title: Induction of a type 1 immune response to a recombinant antigen from Mycobacterium tuberculosis expressed in Mycobacterium vaccae.
abstract: A 19-kDa lipoprotein from Mycobacterium tuberculosis was expressed as a recombinant antigen in the nonpathogenic mycobacterial host strain M. vaccae. Immunization of mice with the recombinant M. vaccae resulted in induction of a strong type 1 immune response to the 19-kDa antigen, characterized by immunoglobulin G2a (IgG2a) antibodies and gamma interferon (IFN-gamma) production by splenocytes. Immunization with the same antigen in incomplete Freund's adjuvant induced a strong IgG1 response with only low levels of IFN-gamma. Subsequent intravenous and aerosol challenges of immunized mice with virulent M. tuberculosis demonstrated no evidence of protection associated with the response to the 19-kDa antigen; in fact, the presence of the recombinant 19-kDa antigen abrogated the limited protection conferred by M. vaccae (vector control). The recombinant M. vaccae system is a convenient approach to induction of type 1 responses to M. tuberculosis antigens. However, the unexpected reduction in protective efficacy of M. vaccae expressing the 19-kDa antigen highlights the complexity of testing recombinant subunit vaccines and the need for a better understanding of the immune mechanisms required for effective vaccination against tuberculosis.
authors.affiliation: Department of Medical Microbiology, Imperial College School of Medicine at St. Mary's, London, United Kingdom. c.abouzeid@ic.ac.uk
authors.forename: C
authors.initials: C
authors.lastname: Abou-Zeid
authors.forename: M P
authors.initials: MP
authors.lastname: Gares
authors.forename: J
authors.initials: J
authors.lastname: Inwald
authors.forename: R
authors.initials: R
authors.lastname: Janssen
authors.forename: Y
authors.initials: Y
authors.lastname: Zhang
authors.forename: D B
authors.initials: DB
authors.lastname: Young
authors.forename: C
authors.initials: C
authors.lastname: Hetzel
authors.forename: J R
authors.initials: JR
authors.lastname: Lamb
authors.forename: S L
authors.initials: SL
authors.lastname: Baldwin
authors.forename: I M
authors.initials: IM
authors.lastname: Orme
authors.forename: V
authors.initials: V
authors.lastname: Yeremeev
authors.forename: B V
authors.initials: BV
authors.lastname: Nikonenko
authors.forename: A S
authors.initials: AS
authors.lastname: Apt
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000907:Antibodies, Bacterial / Q000032:analysis; D000942:Antigens, Bacterial / Q000235:genetics* / Q000276:immunology*; D001681:Biological Assay; D015153:Blotting, Western; D004198:Disease Susceptibility / Q000276:immunology; D004591:Electrophoresis, Polyacrylamide Gel; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005620:Freund's Adjuvant / Q000276:immunology; D015964:Gene Expression Regulation, Bacterial; D020022:Genetic Predisposition to Disease; D006969:Hypersensitivity, Immediate / Q000276:immunology*; D007114:Immunization / Q000379:methods; D007074:Immunoglobulin G / Q000096:biosynthesis / Q000276:immunology; D007371:Interferon-gamma / Q000096:biosynthesis / Q000276:immunology; D008074:Lipoproteins / Q000235:genetics* / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009161:Mycobacterium / Q000235:genetics*; D009164:Mycobacterium Infections / Q000235:genetics* / Q000276:immunology*; D009169:Mycobacterium tuberculosis / Q000235:genetics* / Q000276:immunology*; D010957:Plasmids; D011994:Recombinant Proteins / Q000276:immunology*; D011995:Recombination, Genetic; D013154:Spleen / Q000276:immunology; D014400:Tuberculosis, Splenic / Q000235:genetics* / Q000276:immunology* / Q000517:prevention & control; D014614:Vaccines, Synthetic / Q000009:adverse effects / Q000276:immunology
chemical_list: D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; D007074:Immunoglobulin G; D008074:Lipoproteins; D011994:Recombinant Proteins; D014614:Vaccines, Synthetic; D007371:Interferon-gamma; D005620:Freund's Adjuvant