1. Recombinant Mycobacterium bovis BCG expressing pertussis toxin subunit S1 induces protection against an intracerebral challenge with live Bordetella pertussis in mice (vol 68, pg 4877, 2000)
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Nascimento, Ip, Dias, Wo, Mazzantini, Pp, Miyaji, En, Gamberini, M., Quintilio, W., Gebara, Vc, Cardoso, Df, Ho, Pl, Raw, I., Winter, N., Gicquel, B., Rappuoli, R., Luciana Leite, Centro de Biotecnologia [Sao Paulo], Instituto Butantan [São Paulo], Departamento de Bioquímica, Instituto de Química, Universidade de São Paulo (USP), Universidade Federal de São Paulo, Institut Pasteur [Paris], Génétique mycobactérienne - Mycobacterial genetics, Immunobiological Research Institute of Siena, and Partenaires INRAE
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[SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology ,SURFACE PROTEIN-A ,ESCHERICHIA-COLI ,T-CELL CLONES ,PHOA GENE FUSIONS ,ANTIBODIES ,INFECTION ,VACCINE ,TUBERCULOSIS ,BACILLUS-SUBTILIS ,RESPONSES - Abstract
Erratum : Infection and Immunity Volume 68, no. 9, p. 4877–4883, 2000. Page 4881, legend to Fig. 6, line 3: “Squares” should read “circles.” Line 4: “(Circles)” should read “(squares).”; International audience; The recent development of acellular pertussis vaccines has been a significant improvement in the conventional whole-cell diphtheria-pertussis-tetanus toxoid vaccines, but high production costs will limit its wide-spread use in developing countries. Since Mycobacterium bovis BCG vaccination against tuberculosis is used in most developing countries, a recombinant BCG-pertussis vaccine could be a more viable alternative. We have constructed recombinant BCG (rBCG) strains expressing the genetically detoxified S1 subunit of pertussis toxin 9K/129G (S1PT) in fusion with either the beta-lactamase signal sequence or the whole beta-lactamase protein, under control of the upregulated ill. fortuitum beta-lactamase promoter, pBlaF*. Expression levels were higher in the fusion with the whole beta-lactamase protein, and both were localized to the mycobacterial cell wall. The expression vectors were relatively stable in vivo, since at two months 85% of the BCG recovered from the spleens of vaccinated mice maintained kanamycin resistance. Spleen cells from rBCG-S1PT-vaccinated mice showed elevated gamma interferon (IFN-gamma) and low interleukin-4 (IL-4) production, as well as increased proliferation, upon pertussis toxin (PT) stimulation, characterizing a strong antigen-specific Th1-dominant cellular response. The rBCG-S1PT strains induced a low humoral response against PT after 2 months. Mice immunized with rBCG-S1PT strains displayed high-level protection against an intracerebral challenge with live Bordetella pertussis, which correlated with the induction of a PT-specific cellular immune response, reinforcing the importance of cell-mediated immunity in the protection against B. pertussis infection. Our results suggest that rBCG-expressing pertussis antigens could constitute an effective, low-cost combined vaccine against tuberculosis and pertussis.
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- 2001