title: Protective efficacy of a lipid antigen vaccine in a guinea pig model of tuberculosis.
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.
authors.affiliation: Institut de Pharmacologie et de Biologie Structurale, Université de Toulouse, CNRS, UPS, France.
authors.forename: Gérald
authors.initials: G
authors.lastname: Larrouy-Maumus
authors.affiliation: Institut de Pharmacologie et de Biologie Structurale, Université de Toulouse, CNRS, UPS, France.
authors.forename: Emilie
authors.initials: E
authors.lastname: Layre
authors.affiliation: Public Health England, National Infections Service, Porton Down, Wiltshire SP4 0JG, UK.
authors.forename: Simon
authors.initials: S
authors.lastname: Clark
authors.affiliation: Institut de Pharmacologie et de Biologie Structurale, Université de Toulouse, CNRS, UPS, France.
authors.forename: Jacques
authors.initials: J
authors.lastname: Prandi
authors.affiliation: Public Health England, National Infections Service, Porton Down, Wiltshire SP4 0JG, UK.
authors.forename: Emma
authors.initials: E
authors.lastname: Rayner
authors.affiliation: Experimental Immunology, Department of Biomedicine, University Hospital and University of Basel, Basel 4031, Switzerland.
authors.forename: Marco
authors.initials: M
authors.lastname: Lepore
authors.affiliation: Experimental Immunology, Department of Biomedicine, University Hospital and University of Basel, Basel 4031, Switzerland.
authors.forename: Gennaro
authors.initials: G
authors.lastname: de Libero
authors.affiliation: Public Health England, National Infections Service, Porton Down, Wiltshire SP4 0JG, UK.
authors.forename: Ann
authors.initials: A
authors.lastname: Williams
authors.affiliation: Institut de Pharmacologie et de Biologie Structurale, Université de Toulouse, CNRS, UPS, France.
authors.forename: Germain
authors.initials: G
authors.lastname: Puzo
authors.affiliation: Institut de Pharmacologie et de Biologie Structurale, Université de Toulouse, CNRS, UPS, France. Electronic address: Martine.Gilleron@ipbs.fr.
authors.forename: Martine
authors.initials: M
authors.lastname: Gilleron
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage; D000818:Animals; D000942:Antigens, Bacterial / Q000008:administration & dosage / Q000276:immunology* / Q000302:isolation & purification; D058491:Bacterial Load; D004195:Disease Models, Animal; D005260:Female; D006017:Glycolipids / Q000008:administration & dosage / Q000276:immunology* / Q000302:isolation & purification; D006168:Guinea Pigs; D008081:Liposomes / Q000008:administration & dosage; D008168:Lung / Q000382:microbiology / Q000473:pathology; D009169:Mycobacterium tuberculosis / Q000276:immunology*; D013154:Spleen / Q000382:microbiology / Q000473:pathology; D016896:Treatment Outcome; D014376:Tuberculosis / Q000382:microbiology / Q000473:pathology / Q000517:prevention & control*; D032581:Tuberculosis Vaccines / Q000008:administration & dosage / Q000276:immunology* / Q000302:isolation & purification
chemical_list: D000276:Adjuvants, Immunologic; D000942:Antigens, Bacterial; D006017:Glycolipids; D008081:Liposomes; D032581:Tuberculosis Vaccines
keywords: CD1b; Glycolipid; Guinea pig; Liposome; Tuberculosis; Vaccine