Prehension kinematics in humans and macaques

2021 ◽  
Author(s):  
Yuke Yan ◽  
Anton Sobinov ◽  
Sliman J Bensmaia
Keyword(s):  
Neural Circuits ◽  
Rhesus Macaques ◽  
Sensorimotor Control ◽  
Neural Mechanisms ◽  
Experimental Setup ◽  
Sensorimotor System ◽  
Dominant Model ◽  
Upper Limbs ◽  
Macaque Model ◽  
Human Counterpart

Non-human primates, especially rhesus macaques, have been a dominant model to study sensorimotor control of the upper limbs. Indeed, human and macaques have similar hands and homologous neural circuits to mediate manual behavior. However, few studies have systematically and quantitatively compared the manual behaviors of the two species. Such comparison is critical for assessing the validity of using the macaque sensorimotor system as a model of its human counterpart. In this study, we systematically compared the prehensile behaviors of humans and rhesus macaques using an identical experimental setup. We found human and macaque prehension kinematics to be generally similar but with a few subtle differences. Humans and macaques have similar major axes of movements and similar kinematics subspaces. Human grasps are more object-specific and the movement of human digits are less correlated with each other. Monkeys demonstrate more stereotypical grasping behaviors that are common across all grasp conditions. Our results bolster the use of the macaque model to understand the neural mechanisms of manual dexterity.

scholarly journals Prevention and treatment of SHIVAD8 infection in rhesus macaques by a potent d-peptide HIV entry inhibitor

2020 ◽  
Vol 117 (36) ◽  
pp. 22436-22442
Author(s):  
Yoshiaki Nishimura ◽  
J. Nicholas Francis ◽  
Olivia K. Donau ◽  
Eric Jesteadt ◽  
Reza Sadjadpour ◽  
...  
Keyword(s):  
Rhesus Macaques ◽  
Entry Inhibitor ◽  
High Dose ◽  
Combination Antiretroviral Therapy ◽  
Promising Candidate ◽  
Macaque Model ◽  
Prevention And Treatment ◽  
Hiv Entry ◽  
Virus Isolates ◽  
Primary Virus

Cholesterol-PIE12-trimer (CPT31) is a potentd-peptide HIV entry inhibitor that targets the highly conserved gp41 N-peptide pocket region. CPT31 exhibited strong inhibitory breadth against diverse panels of primary virus isolates. In a simian-HIV chimeric virus AD8 (SHIVAD8) macaque model, CPT31 prevented infection from a single high-dose rectal challenge. In chronically infected animals, CPT31 monotherapy rapidly reduced viral load by ∼2 logs before rebound occurred due to the emergence of drug resistance. In chronically infected animals with viremia initially controlled by combination antiretroviral therapy (cART), CPT31 monotherapy prevented viral rebound after discontinuation of cART. These data establish CPT31 as a promising candidate for HIV prevention and treatment.

scholarly journals Anti-α4β7 monoclonal antibody–conjugated nanoparticles block integrin α4β7 on intravaginal T cells in rhesus macaques

2020 ◽  
Vol 6 (34) ◽  
pp. eabb9853
Author(s):  
Sidi Yang ◽  
Geraldine Arrode-Bruses ◽  
Ines Frank ◽  
Brooke Grasperge ◽  
James Blanchard ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
T Cells ◽  
Single Dose ◽  
Side Effects ◽  
Rhesus Macaque ◽  
Rhesus Macaques ◽  
Vaginal Infection ◽  
Macaque Model ◽  
Immunodeficiency Virus ◽  
Vaginal Tract

