Characterisation of a live Salmonella vaccine stably expressing the Mycobacterium tuberculosis Ag85B-ESAT6 fusion protein

Lindsay J. Hall; Simon Clare; Derek Pickard; Simon O. Clark; Dominic L.F. Kelly; Moataz Abd El Ghany; Christine Hale; Jes Dietrich; Peter Andersen; Philip D. Marsh; Gordon Dougan

doi:10.1016/j.vaccine.2009.09.007

Characterisation of a live Salmonella vaccine stably expressing the Mycobacterium tuberculosis Ag85B-ESAT6 fusion protein

Lindsay J. Hall^*, Simon Clare, Derek Pickard, Simon O. Clark, Dominic L.F. Kelly, Moataz Abd El Ghany, Christine Hale, Jes Dietrich, Peter Andersen, Philip D. Marsh, Gordon Dougan

^*Corresponding author for this work

NIS: Research & Technical Staff

Research output: Contribution to journal › Article › peer-review

30 Citations (Scopus)

Abstract

A recombinant Salmonella enterica serovar Typhimurium (S. Typhimurium) vaccine strain was constructed that stably expressed the Mycobacterium tuberculosis fusion antigen Ag85B-ESAT6 from the chromosome. Live oral vaccination of mice with the Salmonella/Ag85B-ESAT6 strain generated a potent anti-Ag85B-ESAT6 T_H1 response with high antibody titres with a IgG2a-bias and significant IFN-γ production lasting over a 120-day period. When mice primed with the Salmonella/Ag85B-ESAT6 vaccine were mucosally boosted with the Ag85B-ESAT6 antigen and adjuvant the IFN-γ responses increased markedly. To determine the protective efficacy of this vaccine strain, guinea pigs were immunised and followed for a 30-week period after aerosol challenge with M. tuberculosis. The heterologous prime-boost strategy of live Salmonella vaccine followed by a systemic boost of antigen and adjuvant reduced the levels of M. tuberculosis bacteria in the lungs and spleen to the same extent as BCG. Additionally, this vaccination regimen was observed to be statistically equivalent in terms of protection to immunisation with BCG. Thus, live oral priming with the recombinant Salmonella/Ag85B-ESAT6 and boosting with Ag85B-ESAT6 plus the adjuvant LTK63 represents an effective mucosal vaccination regimen.

Original language	English
Pages (from-to)	6894-6904
Number of pages	11
Journal	Vaccine
Volume	27
Issue number	49
DOIs	https://doi.org/10.1016/j.vaccine.2009.09.007
Publication status	Published - 16 Nov 2009

Bibliographical note

Funding Information:
This study was carried out with financial support from the Commission of the European Communities, Sixth Framework Programme, contract LSHP-CT-2003-503240, Mucosal Vaccines for Poverty-Related Diseases (MUVAPRED) and The Wellcome Trust. We would also like to thank Novartis, Italy, for their kind gifts of purified LT and LTK63, and Statens Serum Institute, Denmark for Ag85B–ESAT6. The staff in the biological investigations group are sincerely thanked for their technical support.

Keywords

M. tuberculosis
Mucosal vaccine
Salmonella vector

UN SDGs

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

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10.1016/j.vaccine.2009.09.007

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@article{34ea2cabbf384f8580de4882bfb66279,

title = "Characterisation of a live Salmonella vaccine stably expressing the Mycobacterium tuberculosis Ag85B-ESAT6 fusion protein",

abstract = "A recombinant Salmonella enterica serovar Typhimurium (S. Typhimurium) vaccine strain was constructed that stably expressed the Mycobacterium tuberculosis fusion antigen Ag85B-ESAT6 from the chromosome. Live oral vaccination of mice with the Salmonella/Ag85B-ESAT6 strain generated a potent anti-Ag85B-ESAT6 TH1 response with high antibody titres with a IgG2a-bias and significant IFN-γ production lasting over a 120-day period. When mice primed with the Salmonella/Ag85B-ESAT6 vaccine were mucosally boosted with the Ag85B-ESAT6 antigen and adjuvant the IFN-γ responses increased markedly. To determine the protective efficacy of this vaccine strain, guinea pigs were immunised and followed for a 30-week period after aerosol challenge with M. tuberculosis. The heterologous prime-boost strategy of live Salmonella vaccine followed by a systemic boost of antigen and adjuvant reduced the levels of M. tuberculosis bacteria in the lungs and spleen to the same extent as BCG. Additionally, this vaccination regimen was observed to be statistically equivalent in terms of protection to immunisation with BCG. Thus, live oral priming with the recombinant Salmonella/Ag85B-ESAT6 and boosting with Ag85B-ESAT6 plus the adjuvant LTK63 represents an effective mucosal vaccination regimen.",

