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 Dalemans; Joe 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

doi:10.1016/j.tube.2004.09.009

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 journal › Article › peer-review

156 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 language	English
Pages (from-to)	29-38
Number of pages	10
Journal	Tuberculosis
Volume	85
Issue number	1-2 SPEC.ISS.
DOIs	https://doi.org/10.1016/j.tube.2004.09.009
Publication status	Published - 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

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.tube.2004.09.009

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Williams, A., Hatch, G. J., Clark, S., Gooch, K. E., Hatch, K. A., Hall, G., Huygen, K., Ottenhoff, T. H. M., Franken, K. L. M. C., Andersen, P., Doherty, T. M., Kaufmann, S. H. E., Grode, L., Seiler, P., Martin, C., Gicquel, B., Cole, S. T., Brodin, P., Pym, A. S., ... Marsh, P. D. (2005). Evaluation of vaccines in the EU TB Vaccine Cluster using a guinea pig aerosol infection model of tuberculosis. Tuberculosis, 85(1-2 SPEC.ISS.), 29-38. https://doi.org/10.1016/j.tube.2004.09.009

@article{64a22d03ce4a407380a31a3f4b417acc,

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

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.",

keywords = "Aerosol, Guinea pig, Tuberculosis, Vaccine",

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

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. ",

year = "2005",

doi = "10.1016/j.tube.2004.09.009",

language = "English",

volume = "85",

pages = "29--38",

journal = "Tuberculosis",

issn = "1472-9792",

publisher = "Churchill Livingstone",

number = "1-2 SPEC.ISS.",

}

Williams, A, Hatch, GJ , Clark, S , Gooch, KE, Hatch, KA, Hall, G, Huygen, K, Ottenhoff, THM, Franken, KLMC, Andersen, P, Doherty, TM, Kaufmann, SHE, Grode, L, Seiler, P, Martin, C, Gicquel, B, Cole, ST, Brodin, P, Pym, AS, Dalemans, W, Cohen, J, Lobet, Y, Goonetilleke, N, McShane, H, Hill, A, Parish, T, Smith, D, Stoker, NG, Lowrie, DB, Källenius, G, Svenson, S, Pawlowski, A, Blake, K & Marsh, PD 2005, 'Evaluation of vaccines in the EU TB Vaccine Cluster using a guinea pig aerosol infection model of tuberculosis', Tuberculosis, vol. 85, no. 1-2 SPEC.ISS., pp. 29-38. https://doi.org/10.1016/j.tube.2004.09.009

TY - JOUR

T1 - Evaluation of vaccines in the EU TB Vaccine Cluster using a guinea pig aerosol infection model of tuberculosis

AU - Williams, Ann

AU - Hatch, Graham J.

AU - Clark, Simon

AU - Gooch, Karen E.

AU - Hatch, Kim A.

AU - Hall, Graham

AU - Huygen, Kris

AU - Ottenhoff, Tom H.M.

AU - Franken, Kees L.M.C.

AU - Andersen, Peter

AU - Doherty, T. Mark

AU - Kaufmann, Stefan H.E.

AU - Grode, Leander

AU - Seiler, Peter

AU - Martin, Carlos

AU - Gicquel, Brigitte

AU - Cole, Stewart T.

AU - Brodin, Priscille

AU - Pym, Alexander S.

AU - Dalemans, Wilfried

AU - Cohen, Joe

AU - Lobet, Yves

AU - Goonetilleke, Nilu

AU - McShane, Helen

AU - Hill, Adrian

AU - Parish, Tanya

AU - Smith, Debbie

AU - Stoker, Neil G.

AU - Lowrie, Douglas B.

AU - Källenius, Gunilla

AU - Svenson, Stefan

AU - Pawlowski, Andrzej

AU - Blake, Karen

AU - Marsh, Philip D.

N1 - 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.

PY - 2005

Y1 - 2005

N2 - 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.

AB - 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.

KW - Aerosol

KW - Guinea pig

KW - Tuberculosis

KW - Vaccine

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U2 - 10.1016/j.tube.2004.09.009

DO - 10.1016/j.tube.2004.09.009

M3 - Article

C2 - 15687025

AN - SCOPUS:20144389346

SN - 1472-9792

VL - 85

SP - 29

EP - 38

JO - Tuberculosis

JF - Tuberculosis

IS - 1-2 SPEC.ISS.

ER -

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

Abstract

Bibliographical note

Keywords

UN SDGs

Access to Document

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