Evaluation of vaccines in the EU TB Vaccine Cluster using a guinea pig aerosol infection model of tuberculosis

Ann Williams*, Graham J. Hatch, Simon Clark, Karen E. Gooch, Kim A. Hatch, Graham Hall, Kris Huygen, Tom H.M. Ottenhoff, Kees L.M.C. Franken, Peter Andersen, T. Mark Doherty, Stefan H.E. Kaufmann, Leander Grode, Peter Seiler, Carlos Martin, Brigitte Gicquel, Stewart T. Cole, Priscille Brodin, Alexander S. Pym, Wilfried DalemansJoe Cohen, Yves Lobet, Nilu Goonetilleke, Helen McShane, Adrian Hill, Tanya Parish, Debbie Smith, Neil G. Stoker, Douglas B. Lowrie, Gunilla Källenius, Stefan Svenson, Andrzej Pawlowski, Karen Blake, Philip D. Marsh

*Corresponding author for this work

    Research output: Contribution to journalArticlepeer-review

    144 Citations (Scopus)

    Abstract

    The TB Vaccine Cluster project funded by the EU Fifth Framework programme aims to provide novel vaccines against tuberculosis that are suitable for evaluation in humans. This paper describes the studies of the protective efficacy of vaccines in a guinea pig aerosol-infection model of primary tuberculosis. The objective was to conduct comparative evaluations of vaccines that had previously demonstrated efficacy in other animal models. Groups of 6 guinea pigs were immunized with vaccines provided by the relevant EU Vaccine Cluster partners. Survival over 17 or 26 weeks was used as the principal measure of vaccine efficacy following aerosol challenge with H37Rv. Counts of mycobacteria in lungs and spleens, and histopathological changes in the lungs, were also used to provide evidence of protection. A total of 24 vaccines were evaluated in 4 experiments each of a different design. A heterologous prime-boost strategy of DNA and MVA, each expressing Ag85A and a fusion protein of ESAT-6 and Ag85B in adjuvant, protected the guinea pigs to the same extent as BCG. Genetically modified BCG vaccines and boosted BCG strategies also protected guinea pigs to the same extent as BCG but not statistically significantly better. A relatively high aerosol-challenge dose and evaluation over a protracted time post-challenge allowed superior protection over BCG to be demonstrated by BCG boosted with MVA and fowl pox vectors expressing Ag85A.

    Original languageEnglish
    Pages (from-to)29-38
    Number of pages10
    JournalTuberculosis
    Volume85
    Issue number1-2 SPEC.ISS.
    DOIs
    Publication statusPublished - 2005

    Bibliographical note

    Funding Information:
    This work was funded by the European Community (QKL2-CT1999-01093) and the Department of Health (UK). The views expressed in this publication are those of the authors and not necessarily those of the funding bodies. All the providers of the vaccines, as listed in Table 1 are gratefully acknowledged, as are members of the TB Cluster Steering Committee, namely Prof. Brigitte Gicquel, Prof. Douglas Young, Prof. Stefan H.E. Kaufmann, Prof. THM Ottenhoff, Dr. Jelle Thole, Dr. Carlos Martin, Dr. Jean-Jacques Fournie and Prof. Peter Andersen. The staff in the Biological Investigations Group at HPA Porton Down are sincerely thanked for their technical support.

    Keywords

    • Aerosol
    • Guinea pig
    • Tuberculosis
    • Vaccine

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