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Generation of high-level cytotoxic T...
~
Haglund, Karl Erick.
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Generation of high-level cytotoxic T-lymphocyte responses to human immunodeficiency virus proteins using live recombinant viruses (Immune deficiency).
Record Type:
Language materials, printed : Monograph/item
Title/Author:
Generation of high-level cytotoxic T-lymphocyte responses to human immunodeficiency virus proteins using live recombinant viruses (Immune deficiency)./
Author:
Haglund, Karl Erick.
Description:
240 p.
Notes:
Director: John K. Rose.
Contained By:
Dissertation Abstracts International63-03B.
Subject:
Biology, Microbiology. -
Online resource:
http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3046162
ISBN:
0493603735
Generation of high-level cytotoxic T-lymphocyte responses to human immunodeficiency virus proteins using live recombinant viruses (Immune deficiency).
Haglund, Karl Erick.
Generation of high-level cytotoxic T-lymphocyte responses to human immunodeficiency virus proteins using live recombinant viruses (Immune deficiency).
- 240 p.
Director: John K. Rose.
Thesis (Ph.D.)--Yale University, 2002.
The pandemic nature of human immunodeficiency virus-type 1 (HIV-1) infection mandates the rapid development of an HIV vaccine, and effective cytotoxic T-lymphocyte (CTL) responses are known to be important in controlling HIV. The primary goal of these studies was to quantitate <italic>in vivo</italic> primary and secondary CTL responses to human immunodeficiency virus-type 1 (HIV-1) Gag and Env expressed in recombinant vesicular stomatitis viruses (rVSVs). These responses were compared to those elicited by recombinant vaccinia viruses (rVVs) expressing Gag and Env.
ISBN: 0493603735Subjects--Topical Terms:
1017734
Biology, Microbiology.
Generation of high-level cytotoxic T-lymphocyte responses to human immunodeficiency virus proteins using live recombinant viruses (Immune deficiency).
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Generation of high-level cytotoxic T-lymphocyte responses to human immunodeficiency virus proteins using live recombinant viruses (Immune deficiency).
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240 p.
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Director: John K. Rose.
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Source: Dissertation Abstracts International, Volume: 63-03, Section: B, page: 1155.
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Thesis (Ph.D.)--Yale University, 2002.
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The pandemic nature of human immunodeficiency virus-type 1 (HIV-1) infection mandates the rapid development of an HIV vaccine, and effective cytotoxic T-lymphocyte (CTL) responses are known to be important in controlling HIV. The primary goal of these studies was to quantitate <italic>in vivo</italic> primary and secondary CTL responses to human immunodeficiency virus-type 1 (HIV-1) Gag and Env expressed in recombinant vesicular stomatitis viruses (rVSVs). These responses were compared to those elicited by recombinant vaccinia viruses (rVVs) expressing Gag and Env.
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Mice vaccinated with rVSVs generated robust primary CTL responses to Env and Gag. Approximately 40% of CD8<super>+</super> splenocytes recognized an immunodominant epitope in Env and were activated (CD62L<super>Lo</super>) after vaccination with a VSV-Env recombinant, and 3% recognized an immunodominant epitope in Gag and were CD62L<super>Lo</super> after vaccination with a VSV-Gag recombinant. A rVSV expressing Gag and Env simultaneously elicited similar responses to both proteins. Antigen-specific CTL elicited by vaccination produced interferon (IFN)-γ and lysed peptide-loaded target cells. Finally, the primary responses elicited by rVSVs were six- to eight-fold higher than those elicited by rVVs expressing Gag and Env.
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Recombinant VSV also elicited long-term memory responses. Seven months after vaccination with a VSV-Env recombinant, 6% of CD8<super>+</super> splenocytes were Env-specific and exhibited a memory phenotype (CD44<super>Hi</super>). When recall responses in mice primed with rVSVs were elicited by boosting with rVVs expressing Env or Gag, 40–45% of CD8<super>+</super> splenocytes were specific for Env or Gag. However, only half this response was elicited when the prime-boost order was reversed. Recalled CTL produced IFN-γ in response to antigen stimulation. Long after boosting with rVVs, Env- and Gag-specific CTL with a memory phenotype (CD44<super>Hi</super>) constituted 20–30% of CD8<super>+</super> splenocytes. Five-fold lower recall and resting memory responses were elicited by boosting with a VSV/HIV recombinant expressing a different serotype VSV glycoprotein.
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These results indicate that high-level primary and memory CTL responses are elicited to foreign proteins expressed in rVSVs. A heterologous boosting vector elicits higher recall and resting memory responses than does a homologous vector, possibly by focusing CTL responses on common antigens. These robust responses attest to the promise of rVSVs as HIV vaccines.
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School code: 0265.
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http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3046162
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