Recombinant Ag85B vaccine by taking advantage of characteristics of human parainfluenza type 2 virus vector showed Mycobacteria-specific immune responses by intranasal immunization.
Viral vectors are promising vaccine candidates for eliciting suitable Ag-specific immune response. Since Mycobacterium tuberculosis (Mtb) normally enters hosts via the mucosal surface of the lung, the best defense against Mtb is mucosal vaccines that are capable of inducing both systemic and mucosal immunity. Although Mycobacterium bovis bacille Calmette-Guérin is the only licensed tuberculosis (TB) vaccine, its efficacy against adult pulmonary forms of TB is variable. In this study, we assessed the effectiveness of a novel mucosal TB vaccine using recombinant human parainfluenza type 2 virus (rhPIV2) as a vaccine vector in BALB/c mice. Replication-incompetent rhPIV2 (M gene-eliminated) expressing Ag85B (rhPIV2-Ag85B) was constructed by reverse genetics technology. Intranasal administration of rhPIV2-Ag85B induced Mtb-specific immune responses, and the vaccinated mice showed a substantial reduction in the number of CFU of Mtb in lungs and spleens. Unlike other viral vaccine vectors, the immune responses against Ag85B induced by rhPIV2-Ag85B immunization had an advantage over that against the viral vector. In addition, it was revealed that rhPIV2-Ag85B in itself has an adjuvant activity through the retinoic acid-inducible gene I receptor. These findings provide further evidence for the possibility of rhPIV2-Ag85B as a novel TB vaccine.
Laboratory of Immunoregulation and Vaccine Research, Tsukuba Primate Research Center, National Institute of Biomedical Innovation, Tsukuba, Ibaraki 305-0843, Japan.
Kenta
K
Watanabe
Laboratory of Immunoregulation and Vaccine Research, Tsukuba Primate Research Center, National Institute of Biomedical Innovation, Tsukuba, Ibaraki 305-0843, Japan; Division of Immunoregulation, Department of Molecular and Experimental Medicine, Mie University Graduate School of Medicine, Tsu, Mie 514-8507, Japan.
Akihiro
A
Matsubara
Department of Microbiology and Molecular Genetics, Mie University Graduate School of Medicine, Tsu, Mie 514-8507, Japan.
Mitsuo
M
Kawano
Research and Development Department, Japan BCG Laboratory, Kiyose, Tokyo 204-0022, Japan; The Research Institute of Tuberculosis, Kiyose, Tokyo 204-8533, Japan.
Satoru
S
Mizuno
Laboratory of Immunoregulation and Vaccine Research, Tsukuba Primate Research Center, National Institute of Biomedical Innovation, Tsukuba, Ibaraki 305-0843, Japan.
Tomotaka
T
Okamura
Laboratory of Immunoregulation and Vaccine Research, Tsukuba Primate Research Center, National Institute of Biomedical Innovation, Tsukuba, Ibaraki 305-0843, Japan.
Yusuke
Y
Tsujimura
Department of Pathology, Faculty of Pharmaceutical Science, Suzuka University of Medical Science, Suzuka, Mie 513-8670, Japan.
Hiroyasu
H
Inada
Department of Microbiology and Molecular Genetics, Mie University Graduate School of Medicine, Tsu, Mie 514-8507, Japan.
Tetsuya
T
Nosaka
Research and Development Department, Japan BCG Laboratory, Kiyose, Tokyo 204-0022, Japan.
Kazuhiro
K
Matsuo
Laboratory of Immunoregulation and Vaccine Research, Tsukuba Primate Research Center, National Institute of Biomedical Innovation, Tsukuba, Ibaraki 305-0843, Japan; Division of Immunoregulation, Department of Molecular and Experimental Medicine, Mie University Graduate School of Medicine, Tsu, Mie 514-8507, Japan. Electronic address: yasutomi@nibio.go.jp.
Yasuhiro
Y
Yasutomi
D000217:Acyltransferases / Q000276:immunology*; D000281:Administration, Intranasal; D000818:Animals; D000942:Antigens, Bacterial / Q000276:immunology*; D001426:Bacterial Proteins / Q000276:immunology*; D002478:Cells, Cultured; D005260:Female; D006801:Humans; D007111:Immunity, Cellular; D007113:Immunity, Innate; D018928:Immunity, Mucosal; D051379:Mice; D008807:Mice, Inbred BALB C; D009169:Mycobacterium tuberculosis; D010223:Parainfluenza Virus 2, Human; D011994:Recombinant Proteins / Q000276:immunology; D059386:Reverse Genetics; D032581:Tuberculosis Vaccines / Q000235:genetics / Q000276:immunology*; D014614:Vaccines, Synthetic / Q000235:genetics / Q000276:immunology
D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D011994:Recombinant Proteins; D032581:Tuberculosis Vaccines; D014614:Vaccines, Synthetic; D000217:Acyltransferases; C121433:antigen 85B, Mycobacterium tuberculosis
Ag85B; Human parainfluenza virus; Mucosal immunity; Tuberculosis