Enhanced Immunogenicity and Protective Efficacy Against Mycobacterium tuberculosis of Bacille Calmette-Guérin Vaccine Using Mucosal Administration and Boosting with a Recombinant Modified Vaccinia Virus Ankara
Nilu Goonetilleke,Helen McShane,Carolyn M. Hannan,Richard J. Anderson,Roger H. Brookes,Adrian V. S. Hill +5 more
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TLDR
It is shown that recombinant modified vaccinia virus Ankara, expressing Mycobacterium tuberculosis Ag 85A (M.85A), strongly boosts bacille Calmette-Guérin (BCG)-induced Ag85A specific CD4+ and CD8+ T cell responses in mice, which support further evaluation of mucosally targeted prime-boost vaccination approaches for tuberculosis.Abstract:
Heterologous prime-boost immunization strategies can evoke powerful T cell immune responses and may be of value in developing an improved tuberculosis vaccine. We show that recombinant modified vaccinia virus Ankara, expressing Mycobacterium tuberculosis Ag 85A (M.85A), strongly boosts bacille Calmette-Guerin (BCG)-induced Ag 85A specific CD4(+) and CD8(+) T cell responses in mice. A comparison of intranasal (i.n.) and parenteral immunization of BCG showed that while both routes elicited comparable T cell responses in the spleen, only i.n. delivery elicited specific T cell responses in the lung lymph nodes, and these responses were further boosted by i.n. delivery of M.85A. Following aerosol challenge with M. tuberculosis, i.n. boosting of BCG with either BCG or M.85A afforded unprecedented levels of protection in both the lungs (2.5 log) and spleens (1.5 log) compared with naive controls. Protection in the lung correlated with the induction of Ag 85A-specific, IFN-gamma-secreting T cells in lung lymph nodes. These findings support further evaluation of mucosally targeted prime-boost vaccination approaches for tuberculosis.read more
Citations
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Journal ArticleDOI
Cell-Mediated Immune Responses in Tuberculosis
TL;DR: To improve current vaccine strategies, it is necessary to understand the factors that mediate induction, expression, and regulation of the immune response in the lung and determine how to induce both known and novel immunoprotective responses without inducing immunopathologic consequences.
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Safety and efficacy of MVA85A, a new tuberculosis vaccine, in infants previously vaccinated with BCG: a randomised, placebo-controlled phase 2b trial
Michele Tameris,Mark Hatherill,Bernard Landry,Thomas J. Scriba,Margaret A Snowden,Stephen Lockhart,Jacqueline E. Shea,J. Bruce McClain,Gregory D. Hussey,Willem A. Hanekom,Hassan Mahomed,Hassan Mahomed,Helen McShane +12 more
TL;DR: MVA85A was well tolerated and induced modest cell-mediated immune responses against tuberculosis and Mycobacterium tuberculosis infection in infants and did not differ between groups.
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The success and failure of BCG - implications for a novel tuberculosis vaccine.
TL;DR: The potential mechanisms behind the variation of BCG efficacy and their implications for an improved TB vaccination strategy are discussed.
Journal ArticleDOI
Recombinant modified vaccinia virus Ankara expressing antigen 85A boosts BCG-primed and naturally acquired antimycobacterial immunity in humans.
Helen McShane,Ansar A. Pathan,Clare R. Sander,Sheila M. Keating,Sarah C. Gilbert,Kris Huygen,Helen A. Fletcher,Adrian V. S. Hill,Adrian V. S. Hill +8 more
TL;DR: Recombinant modified vaccinia virus Ankara expressing antigen 85A (MVA85A) was found to induce high levels of antigen-specific IFN-γ-secreting T cells when used alone in bacille Calmette-Guérin (BCG)-naive healthy volunteers.
Journal ArticleDOI
Increased vaccine efficacy against tuberculosis of recombinant Mycobacterium bovis bacille Calmette-Guerin mutants that secrete listeriolysin
Leander Grode,Peter Seiler,Sven Baumann,Jürgen Hess,Volker Brinkmann,Ali Nasser Eddine,Peggy Mann,Christian Goosmann,Silke Bandermann,Debbie A. Smith,Gregory J. Bancroft,Jean-Marc Reyrat,Dick van Soolingen,Bärbel Raupach,Stefan H. E. Kaufmann +14 more
TL;DR: In this paper, the tuberculosis vaccine Mycobacterium bovis bacille Calmette-Guerin (BCG) was equipped with the membrane-perforating listeriolysin (Hly) of Listeria monocytogenes.
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