Intravenous administration of anti-α4β7 monoclonal antibody in macaques decreases simian immunodeficiency virus (SIV) vaginal infection and reduces gut SIV loads. Because of potential side effects of systemic administration, a prophylactic strategy based on mucosal administration of anti-α4β7 antibody may be safer and more effective. With this in mind, we developed a novel intravaginal formulation consisting of anti-α4β7 monoclonal antibody–conjugated nanoparticles (NPs) loaded in a 1% hydroxyethylcellulose (HEC) gel (NP-α4β7 gel). When intravaginally administered as a single dose in a rhesus macaque model, the formulation preferentially bound to CD4+ or CD3+ T cells expressing high levels of α4β7, and occupied ~40% of α4β7 expressed by these subsets and ~25% of all cells expressing α4β7. Blocking of the α4β7 was restricted to the vaginal tract without any changes detected systemically.

scholarly journals Prevention and Treatment of SHIVAD8 Infection in Rhesus Macaques by a Potent D-peptide HIV Entry Inhibitor

2020 ◽  
Author(s):  
Y. Nishimura ◽  
J.N. Francis ◽  
O. Donau ◽  
E. Jesteadt ◽  
R. Sadjadpour ◽  
...  
Keyword(s):  
Rhesus Macaques ◽  
Entry Inhibitor ◽  
High Dose ◽  
Viral Rebound ◽  
Combination Antiretroviral Therapy ◽  
Macaque Model ◽  
Prevention And Treatment ◽  
Hiv Entry ◽  
Virus Isolates ◽  
Primary Virus

AbstractCholesterol-PIE12-trimer (CPT31) is a potent D-peptide HIV entry inhibitor that targets the highly conserved gp41 N-peptide pocket region. CPT31 exhibited strong inhibitory breadth against diverse panels of primary virus isolates. In a SHIV macaque model, CPT31 prevented infection from a single high-dose rectal challenge. In chronically infected animals, CPT31 monotherapy rapidly reduced viral load by ~2 logs before rebound occurred due to the emergence of drug resistance. In chronically infected animals with viremia initially controlled by combination antiretroviral therapy (cART), CPT31 monotherapy prevented viral rebound after discontinuation of cART. These data establish CPT31 as a promising new candidate for HIV prevention and treatment.

scholarly journals Effective Prophylaxis of COVID-19 in Rhesus Macaques Using a Combination of Two Parenterally-Administered SARS-CoV-2 Neutralizing Antibodies

2021 ◽  
Vol 11 ◽  
Author(s):  
Brandon J. Beddingfield ◽  
Nicholas J. Maness ◽  
Alyssa C. Fears ◽  
Jay Rappaport ◽  
Pyone Pyone Aye ◽  
...  
Keyword(s):  
Neutralizing Antibodies ◽  
Rhesus Macaques ◽  
Disease Model ◽  
Low Grade ◽  
Kinetics Study ◽  
Mucosal Tissue ◽  
Macaque Model ◽  
High Affinity ◽  
Effective Prophylaxis ◽  
Added Benefit

SARS-CoV-2 is a respiratory borne pathogenic beta coronavirus that is the source of a worldwide pandemic and the cause of multiple pathologies in man. The rhesus macaque model of COVID-19 was utilized to test the added benefit of combinatory parenteral administration of two high-affinity anti-SARS-CoV-2 monoclonal antibodies (mAbs; C144-LS and C135-LS) expressly developed to neutralize the virus and modified to extend their pharmacokinetics. After completion of kinetics study of mAbs in the primate, combination treatment was administered prophylactically to mucosal viral challenge. Results showed near complete virus neutralization evidenced by no measurable titer in mucosal tissue swabs, muting of cytokine/chemokine response, and lack of any discernable pathologic sequalae. Blocking infection was a dose-related effect, cohorts receiving lower doses (6, 2 mg/kg) resulted in low grade viral infection in various mucosal sites compared to that of a fully protective dose (20 mg/kg). A subset of animals within this cohort whose infectious challenge was delayed 75 days later after mAb administration were still protected from disease. Results indicate this combination mAb effectively blocks development of COVID-19 in the rhesus disease model and accelerates the prospect of clinical studies with this effective antibody combination.

scholarly journals A synthetic peptide CTL vaccine targeting nucleocapsid confers protection from SARS-CoV-2 challenge in rhesus macaques

