Maia Lintner
Research Mentor(s): Michal Olszewski
Department or Program: Internal Medicine/Microbology&Immunology
Authors: M. Lintner, A. Ballesteros, Y. Sinitsyna, R. Hissong, H. Lee, J. Xu, J. Perfect, K. Goughenour, M. Olszewski
Session: Session 2: 1:00pm-1:50pm
Poster: 27
Abstract
Cryptococcus neoformans (C. neo) is an environmental fungal pathogen that results in severe infections in immunocompromised individuals. C. neo infection has a high mortality due to the limited number of therapeutic options, as many antifungals are toxic or ineffective. The enzyme trehalose-6-phosphate synthase (TPS1), is the first step in the biosynthesis of the disaccharide trehalose. Recently, we found that a tps1 knockout (tps1Δ) C.neo is quickly cleared by pulmonary defenses. In this study, we wanted to investigate the role of tps1Δ on the adaptive immune response and its possible role in generating a protective immune response memory. Therefore, mice were infected intranasally with PBS (negative control), or live or heat-killed tps1Δ at -28 days and -14 days prior to WT challenge. Mice were then infected intratracheally with C. neo strain H99 as a challenge. Mice were monitored for survival. PBS-treated mice succumbed to infection at a mean of 23 days post-infection, while both live and heat-killed tps1Δ immunized mice survived to 70 days post-infection. Fungal burdens were quantified at the time of death or 70 days post infection. Vaccination with both live and heat-killed tps1Δ reduced fungal burdens in the lungs and greatly limited C.neo dissemination from lung to the other organs. Currently, we are investigating how vaccination alters the immune polarization of the adaptive immune response. The data indicate that tps1Δ mutant exposure can provide protection against subsequent WT infections. Thus, tps1Δ C. neo can serve as a promising vaccine candidate.
