title: Enhanced immune response by amphotericin B following NS1 protein prime-oral recombinant Salmonella vaccine boost vaccination protects mice from dengue virus challenge.
abstract: A recombinant vaccine strain SL3261/pLT105 of attenuated aroA Salmonella enterica serovar Typhimurium SL3261 strain expressing a secreted dengue virus type 2 non-structural NS1 and Yersinia pestis F1 (Caf1) fusion protein, rNS1:Caf1, was generated. Immunological evaluation was performed by prime-boost vaccine regimen. Oral immunization of mice with 1 x 10(9)cfu of SL3261/pLT105 only induced low levels of NS1-specific antibody response and protective immunity following dengue virus challenge. The parenteral NS1 protein priming-oral Salmonella boosting protocol enhanced both NS1-specific serum IgG response and protective efficacy as compared to mice immunized with each type vaccine alone. Addition of an antifungal antibiotic amphotericin B (AmB) to Salmonella vaccine further enhanced the synergic effects of prime-boost vaccine regimen on the elicited NS1-specific serum IgG response and the protective efficacy. Together, the results demonstrated that the rNS1:Caf1 producing Salmonella SL3261/pLT105 strain fails to provide effective protection as an oral vaccine alone despite co-administration of AmB as an adjuvant capable of enhancing the immune responses, and moreover, the protein priming-oral Salmonella vaccine boosting approach in combination with AmB as an immunization regimen may have the potential to be further explored as an alternative approach for dengue vaccine development.
authors.affiliation: Institute of Preventive Medicine, National Defense Medical Center, P.O. Box 90048-505, Neihu, Taipei, Taiwan.
authors.forename: Wen-Tssann
authors.initials: WT
authors.lastname: Liu
authors.forename: Wei-Ting
authors.initials: WT
authors.lastname: Lin
authors.forename: Chung-Chin
authors.initials: CC
authors.lastname: Tsai
authors.forename: Chuan-Chang
authors.initials: CC
authors.lastname: Chuang
authors.forename: Chin-Len
authors.initials: CL
authors.lastname: Liao
authors.forename: Huang-Chi
authors.initials: HC
authors.lastname: Lin
authors.forename: Yao-Wen
authors.initials: YW
authors.lastname: Hung
authors.forename: Shih-Shiung
authors.initials: SS
authors.lastname: Huang
authors.forename: Chung-Chih
authors.initials: CC
authors.lastname: Liang
authors.forename: Hui-Ling
authors.initials: HL
authors.lastname: Hsu
authors.forename: Hsian-Jenn
authors.initials: HJ
authors.lastname: Wang
authors.forename: Yu-Tien
authors.initials: YT
authors.lastname: Liu
mesh_terms: D000284:Administration, Oral; D000666:Amphotericin B / Q000008:administration & dosage* / Q000276:immunology; D000818:Animals; D003715:Dengue / Q000276:immunology / Q000517:prevention & control*; D003716:Dengue Virus / Q000276:immunology; D005260:Female; D007117:Immunization, Secondary / Q000379:methods; D051379:Mice; D008807:Mice, Inbred BALB C; D022562:Salmonella Vaccines / Q000008:administration & dosage* / Q000276:immunology; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000276:immunology; D017361:Viral Nonstructural Proteins / Q000008:administration & dosage* / Q000276:immunology
chemical_list: C079340:NS1 protein, Dengue virus type 2; D022562:Salmonella Vaccines; D014614:Vaccines, Synthetic; D017361:Viral Nonstructural Proteins; D000666:Amphotericin B