Abstract/Details

Vaccine-elicited memory cytotoxic T lymphocytes


2005 2005

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Abstract (summary)

Attempts to create an effective and safe vaccine for the prevention of human immunodeficiency virus (HIV) infection and disease have so far proven unsuccessful. Since virus-specific cytotoxic T lymphocytes (CTL) contribute to the control of HIV/SIV replication, most vaccine approaches being pursued include strategies for stimulating T cell responses. To facilitate the rational development of vaccine strategies that will elicit such memory T cell populations, we need to understand the mechanisms contributing to the development of vaccine-elicited memory CTL. We here describe the kinetics of the virus-specific CD8 + T lymphocyte responses following immunization of mice with three different vaccine vectors encoding HIV-1 Envelope (Env): plasmid DNA, recombinant vaccinia virus (rVac), and recombinant adenovirus (rAd). We prospectively monitored levels of antigen-specific CD8+ T cells in the blood and spleens of these mice using tetramers and characterized the effector and memory CTL elicited by each of these vaccine vectors by measuring their cell-surface expression of a variety of activation- and maturation-associated molecules. We found that the kinetics of CTL generation differed with each different vaccine modality, and observed no correlation between the phenotypic characteristics of rVac-elicited Env-specific CD8+ memory T cells and their functional capacities. The immunogenicity and pathogenicity of novel rVac constructs were assessed as part of an effort to create novel, safe immunogenic vaccine vectors for use in human populations. Finally, we observed that interferon-gamma (IFNγ) plays a role in damping the development of effector and memory CD8+ T cell populations generated by rAd immunization. Attempts to rationally design HIV-1 vaccines remain confounded by limitations in our understanding of the mechanisms underlying memory T cell generation. With a better understanding of these processes, we will be able to better define interventions for improving their development.

Indexing (details)


Subject
Immunology;
Cellular biology
Classification
0982: Immunology
0379: Cellular biology
Identifier / keyword
Health and environmental sciences; Biological sciences; CD8+; HIV; Interferon-gamma; Memory cytotoxic T lymphocytes; T lymphocytes; Vaccine-elicited memory CTL
Title
Vaccine-elicited memory cytotoxic T lymphocytes
Author
Jackson, Shawn Saliba
Number of pages
308
Publication year
2005
Degree date
2005
School code
0084
Source
DAI-B 66/05, Dissertation Abstracts International
Place of publication
Ann Arbor
Country of publication
United States
ISBN
0542113805, 9780542113802
Advisor
Letvin, Norman L.
University/institution
Harvard University
University location
United States -- Massachusetts
Degree
Ph.D.
Source type
Dissertations & Theses
Language
English
Document type
Dissertation/Thesis
Dissertation/thesis number
3173933
ProQuest document ID
305011772
Copyright
Database copyright ProQuest LLC; ProQuest does not claim copyright in the individual underlying works.
Document URL
http://search.proquest.com/docview/305011772
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