Preclinical evaluation of transaxial intraputaminal trajectory for enhanced distribution of grafted cells in Parkinson's disease.

Objective: The objective of this study was to develop and evaluate the feasibility and safety of a novel transaxial surgical approach for the delivery of human induced pluripotent stem cell-derived dopaminergic neuroprogenitor cells (DANPCs) into the putamen nucleus using nonhuman primates and surgical techniques and tools relevant to human clinical translation.

Methods: Nine immunosuppressed, unlesioned adult cynomolgus macaques (4 females, 5 males) received intraputaminal injections of vehicle or DANPCs (0.9 × 105 to 1.

Evaluating depression- and anxiety-like behaviors in non-human primates.

Depression and anxiety are some of the most prevalent and debilitating mental health conditions in humans. They can present on their own or as co-morbidities with other disorders. Like humans, non-human primates (NHPs) can develop depression- and anxiety-like signs.

Quantification of early gait development: Expanding the application of Catwalk technology to an infant rhesus macaque model.

Background: Understanding gait development is essential for identifying motor impairments in neurodevelopmental disorders. Defining typical gait development in a rhesus macaque model is critical prior to characterizing abnormal gait. The goal of this study was to 1) explore the feasibility of using the Noldus Catwalk to assess gait in infant rhesus macaques and 2) provide preliminary normative data of gait development during the first month of life.

Previous exposure to dengue virus is associated with increased Zika virus burden at the maternal-fetal interface in rhesus macaques.

Concerns have arisen that pre-existing immunity to dengue virus (DENV) could enhance Zika virus (ZIKV) disease, due to the homology between ZIKV and DENV and the observation of antibody-dependent enhancement (ADE) among DENV serotypes. To date, no study has examined the impact of pre-existing DENV immunity on ZIKV pathogenesis during pregnancy in a translational non-human primate model. Here we show that macaques with a prior DENV-2 exposure had a higher burden of ZIKV vRNA in maternal-fetal interface tissues as compared to DENV-naive macaques.

African-Lineage Zika Virus Replication Dynamics and Maternal-Fetal Interface Infection in Pregnant Rhesus Macaques.

Following the Zika virus (ZIKV) outbreak in the Americas, ZIKV was causally associated with microcephaly and a range of neurological and developmental symptoms, termed congenital Zika syndrome (CZS). The viruses responsible for this outbreak belonged to the Asian lineage of ZIKV. However, and studies assessing the pathogenesis of African-lineage ZIKV demonstrated that African-lineage isolates often replicated to high titers and caused more-severe pathology than Asian-lineage isolates.

Current practices in nutrition management and disease incidence of common marmosets (Callithrix jacchus).

Background: A survey was developed to characterize disease incidence, common pathology lesions, environmental characteristics, and nutrition programs within captive research marmoset colonies.

Methods: Seventeen research facilities completed the electronic survey.

Results: Nutritional management programs varied amongst research institutions housing marmosets; eight primary base diets were reported.

Autologous transplant therapy alleviates motor and depressive behaviors in parkinsonian monkeys.

Degeneration of dopamine (DA) neurons in the midbrain underlies the pathogenesis of Parkinson's disease (PD). Supplement of DA via L-DOPA alleviates motor symptoms but does not prevent the progressive loss of DA neurons. A large body of experimental studies, including those in nonhuman primates, demonstrates that transplantation of fetal mesencephalic tissues improves motor symptoms in animals, which culminated in open-label and double-blinded clinical trials of fetal tissue transplantation for PD.

Quantitative definition of neurobehavior, vision, hearing and brain volumes in macaques congenitally exposed to Zika virus.

Congenital Zika virus (ZIKV) exposure results in a spectrum of disease ranging from severe birth defects to delayed onset neurodevelopmental deficits. ZIKV-related neuropathogenesis, predictors of birth defects, and neurodevelopmental deficits are not well defined in people. Here we assess the methodological and statistical feasibility of a congenital ZIKV exposure macaque model for identifying infant neurobehavior and brain abnormalities that may underlie neurodevelopmental deficits.

