title: Cholera toxin B subunit acts as a potent systemic adjuvant for HIV-1 DNA vaccination intramuscularly in mice.
abstract: Cholera toxin B subunit (CTB) was investigated as a classical mucosal adjuvant that can increase vaccine immunogenicity. In this study, we found out the in vitro efficacy of cholera toxin B subunit (CTB) in activating mice bone marrow-derived dendritic cells (BMDCs) through Toll-like receptor signaling pathways. In vitro RNA and transcriptional level profiling arrays revealed that CTB guides high levels of Th1 and Th2 type cytokines, inflammatory cytokines, and chemokines. Based on the robustness of these profiling results, we examined the induction of HIV Env-specific immunity by CTB co-inoculated with HIV Env DNA vaccine intramuscularly in vivo. CTB enhanced HIV-Env specific cellular immune responses in Env-specific IFN-γ ELISPOT, compared with DNA vaccine alone. Moreover, CTB induced high levels of Env specific humoral response and promoted antibody maturation after the third round of vaccination. This combination immunization strategy induced a Th2-type bias response which is indicative of a high ratio of IgG1/IgG2a. This study reports that CTB as a classical mucosal adjuvant could enhance HIV-1 DNA-based vaccine immunogenicity intramuscularly; therefore, these findings suggest that CTB could serve as an effective candidate adjuvant for DNA vaccination.
authors.affiliation: State Key Laboratory for Infectious Disease Prevention and Control; National Center for AIDS/STD Control and Prevention; Chinese Center for Disease Control and Prevention; Beijing, PR China; Center of Medical Physics and Technology; Hefei Institutes of Physical Science; Chinese Academy of Sciences; Hefei, PR China.
authors.forename: Jue
authors.initials: J
authors.lastname: Hou
authors.affiliation: State Key Laboratory for Infectious Disease Prevention and Control; National Center for AIDS/STD Control and Prevention; Chinese Center for Disease Control and Prevention; Beijing, PR China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Liu
authors.affiliation: State Key Laboratory for Infectious Disease Prevention and Control; National Center for AIDS/STD Control and Prevention; Chinese Center for Disease Control and Prevention; Beijing, PR China.
authors.forename: Jenny
authors.initials: J
authors.lastname: Hsi
authors.affiliation: Center of Medical Physics and Technology; Hefei Institutes of Physical Science; Chinese Academy of Sciences; Hefei, PR China.
authors.forename: Hongzhi
authors.initials: H
authors.lastname: Wang
authors.affiliation: The Fourth Affiliated Hospital of Anhui Medical University; Hefei, PR China.
authors.forename: Ran
authors.initials: R
authors.lastname: Tao
authors.affiliation: State Key Laboratory for Infectious Disease Prevention and Control; National Center for AIDS/STD Control and Prevention; Chinese Center for Disease Control and Prevention; Beijing, PR China.
authors.forename: Yiming
authors.initials: Y
authors.lastname: Shao
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage*; D000818:Animals; D002478:Cells, Cultured; D002772:Cholera Toxin / Q000008:administration & dosage* / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology*; D055261:Immunogenetic Phenomena / Q000187:drug effects / Q000276:immunology; D007273:Injections, Intramuscular; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D014611:Vaccination / Q000379:methods; D019444:Vaccines, DNA / Q000008:administration & dosage* / Q000276:immunology*
chemical_list: D000276:Adjuvants, Immunologic; D019444:Vaccines, DNA; D002772:Cholera Toxin
keywords: DNA vaccine; DNA vaccine adjuvant; cholera toxin B subunit; immunogenicity; in vitro profiling