Enhanced immune response by amphotericin B following NS1 protein prime-oral recombinant Salmonella vaccine boost vaccination protects mice from dengue virus challenge.
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.
Liu
Wen-Tssann
WT
Institute of Preventive Medicine, National Defense Medical Center, P.O. Box 90048-505, Neihu, Taipei, Taiwan.
Lin
Wei-Ting
WT
Tsai
Chung-Chin
CC
Chuang
Chuan-Chang
CC
Liao
Chin-Len
CL
Lin
Huang-Chi
HC
Hung
Yao-Wen
YW
Huang
Shih-Shiung
SS
Liang
Chung-Chih
CC
Hsu
Hui-Ling
HL
Wang
Hsian-Jenn
HJ
Liu
Yu-Tien
YT
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
C079340:NS1 protein, Dengue virus type 2; D022562:Salmonella Vaccines; D014614:Vaccines, Synthetic; D017361:Viral Nonstructural Proteins; D000666:Amphotericin B