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Yasuhiro Yasutomi

Intranasal immunization with recombinant human parainfluenza type 2 virus-Ag85B showed protective effects against Mycobacterium tuberculosis infectio n. Yasuhiro Yasutomi. National Institute of Biomedical Innovation Mie University Graduate School of Medicine.

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Yasuhiro Yasutomi

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  1. Intranasal immunization with recombinant human parainfluenza type 2 virus-Ag85B showed protective effects against Mycobacterium tuberculosis infection Yasuhiro Yasutomi National Institute of Biomedical Innovation Mie University Graduate School of Medicine

  2. Human parainfluenza type 2 virus Human parainfluenza type 2 virus (hPIV2)is - human respiratory virus. - Rubulavirus of the family Paramyxoviridae . - negative-stranded RNA genome~ 15.6 kb. - able to infect with human, macaque and suckling hamster. - extremely low pathogenicity. Schematic representation of hPIV2 Electron micrograph of hPIV2

  3. 5’ - Not I - ggtcgccaccATG - - ATT - PIV2 NP (R2) - IG - PIV2 P (R1) - Not I - 3’ AAA AAA AAA AAA AAA AAA AAA NP V P M F HN L Construction of hPIV2 vector hPIV2 vector is - developed by technology of reverse genetics. - high-level expression systems of products by foreign gene. - replication incompetent by elimination of M, F or NH gene. Ag85B VeroT7/5 cell NP (Met) P or or Leder NP V/P F HN L Trailer M L Genome RNP Transfection Genome L NP P Infection Transcription Virus stock Genome RNP Virus protein Vero cell Replication

  4. Ag expression by rhPIV2-Ag85B infection Ag85B Ag85B Ag85B Other viral proteins Other viral proteins Other viral proteins

  5. Local Innate Immunity Adoptive Immunity ICAM-1 TB RIG-I IPS-1 Mφ TRAF3 RIP1 FADD TBK1 IKKi DC IRF3 IRF7 TRAF6 IRF3 IRF7 Type1 IFNs NEMO CD4+ T cell IKKβ IKKα CD8+ T cell IkB p50 Cytokines Chemokines p65 p50 p65 nucleus

  6. CONCLUSIONS 1. Characteristics of Ag expression system - Abundant and rapid production of Ag85B was observed in cells infected with rhPIV2-Ag85B compared with other viral vector products. - The rhPIV2-Ag85B immunization elicited inserted Ag85B-specific immune responses without being hidden by vector responses. - The rhPIV2 vector is not affected pre-existing immune responses to rhPIV2 . 2. Induction of mucosal immune responses - Effector cells in pulmonary LN cells was increased by intranasal immunization with rhPIV2-Ag85B . - Effector cells occurred after Mtb challenge in BAL cells in rhPIV2-Ag85B intranasal immunization. 3. Adjuvant activity - rhPIV2-Ag85B in itself has an adjuvant activity through the RIG-I receptor.

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