2021 ◽  
Author(s):  
Paul E. Harris ◽  
Trevor Brasel ◽  
Christopher Massey ◽  
C. V. Herst ◽  
Scott Burkholz ◽  
...  
Keyword(s):  
Nucleocapsid Protein ◽  
Clinical Symptoms ◽  
Rhesus Macaques ◽  
Peptide Vaccine ◽  
Hla Class I ◽  
Class I ◽  
Vaccination Programs ◽  
Macaque Model ◽  
Unvaccinated Control ◽  
Downstream Analysis

AbstractBackgroundPersistent transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has given rise to a COVID-19 pandemic. Several vaccines, evoking protective spike antibody responses, conceived in 2020, are being deployed in mass public health vaccination programs. Recent data suggests, however, that as sequence variation in the spike genome accumulates, some vaccines may lose efficacy.MethodsUsing a macaque model of SARS-CoV-2 infection, we tested the efficacy of a peptide-based vaccine targeting MHC Class I epitopes on the SARS-CoV-2 nucleocapsid protein. We administered biodegradable microspheres with synthetic peptides and adjuvants to rhesus macaques. Unvaccinated control and vaccinated macaques were challenged with 1 x 108 TCID50 units of SARS-CoV-2, followed by assessment of clinical symptoms, viral load, chest radiographs, sampling of peripheral blood and bronchoalveolar lavage (BAL) fluid for downstream analysis.ResultsVaccinated animals were free of pneumonia-like infiltrates characteristic of SARS-CoV-2 infection and presented with lower viral loads relative to controls. Gene expression in cells collected from BAL samples of vaccinated macaques revealed a unique signature associated with enhanced development of adaptive immune responses relative to control macaques.ConclusionsWe demonstrate that a room temperature stable peptide vaccine based on known immunogenic HLA Class I bound CTL epitopes from the nucleocapsid protein can provide protection against SARS-CoV-2 infection in non-human primates.Graphical Abstract

scholarly journals Development of an antibody cocktail for treatment of Sudan virus infection

2020 ◽  
Vol 117 (7) ◽  
pp. 3768-3778 ◽  
Author(s):  
Andrew S. Herbert ◽  
Jeffery W. Froude ◽  
Ramon A. Ortiz ◽  
Ana I. Kuehne ◽  
Danielle E. Dorosky ◽  
...  
Keyword(s):  
Treatment Option ◽  
Ebola Virus ◽  
Protective Efficacy ◽  
Rhesus Macaques ◽  
Macaque Model ◽  
Mammalian Expression ◽  
Significant Difference ◽  
Antibody Cocktail

Antibody-based therapies are a promising treatment option for managing ebolavirus infections. Several Ebola virus (EBOV)-specific and, more recently, pan-ebolavirus antibody cocktails have been described. Here, we report the development and assessment of a Sudan virus (SUDV)-specific antibody cocktail. We produced a panel of SUDV glycoprotein (GP)-specific human chimeric monoclonal antibodies (mAbs) using both plant and mammalian expression systems and completed head-to-head in vitro and in vivo evaluations. Neutralizing activity, competitive binding groups, and epitope specificity of SUDV mAbs were defined before assessing protective efficacy of individual mAbs using a mouse model of SUDV infection. Of the mAbs tested, GP base-binding mAbs were more potent neutralizers and more protective than glycan cap- or mucin-like domain-binding mAbs. No significant difference was observed between plant and mammalian mAbs in any of our in vitro or in vivo evaluations. Based on in vitro and rodent testing, a combination of two SUDV-specific mAbs, one base binding (16F6) and one glycan cap binding (X10H2), was down-selected for assessment in a macaque model of SUDV infection. This cocktail, RIID F6-H2, provided protection from SUDV infection in rhesus macaques when administered at 50 mg/kg on days 4 and 6 postinfection. RIID F6-H2 is an effective postexposure SUDV therapy and provides a potential treatment option for managing human SUDV infection.

