Protective efficacy of a lipid antigen vaccine in a guinea pig model of tuberculosis

Gérald Larrouy-Maumus; Emilie Layre; Simon Clark; Jacques Prandi; Emma Rayner; Marco Lepore; Gennaro de Libero; Ann Williams; Germain Puzo; Martine Gilleron

doi:10.1016/j.vaccine.2017.01.079

Protective efficacy of a lipid antigen vaccine in a guinea pig model of tuberculosis

Gérald Larrouy-Maumus, Emilie Layre, Simon Clark, Jacques Prandi, Emma Rayner, Marco Lepore, Gennaro de Libero, Ann Williams, Germain Puzo, Martine Gilleron^*

^*Corresponding author for this work

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Abstract

The bacillus Calmette Guérin (BCG) vaccine, the only licensed vaccine against TB, displays partial and variable efficacy, thus making the exploitation of novel vaccination strategies a major priority. Most of the current vaccines in pre-clinical or clinical development are based on the induction of T cells recognizing protein antigens. However, a large number of T cells specific for mycobacterial lipids are induced during infection, suggesting that lipid-based vaccines might represent an important component of novel sub-unit vaccines. Here, we investigated whether immunization with defined mycobacterial lipid antigens induces protection in guinea pigs challenged with M. tuberculosis. Two purified mycobacterial lipid antigens, the diacylated sulfoglycolipids (Ac₂SGL) and the phosphatidyl-myo-inositol dimannosides (PIM₂) were formulated in biophysically characterized liposomes made of dimethyl-dioctadecyl-ammonium (DDA) and synthetic trehalose 6,6′-dibehenate (TDB). In three protection trials, a reduction of bacterial load in the spleen of inoculated animals was consistently observed compared to the unvaccinated group. Moreover, a reduction in the number of lesions and severity of pathology was detected in the lungs and spleen of the lipid vaccine group compared to unvaccinated controls. As the degree of protection achieved is similar to that observed using protein antigens in the same guinea pig model, these promising results pave the way to future investigations of lipid antigens as subunit vaccines.

Original language	English
Pages (from-to)	1395-1402
Number of pages	8
Journal	Vaccine
Volume	35
Issue number	10
DOIs	https://doi.org/10.1016/j.vaccine.2017.01.079
Publication status	Published - 7 Mar 2017

Bibliographical note

Funding Information:
This work was supported by the Centre National de la Recherche Scientifique, the European Community's Seventh Framework Program under grant agreement HEALTH-F7-2009-241745 (EU-FP7), NEWTBVAC, Research Grant from Mérieux Alliance (23/4/2009–22/04/2011), the Swiss National Foundation (310030-149571), the BMRC-SERC Diagnostic grant 1121480006 and the Department of Health, UK. The views expressed in this publication are those of the authors and not necessarily those of the Department of Health. We thank the staff of the Biological Investigations Group at PHE Porton for assistance in conducting studies and to Emma Rayner and her PHE Pathology team for the provision of histopathology data. We also thank Dr Julien Vaubourgeix and Dr Diane Cala for purification of natural Ac2SGL and Dr Alexiane Decout for formulation preparation.

Publisher Copyright:
© 2017 Elsevier Ltd

Keywords

CD1b
Glycolipid
Guinea pig
Liposome
Tuberculosis
Vaccine

UN SDGs

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

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10.1016/j.vaccine.2017.01.079

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title = "Protective efficacy of a lipid antigen vaccine in a guinea pig model of tuberculosis",

abstract = "The bacillus Calmette Gu{\'e}rin (BCG) vaccine, the only licensed vaccine against TB, displays partial and variable efficacy, thus making the exploitation of novel vaccination strategies a major priority. Most of the current vaccines in pre-clinical or clinical development are based on the induction of T cells recognizing protein antigens. However, a large number of T cells specific for mycobacterial lipids are induced during infection, suggesting that lipid-based vaccines might represent an important component of novel sub-unit vaccines. Here, we investigated whether immunization with defined mycobacterial lipid antigens induces protection in guinea pigs challenged with M. tuberculosis. Two purified mycobacterial lipid antigens, the diacylated sulfoglycolipids (Ac2SGL) and the phosphatidyl-myo-inositol dimannosides (PIM2) were formulated in biophysically characterized liposomes made of dimethyl-dioctadecyl-ammonium (DDA) and synthetic trehalose 6,6′-dibehenate (TDB). In three protection trials, a reduction of bacterial load in the spleen of inoculated animals was consistently observed compared to the unvaccinated group. Moreover, a reduction in the number of lesions and severity of pathology was detected in the lungs and spleen of the lipid vaccine group compared to unvaccinated controls. As the degree of protection achieved is similar to that observed using protein antigens in the same guinea pig model, these promising results pave the way to future investigations of lipid antigens as subunit vaccines.",

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author = "G{\'e}rald Larrouy-Maumus and Emilie Layre and Simon Clark and Jacques Prandi and Emma Rayner and Marco Lepore and {de Libero}, Gennaro and Ann Williams and Germain Puzo and Martine Gilleron",

note = "Funding Information: This work was supported by the Centre National de la Recherche Scientifique, the European Community's Seventh Framework Program under grant agreement HEALTH-F7-2009-241745 (EU-FP7), NEWTBVAC, Research Grant from M{\'e}rieux Alliance (23/4/2009–22/04/2011), the Swiss National Foundation (310030-149571), the BMRC-SERC Diagnostic grant 1121480006 and the Department of Health, UK. The views expressed in this publication are those of the authors and not necessarily those of the Department of Health. We thank the staff of the Biological Investigations Group at PHE Porton for assistance in conducting studies and to Emma Rayner and her PHE Pathology team for the provision of histopathology data. We also thank Dr Julien Vaubourgeix and Dr Diane Cala for purification of natural Ac2SGL and Dr Alexiane Decout for formulation preparation. Publisher Copyright: {\textcopyright} 2017 Elsevier Ltd",

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AU - Clark, Simon

AU - Prandi, Jacques

AU - Rayner, Emma

AU - Lepore, Marco

AU - de Libero, Gennaro

AU - Williams, Ann

AU - Puzo, Germain

AU - Gilleron, Martine

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Protective efficacy of a lipid antigen vaccine in a guinea pig model of tuberculosis

Abstract

Bibliographical note

Keywords

UN SDGs

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