title: Protection of macaques against Mycobacterium tuberculosis infection by a subunit vaccine based on a fusion protein of antigen 85B and ESAT-6.
abstract: Various new tuberculosis (TB) vaccine candidates in combination with new delivery systems, including subunit vaccines, are currently being evaluated by a number of laboratories. One vaccine candidate that has shown promising protective capacity in mice and guinea pigs is a fusion of Ag85B and ESAT-6. In this study, we have investigated the efficacy of this Ag85B-ESAT-6 fusion protein vaccine in a non-human primate model for TB. Vaccination of cynomolgus monkeys with the Ag85B-ESAT-6 fusion protein in two different adjuvant (DDA/MPL, AS02A) resulted in a reduction in bacterial number and/or lung pathology in animals challenged with Mycobacterium tuberculosis. Vaccination prevented an increase in C-reactive protein serum levels, general activation of CD4 and CD8 subsets and boosted development of humoral and cellular immune responses to a spectrum of mycobacterial antigens on exposure to M. tuberculosis infection. We show, in two independent experiments, that vaccination of primates with Ag85B-ESAT-6 induces protective immune responses, suggesting that Ag85B-ESAT-6 is a strong candidate for further clinical evaluation. As far as we are aware this is the first report of protection in primates with a subunit vaccine.
authors.affiliation: Department of Parasitology, Biomedical Primate Research Centre, P.O. Box 3306, 2280 GH Rijswijk, The Netherlands.
authors.forename: Jan A M
authors.initials: JA
authors.lastname: Langermans
authors.forename: T Mark
authors.initials: TM
authors.lastname: Doherty
authors.forename: Richard A W
authors.initials: RA
authors.lastname: Vervenne
authors.forename: Tridia
authors.initials: T
authors.lastname: van der Laan
authors.forename: Konstantin
authors.initials: K
authors.lastname: Lyashchenko
authors.forename: Rena
authors.initials: R
authors.lastname: Greenwald
authors.forename: Else Marie
authors.initials: EM
authors.lastname: Agger
authors.forename: Claus
authors.initials: C
authors.lastname: Aagaard
authors.forename: Horst
authors.initials: H
authors.lastname: Weiler
authors.forename: Dick
authors.initials: D
authors.lastname: van Soolingen
authors.forename: Wilfried
authors.initials: W
authors.lastname: Dalemans
authors.forename: Alan W
authors.initials: AW
authors.lastname: Thomas
authors.forename: Peter
authors.initials: P
authors.lastname: Andersen
mesh_terms: D000217:Acyltransferases / Q000276:immunology*; D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood; D000942:Antigens, Bacterial / Q000276:immunology*; D001426:Bacterial Proteins / Q000276:immunology*; D016516:CD4-CD8 Ratio; D007371:Interferon-gamma / Q000096:biosynthesis; D008252:Macaca fascicularis; D008297:Male; D011993:Recombinant Fusion Proteins / Q000276:immunology*; D014376:Tuberculosis / Q000517:prevention & control; D032581:Tuberculosis Vaccines / Q000276:immunology*; D014611:Vaccination; D022223:Vaccines, Subunit / Q000276:immunology; D014614:Vaccines, Synthetic / Q000276:immunology*
chemical_list: D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; D001426:Bacterial Proteins; C093276:ESAT-6 protein, Mycobacterium tuberculosis; D011993:Recombinant Fusion Proteins; D032581:Tuberculosis Vaccines; D022223:Vaccines, Subunit; D014614:Vaccines, Synthetic; D007371:Interferon-gamma; D000217:Acyltransferases; C121433:antigen 85B, Mycobacterium tuberculosis