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conferenceseries.com
November 28-29, 2016 Valencia, Spain
4th World Congress on
Infection Prevention and Control
Volume 4, Issue 8 (Suppl) J Infect Dis Ther 2016
ISSN: 2332-0877, JIDT an open access journal Infection Control 2016
November 28-29, 2016
Importance of Salmonella Typhi-specific CD8+ T cells in typhoid fever immunity in a human challenge
model
Stephanie Fresnay1, Monica A McArthur1, Thomas C Darton2, Claire Jones2 , Claire S Waddington2, Christoph J Blohmke2, Brian Angus2, Myron M Levine1,
Andrew J Pollard2 and Marcelo B Sztein1
1University of Maryland, USA
2University of Oxford, UK
Salmonella enterica serovar Typhi (S. Typhi) is a human restricted pathogen which causes significant morbidity and mortality,
particularly in developing countries. A better understanding of the immune responses which result in protection from S. Typhi
infection is imperative for the development of improved attenuated vaccines. Recently, a controlled human infection model was
re-established in which participants received ~104 cfu wild-type S. Typhi (Quailes strain) orally. 20 participants were evaluated
for their cell-mediated immune (CMI) responses. Ex vivo PBMC isolated before and up to 28 days after challenge were exposed
to 3 S. Typhi-infected targets, i.e., autologous B lymphoblastoid cell-lines (B-LCL), autologous blasts and HLA-E restricted AEH
B-LCL cells. CMI responses were evaluated using 14-color multiparametric flow cytometry to detect simultaneously 5 intracellular
cytokines/chemokines (i.e., IL-17A, IL-2, IFN-γ, TNF-α and MIP-1β) and a marker of degranulation/cytotoxic activity (CD107a) in
distinct T cell memory subsets. Pre-challenge production of IFN-γ, TNF-α and MIP-1β by S. Typhi-specific CD8+ multifunctional T
effector memory (TEM) following exposure to S. Typhi-infected targets were higher in most participants who develop infection. Early
decreases were observed in both S. Typhi-specific integrin α4β7-and integrin α4β7+CD8+ TEM cells after challenge, suggesting a
potential for these cells to home to mucosal, as well as to extra-intestinal sites. Higher baseline S. Typhi-specific CD8+ TEM responses
also correlated with delayed typhoid diagnosis. No changes in these responses were found in NoTD participants after challenge. These
studies demonstrate that S. Typhi-specific CD8+ baseline responses correlate with clinical outcome in humans challenged with wild-
type S. Typhi, and provide novel insights into the protective immune responses against typhoid disease that will aid in the selection
and development of new vaccine candidates.
Biography
Stephanie Fresnay is a Postdoctoral Fellow in the Cellular Immunology Section of the Center for Vaccine Development at the University of Maryland, USA. She
is a Co-Investigator for the clinical trial entitled “Understanding Typhoid Disease: Development of a Salmonella Typhi Challenge Model in Healthy Adults” and has
published in the Journal of Translational Medicine. She is also the co-author of several papers investigating regulatory T cells and antigen presenting cells function
after challenge with wild-type S. Typhi as well as the co-author of a study characterizing S. Typhi, S. Paratyphi A and S. Paratyphi B cross-reactive CD4+ T cell
responses elicited following vaccination.
Stephanie Fresnay et al., J Infect Dis Ther 2016, 4:8 (Suppl)