Cervico-Vaginal Inflammatory Cytokine and Chemokine Responses to Two Different SIV Immunogens.

Studies have shown that vaccine vectors and route of immunization can differentially activate different arms of the immune system. However, the effects of different HIV vaccine immunogens on mucosal inflammation have not yet been studied. Because mucosal sites are the primary route of HIV infection, we evaluated the cervico-vaginal inflammatory cytokine and chemokine levels of Mauritian cynomolgus macaques following immunization and boost using two different SIV vaccine immunogens.

Vaccine targeting SIVmac251 protease cleavage sites protects macaques against vaginal infection.

After over 3 decades of research, an effective anti-HIV vaccine remains elusive. The recently halted HVTN702 clinical trial not only further stresses the challenge to develop an effective HIV vaccine but also emphasizes that unconventional and novel vaccine strategies are urgently needed. Here, we report that a vaccine focusing the immune response on the sequences surrounding the 12 viral protease cleavage sites (PCSs) provided greater than 80% protection to Mauritian cynomolgus macaques against repeated intravaginal SIVmac251 challenges.

A direct-acting antiviral drug abrogates viremia in Zika virus-infected rhesus macaques.

Zika virus infection in humans has been associated with serious reproductive and neurological complications. At present, no protective antiviral drug treatment is available. Here, we describe the testing and evaluation of the antiviral drug, galidesivir, against Zika virus infection in rhesus macaques.

Long-Term Protection of Rhesus Macaques from Zika Virus Reinfection.

By the end of the 2016 Zika virus (ZIKV) outbreak, it is estimated that there were up to 100 million infections in the Americas. In approximately one in seven infants born to mothers infected during pregnancy, ZIKV has been linked to microcephaly, developmental delays, or other congenital disorders collectively known as congenital Zika syndrome, as well as Guillain-Barré syndrome, in ZIKV-infected adults. It is a global health priority to develop a vaccine against ZIKV that elicits long-lasting immunity; however, the durability of immunity to ZIKV is unknown.

Spatiotemporal quantification of gait in common marmosets.

Background: Objective gait evaluation in humans is used as a predictive disability outcome measure as well as an indicator for intervention effectiveness. Parallel methods of gait analysis in nonhuman primate models are essential for clinical translation. The goal of this study was to first assess whether marmosets' gait data could be reliably collected in a Noldus CatWalk XT10.

Primary infection with dengue or Zika virus does not affect the severity of heterologous secondary infection in macaques.

Zika virus (ZIKV) and dengue virus (DENV) are genetically and antigenically related flaviviruses that now co-circulate in much of the tropical and subtropical world. The rapid emergence of ZIKV in the Americas in 2015 and 2016, and its recent associations with Guillain-Barré syndrome, birth defects, and fetal loss have led to the hypothesis that DENV infection induces cross-reactive antibodies that influence the severity of secondary ZIKV infections. It has also been proposed that pre-existing ZIKV immunity could affect DENV pathogenesis.

AAV-delivered eCD4-Ig protects rhesus macaques from high-dose SIVmac239 challenges.

A number of simian and simian human immunodeficiency viruses (SIV and SHIV, respectively) have been used to assess the efficacy of HIV-1 vaccine strategies. Among these, SIVmac239 is considered among the most stringent because, unlike SHIV models, its full genome has coevolved in its macaque host and its tier 3 envelope glycoprotein (Env) is exceptionally hard to neutralize. Here, we investigated the ability of eCD4-Ig, an antibody-like entry inhibitor that emulates the HIV-1 and SIV receptor and coreceptor, to prevent SIVmac239 infection.

Comparative genomics of Bifidobacterium species isolated from marmosets and humans.

The genus Bifidobacterium is purported to have beneficial consequences for human health and is a major component of many gastrointestinal probiotics. Although species of Bifidobacterium are generally at low relative frequency in the adult human gastrointestinal tract, they can constitute high proportions of the gastrointestinal communities of adult marmosets. To identify genes that might be important for the maintenance of Bifidobacterium in adult marmosets, ten strains of Bifidobacterium were isolated from the feces of seven adult marmosets, and their genomes were sequenced.

