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Pilot Research Projects

Yerkes NPRC 2021 Pilot Projects

Each year, the Yerkes National Primate Research Center awards pilot research grants that provide one year of support for up to $70,000 in direct costs. The projects are selected based on their potential to generate high-impact preliminary data that will result in research project grants from outside sources and in peer-reviewed publications.

The 2021 recipients are: 

Shannon Gourley, PhD

Single-Cell Profiling of Immune Activation After Early Life Adversity

Early life stress adversely affects health, increases the susceptibility to stress and negatively affects immune functions. Leveraging samples collected by researchers in the Yerkes Division of Developmental and Cognitive Neuroscience (DCN) at the center’s Field Station, Dr. Gourley and her research team will identify how chronic social subordination stress in monkeys early in life results in individual differences in immune system functions. The team hypothesizes early life stress induces similar transcriptional changes in peripheral blood monocytes in rhesus macaques and mice, and the number and gene expression profiles of monocytes correlates with behavioral deficits in mice exposed to early life social adversity. 

Aim 1: The research team will analyze cell-type specific immune functions in macaques, comparing animals that experienced chronic social subordination stress to others that did not experience such stress.

Aim 2: The research team will carry out similar studies in mice.  

Susan P. Ribeiro, PhD

Dissecting the Mechanisms of SARS-COV2 Protection Induced by 3M-052+alum+RBD Vaccination in the Upper Respiratory Tract of Rhesus Macaques

The effectiveness of current COVID-19 vaccines varies from 60% to more than 90%. While vaccination reduces hospitalization, it does not avoid infection. Dr. Ribeiro’s research team has developed a vaccine based on the receptor binding domain (RBD) of the SARS-CoV-2

spike protein formulated with alum, with or without the 3M-052, a TLR-7/8 agonist. They found adding 3M-052 to the vaccination in rhesus macaques significantly decreased virus replication in nasal swabs (thus, reduced infectivity), despite inducing similar titers of neutralizing antibody in the bronchioalveolar lavage fluid. This suggests the 3M-052 vaccination induces additional immune modulation in the upper respiratory tract, an effect that could be used to develop next-generation vaccination approaches.

Aim 1: The researchers will study vaccination-induced changes in gene signatures of immune cells in the upper respiratory tract.

Aim 2: The researchers will evaluate the lung microenvironment in which such gene signature changes occur.

 

Yerkes NPRC 2020 Pilot Project Recipients

 

Sudhir Pai Kasturi, PhD

Evaluating a new SARS-CoV-2 receptor binding domain (RBD) based COVID-19 vaccine with clinical alum and alum adsorbed 3M-052 adjuvants in rhesus macaques

Significance: COVID-19 is a new infectious disease in humans caused by a novel coronavirus (CoV) named SARS-CoV-2. The rapid global spread of SARS-CoV-2 infections highlights an urgent need for a vaccine and/or therapeutics to stem the pandemic.

Specific Aim: To evaluate a new SARS-CoV-2 receptor binding domain (RBD) based COVID-19 vaccine with clinical alum and alum adsorbed 3M-052 adjuvants in rhesus macaques

  

Mirko Paiardini, PhD

Determining SARS-CoV-2 pathogenesis, viral dynamics, and immune responses in nonhuman primate models

Significance: Little is known regarding the viral pathogenesis and immune response to SARS-CoV-2. Given the devastation the disease is causing worldwide, it is imperative to elucidate the viral pathogenesis and early immune responses that may inform the treatment of infected individuals, identification of correlates of protection, and design of therapeutics and vaccines.

Specific Aim #1: To characterize the breadth of the early innate and adaptive immune response and pathogenesis of SARSCoV-2 infection systemically and localized within the respiratory tract. 

Specific Aim #2: To assess the replication kinetics and tissue localization of SARS-CoV-2. Thomas Vanderford, PhD, Director of the Yerkes Virology Core will lead this component of the pilot project. 

 

Yerkes NPRC 2019 Pilot Project Recipients

Kelly Ethun, DVM, PhD, Adam Ericsen, PhD, and Mar Sanchez, PhD

Variability and heritability of milk immunological phenotypes in rhesus macaques (Macaca mulatta)

The researchers will study milk immunological profiles in rhesus macaques and their associations with infant gastrointestinal bacterial communities.

Specific Aim 1: To determine what different types of milk immunological phenotypes exist in the Yerkes rhesus macaque breeding colony and whether the phenotypes exhibit familial patterns.

Specific Aim 2: To determine whether these milk immunological profiles predict the composition of infant gastrointestinal microbiome and incidence of infantile enteritis.

 

Adriana Galvan, PhD, and Thomas Wichmann, MD

A calcium imaging-based platform for studies of parkinsonism and the effects of deep brain stimulation on cortical activity in primates

The researchers will establish techniques to visualize the activity of cortical neurons in awake monkeys, using miniature microscopes and artificial proteins that emit fluorescent signals in response to the levels of calcium in the neurons (as a measure of the cells’ activity).

Specific Aim 1:  To characterize the spontaneous and task-related activity of neurons in the motor regions of the cerebral cortex.

Specific Aim 2: To monitor changes in the activity of the neurons in the motor cortex during electrical stimulation of subcortical brain nuclei.

Specific Aim 3: To assess the temporal stability of the patterns of activity of motor cortex neurons.

 

Maud Mavigner, PhD, and Guido Silvestri, MD

Inhibiting stemness pathways to reduce HIV persistence in long-lived latently infected memory CD4+ T-cells

The key obstacle to cure HIV infection is a reservoir of latently infected memory CD4+ T-cells that persist despite long-term antiretroviral therapy and are maintained through cellular proliferation. Dr. Mavigner will explore stemness pathways regulating the proliferation of the long-lived central memory (CM) and stem cell memory (SCM) CD4+ T-cells by performing, in the rhesus macaque model, a detailed ex vivo analysis of the impact of pharmacological modulation of these pathways on memory CD4+ T-cell biology and on SIV latency.

Specific Aim 1: To explore stemness pathways that maintain the proliferation and survival of CM and SCM CD4+ T-cells in healthy rhesus macaques.

Specific Aim 2: To investigate the role of stemness pathways on SIV persistence in CM and SCM CD4+ T-cells.

This research project is funded jointly with the Emory Center for AIDS Research (CFAR)

 

Eduardo Salinas, PhD, and Arash Grakoui, PhD

Defining mechanisms of hepatitis E virus evasion to host antibody responses during acute infection

The researchers will determine how the virally encoded soluble ORF2 (ORF2S) contributes to hepatitis E virus (HEV) replicative fitness in vivo and whether ORF2S promotes evasion of the host antibody response during acute HEV infection.

Specific Aim 1: To determine the contribution of soluble ORF2 to viral replication during acute HEV infection.

Specific Aim 2: To define changes in repertoire and neutralizing activity of HEV-specific antibodies from macaques infected with wildtype or ORF2S-null HEV.