title: Early cellular immune response to a new candidate mycobacterial vaccine antigen in childhood tuberculosis.
abstract: The search for novel vaccines against tuberculosis (TB) would benefit from in-depths knowledge of the human immune responses to Mycobacterium tuberculosis (Mtb) infection. Here, we characterised in a low TB incidence country, the immune responses to a new candidate vaccine antigen against TB, the heparin-binding haemagglutinin (HBHA), in young children in contact with an active TB case (aTB). Children with no history of BCG vaccination were compared to those vaccinated at birth to compare the initial immune responses to HBHA with secondary immune responses. Fifty-eight children with aTB and 76 with latent TB infection (LTBI) were included and they were compared to 90 non-infected children. Whereas Mtb-infected children globally secreted more interferon-gamma (IFN-γ) in response to HBHA compared to the non-infected children, these IFN-γ concentrations were higher in previously BCG-vaccinated compared to non-vaccinated children. The IFN-γ concentrations were similar in LTBI and aTB children, but appeared to differ qualitatively. Whereas the IFN-γ secretion induced by native methylated and recombinant non-methylated HBHA were well correlated for aTB, this was not the case for LTBI children. Thus, Mtb-infected young children develop IFN-γ responses to HBHA that are enhanced by prior BCG vaccination, indicating BCG-induced priming, thereby supporting a prime-boost strategy for HBHA-based vaccines. The qualitative differences between aTB and LTBI in their HBHA-induced IFN-γ responses may perhaps be exploited for diagnostic purposes.
authors.affiliation: Laboratory of Vaccinology and Mucosal Immunity, Université Libre de Bruxelles (U.L.B.), Brussels, Belgium; Immunodeficiency Unit, Hôpital Erasme, Université libre de Bruxelles (U.L.B.), Brussels, Belgium.
authors.forename: K
authors.initials: K
authors.lastname: Schepers
authors.affiliation: Laboratory of Vaccinology and Mucosal Immunity, Université Libre de Bruxelles (U.L.B.), Brussels, Belgium.
authors.forename: V
authors.initials: V
authors.lastname: Dirix
authors.affiliation: Department of Pediatrics, CHU Saint-Pierre, Université Libre de Bruxelles (U.L.B.), Brussels, Belgium.
authors.forename: F
authors.initials: F
authors.lastname: Mouchet
authors.affiliation: Laboratory of Vaccinology and Mucosal Immunity, Université Libre de Bruxelles (U.L.B.), Brussels, Belgium.
authors.forename: V
authors.initials: V
authors.lastname: Verscheure
authors.affiliation: INSERM U 1019, Lille, France; CNRS, UMR8204, Lille, France; Université de Lille Nord de France, Lille, France; Institut Pasteur de Lille, Center for Infection and Immunity of Lille, Lille, France.
authors.forename: S
authors.initials: S
authors.lastname: Lecher
authors.affiliation: INSERM U 1019, Lille, France; CNRS, UMR8204, Lille, France; Université de Lille Nord de France, Lille, France; Institut Pasteur de Lille, Center for Infection and Immunity of Lille, Lille, France.
authors.forename: C
authors.initials: C
authors.lastname: Locht
authors.affiliation: Laboratory of Vaccinology and Mucosal Immunity, Université Libre de Bruxelles (U.L.B.), Brussels, Belgium; Immunobiology Clinic, Hôpital Erasme, Université Libre de Bruxelles (U.L.B.), Brussels, Belgium. Electronic address: fmascart@ulb.ac.be.
authors.forename: F
authors.initials: F
authors.lastname: Mascart
mesh_terms: D000293:Adolescent; D000942:Antigens, Bacterial / Q000276:immunology*; D001500:BCG Vaccine / Q000276:immunology; D002648:Child; D002675:Child, Preschool; D016207:Cytokines / Q000378:metabolism; D005260:Female; D006801:Humans; D007111:Immunity, Cellular; D007223:Infant; D007231:Infant, Newborn; D007371:Interferon-gamma / Q000096:biosynthesis; D008297:Male; D009169:Mycobacterium tuberculosis / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism; D014376:Tuberculosis / Q000276:immunology* / Q000378:metabolism / Q000517:prevention & control*; D032581:Tuberculosis Vaccines / Q000276:immunology*; D014611:Vaccination; D055815:Young Adult
chemical_list: D000942:Antigens, Bacterial; D001500:BCG Vaccine; D016207:Cytokines; D032581:Tuberculosis Vaccines; D007371:Interferon-gamma
keywords: Childhood tuberculosis; Cytokines; Heparin binding haemagglutinin (HBHA); Interferon-γ; Primary tuberculosis