title: Live attenuated Salmonella displaying HIV-1 10E8 epitope on fimbriae: systemic and mucosal immune responses in BALB/c mice by mucosal administration.
abstract: The HIV-1 membrane proximal external region (MPER) that is targeted by several broadly neutralizing antibodies (BNAbs) has been considered a potential immunogen for vaccine development. However, to date the immunogenicity of these BNAb epitopes has not been made sufficiently adequate. In the present work, we used live attenuated Salmonella as a platform to present the HIV-1 MPER 10E8 epitope in the fimbriae. The insertion of the 10E8 epitope into the fimbriae had no significant influence on the expression and the absorption capacity of bacterial fimbriae, nor on the virulence and invasiveness of the attenuated Salmonella. After oral administration of the vaccine construct to mice followed by 10E8 epitope peptide boost, specific antibody responses in serum and mucosa as well as memory lymphocytes in spleen and plasma cells in bone marrow were induced. We also found that the live attenuated Salmonella vector directed the immunity toward Th1 bias, induced Th1 and Th2 cytokine responses and stimulated significant B cell differentiation into GC B, memory B and plasma cells. Therefore, we propose that the live attenuated Salmonella constitutively expressing HIV-1 BNAb epitopes on the fimbriae will be an effective approach to improving immune microenvironment and enhancing the immunogenicity of HIV-1 epitope vaccines.
authors.affiliation: Systemomics Center, College of Pharmacy, and Genomics Research Center (State-Province Key Laboratories of Biomedicine-Pharmaceutics of China), Harbin Medical University, Harbin, China.
authors.forename: Qing-Hai
authors.initials: QH
authors.lastname: Li
authors.affiliation: Systemomics Center, College of Pharmacy, and Genomics Research Center (State-Province Key Laboratories of Biomedicine-Pharmaceutics of China), Harbin Medical University, Harbin, China.
authors.forename: Gang
authors.initials: G
authors.lastname: Jin
authors.affiliation: Department of Microbiology, Harbin Medical University, Harbin, China.
authors.forename: Jia-Ye
authors.initials: JY
authors.lastname: Wang
authors.affiliation: Systemomics Center, College of Pharmacy, and Genomics Research Center (State-Province Key Laboratories of Biomedicine-Pharmaceutics of China), Harbin Medical University, Harbin, China.
authors.forename: Hai-Ning
authors.initials: HN
authors.lastname: Li
authors.affiliation: Systemomics Center, College of Pharmacy, and Genomics Research Center (State-Province Key Laboratories of Biomedicine-Pharmaceutics of China), Harbin Medical University, Harbin, China.
authors.forename: Huidi
authors.initials: H
authors.lastname: Liu
authors.affiliation: Systemomics Center, College of Pharmacy, and Genomics Research Center (State-Province Key Laboratories of Biomedicine-Pharmaceutics of China), Harbin Medical University, Harbin, China.
authors.forename: Xiao-Yun
authors.initials: XY
authors.lastname: Chang
authors.affiliation: Department of Infectious Diseases, The Fourth Affiliated Hospital of Harbin Medical University, Harbin, China.
authors.forename: Fu-Xiang
authors.initials: FX
authors.lastname: Wang
authors.affiliation: Systemomics Center, College of Pharmacy, and Genomics Research Center (State-Province Key Laboratories of Biomedicine-Pharmaceutics of China), Harbin Medical University, Harbin, China.|Department of Infectious Diseases, The First Affiliated Hospital, Harbin Medical University, Harbin, China.|Department of Microbiology, Immunology and Infectious Diseases, University of Calgary, Calgary, Canada.
authors.forename: Shu-Lin
authors.initials: SL
authors.lastname: Liu
mesh_terms: D016915:AIDS Vaccines / Q000008:administration & dosage / Q000276:immunology*; D058956:Administration, Mucosal; D000818:Animals; D057134:Antibodies, Neutralizing / Q000276:immunology; D000939:Epitopes; D005260:Female; D010861:Fimbriae, Bacterial / Q000235:genetics / Q000276:immunology; D015497:HIV-1 / Q000235:genetics / Q000276:immunology*; D008807:Mice, Inbred BALB C; D012475:Salmonella / Q000235:genetics / Q000276:immunology*
chemical_list: D016915:AIDS Vaccines; D057134:Antibodies, Neutralizing; D000939:Epitopes