scholarly journals Schistosoma mansoni Infection Impairs Antimalaria Treatment and Immune Responses of Rhesus Macaques Infected with Mosquito-Borne Plasmodium coatneyi

2012 ◽  
Vol 80 (11) ◽  
pp. 3821-3827 ◽  
Author(s):  
Amma A. Semenya ◽  
JoAnn S. Sullivan ◽  
John W. Barnwell ◽  
W. Evan Secor
Keyword(s):  
Immune Responses ◽  
Schistosoma Mansoni ◽  
Malaria Infection ◽  
Rhesus Macaques ◽  
Antibody Responses ◽  
Content Type ◽  
Macaque Model ◽  
Malaria Parasitemia ◽  
Intravenous Inoculation ◽  
Plasmodium Coatneyi

ABSTRACTMalaria and schistosomiasis are the world's two most important parasitic infections in terms of distribution, morbidity, and mortality. In areas wherePlasmodiumandSchistosomaspecies are both endemic, coinfections are commonplace. Mouse models demonstrate that schistosomiasis worsens a malaria infection; however, just as mice and humans differ greatly, the murine-infectingPlasmodiumspecies differ as much from those that infect humans. Research into human coinfections (Schistosoma haematobium-Plasmodium falciparumversusSchistosoma mansoni-P. falciparum) has produced conflicting results. The rhesus macaque model provides a helpful tool for understanding the role ofS. mansonion malaria parasitemia and antimalarial immune responses usingPlasmodium coatneyi, a malaria species that closely resemblesP. falciparuminfection in humans. Eight rhesus macaques were exposed toS. mansonicercariae. Eight weeks later, these animals plus 8 additional macaques were exposed to malaria either through bites of infected mosquitos or intravenous inoculation. When malaria infection was initiated from mosquito bites, coinfected animals displayed increased malaria parasitemia, decreased hematocrit levels, and suppressed malaria-specific antibody responses compared to those of malaria infection alone. However, macaques infected by intravenous inoculation with erythrocytic-stage parasites did not display these same differences in parasitemia, hematocrit, or antibody responses between the two groups. Use of the macaque model provides information that begins to unravel differences in pathological and immunological outcomes observed between humans withP. falciparumthat are coinfected withS. mansoniorS. haematobium. Our results suggest that migration of malaria parasites through livers harboring schistosome eggs may alter host immune responses and infection outcomes.

scholarly journals Myeloid differentiation architecture of leukocyte transcriptome dynamics in perceived social isolation

2015 ◽  
Vol 112 (49) ◽  
pp. 15142-15147 ◽  
Author(s):  
Steven W. Cole ◽  
John P. Capitanio ◽  
Katie Chun ◽  
Jesusa M. G. Arevalo ◽  
Jeffrey Ma ◽  
...  
Keyword(s):  
Social Isolation ◽  
Rhesus Macaques ◽  
Transcriptional Response ◽  
Population Expansion ◽  
Myeloid Cell ◽  
Type I ◽  
Cellular Mechanisms ◽  
Macaque Model ◽  
Immunodeficiency Virus ◽  
Perceived Social Isolation

To define the cellular mechanisms of up-regulated inflammatory gene expression and down-regulated antiviral response in people experiencing perceived social isolation (loneliness), we conducted integrative analyses of leukocyte gene regulation in humans and rhesus macaques. Five longitudinal leukocyte transcriptome surveys in 141 older adults showed up-regulation of the sympathetic nervous system (SNS), monocyte population expansion, and up-regulation of the leukocyte conserved transcriptional response to adversity (CTRA). Mechanistic analyses in a macaque model of perceived social isolation confirmed CTRA activation and identified selective up-regulation of the CD14++/CD16−classical monocyte transcriptome, functional glucocorticoid desensitization, down-regulation of Type I and II interferons, and impaired response to infection by simian immunodeficiency virus (SIV). These analyses identify neuroendocrine-related alterations in myeloid cell population dynamics as a key mediator of CTRA transcriptome skewing, which may both propagate perceived social isolation and contribute to its associated health risks.

