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Scientific Discoveries

The Tulane National Primate Research Center has been involved in a variety of important multidisciplinary projects focusing on areas of biomedical research with high priority concerns for human health. The information below highlights some of these scientific discoveries.

AIDS
Animal Welfare
Assisted Reproductive Technology
Biodefense
Chikungunya and West Nile Virus
Cytomegalovirus (CMV)
Enteric Viruses
Gastrointestinal Disease
Human T-Cell Lymphotrophic Virus (HTLV)
Immunology of Aging
Krabbe's Disease
Leprosy
Lyme Disease
Macrophages in Disease
Malaria
Microsporidiosis
Regenerative Medicine
Relapsing Fever
Simian Varicella Virus (SVV)
Tuberculosis
Zika

AIDS

AIDS Pathogenesis
  • Demonstrated the intestinal immune system is the primary target of SIV infection which was later validated in humans.
  • Defined the early time course and key target cells of SIV infection, which was also validated in HIV-infected humans.
  • Developed the macaque model of neurologic AIDS.
  • Demonstrated that neuroinvasion by SIV occurs within days of infection and involves specific leukocyte and endothelial adhesion molecules and chemokines.
  • Described the early targets and effects of SIV infection on immune cells and responses in the gut, spleen, bone marrow, brain, liver, and thymus in vivo.
AIDS Vaccines
  • Developed novel mucosal vaccine protocols and approaches.
  • Tested new vaccine candidates and adjuvants in infant and adult macaques
Heterosexual Transmission of AIDS
  • Developed the macaque model of heterosexual transmission of SIV.
  • Defined hormonal influences on vaginal transmission of SIV, and first demonstrated progesterone increases SIV/HIV vaginal transmission rates.
  • Demonstrated the protective effects of topical vaginal microbicides to prevent heterosexual transmission of AIDS.
  • Identified the first cellular and molecular targets involved in both vaginal and rectal SIV/SHIV transmission.
Origins of AIDS
  • Proved that SIV was an ancient virus much older than originally believed.
  • Identified the sooty mangabey as the natural host of SIV and the most likely source of Human Immunodeficiency Virus-2 (HIV-2).
  • Identified a novel SIV in red-capped and mandrills.

Animal Welfare

  • Developed a minimally invasive thoracoscopic surgical procedure to acquire biopsies of the thymus, dramatically decreasing surgical morbidity. 
  • Confirmed the efficacy of a commercially available transdermal anthelmintic agent, reducing the need for injections. 
  • Implemented the use of videoendopic biopsy procedures in nonhuman primate instestines, to replace full thickness intestinal resection and anastomosis for biopsy procedures.
  • Established that the social housing of nonhuman primates improved their ability to adapt to stressors in their environment. 
  • Performed chorionic villous sampling in pregnant rhesus macaques to collect biopsies for genetic testing.
  • Developed a chorionic catheterization model for the thoracic duct to collect cells for studies in AIDS immunity. 
  • Demonstrated the feasibility and positive effects of social housing of adult male rhesus monkeys. 
  • Demonstrated that clinical observations captured on video compared to direct observation by humans provides information important to developing an accurate clinical diagnosis in rhesus monkeys. 
  • Demonstrated that an effective multiple drug antibiotic therapy used to treat idiopathic enterocolitis in rhesus monkeys only transiently and insignificantly alters the instestinal microbiome.

Assisted Reproductive Technology

  • Developed a system for the in vitro production of rhesus embryos.
  • Superovulation and retrieval of mature rhesus oocytes.
  • Developed rhesus embryos to the blastocyst stage following in vitro fertilization and culture.
  • Cryopreserved in vitro-derived rhesus embryos.
  • Successfully transferred fresh and cryopreserved normal rhesus embryos resulting in five single and two sets of twin pregnancies.

Biodefense

  • Developed an array of biodefense-relevant nonhuman primate disease models including the pathogenic alphaviruses and poxviruses. 
  • Demonstrated the first therapeutic treatment and rescue of nonhuman primates from a lethal aerosol of ricin toxin. 
  • Demonstrated the utility and correlative association of physiological response as an endpoint in vaccine evaluation utilizing nonhuman primate model of Eastern Equine Encephalitis infection. 
  • Established a nonhuman primate model of inhalation glanders (Burkholderia mallei) and demonstrated utility in a candidate vaccine trial. 
  • Established the immunogenicity and protective efficacy of a ricin vaccine in a nonhuman primate model of aerosolized ricin toxin. 

Chikungunya and West Nile Virus

  • Demonstrated glial activation in flavivirus infection.

