Collaborative Research

The Division of Collaborative Research facilitates the investigations of scientists outside the Tulane National Primate Research Center (TNPRC) with the resources at the TNPRC.

The Division consists of five full time members and two part time members including two faculty, three research technicians and two administrative staff. Dr. James L. Blanchard, Executive Director of Tulane’s Comparative Medicine Program, is Chairman of the Division. Dr. Pyone Aye is the Division’s Study Coordinator and also oversees the TNPRC’s Pilot Study Program.

The functions of the Division can be divided into two main areas: 1) Research and 2) Research Resources .

RESEARCH PROGRAMS

Most of the research within the Division is collaborative with the Principal Investigator at a distant site. Below are examples of such projects.

Role of the Thymus in T Cell Homeostasis

By monitoring the changes in phenotypic T cell markers as well as in the numbers of T cell Receptor (TCR) excisional circles – a recently described marker for recent thymic emigrants – following thymectomy, we have found evidence that surgical thymectomy in juvenile macaques results in a faster decay of peripheral CD4+ T cells, but does not cause a substantial shift in CD45RA+ (naive) and CD45RA- (memory) populations. No compensatory extra-thymic source was detected in lymphoid tissues, although there was a small compensatory increase in T cell proliferation in the peripheral T cell pool. After SIV infection, thymectomized animals did not have higher viral loads, greater T cell decay, or faster disease progression. We therefore conclude that peripheral destructive processes, rather than a loss of thymic output, appear to be the main causes of T cell depletion in SIV infection. Aaron Diamond AIDS Research Center.

Microbicides to Prevent AIDS Transmission

Cellulose acetate phthalate (CAP), a pharmaceutical excipient designed as a coating material for tablets or granules, has been demonstrated to be effective against herpes simplex virus type 2 (HSV-2) infection in mice, and to protect four of six rhesus monkeys from vaginal challenge with simian immunodeficiency virus SIVmac251. To assess whether CAP confers protection against primary viral strains that are transmitted in humans, infections with pathogenic simian/human immunodeficiency viruses (SHIVs) expressing the envelopes of X4 and R5HIV-1 strains (SHIVSF33A and SHSIVSF162P3, respectively) were performed. Seven of ten CAP treated macaques were protected from challenge with a mixture of X4-SHIVSF33A and R5-SHIVSF162P3. These findings in macaques suggest that CAP is efficacious against both X4 and R5 SHIV viruses in vivo, and should therefore be considered as a viable topical microbicide candidate in the prevention of HIV-1 infection. Aaron Diamond AIDS Research Center.

SIV Epitope Specific CTL Responses in MAMU-A01A02 Double-positive Macaques

A vaccine-elicited cytotoxic T-cell lymphocyte (CTL) response with a maximal breadth of epitope specificities should mediate the most efficient control of HIV-1 replication following infection. We studied the evolution of epitope-specific immune responses in naïve rhesus monkeys following infection with SIVmac251. The delay in the peak Mamu-A*02/pl99RY-specific CTL response in the presence of highly immunodominant Mamu-A*01-restricted CTL responses is most likely due to immunodomination, and represents the first demonstration of immunodomination in outbred primate species. Beth Israel Deaconess Medical Hospital, Harvard Medical School.

AT-2 SIV Vaccination after Dendritic Cell Mobilization

While both immature and mature monocytes-derived dendritic cells capture and present AT-2SIV to primed T cells in vitro, mature dendritic cells activate both CD4 and CD8 T cells but immature dendritic cells predominantly activated CD4 T cells. This supports the rationale for targeting activated dendritic cells with antigen for induction of the most effective immunity. Peripheral dendritic cells and mucosal dendritic cells respond to various stimuli comparable to human dendritic cells and can be mobilized in vivo following treatment with Flt3L. As little as 7 days treatment significantly increases dendritic cell numbers. The peak of the increase in dendritic cell numbers post treatment is under investigation. A study applying AT-2 SIV to the tonsils of naïve macaques revealed that SIV-specific T cells are primed and that pretreatment with immuno-stimulatory oligodeoxynucleotides (ISS-ODNs that activate peripheral dendritic cells), tends to increase the responses seen. Population Council, New York.

Implications for Viral Myocarditis

Coxsackie Virus B and Adenoviruses are the most common viral pathogens implicated in the development of human myocarditis. Both viruses gain entry into cells via the Coxsackie Adenovirus Receptor (CAR). We hypothesize that age-dependent CAR expression in cardiac myocytes may help explain the greater severity and higher mortality of coxsackie B (CVB) myocarditis in children, compared to adults. These data suggest that myocarditis and other manifestations of CVB infection in newborns may reflect higher CAR expression. To gain additional data, a macaque model of CVB myocarditis is being developed. UCLA School of Medicine.

RESEARCH RESOURCES

Research resources provided by the Division are varied, but focus on providing outside investigators with the support needed to perform a research study at the TNPRC. This includes assistance with experiment design, budget preparation, regulatory paperwork, and sample acquisition, processing and shipping. In addition, the Division maintains a database on researchers assisted and quantifies the use of TNPRC resources being used to meet the needs of these investigators.

In the most recent reporting year, more than 11,000 tissue and blood samples were shipped to 61 outside collaborators in 22 states and 2 foreign countries. The Division also processed and shipped over 23,000 samples for diagnostic testing. Budget requests from over 30 core and non-core investigators were processed, resulting in 83 budgets totaling more than $56 million in animal related work. The Division also maintains a database of TNPRC collaborators totaling 489 investigators from 38 states and 22 countries. Monitoring these types of activities results in accurate documentation of the TNPRC’s role in supporting NIH-funded investigators throughout the U.S. In fact, in recent years, it has been shown that the TNPRC collaborative efforts have supported over $200 million in NIH funded research.

STAFF (View Publications)

Chair – James L. Blanchard, DVM, PhD, Adjunct Professor of Medicine (send email)

Faculty

Aye, Pyone DVM, PhD, Research Assistant Professor
Blanchard, James L. DVM, PhD, Adjunct Professor