METHYLATED HEPARIN-BINDING HEMAGGLUTININ (HBHA) RECOMBINANT MYCOBACTERIAL ANTIGEN

L'invention concerne une séquence peptidique recombinante immunogène méthylé e comprenant l'hémagglutinine de liaison à l'héparine (HBHA) mycobactérienne. L'invention concerne également des procédés de préparation, chimiques et enzymatiques, d'une telle séquence, ladite séquence étant préalablement produite sous une forme recombinante non méthylée puis méthylée par modification post-traductionnelle. L'invention concerne en outre des outils, vecteurs et hôtes cellulaires recombinants, pour la mise en oeuvre des procédés enzymatiques de méthylation post-traductionnelle de la HBHA recombinante. L'invention concerne enfin des compositions immunogènes comprenant la HBHA méthylée, native ou recombinante, de telles compositions étant utiles pour la préparation de vaccins contre les infections mycobactériennes. Immunogenic recombinant peptide (I) is the methylated form of an expression product of a nucleic acid (II) that encodes a mycobacterial heparin-binding hemagglutinin antigen (HBHA), especially from Mycobacterium bovis BCG or M. tuberculosis, is new. Independent claims are also included for: (1) processes for preparing (I); (2) recombinant vector that encodes HBHA and at least one recombinant mycobacterial methyltransferase; (3) host cell that harbors a vector of (2); (4) (I) produced by method (1); and (5) immunogenic composition containing any methylated form of HBHA. ACTIVITY : Tuberculostatic. Mice were immunized with native HBHA (5 mu g), 3 times at 2 week intervals. The titer of HBHA-specific immunoglobulin G (IgG) was then 5000, principally IgG1. Ten weeks after the first immunization, the animals were challenged with 10 5> colony-forming units (cfu) of M. tuberculosis and after 6 weeks the number of cfu in various organs was measured. Compared with adjuvant-only controls, the vaccination caused a reduction, in log10 cfu, of 0.94 in liver; 0.85 in spleen and 0.93 in lungs. Equivalent results (not quoted) were achieved with recombinant methylated HBHA. MECHANISM OF ACTION : Vaccine.