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
In The Lab
SIV transmission. Our lab is investigating the early events of SIV transmission in macaques using a recombinant SIV tagged with a green fluorescent protein (GFP) as a sensitive tool to monitor infected cells in vivo. This construct allows us to identify the:
- initial infected cells, their phenotype and function
- mechanisms, time course, and routes of viral spread from the site of initial infection to lymphoid organs and blood
- generation of early SIV-specific immune response from the mucosal site of infection
These factors are critical for the development of effective vaccines.
HIV vaccine design and development. One key obstacle to an effective AIDS vaccine has been the inability to deliver antigen for a sufficient period of time. Because HIV transmission occurs mainly across mucosal surfaces, the ideal vaccine strategy would be to target HIV at mucosal entry sites of transmission to prevent infection. Our lab developed a novel vaccine strategy based on gene therapy with the goal to elicit a long-term immunity against HIV infection at the entry site of the virus. This strategy is based on the ability of therapeutic lentiviral vectors integrated in epidermal or mucosal epithelial stem cells to induce virus-specific cellular immune responses at mucosal sites against HIV/ SIV. It represents an alternative approach using epithelial stem cells as a permanent source of viral antigen and their differentiated offspring as antigen-producing presenting cells.
Maternal transmission of HIV-1 accounts for most cases of pediatric HIV-1 infection. Using a macaque model, we are investigating the early virus-specific T cell responses in neonatesorally infected with a pathogenic or non-pathogenic strain of SIV, (an HIV laboratory surrogate). We have 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. Our present emphasis is on defining the mechanisms involved in oral SIV transmission to develop effective strategies to successfully block SIV transmission.
Tuberculosis (TB) is the leading cause of death among people with HIV, and pregnant women living with active TB and HIV are at greatest risk. Our group established an acute Mycobacterium tuberculosis infection in the newborn macaque model, optimized techniques to study acute pediatric TB infection in young macaques, and successfully demonstrated that it clinically and pathologically mimics the disease as seen in human infants. We confirmed that newborn macaques are highly susceptible to TB infection and can serve as a suitable animal model to study latent TB.
Our goal is the optimization of this model for TB/HIV co-infection to study immunopathogenesis of TB/SIV interactions and the impact of treatment and treatment interruption on the evolution of tuberculosis.
The development of an effective vaccine that restricts viral replication at the mucosal portal of entry may be our best hope for controlling HIV infection. Our experiments further refine the rationale for using vector vaccine strategies in advancing our understanding of the role of mucosal immune responses in protection, an area of considerable importance for AIDS vaccine research.
Main Technologies And Methods Used
- Vector-vaccine designs and development
- Cutting-edge quantitative virologic assays
- Polyfunctional intracellular staining techniques
- Humoral/cellular mucosal immune responses
- Vaccine efficacy and correlates of protection
- Non-human primate models for AIDS and TB