Lack of Immune Responses to
Mycobacterium tuberculosis
DosR Regulon Proteins following
Mycobacterium bovis
BCG Vaccination
-
Published:2007-07
Issue:7
Volume:75
Page:3523-3530
-
ISSN:0019-9567
-
Container-title:Infection and Immunity
-
language:en
-
Short-container-title:Infect Immun
Author:
Lin May Young1, Geluk Annemieke1, Smith Steven G.2, Stewart Amanda L.3, Friggen Annemieke H.1, Franken Kees L. M. C.1, Verduyn Marleen J. C.1, van Meijgaarden Krista E.1, Voskuil Martin I.3, Dockrell Hazel M.2, Huygen Kris4, Ottenhoff Tom H. M.1, Klein Michèl R.1
Affiliation:
1. Department of Immunohematology and Blood Transfusion and Department of Infectious Diseases, Leiden University Medical Center, Leiden, The Netherlands 2. Department of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, Keppel Street, London, United Kingdom 3. Department of Microbiology, University of Colorado Health Sciences Center, Denver, Colorado 4. Laboratory of Mycobacterial Immunology, WIV-Pasteur Institute, B1180 Brussels, Belgium
Abstract
ABSTRACT
Mycobacterium bovis
BCG is widely used as a vaccine against tuberculosis (TB), despite its variable protective efficacy. Relatively little is known about the immune response profiles following BCG vaccination in relation to protection against TB. Here we tested whether BCG vaccination results in immune responses to DosR (Rv3133c) regulon-encoded proteins. These so-called TB latency antigens are targeted by the immune system during persistent
Mycobacterium tuberculosis
infection and have been associated with immunity against latent
M. tuberculosis
infection. In silico analysis of the DosR regulon in BCG and
M. tuberculosis
showed at least 97% amino acid sequence homology, with 41 out of 48 genes being identical. Transcriptional profiling of 14 different BCG strains, under hypoxia and nitric oxide exposure in vitro, revealed a functional DosR regulon similar to that observed in
M. tuberculosis
. Next, we assessed human immune responses to a series of immunodominant TB latency antigens and found that BCG vaccination fails to induce significant responses to latency antigens. Similar results were obtained with BCG-vaccinated BALB/c mice. In contrast, responses to latency antigens were observed in individuals with suspected exposure to TB (as indicated by positive gamma interferon responses to TB-specific antigens ESAT-6 and CFP-10) and in mice vaccinated with plasmid DNA encoding selected latency antigens. Since immune responses to TB latency antigens have been associated with control of latent
M. tuberculosis
infection, our findings support the development of vaccination strategies incorporating DosR regulon antigens to complement and improve the current BCG vaccine.
Publisher
American Society for Microbiology
Subject
Infectious Diseases,Immunology,Microbiology,Parasitology
Reference43 articles.
1. Armbruster, C., W. Junker, N. Vetter, and G. Jaksch. 1990. Disseminated bacille Calmette-Guerin infection in an AIDS patient 30 years after BCG vaccination. J. Infect. Dis.162:1216. 2. Behr, M. A., and P. M. Small. 1997. Has BCG attenuated to impotence? Nature389:133-134. 3. Black, G. F., P. E. M. Fine, D. K. Warndorff, S. Floyd, R. E. Weir, J. M. Blackwell, L. Bliss, L. Sichali, L. Mwaungulu, S. Chaguluka, E. Jarman, B. Ngwira, and H. M. Dockrell. 2001. Relationship between IFN-γ and skin test responsiveness to Mycobacterium tuberculosis PPD in healthy, non-BCG-vaccinated young adults in Northern Malawi. Int. J. Tuber. Lung Dis.5:664-672. 4. Black, G. F., R. E. Weir, S. Floyd, L. Bliss, D. K. Warndorff, A. C. Crampin, B. Ngwira, L. Sichali, B. Nazareth, J. M. Blackwell, K. Branson, S. D. Chaguluka, L. Donovan, E. Jarman, E. King, P. E. Fine, and H. M. Dockrell. 2002. BCG-induced increase in interferon-gamma response to mycobacterial antigens and efficacy of BCG vaccination in Malawi and the UK: two randomised controlled studies. Lancet359:1393-1401. 5. Mycobacterium bovis
BCG Response Regulator Essential for Hypoxic Dormancy
Cited by
90 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献
|
|