Preclinical Development of an In Vivo BCG Challenge Model for Testing Candidate TB Vaccine Efficacy
Open Access
- 24 May 2011
- journal article
- research article
- Published by Public Library of Science (PLoS) in PLOS ONE
- Vol. 6 (5), e19840
- https://doi.org/10.1371/journal.pone.0019840
Abstract
There is an urgent need for an immunological correlate of protection against tuberculosis (TB) with which to evaluate candidate TB vaccines in clinical trials. Development of a human challenge model of Mycobacterium tuberculosis (M.tb) could facilitate the detection of such correlate(s). Here we propose a novel in vivo Bacille Calmette-Guérin (BCG) challenge model using BCG immunization as a surrogate for M.tb infection. Culture and quantitative PCR methods have been developed to quantify BCG in the skin, using the mouse ear as a surrogate for human skin. Candidate TB vaccines have been evaluated for their ability to protect against a BCG skin challenge, using this model, and the results indicate that protection against a BCG skin challenge is predictive of BCG vaccine efficacy against aerosol M.tb challenge. Translation of these findings to a human BCG challenge model could enable more rapid assessment and down selection of candidate TB vaccines and ultimately the identification of an immune correlate of protection.Keywords
This publication has 52 references indexed in Scilit:
- Imaging tuberculosis with endogenous β-lactamase reporter enzyme fluorescence in live miceProceedings of the National Academy of Sciences of the United States of America, 2010
- Immunogenicity and Protective Efficacy of Prime-Boost Regimens with Recombinant Δ ureC hly + Mycobacterium bovis BCG and Modified Vaccinia Virus Ankara Expressing M. tuberculosis Antigen 85A against Murine TuberculosisInfection and Immunity, 2009
- Mycobacterium bovisBCG Immunization Induces Protective Immunity against Nine DifferentMycobacterium tuberculosisStrains in MiceInfection and Immunity, 2008
- Single-Dose Protection againstPlasmodium bergheiby a Simian Adenovirus Vector Using a Human Cytomegalovirus Promoter Containing Intron AJournal of Virology, 2008
- Time Lines of Infection and Disease in Human Influenza: A Review of Volunteer Challenge StudiesAmerican Journal of Epidemiology, 2008
- Intranasal Boosting with an Adenovirus-Vectored Vaccine Markedly Enhances Protection by Parenteral Mycobacterium bovis BCG Immunization against Pulmonary TuberculosisInfection and Immunity, 2006
- The Influence of Remaining Live BCG Organisms in Vaccinated Mice on the Maintenance of Immunity to TuberculosisScandinavian Journal of Immunology, 2004
- CD4+and CD8+T Cells Mediate Adoptive Immunity to Aerosol Infection ofMycobacterium bovisBacillus Calmette‐GuérinThe Journal of Infectious Diseases, 2000
- Immune response to Mycobacterium bovis bacille Calmette Guérin infection in major histocompatibility complex class I‐ and II‐deficient knock‐out mice: contribution of CD4 and CD8 T cells to acquired resistanceEuropean Journal of Immunology, 1995
- TEMPORAL DEVELOPMENT OF RESISTANCE TO PULMONARY TUBERCULOSIS IN SWISS ALBINO MICEThe Journal of Experimental Medicine, 1971