Dr. Gauduin has more than 25 years of experience in HIV/AIDS research and medical microbiology. She has been working extensively on HIV and the development of novel vaccine strategies using the non-human primate model for AIDS. In her work, she uses epithelial stem cells and weakened recombinant papillomavirus as vaccine- vectors to protect against multiple low-dose mucosal challenges. Dr. Gauduin is also developing a neonatal model for tuberculosis to study HIV/TB co-infection in pediatric AIDS.
Her specific research interests are:
- Early events of simian immunodeficiency virus (SIV) transmission in a macaque model
- Host immune responses to infectious diseases
- Early virus-specific T cell responses in neonates
- Tuberculosis/SIV coinfection in pediatric AIDS
Gauduin’s laboratory is investigating the early events of SIV transmission in macaque using a recombinant SIV tagged with a “green fluorescent protein” as a sensitive tool to monitor infected cells in vivo. This construct allows the team to identify: 1) the initial infected cells, their phenotype and function; 2) the mechanisms involved, time course and routes of viral spread from the site of initial infection to lymphoid organs and blood; and 3) the generation of early SIV-specific immune response from the mucosal site of infection. This is critical for the development of effective vaccines.
Maternal transmission of HIV-1 accounts for most cases of pediatric HIV-1 infection. Gauduin’s group is investigating the early virus-specific T cell responses in neonates orally infected with a pathogenic or non-pathogenic strain of simian immunodeficiency virus (SIV), an HIV laboratory surrogate. She has shown that newborn monkeys infected with a less pathogenic SIV can control infection even in the absence of antiviral treatment, which suggests that treatment may be quite successful in "rescuing" or preserving the infant’s immune response. The laboratory is now focusing on defining the mechanisms involved in oral SIV transmission to develop effective strategies to successfully block SIV transmission.
One key obstacle to an effective AIDS vaccine has been the inability to deliver antigen for a sufficient period of time leading to weak and transient protection. Because HIV transmission occurs predominantly across mucosal surfaces, the ideal vaccine strategy would be to target HIV at mucosal entry sites of transmission to prevent infection. Gauduin proposes to develop a novel genetic vaccine strategy that delivers viral proteins. A promoter will drive antigen expression and stem cells will continuously yield new (daughter) antigenproducing cells without being eliminated by the immune response.
TB is the leading cause of death among people with HIV, and pregnant women living with active TB and HIV are at far greater risk of maternal mortality than those without HIV infection Gauduin has established an experimental acute M. tuberculosis infection in the newborn primate model to produce progressive and/ or active but asymptomatic infections that mimic the clinical and pathologic effects of pediatric tuberculosis. The ultimate goal is to optimize neonatal primate model for TB/HIV co-infection to study immunopathogenesis of TB/SIV interactions, the impact of treatment and treatment interruption on the evolution of tuberculosis.
High cell-free virus load and robust autologous adaptive immune responses in breast milk of SIV-infected African green monkeys. Wilks AB, Perry JR, Ehlinger EP, Zahn RC, White B, Gauduin MC, Carville A, Seaman MS, Schmitz JE, Permar AR. J Virol 85: 9517-26, 2011
PubMed ID: 21734053
Vaccine protection by live, attenuated simian immunodeficiency virus in the absence of high-titer antibody responses and high-frequency cellular immune responses measurable in the periphery. Mansfield K, Lang SM, Gauduin M-C, Sanford HB, Lifson JD, Johnson RP, Desrosiers RC. J Virol 82 (8): 4135-4148, 2008
PubMed ID: 18272584
Expression of CD8alpha identifies a distinct subset of effector memory CD4+ T lymphocytes. Macchia I, Gauduin M-C, Kaur A, and Johnson RP. Immunology 119 (2): 232-242, 2006
PubMed ID: 16836648
Induction of a virus-specific CD4+ T cell responses by attenuated SIV infection.Gauduin M-C, Yu Y, Piatak M, Lifson J, Desrosiers RC, and Johnson RP. J Exp Med 203 (12): 2661-2672, 2006
PubMed ID: 17116733
Intracellular cytokine staining for the characterization and quantitation of antigenspecific T lymphocyte responses. Gauduin M-C. Methods 38 (4): 263-273, 2006
PubMed ID: 16481196
Elevated interleukin-7 levels are not sufficient to maintain T-cell homeostasis during simian immunodeficiency virus induced disease progression.Muthukumar A, Wozniakowski A, Gauduin M-C, Johnson RP, McClure HM, Silvestri G, and Sodora DL. Blood 103: 973-979, 2004
PubMed ID: 14525780
Optimization of intracellular cytokine staining for quantitation of Ag-specific CD4+ T cell responses in macaques.Gauduin M-C, Kaur A, Ahmad S, Yilma T, Lifson JD, and Johnson RP. J Immunol 288: 61-79, 2004
PubMed ID: 15183086