Congenital Cytomegalovirus (CMV) 

  • Developed the first experimental nonhuman primate model of primary congenital CMV infection in rhesus macaques for studies on immune protection and CMV vaccine development
  • First demonstration of placental rhesus CMV transmission in pregnant macaques
  • Demonstrated that maternal CD4+ T lymphocytes are critical for preventing placental CMV transmission and protecting against fetal loss
  • Showed that delayed onset of anti-CMV neutralizing antibodies and CMV-specific T cell immunity increased risk of congenital CMV transmission
  • Demonstrated that passively infused pre-existing high titer anti-CMV antibodies are sufficient for protection against congenital CMV infection
  • Showed evidence of immune selection pressure on transmitted viral variants

Enteric Viruses

  • Isolated and characterized a new rotavirus from juvenile monkeys (TUCH)
  • TUCH classified as simian rotavirus, genotype G1P[8].
  • Identified rotavirus VP6-specific CD4+ T cell epitopes.
  • Reported role of rotavirus VP4 in biliary atresia and cholangiopathy.
  • Reported rotavirus interspecies transmission and reassortment.
  • Isolated and characterized a new enteric calicivirus of rhesus origin (TV):
  • New genus within family Caliciviridae, i.e., Recovirus.
  • Recovered infectious TV from transfected cells in vitro.
  • Established juvenile rhesus macaque model of TV infection.
  • Demonstrated presence of TV antibodies in humans.
  • Described genetic diversity and human HBGA-TV interactions.

Gastrointestinal Disease

Established a nonhuman primate model of rotavirus infection
  • Isolated and characterized a new rotavirus of simian origina that was classified as genotype P.
  • Developed new molecular tool (real time PCR) for quantitative evaluation of rotavirus infection.
Chronic enterocolitis of rhesus macaques
  • Described new cytolethal distending toxin-producing strain of Campylobacter jejuni isolated from nonhuman primates. 
  • Determined inflammatory cytolethal distending toxin-producing strain of Campylobacter jejuni isolated from nonhuman primates. 
  • Determined inflammatory cytokine genes that are upregulated during chronic enterocolitis. 
  • Visualized in situ cytokine-producing macrophage and T cell subsets that are involved in chronic enterocolitis. 
  • Demonstrated polymicrobial origins of chronic entrocolitis in rhesus macaques and its similarieis to Inflammatory Bowel Disease of humans. 

Human T-Cell Lymphotrophic Virus (HTLV)

  • Developed a rhesus model of HTLV-1 infection that produced early signs of disease, both adult T-cell lymphoma/leukemia and HTLV-associated myelopathy.
  • Co-infection of HTLV-I and SIV in rhesus produced accelerated HTLV-I disease symptoms.

Immunology of Aging

  • Characterized immune correlates of aging and inflammation in rhesus macaques as a model for human aging. 
  • Demonstrated that SIV infection progresses more rapidly in tandem with higher monocyte turnover in older than younger adult rhesus macaques. 
  • Applied mathematical modeling to demonstrate changes in neutrophil and macrophage kinetics during aging in rhesus macques. 

Krabbe's Disease

  • Established a model of Krabbe's Disease in macaques. 

Leprosy

  • Discovered the sooty mangabese to be a natural host of Mycobacterium leprae.

Lyme Disease

Lyme Disease Diagnosis and Treatment
  • Developed a peptide-based diagnostic immunoassay (C6) that outperforms the currently available two-tier test. This assay is now approved by the Food and Drug Administration (FDA) for use in humans and by the USDA for use in animals.
  • Discovered the antigen-dependent dynamics of longitudinal antibody responses to B. burgdorferi infection in monkeys; used these findings to select a combination of antigens for diagnostic test development.
  • Developed a Luminex®-based multi-antigen diagnostic test for serodiagnosis of Lyme disease. This test expands the specificity of detection across early and late phases of disease.
  • Discovered that current antibiotic monotherapy does not clear B. burgdorferi from infected primates. Further study revealed that the persistent spirochetes are living and induce mild to moderate inflammation in multiple organs, including the heart, joints and peripheral nervous system.
Lyme Disease Pathogenesis and Spirochete Biology
  • Established the rhesus monkey model of Lyme disease.
  • Discovered that neuronal degeneration secondary to inflammation could cause the mononeuropathy multiplex commonly observed in neuroborreliosis of the peripheral nervous system.
  • Discovered that inflammation is the key effector of Lyme disease in the central nervous system.
  • Discovered an immune evasion mechanism that Borrelia burgdorferi, the spirochete that causes the disease, may use to cause persistent infections.
  • Discovered that spirochetes elicit not only inflammatory but also anti-inflammatory cytokines from monocytes, thus contributing a method to control the inflammation they themselves cause.
  • Discovered that B. burgdorferi regulates gene expression in a cell-density dependent manner.
  • Discovered that B. burgdorferi antigenic variation does not occur in the tick.

