title: Successive site translocating inoculation potentiates DNA/recombinant vaccinia vaccination.
abstract: DNA vaccines have advantages over traditional vaccine modalities; however the relatively low immunogenicity restrains its translation into clinical use. Further optimizations are needed to get the immunogenicity of DNA vaccine closer to the level required for human use. Here we show that intramuscularly inoculating into a different limb each time significantly improves the immunogenicities of both DNA and recombinant vaccinia vaccines during multiple vaccinations, compared to repeated vaccination on the same limb. We term this strategy successive site translocating inoculation (SSTI). SSTI could work in synergy with genetic adjuvant and DNA prime-recombinant vaccinia boost regimen. By comparing in vivo antigen expression, we found that SSTI avoided the specific inhibition of in vivo antigen expression, which was observed in the limbs being repeatedly inoculated. Employing in vivo T cell depletion and passive IgG transfer, we delineated that the inhibition was not mediated by CD8(+) T cells but by specific antibodies. Finally, by using C3(-/-) mouse model and in vivo NK cells depletion, we identified that specific antibodies negatively regulated the in vivo antigen expression primarily in a complement depended way.
authors.affiliation: Shanghai Public Health Clinical Center, Fudan University, Shanghai, 201508, China.
authors.forename: Yanqin
authors.initials: Y
authors.lastname: Ren
authors.affiliation: Shanghai Cancer Center and Institutes of Biomedical Sciences, Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China.
authors.forename: Na
authors.initials: N
authors.lastname: Wang
authors.affiliation: Shanghai Cancer Center and Institutes of Biomedical Sciences, Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China.
authors.forename: Weiguo
authors.initials: W
authors.lastname: Hu
authors.affiliation: Shanghai Public Health Clinical Center, Fudan University, Shanghai, 201508, China.|Institutes of Biomedical Sciences, Shanghai Medical College of Fudan University, Shanghai, 200032, China.
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Shanghai Public Health Clinical Center, Fudan University, Shanghai, 201508, China.|Institutes of Biomedical Sciences, Shanghai Medical College of Fudan University, Shanghai, 200032, China.
authors.forename: Jianqing
authors.initials: J
authors.lastname: Xu
authors.affiliation: Shanghai Public Health Clinical Center, Fudan University, Shanghai, 201508, China.
authors.forename: Yanmin
authors.initials: Y
authors.lastname: Wan
mesh_terms: D000818:Animals; D000917:Antibody Formation / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D002465:Cell Movement / Q000276:immunology; D002478:Cells, Cultured; D058501:Enzyme-Linked Immunospot Assay; D005260:Female; D005434:Flow Cytometry; D007074:Immunoglobulin G / Q000097:blood / Q000276:immunology; D007273:Injections, Intramuscular; D007371:Interferon-gamma / Q000276:immunology / Q000378:metabolism; D007694:Killer Cells, Natural / Q000276:immunology / Q000378:metabolism; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018482:Muscle, Skeletal / Q000276:immunology; D014611:Vaccination / Q000379:methods; D019444:Vaccines, DNA / Q000008:administration & dosage / Q000276:immunology*; D014615:Vaccinia / Q000276:immunology*; D014616:Vaccinia virus / Q000276:immunology*; D014765:Viral Vaccines / Q000276:immunology*
chemical_list: D007074:Immunoglobulin G; D019444:Vaccines, DNA; D014765:Viral Vaccines; D007371:Interferon-gamma