Mucosal antibody responses to vaccines targeting SIV protease cleavage sites or full-length Gag and Env proteins in Mauritian cynomolgus macaques.

HIV mutates rapidly and infects CD4+ T cells, especially when they are activated. A vaccine targeting conserved, essential viral elements while limiting CD4+ T cell activation could be effective. Learning from natural immunity observed in a group of highly HIV-1 exposed seronegative Kenyan female sex workers, we are testing a novel candidate HIV vaccine targeting the 12 viral protease cleavage sites (PCSs) (the PCS vaccine), in comparison with a vaccine targeting full-length Gag and Env (the Gag/Env vaccine) in a Mauritian cynomolgus macaque/SIV model.

Radiolabel validation of cortisol in the hair of rhesus monkeys.

Analysis of cortisol in hair has become a widespread tool for assessment of hypothalamic-pituitary-adrenal (HPA) axis activity because of its ease of collection and its ability to provide cumulative data over a period of months. In order to meaningfully interpret hair cortisol, however a direct validation by radio-metabolism is required to understand cortisol incorporation into hair. Tritiated [H]-cortisol was IV administered to adult rhesus monkeys to determine 1) if [H] is found in the hair after injection of [H]-cortisol, 2) the growth rate of hair and 3) the form in which cortisol is found in hair.

Molecularly barcoded Zika virus libraries to probe in vivo evolutionary dynamics.

Defining the complex dynamics of Zika virus (ZIKV) infection in pregnancy and during transmission between vertebrate hosts and mosquito vectors is critical for a thorough understanding of viral transmission, pathogenesis, immune evasion, and potential reservoir establishment. Within-host viral diversity in ZIKV infection is low, which makes it difficult to evaluate infection dynamics. To overcome this biological hurdle, we constructed a molecularly barcoded ZIKV.

Vocalization development in common marmosets for neurodegenerative translational modeling.

Objectives In order to facilitate the study of vocalizations in emerging genetic common marmoset models of neurodegenerative disorders, we aimed to analyze call-type changes across age in a translational research environment. We hypothesized that acoustic parameters of vocalizations would change with age, reflecting growth of the vocal apparatus and a maturation of control needed to make adult-like calls. Methods Nineteen developing common marmosets were longitudinally video- and audio-recorded between the ages of 1-149 days in a naturalistic setting without any vocalization elicitation protocol.

Ocular and uteroplacental pathology in a macaque pregnancy with congenital Zika virus infection.

Congenital Zika virus (ZIKV) infection impacts fetal development and pregnancy outcomes. We infected a pregnant rhesus macaque with a Puerto Rican ZIKV isolate in the first trimester. The pregnancy was complicated by preterm premature rupture of membranes (PPROM), intraamniotic bacterial infection and fetal demise 49 days post infection (gestational day 95).

Natural and cross-inducible anti-SIV antibodies in Mauritian cynomolgus macaques.

Cynomolgus macaques are an increasingly important nonhuman primate model for HIV vaccine research. SIV-free animals without pre-existing anti-SIV immune responses are generally needed to evaluate the effect of vaccine-induced immune responses against the vaccine epitopes. Here, in order to select such animals for vaccine studies, we screened 108 naïve female Mauritian cynomolgus macaques for natural (baseline) antibodies to SIV antigens using a Bio-Plex multiplex system.

A modified vaccinia Ankara vaccine vector expressing a mosaic H5 hemagglutinin reduces viral shedding in rhesus macaques.

The rapid antigenic evolution of influenza viruses requires frequent vaccine reformulations. Due to the economic burden of continuous vaccine reformulation and the threat of new pandemics, there is intense interest in developing vaccines capable of eliciting broadly cross-reactive immunity to influenza viruses. We recently constructed a "mosaic" hemagglutinin (HA) based on subtype 5 HA (H5) and designed to stimulate cellular and humoral immunity to multiple influenza virus subtypes.