Macrophages in Disease

  • Determined that increased frequency monocyte turnover rate is indicate of tissue macrophage destruction and onset of terminal disease progression to AIDS in SIV-infected rhesus macaques. 
  • Showed that increased monocyte turnover is associated with reactivation of latent tuberculosis in SIV and Mtb co-infected rhesus macaques. 
  • Reported that higher physiologic monocyte turnover may contribute to faster disease progression in SIV-infected neonatal rhesus macaques. 

Malaria

  • Discovered the parasite stage responsible for malaria relapse (the hypnozoite).
  • Developed molecular markers for malaria relapse.
  • Developed the first monkey model of malaria during pregnancy.
  • Developed the only successful model of congenital malaria.
  • Established that placental malaria in the macaque is similar to human placental malaria.
  • Ultrasonographic exams established intrauterine growth retardation (IUGR) and not prematurity as the cause of low birth weight (potential model of IUGR).

Microsporidiosis

  • Identified for the first time a prokaryotic gene in a eukaryotic organism, the microsporidian Vittaforma corneae. This led to the inclusion of fluoroquinolones as lead compounds for treating microsporidiosis.
  • Isolated and identified a new microsporidian species, Encephalitozoon hellem, which infects humans and birds.
  • Identified unique genotype markers among isolates of Encephalitozoon cuniculi.
  • Developed improved Polymerase Chain Reaction (PCR)-based methods for diagnosing microsporidiosis.
  • Developed in vitro and in vivo models for testing and identifying drugs with antimicrosporidial activity.
  • Applied genotyping diagnostics to identify animal reservoirs of microsporidia species that pose a risk for transmission to humans.
  • Contributed to genome sequencing and transcriptome projects for several microsporidia species that infect humans, nonhuman primates (and other animals). 
  • Defined mechanisms of macrophage-mediated destruction of intracellular microsporidia species that infect humans and nonhuman primates.

Regenerative Medicine

  • Characterized and applied as therapies mesenchymal stem cells from bone marrow and adipose tissue of rhesus macaques.
  • Developed and tested novel CAR-T cell strategies targeting SIV.
  • Started a tissue engineering research program focused on the nonhuman primate model.
  • Successfully developed a tissue engineered nipple areolar complex in the NHP model.
  • Developing novel neurotropic adeno-associated virus vectors via virus evolution for gene therapy applications.
  • Developed novel gene therapy vectors targeting both the brain and hematopoietic stem cells for the treatment of Krabbe’s disease.

Relapsing Fever

  • Established a rhesus macaque model of tick-borne relapsing fever using infection with Borrelia turicatae. Using real-time monitoring, quantified febrile episodes corresponding to high spirochete loads in the blood and discovered that cardiac function is impaired.
  • Discovered inflammatory mediators of blood cells induced specifically by B. turicatae and antibody responses to conserved antigens that may serve as vaccine candidates. 

Respiratory Syncytial Virus (RSV)

  • Developed a monkey model of RSV infection.
  • Successfully tested multiple RSV vaccines.
  • Successfully tested monoclonal antibody treatment against RSV F glycoprotein, that was later FDA approved. 

Simian Varicella Virus (SVV)

  • Developed a monkey model of varicella (chickenpox) and zoster (shingles.)
  • Successfully tested the first antiviral treatment Acyclovir, that was later FDA approved. 

Tuberculosis

  • Established various model of TB in rhesus monkeys to study active TB, chemotherapy and response to vaccination, as well as to study TB latency, reactivation by various factors including SIV co-infection, and the impact of ART and LTBI chemotherapy.
  • Developed a new experimental vaccine which shows exceptional promise as a novel anti-TB vaccine vehicle.
  • Established various model of TB in rhesus monkeys to study active TB, chemotherapy and response to vaccination, as well as to study TB latency, reactivation by various factors including SIV co-infection, and the impact of ART and LTBI chemotherapy.
  • Developed a new research area in the field of host-directed therapies against TB, including testing anti-cancer compound Imatinib, which is now included in an NIH-funded clinical trial in South Africa.
  • Developed a new approach to testing the effectiveness of LTBI chemotherapy in the macaque model.
  • Identified a major role for hypoxia response program of M. tuberculosis in persistence in lung granulomas.
  • Identified a major role for B cells in protection from TB.

Zika

  • Zika virus infection of pregnant animals and pathology in infants. 
  • Discovered that Zika virus infection during early pregnancy results in frequent fetal loss.