The relationship between T and B cell hepatitis B virus vaccine-specific responses in a cohort of healthy infants
department or school: Medicine, Faculty of
department or school: Medicine, Department of
data provider: DSpace
degree campus: UBCV
creator: Gelinas, Laura Clinckett
issued: 2013-07-04T09:10:03Z
issued: 2013
related degree: Master of Science - MSc
degree grantor: University of British Columbia
description: Vaccines are one of the greatest medical triumphs. Due to the empirical nature of vaccine development, however, it is still unclear how we maintain immunological memory and protection following vaccination. Using cells from a cohort of healthy infants and the hepatitis B virus (HBV) vaccine as a model, I developed a vaccine-specific stimulation assay that detects multiple immune readouts simultaneously from memory T cells in response to antigen stimulation in vitro. By stratifying my cohort by their anti-HBV surface antigen antibody (anti-HBs) titers, I determined how their HBV-specific memory T cell immune responses differed stratified by serological response. Based on my results, interferon (IFN)-γ appeared to be the most consistent predictor of a stronger serological response to HBV vaccination. The most striking trend was a positive correlation between bulk IFN-γ secretion and anti-HBs titers at 6 and 18 months following vaccination. A similar trend was noted for interleukin (IL)-10 secretion, but it did not extend past the 6-month time point. Tumor necrosis factor (TNF)-α, on the other hand, had a dynamic production profile. Overall, TNF-α production in proliferating CD8 T cells was increased in those subjects who produced lower levels of anti-HBs six months after vaccination. This observation was reversed by the 18-month time point—children who had anti-HBs titers less than 10 IU/l secreted lower levels of TNF-α. Many poor responders, as defined by their anti-HBs titers, demonstrated evidence of T cell memory either by HBsAg-specific proliferation, intracellular cytokine production, or cytokine secretion—indicating that an alternative or additional immunological mechanism might also correlate with vaccine-induced protection. The ultimate goal of this research project was to develop an in vitro antigen stimulation protocol that minimized sample usage and gathered data to help generate hypotheses regarding how the adaptive immune system, as a whole, responds to …
aggregated CHO: https://circle.library.ubc.ca/rest/handle/2429/44624
note: THE RELATIONSHIP BETWEEN T AND B CELL HEPATITIS B VIRUS VACCINE- SPECIFIC RESPONSES IN A COHORT OF HEALTHY INFANTS by Laura Clinckett Gelinas B.Sc.(Hons), Dalhousie University, 2010 A THESIS SUBMITTED IN PARTIAL FULFILLMENT OF THE REQUIREMENTS FOR THE DEGREE OF MASTER OF SCIENCE in The Faculty of Graduate Studies (Experimental Medicine) THE UNIVERSITY OF BRITISH COLUMBIA (Vancouver) June 2013 © Laura Clinckett Gelinas, 2013 ii ABSTRACT Vaccines are one of the greatest medical triumphs. Due to the empirical nature of vaccine development, however, it is still unclear how we maintain immunological memory and protection following vaccination. Using cells from a cohort of healthy infants and the hepatitis B virus (HBV) vaccine as a model, I developed a vaccine-specific stimulation assay that detects multiple immune readouts simultaneously from memory T cells in response to antigen stimulation in vitro. By stratifying my cohort by their anti-HBV surface antigen antibody (anti- HBs) titers, I determined how their HBV-specific memory T cell immune responses differed stratified by serological response. Based on my results, interferon (IFN)-γ appeared to be the most consistent predictor of a stronger serological response to HBV vaccination. The most striking trend was a positive correlation between bulk IFN-γ secretion and anti-HBs titers at 6 and 18 months following vaccination. A similar trend was noted for interleukin (IL)-10 secretion, but it did not extend past the 6-month time point. Tumor necrosis factor (TNF)-α, on the other hand, had a dynamic production profile. Overall, TNF-α production in proliferating CD8 T cells was increased in those subjects who produced lower levels of anti-HBs six months after vaccination. This observation was reversed by the 18-month time point—children who had anti-HBs titers less than 10 IU/l secreted lower levels of TNF-α. Many poor responders, as defined by their anti-HBs titers, demonstrated evidence of T cell memory either by HBsAg-sp…
has type: Thesis/Dissertation
date issued: 2013-11
is shown at: 10.14288/1.0073932
language: eng
degree discipline: Experimental Medicine
provider: Vancouver : University of British Columbia Library
publisher: University of British Columbia
rights: Attribution-NonCommercial-NoDerivs 3.0 Unported
rights URI: http://creativecommons.org/licenses/by-nc-nd/3.0/
scholar level: Graduate
type: Text
identifier URI: http://hdl.handle.net/2429/44624