Daniela Cisneros
Research Mentor: Kristie Goughenour
Mentor Department: Not Available, Medicine
Author(s): Daniela Cisneros, Rylan Hissong, Jane Barnett, Maia Lintner, Alex Ballesteros, Jintao Xu, Michal Olszewski, Kristie Goughenour
Session: Session 1 (9:00 AM – 9:50 AM)
Presentation Type: Poster 136
Abstract
Trehalose-6-phosphate synthase (TPS1), an enzyme that synthesizes trehalose in plants, fungi, and bacteria, was found to be a favorable potential drug target for treating fungal infections such as those caused by Cryptococcus neoformans as the deletion of TPS1 gene led to avirulence in C. neoformans. Previous work in the lab showed that TPS1 protects C. neoformans against pulmonary host defenses in order to establish a long-lasting infection in the lungs. This project investigated whether immunization with a strain of Cryptococcus neoformans that lacked TPS1 would activate the adaptive immune system and if it could potentially be used as a vaccine candidate. Initially, mice were infected intranasally with 2 live-doses of a TPS1-deficient (tps1?) mutant strain of C. neoformans. Following their recovery from the tps1? strain, they were infected intratracheally with the highly virulent H99 strain of C. neoformans. Mice that were initially infected with tps1? showed improved rates of survival over a 70 day infection period and lower fungal burdens in multiple organs compared to the control group that was mock-infected with PBS. Immune analysis of the vaccinated mice showed a protective polarization of the T cell responses. Subsequent depletion of CD4+ T cells via treatment with a-CD4 antibody hindered the effectiveness of the initial immunization and led to no significant difference in survival rates between the tps1?-exposed and the PBS-exposed mice. Thus, the tps1? strain has the potential to interact with the adaptive immune system as a vaccine and provide long-term protection.
