title: Robust immune response elicited by a novel and unique Mycobacterium tuberculosis protein using an optimized DNA/protein heterologous prime/boost protocol.
abstract: An efficacious tuberculosis (TB) vaccine will probably need to induce both CD4 and CD8 T-cell responses specific to a protective Mycobacterium tuberculosis antigen(s). To achieve this broad cellular immune response we tested a heterologous DNA/protein combination vaccine strategy. We used a purified recombinant protein preparation of a unique M. tuberculosis antigen (rMT1721) found in the urine of TB patients, an optimized plasmid DNA expressing this protein (DNA-MT1721), and a Toll-like receptor 4 agonist adjuvant. We found that priming mice with DNA-MT1721 and subsequently boosting with rMT1721 elicited high titres of specific IgG1 and IgG2a antibodies as well as high magnitude and polyfunctional CD4(+)  T-cell responses. However, no detectable CD8(+)  T-cell response was observed using this regimen of immunization. In contrast, both CD4(+)  and CD8(+)  T-cell responses were detected after a prime/boost vaccination regimen using rMT1721 as the priming antigen and DNA-MT1721 as the boosting immunogen. These findings support the exploration of heterologous DNA/protein immunization strategies in vaccine development against TB and possibly other infectious diseases.
authors: Global Infectious Disease Research Center, The Forsyth Institute, Cambridge, MA, USA.
authors: Mark J
authors: MJ
authors: Cayabyab
authors: Suely S
authors: SS
authors: Kashino
authors: Antonio
authors: A
authors: Campos-Neto
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage; D000818:Animals; D000907:Antibodies, Bacterial / Q000096:biosynthesis; D000942:Antigens, Bacterial / Q000008:administration & dosage / Q000235:genetics; D001426:Bacterial Proteins / Q000008:administration & dosage* / Q000235:genetics / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D004269:DNA, Bacterial / Q000008:administration & dosage / Q000235:genetics; D005260:Female; D007117:Immunization, Secondary; D007074:Immunoglobulin G / Q000096:biosynthesis; D007371:Interferon-gamma / Q000096:biosynthesis; D051379:Mice; D008810:Mice, Inbred C57BL; D009169:Mycobacterium tuberculosis / Q000276:immunology*; D051197:Toll-Like Receptor 4 / Q000819:agonists; D032581:Tuberculosis Vaccines / Q000008:administration & dosage* / Q000235:genetics; D019444:Vaccines, DNA / Q000008:administration & dosage / Q000235:genetics; D014614:Vaccines, Synthetic / Q000008:administration & dosage
chemical_list: D000276:Adjuvants, Immunologic; D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D004269:DNA, Bacterial; D007074:Immunoglobulin G; C493487:Tlr4 protein, mouse; D051197:Toll-Like Receptor 4; D032581:Tuberculosis Vaccines; D019444:Vaccines, DNA; D014614:Vaccines, Synthetic; D007371:Interferon-gamma