The factors essential to induction of a protective immune response to bacterial infections are incompletely understood. In the case of Listeria monocytogenes (LM) infection, a category B Priority Pathogen, CD8 T cells are important in effecting sterilizing immunity. LM interfaces at multiple levels with vaccinology as well as the Biodefense initiative due to the significant potential of LM as a vaccine candidate but also as an agent for intentional contamination and generation of highly virulent recombinant strains. Our work has begun to examine the parameters required for effective immunization with killed or mutant LM as potential vaccine vehicles. Specifically, immunization with heat killed LM (HKL) or irradiated LM (IRL) induced distinct patterns of T cell activation characterized by much more robust CD8 T cell memory induction following vaccination with IRL. However, IRL immunization did not induce the level of T cell activation and memory induction obtained with live LM infection. Thus, this is an excellent system for delineation of the mechanisms involved in promotion of distinct degrees of CD8 T cell activation generated by distinct forms of the same pathogen. Based on our preliminary data, the newly proposed studies focus on integrating the anatomy of effective CD8 T cell immune response initiation and memory T cell reactivation with the costimulatory and genetic programming necessary to drive a protective immune response. The hypothesis that responses induced by live infection versus immunization with attenuated vaccines share common essential components to generate protective memory will be tested in three aims:
Specific Aim 1. To determine the role of costimulation and CD4 T cell help in priming and protective recall responses following LM infection or vaccination.
Specific Aim 2. To determine the anatomical features of effective CD8 T cell vaccination and recall responses.
Specific Aim 3. To define the genetic signature of responding CD8 T cells in response to effective vaccination.

Public Health Relevance

The goal of this proposal is to determine the reasons why some vaccines are more effective than others. By studying different forms of a bacterial vaccine, our studies will help us devise more effective vaccination strategies.

National Institute of Health (NIH)
National Institute of Allergy and Infectious Diseases (NIAID)
Research Project (R01)
Project #
Application #
Study Section
Immunity and Host Defense Study Section (IHD)
Program Officer
Mills, Melody
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
University of Connecticut
Schools of Medicine
United States
Zip Code
Benechet, Alexandre P; Menon, Manisha; Xu, Daqi et al. (2016) T cell-intrinsic S1PR1 regulates endogenous effector T-cell egress dynamics from lymph nodes during infection. Proc Natl Acad Sci U S A 113:2182-7
Romagnoli, P A; Fu, H H; Qiu, Z et al. (2016) Differentiation of distinct long-lived memory CD4 T cells in intestinal tissues after oral Listeria monocytogenes infection. Mucosal Immunol :
Sheridan, Brian S; Pham, Quynh-Mai; Lee, Young-Tae et al. (2014) Oral infection drives a distinct population of intestinal resident memory CD8(+) T cells with enhanced protective function. Immunity 40:747-57
Bose, Tina O; Colpitts, Sara L; Pham, Quynh-Mai et al. (2014) CD11a is essential for normal development of hematopoietic intermediates. J Immunol 193:2863-72
Bose, Tina O; Pham, Quynh-Mai; Jellison, Evan R et al. (2013) CD11a regulates effector CD8 T cell differentiation and central memory development in response to infection with Listeria monocytogenes. Infect Immun 81:1140-51
Xu, Daqi; Fu, Han-Hsuan; Obar, Joshua J et al. (2013) A potential new pathway for PD-L1 costimulation of the CD8-T cell response to Listeria monocytogenes infection. PLoS One 8:e56539
Colpitts, Sara L; Stonier, Spencer W; Stoklasek, Thomas A et al. (2013) Transcriptional regulation of IL-15 expression during hematopoiesis. J Immunol 191:3017-24
Turner, Damian L; Bickham, Kara L; Farber, Donna L et al. (2013) Splenic priming of virus-specific CD8 T cells following influenza virus infection. J Virol 87:4496-506
Sheridan, Brian S; Romagnoli, Pablo A; Pham, Quynh-Mai et al. (2013) γδ T cells exhibit multifunctional and protective memory in intestinal tissues. Immunity 39:184-95
Plumlee, Courtney R; Sheridan, Brian S; Cicek, Basak B et al. (2013) Environmental cues dictate the fate of individual CD8+ T cells responding to infection. Immunity 39:347-56

Showing the most recent 10 out of 28 publications