comparison to Human Diseases
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Magnetic resonance imaging data (MRI) were obtained from 114 Japanese macaques, including 30 animals of both sexes that presented with neurological signs of Japanese macaque encephalomyelitis (JME). Quantitative estimates of blood-brain barrier permeability to gadolinium-based-contrast agent (GBCA) were obtained in acute, GBCA-enhancing lesions, and longitudinal imaging data were acquired for 15 JME animals. Intense, focal neuroinflammation was a key MRI finding in JME. Several features of JME compare directly to human inflammatory demyelinating diseases.
Modulation of MHC-E Transport by Viral Decoy Ligands Is Required for RhCMV/SIV Vaccine Efficacy
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Rhesus cytomegalovirus (RhCMV) strain 68-1-vectored simian immunodeficiency virus (SIV) vaccines elicit strong CD8+ T cell responses that can clear SIV infections. Peptides targeted by these T cells are presented on major histocompatibility complex (MHC) II and MHC-E rather than MHC-Ia. Researchers showed that VL9 drives intracellular transport of MHC-E and recognition of RhCMV-infected targets by MHC-E-restricted CD8+ T cells.
Evidence in Primates Supporting the Use of Chemogenetics for the Treatment of Human Refractory Neuropsychiatric Disorders
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A rhesus macaque model for pathological anxiety was used to investigate the feasibility of decreasing anxiety using chemogenetics, known as DREADDs (designer receptors exclusively activated by designer drugs), to reduce amygdala neuronal activity. A low-dose clozapine administration strategy was developed to induce DREADD-mediated amygdala inhibition. Compared to controls, clozapine selectively decreased anxiety-related freezing behavior in the human intruder paradigm in the chemogentic monkeys, while coo vocalizations and locomotion were unaffected.
Functional Convergence of a Germline-Encoded Neutralizing Antibody Response in Rhesus Macaques Immunized with HCV Envelope Glycoproteins
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Immunoglobulin heavy chain variable gene IGHV1-69-encoded broadly neutralizing antibodies (bnAbs) targeting the hepatitis C virus (HCV) envelope glycoprotein (Env) E2 are important for protection against HCV infection in humans. An IGHV1-69 ortholog, VH1.36, is preferentially used for bnAbs isolated from rhesus macaques immunized against HCV Env. Researchers investigated the genetic, structural, and functional properties of VH1.36-encoded bnAbs generated by HCV Env vaccination of macaques and compared their findings to IGHV1-69-encoded bnAbs from HCV patients.
Sensitive Tracking of Circulating Viral RNA Through All Stages of SARS-CoV-2 Infection
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Circulating SARS-CoV-2 RNA could represent a more reliable indicator of infection than nasal RNA, but quantitative reverse transcription PCR (RT-qPCR) lacks diagnostic sensitivity for blood samples. Researchers developed a CRISPR-amplified, blood-based COVID-19 (CRISPR-ABC) assay to detect SARS-CoV-2 in plasma. They evaluated the assay using samples from SARS-CoV-2-infected African green monkeys and rhesus macaques, as well as from COVID-19 patients. CRISPR-ABC consistently detected viral RNA in the plasma of the experimentally infected primates from 1 to 28 days after infection.
Cytomegaloviral Determinants of CD8+ T Cell Programming and RhCMV/SIV Vaccine Efficacy
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Cytomegalovirus (CMV)-based vaccine vectors were developed to leverage the ability of CMVs to elicit sustained CD4+ and CD8+ T cell responses with broad tissue distribution. The 68-1 rhesus cytomegalovirus (RhCMV) vectors that express simian immunodeficiency virus (SIV) inserts induce major histocompatibility complex E (MHC-E)- and MHC-II-restricted, SIV-specific CD8+T cell responses. The contribution of this unconventional MHC restriction to RhCMV/SIV vaccine efficacy are poorly understood.
Metabolomics Analysis of Follicular Fluid Coupled With Oocyte Aspiration Reveals Importance of Glucocorticoids in Primate Periovulatory Follicle Competency
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Assisted reproductive therapy in primates requires ovarian stimulation protocols, which result in multiple heterogeneous oocytes with variable capacity for fertilization, cleavage, and blastocyst formation. Recovered oocytes from rhesus macaque follicles (n=74 follicles) were fertilized in vitro and classified as failed to cleave, cleaved but arrested, or able to form blastocysts.