scholarly journals Visualizing Cytokine-Secreting Cells In Situ in the Rhesus Macaque Model of Chronic Gut Inflammation

2005 ◽  
Vol 12 (1) ◽  
pp. 192-197 ◽  
Author(s):  
Geeta Ramesh ◽  
Xavier Alvarez ◽  
Juan T. Borda ◽  
Pyone P. Aye ◽  
Andrew A. Lackner ◽  
...  
Keyword(s):  
T Lymphocytes ◽  
Lamina Propria ◽  
Rhesus Macaques ◽  
Epifluorescence Microscopy ◽  
Lymphoid Tissues ◽  
Primate Model ◽  
Necrosis Factor Alpha ◽  
Macaque Model ◽  
Tnf Α

ABSTRACT Cytokine-producing cells in gut-associated lymphoid tissues of rhesus macaques with chronic enterocolitis were studied. The confocal microscopy technique that we developed enables simultaneous in situ visualization of multiple extra- and/or intracellular antigens at a resolution higher than that allowed by light or epifluorescence microscopy. The presence of interleukin-6 (IL-6)-, tumor necrosis factor alpha (TNF-α)-, and IL-1-α-producing cells was focally intense in the colon lamina propria of the affected animals. The IL-1-α-producing cells were T lymphocytes (CD3+), while the TNF-α-producing cells were both macrophages (CD68+/HAM56+/LN5+) and T lymphocytes (CD3+). The IL-6-producing cells within the colon consisted of T lymphocytes and macrophages. The amount of IL-6-producing cells seen in macaques with enterocolitis was significantly higher (P < 0.001) than that seen in the healthy control animal, while TNF-α- and IL-1-α-producing cells were seen only in macaques with enterocolitis. Most of the T lymphocytes that produced cytokines were detected in the lamina propria, while the macrophages were most prominent in highly inflamed regions of the lamina propria. Taken together, our findings indicate that there might be immunological similarity between chronic enterocolitis of rhesus macaques and humans, suggesting the potential use of the nonhuman primate model for the validation of novel therapies.

scholarly journals Mucosal Transmission and Induction of Simian AIDS by CCR5-Specific Simian/Human Immunodeficiency Virus SHIVSF162P3

2001 ◽  
Vol 75 (4) ◽  
pp. 1990-1995 ◽  
Author(s):  
Janet M. Harouse ◽  
Agegnehu Gettie ◽  
Tadesse Eshetu ◽  
Rei Chin How Tan ◽  
Rudolf Bohm ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Large Scale ◽  
Mononuclear Cells ◽  
Opportunistic Infections ◽  
Rhesus Macaques ◽  
Viral Transmission ◽  
Peripheral Blood Mononuclear ◽  
Mucosal Transmission ◽  
Macaque Model ◽  
Immunodeficiency Virus

ABSTRACT Nonhuman primate models are increasingly used in the screening of candidate AIDS vaccine and immunization strategies for advancement to large-scale human trials. The predictive value of such macaque studies is largely dependent upon the fidelity of the model system in mimicking human immunodeficiency virus (HIV) type 1 infection in terms of viral transmission, replication, and pathogenesis. Herein, we describe the efficient mucosal transmission of a CCR5-specific chimeric simian/human immunodeficiency virus, SHIVSF162P3. Female rhesus macaques were infected with SHIVSF162P3 after a single atraumatic application to the cervicovaginal mucosa. The disease course of SHIVSF162P3-infected monkeys is similar and as varied as natural HIV infection in terms of viral replication, gradual loss of CD4+ peripheral blood mononuclear cells, and the development of simian AIDS-defining opportunistic infections. The SHIVSF162P3/macaque model should facilitate direct preclinical assessment of HIV vaccine strategies in addition to antiviral compounds directed towards envelope target cell interactions. Furthermore, this controlled model provides the setting to investigate immunologic responses and putative host-specific susceptibility factors that alter viral transmission and subsequent disease progression.

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