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Title: Evaluation of the ability of N-terminal fragment of lethal factor of Bacillus anthracis for delivery of Mycobacterium T cell antigen ESAT-6 into cytosol of antigen presenting cells to elicit effective cytotoxic T lymphocyte response

Abstract

We report the ability of N-terminal fragment of lethal factor of Bacillus anthracis to deliver genetically fused ESAT-6 (early secretory antigen target), a potent T cell antigen of Mycobacterium tuberculosis, into cytosol to elicit Cytotoxic T lymphocyte (CTL) response. In vitro Th1 cytokines data and CTL assay proved that efficient delivery of LFn.ESAT-6 occurs in cytosol, in the presence of protective antigen (PA), and leads to generation of effective CTL response. Since CTL response is essential for protection against intracellular pathogens and, it is well known that only single T cell epitope or single antigenic protein is not sufficient to elicit protective CTL response due to variation or polymorphism in MHC-I alleles among the individuals, we suggest that as a fusion protein LFn can be used to deliver multiepitopes of T cells or multiproteins which can generate effective CTLs against intracellular pathogens like M. tuberculosis. It can be used to enhance the protective efficacy of BCG vaccine.

Authors:
 [1];  [1];  [1];  [1];  [2]
  1. Center for Biotechnology, Jawaharlal Nehru University, New Delhi 110067 (India)
  2. International Center for Genetic Engineering and Biotechnology, Aruna Asaf Ali Marg, New Delhi 110067 (India)
Publication Date:
OSTI Identifier:
20857928
Resource Type:
Journal Article
Journal Name:
Biochemical and Biophysical Research Communications
Additional Journal Information:
Journal Volume: 351; Journal Issue: 3; Other Information: DOI: 10.1016/j.bbrc.2006.10.099; PII: S0006-291X(06)02353-9; Copyright (c) 2006 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA); Journal ID: ISSN 0006-291X
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; ANTIGENS; BACILLUS; EVALUATION; IN VITRO; LYMPHOCYTES; LYMPHOKINES; MYCOBACTERIUM TUBERCULOSIS; PATHOGENS; TUBERCULOSIS

Citation Formats

Chandra, Subhash, Kaur, Manpreet, Midha, Shuchi, Bhatnagar, Rakesh, and Banerjee-Bhatnagar, Nirupama. Evaluation of the ability of N-terminal fragment of lethal factor of Bacillus anthracis for delivery of Mycobacterium T cell antigen ESAT-6 into cytosol of antigen presenting cells to elicit effective cytotoxic T lymphocyte response. United States: N. p., 2006. Web. doi:10.1016/j.bbrc.2006.10.099.
Chandra, Subhash, Kaur, Manpreet, Midha, Shuchi, Bhatnagar, Rakesh, & Banerjee-Bhatnagar, Nirupama. Evaluation of the ability of N-terminal fragment of lethal factor of Bacillus anthracis for delivery of Mycobacterium T cell antigen ESAT-6 into cytosol of antigen presenting cells to elicit effective cytotoxic T lymphocyte response. United States. https://doi.org/10.1016/j.bbrc.2006.10.099
Chandra, Subhash, Kaur, Manpreet, Midha, Shuchi, Bhatnagar, Rakesh, and Banerjee-Bhatnagar, Nirupama. 2006. "Evaluation of the ability of N-terminal fragment of lethal factor of Bacillus anthracis for delivery of Mycobacterium T cell antigen ESAT-6 into cytosol of antigen presenting cells to elicit effective cytotoxic T lymphocyte response". United States. https://doi.org/10.1016/j.bbrc.2006.10.099.
@article{osti_20857928,
title = {Evaluation of the ability of N-terminal fragment of lethal factor of Bacillus anthracis for delivery of Mycobacterium T cell antigen ESAT-6 into cytosol of antigen presenting cells to elicit effective cytotoxic T lymphocyte response},
author = {Chandra, Subhash and Kaur, Manpreet and Midha, Shuchi and Bhatnagar, Rakesh and Banerjee-Bhatnagar, Nirupama},
abstractNote = {We report the ability of N-terminal fragment of lethal factor of Bacillus anthracis to deliver genetically fused ESAT-6 (early secretory antigen target), a potent T cell antigen of Mycobacterium tuberculosis, into cytosol to elicit Cytotoxic T lymphocyte (CTL) response. In vitro Th1 cytokines data and CTL assay proved that efficient delivery of LFn.ESAT-6 occurs in cytosol, in the presence of protective antigen (PA), and leads to generation of effective CTL response. Since CTL response is essential for protection against intracellular pathogens and, it is well known that only single T cell epitope or single antigenic protein is not sufficient to elicit protective CTL response due to variation or polymorphism in MHC-I alleles among the individuals, we suggest that as a fusion protein LFn can be used to deliver multiepitopes of T cells or multiproteins which can generate effective CTLs against intracellular pathogens like M. tuberculosis. It can be used to enhance the protective efficacy of BCG vaccine.},
doi = {10.1016/j.bbrc.2006.10.099},
url = {https://www.osti.gov/biblio/20857928}, journal = {Biochemical and Biophysical Research Communications},
issn = {0006-291X},
number = 3,
volume = 351,
place = {United States},
year = {Fri Dec 22 00:00:00 EST 2006},
month = {Fri Dec 22 00:00:00 EST 2006}
}