title: HBHA vaccination may require both Th1 and Th17 immune responses to protect mice against tuberculosis.
abstract: Almost one century after the discovery of the BCG vaccine, tuberculosis remains a major cause of global mortality and morbidity, emphasizing the urgent need to design more efficient vaccines. The heparin-binding haemagglutinin (HBHA) appears to be a promising vaccine candidate, as it was shown to afford protection to mice against a challenge infection with Mycobacterium tuberculosis when combined with the strong adjuvant DDA/MPL (dimethyldioctadecyl-ammonium bromide/monophosphoryl lipid A), a TLR4 ligand. In this study, we investigated the immunological response and protection of mice immunized with HBHA formulated in lipid-containing nanoparticles and adjuvanted with CpG, a TLR9 ligand. Subcutaneous immunization with this HBHA formulation led to a marked Th1 response, characterized by high IFN-γ levels, but no significant IL-17 production, both in spleen and lung, in contrast to DDA/MPL MPL-formulated HBHA, which induced both IFN-γ and IL-17. This cytokine profile was also observed in BCG-primed mice and persisted after M. tuberculosis infection. No significant protection was obtained against challenge infection after vaccination with the nanoparticle-CpG formulation, and this was associated with a failure to mount a memory immune response. These results suggest the importance of both Th1 and Th17 immune responses for vaccine-induced immunity.
authors.affiliation: Inserm U1019, Lille, France; CNRS UMR8204, Lille, France; Institut Pasteur de Lille, Center for Infection and Immunity of Lille, Lille, France; Univ Lille Nord de France, Lille, France. Electronic address: claudie.verwaerde@ibl.cnrs.fr.
authors.forename: Claudie
authors.initials: C
authors.lastname: Verwaerde
authors.affiliation: Inserm U1019, Lille, France; CNRS UMR8204, Lille, France; Institut Pasteur de Lille, Center for Infection and Immunity of Lille, Lille, France; Univ Lille Nord de France, Lille, France.
authors.forename: Anne-Sophie
authors.initials: AS
authors.lastname: Debrie
authors.affiliation: Univ Lille Nord de France, Lille, France.
authors.forename: Christophe
authors.initials: C
authors.lastname: Dombu
authors.affiliation: Institut Pasteur de Lille, Center for Infection and Immunity of Lille, Lille, France.
authors.forename: Damien
authors.initials: D
authors.lastname: Legrand
authors.affiliation: Inserm U1019, Lille, France; CNRS UMR8204, Lille, France; Institut Pasteur de Lille, Center for Infection and Immunity of Lille, Lille, France; Univ Lille Nord de France, Lille, France.
authors.forename: Dominique
authors.initials: D
authors.lastname: Raze
authors.affiliation: Inserm U1019, Lille, France; CNRS UMR8204, Lille, France; Institut Pasteur de Lille, Center for Infection and Immunity of Lille, Lille, France; Univ Lille Nord de France, Lille, France.
authors.forename: Sophie
authors.initials: S
authors.lastname: Lecher
authors.affiliation: Univ Lille Nord de France, Lille, France.
authors.forename: Didier
authors.initials: D
authors.lastname: Betbeder
authors.affiliation: Inserm U1019, Lille, France; CNRS UMR8204, Lille, France; Institut Pasteur de Lille, Center for Infection and Immunity of Lille, Lille, France; Univ Lille Nord de France, Lille, France.
authors.forename: Camille
authors.initials: C
authors.lastname: Locht
mesh_terms: D000276:Adjuvants, Immunologic / Q000494:pharmacology; D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood; D005260:Female; D007111:Immunity, Cellular; D007117:Immunization, Secondary; D007371:Interferon-gamma / Q000276:immunology; D020381:Interleukin-17 / Q000276:immunology; D037102:Lectins / Q000276:immunology*; D008050:Lipid A / Q000031:analogs & derivatives / Q000494:pharmacology; D008810:Mice, Inbred C57BL; D053758:Nanoparticles; D009838:Oligodeoxyribonucleotides / Q000494:pharmacology; D018417:Th1 Cells / Q000276:immunology*; D058504:Th17 Cells / Q000276:immunology*; D014376:Tuberculosis / Q000517:prevention & control*; D032581:Tuberculosis Vaccines / Q000276:immunology*
chemical_list: D000276:Adjuvants, Immunologic; D000907:Antibodies, Bacterial; C423449:CpG ODN 1826; D020381:Interleukin-17; D037102:Lectins; D008050:Lipid A; D009838:Oligodeoxyribonucleotides; D032581:Tuberculosis Vaccines; C104578:heparin-binding hemagglutinin; D007371:Interferon-gamma; C048436:monophosphoryl lipid A
keywords: CpG; HBHA; Nanoparticle; Th17 response; Tuberculosis