keywords = "M. tuberculosis, Mucosal vaccine, Salmonella vector",

author = "Hall, {Lindsay J.} and Simon Clare and Derek Pickard and Clark, {Simon O.} and Kelly, {Dominic L.F.} and Ghany, {Moataz Abd El} and Christine Hale and Jes Dietrich and Peter Andersen and Marsh, {Philip D.} and Gordon Dougan",

note = "Funding Information: This study was carried out with financial support from the Commission of the European Communities, Sixth Framework Programme, contract LSHP-CT-2003-503240, Mucosal Vaccines for Poverty-Related Diseases (MUVAPRED) and The Wellcome Trust. We would also like to thank Novartis, Italy, for their kind gifts of purified LT and LTK63, and Statens Serum Institute, Denmark for Ag85B–ESAT6. The staff in the biological investigations group are sincerely thanked for their technical support.",

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doi = "10.1016/j.vaccine.2009.09.007",

language = "English",

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AU - Hall, Lindsay J.

AU - Clare, Simon

AU - Pickard, Derek

AU - Clark, Simon O.

AU - Kelly, Dominic L.F.

AU - Ghany, Moataz Abd El

AU - Hale, Christine

AU - Dietrich, Jes

AU - Andersen, Peter

AU - Marsh, Philip D.

AU - Dougan, Gordon

N1 - Funding Information: This study was carried out with financial support from the Commission of the European Communities, Sixth Framework Programme, contract LSHP-CT-2003-503240, Mucosal Vaccines for Poverty-Related Diseases (MUVAPRED) and The Wellcome Trust. We would also like to thank Novartis, Italy, for their kind gifts of purified LT and LTK63, and Statens Serum Institute, Denmark for Ag85B–ESAT6. The staff in the biological investigations group are sincerely thanked for their technical support.

PY - 2009/11/16

Y1 - 2009/11/16

N2 - A recombinant Salmonella enterica serovar Typhimurium (S. Typhimurium) vaccine strain was constructed that stably expressed the Mycobacterium tuberculosis fusion antigen Ag85B-ESAT6 from the chromosome. Live oral vaccination of mice with the Salmonella/Ag85B-ESAT6 strain generated a potent anti-Ag85B-ESAT6 TH1 response with high antibody titres with a IgG2a-bias and significant IFN-γ production lasting over a 120-day period. When mice primed with the Salmonella/Ag85B-ESAT6 vaccine were mucosally boosted with the Ag85B-ESAT6 antigen and adjuvant the IFN-γ responses increased markedly. To determine the protective efficacy of this vaccine strain, guinea pigs were immunised and followed for a 30-week period after aerosol challenge with M. tuberculosis. The heterologous prime-boost strategy of live Salmonella vaccine followed by a systemic boost of antigen and adjuvant reduced the levels of M. tuberculosis bacteria in the lungs and spleen to the same extent as BCG. Additionally, this vaccination regimen was observed to be statistically equivalent in terms of protection to immunisation with BCG. Thus, live oral priming with the recombinant Salmonella/Ag85B-ESAT6 and boosting with Ag85B-ESAT6 plus the adjuvant LTK63 represents an effective mucosal vaccination regimen.

AB - A recombinant Salmonella enterica serovar Typhimurium (S. Typhimurium) vaccine strain was constructed that stably expressed the Mycobacterium tuberculosis fusion antigen Ag85B-ESAT6 from the chromosome. Live oral vaccination of mice with the Salmonella/Ag85B-ESAT6 strain generated a potent anti-Ag85B-ESAT6 TH1 response with high antibody titres with a IgG2a-bias and significant IFN-γ production lasting over a 120-day period. When mice primed with the Salmonella/Ag85B-ESAT6 vaccine were mucosally boosted with the Ag85B-ESAT6 antigen and adjuvant the IFN-γ responses increased markedly. To determine the protective efficacy of this vaccine strain, guinea pigs were immunised and followed for a 30-week period after aerosol challenge with M. tuberculosis. The heterologous prime-boost strategy of live Salmonella vaccine followed by a systemic boost of antigen and adjuvant reduced the levels of M. tuberculosis bacteria in the lungs and spleen to the same extent as BCG. Additionally, this vaccination regimen was observed to be statistically equivalent in terms of protection to immunisation with BCG. Thus, live oral priming with the recombinant Salmonella/Ag85B-ESAT6 and boosting with Ag85B-ESAT6 plus the adjuvant LTK63 represents an effective mucosal vaccination regimen.

KW - M. tuberculosis

KW - Mucosal vaccine

KW - Salmonella vector

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DO - 10.1016/j.vaccine.2009.09.007

M3 - Article

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SN - 0264-410X

VL - 27

SP - 6894

EP - 6904

JO - Vaccine

JF - Vaccine

IS - 49

ER -

Characterisation of a live Salmonella vaccine stably expressing the Mycobacterium tuberculosis Ag85B-ESAT6 fusion protein

Abstract

Bibliographical note

Keywords

UN SDGs

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