title: Immunogenicity and anti-fecundity effect of nanoparticle coated glutathione S-transferase (SjGST) DNA vaccine against murine Schistosoma japonicum infection.
abstract: There is still urgent need for a vaccine against schistosomiasis, especially in Schistosoma japonicum endemic areas where even a vaccine that will interrupt zoonotic transmission will be potentially effective as an intervention tool. We had developed a novel nanoparticle gene delivery system, which has proven efficacious in gene transfection to target immune cells with complementary adjuvant effect and high protective efficacy in several diseases. Here, we applied this nanoparticle system in combination with S. japonicum glutathione S-transferase (SjGST) DNA vaccine to show the immunogenicity and anti-fecundity effect of the nanoparticle coated vaccine formulation against murine schistosomiasis. The nanoparticle-coated DNA vaccine formulation induced desired immune responses. In comparison with the nanoparticle coated empty vector, it produced significantly increased antigen-specific humoral response, T-helper 1 polarized cytokine environment, higher proportion of IFN-γ producing CD4(+) T-cells and the concomitant decrease in IL-4 producing CD4(+) T-cells. Although there was no effect on worm burden, we recorded a marked reduction in tissue egg burden. There was up to 71.3% decrease in tissue egg burden and 55% reduction in the fecundity of female adult worms. Our data showed that SjGST DNA vaccine, delivered using the nanoparticle gene delivery system, produced anti-fecundity effect on female adult schistosomes as previously described by using conventional subunit vaccine with adjuvant, proving this DNA vaccine formulation as a promising candidate for anti-pathology and transmission blocking application.
authors.affiliation: Department of Immunogenetics, Institute of Tropical Medicine (NEKKEN) and Global COE Program, Nagasaki University, 1-12-4 Sakamoto, 852-8523, Japan; Graduate School of Biomedical Sciences, Nagasaki University, 1-12-4 Sakamoto, 852-8523, Japan; Department of Parasitology and Entomology, Faculty of Bioscience, Nnamdi Azikiwe University, P.M.B. 5025, Awka, Nigeria.
authors.forename: Evaristus Chibunna
authors.initials: EC
authors.lastname: Mbanefo
authors.affiliation: Section of Environmental Parasitology, Tokyo Medical and Dental University Graduate School of Medical and Dental Science, 113-8519, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Kumagai
authors.affiliation: Department of Hospital Pharmacy, Nagasaki University Hospital, 1-7-1 Sakamoto, 852-8501, Japan.
authors.forename: Yukinobu
authors.initials: Y
authors.lastname: Kodama
authors.affiliation: Department of Hospital Pharmacy, Nagasaki University Hospital, 1-7-1 Sakamoto, 852-8501, Japan.
authors.forename: Tomoaki
authors.initials: T
authors.lastname: Kurosaki
authors.affiliation: Section of Environmental Parasitology, Tokyo Medical and Dental University Graduate School of Medical and Dental Science, 113-8519, Japan.
authors.forename: Rieko
authors.initials: R
authors.lastname: Furushima-Shimogawara
authors.affiliation: Department of Immunogenetics, Institute of Tropical Medicine (NEKKEN) and Global COE Program, Nagasaki University, 1-12-4 Sakamoto, 852-8523, Japan; Graduate School of Biomedical Sciences, Nagasaki University, 1-12-4 Sakamoto, 852-8523, Japan.
authors.forename: Mahamoud Sama
authors.initials: MS
authors.lastname: Cherif
authors.affiliation: Department of Immunogenetics, Institute of Tropical Medicine (NEKKEN) and Global COE Program, Nagasaki University, 1-12-4 Sakamoto, 852-8523, Japan; Graduate School of Biomedical Sciences, Nagasaki University, 1-12-4 Sakamoto, 852-8523, Japan.
authors.forename: Shusaku
authors.initials: S
authors.lastname: Mizukami
authors.affiliation: Department of Immunogenetics, Institute of Tropical Medicine (NEKKEN) and Global COE Program, Nagasaki University, 1-12-4 Sakamoto, 852-8523, Japan; Graduate School of Biomedical Sciences, Nagasaki University, 1-12-4 Sakamoto, 852-8523, Japan.
authors.forename: Mihoko
authors.initials: M
authors.lastname: Kikuchi
authors.affiliation: Graduate School of Biomedical Sciences, Nagasaki University, 1-12-4 Sakamoto, 852-8523, Japan; Department of Clinical Product Development, Institute of Tropical Medicine (NEKKEN), Nagasaki University, 1-12-4 Sakamoto, 852-8523, Japan.
authors.forename: Nguyen Tien
authors.initials: NT
authors.lastname: Huy
authors.affiliation: Section of Environmental Parasitology, Tokyo Medical and Dental University Graduate School of Medical and Dental Science, 113-8519, Japan.
authors.forename: Nobuo
authors.initials: N
authors.lastname: Ohta
authors.affiliation: Department of Hospital Pharmacy, Nagasaki University Hospital, 1-7-1 Sakamoto, 852-8501, Japan.
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Sasaki
authors.affiliation: Department of Immunogenetics, Institute of Tropical Medicine (NEKKEN) and Global COE Program, Nagasaki University, 1-12-4 Sakamoto, 852-8523, Japan; Graduate School of Biomedical Sciences, Nagasaki University, 1-12-4 Sakamoto, 852-8523, Japan. Electronic address: hiraken@nagasaki-u.ac.jp.
authors.forename: Kenji
authors.initials: K
authors.lastname: Hirayama
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D016207:Cytokines / Q000276:immunology; D005260:Female; D005298:Fertility; D005982:Glutathione Transferase / Q000235:genetics*; D007111:Immunity, Cellular; D056724:Immunity, Humoral; D007371:Interferon-gamma / Q000276:immunology; D015847:Interleukin-4 / Q000276:immunology; D051379:Mice; D053758:Nanoparticles; D012549:Schistosoma japonicum / Q000276:immunology* / Q000502:physiology*; D012554:Schistosomiasis japonica / Q000469:parasitology / Q000517:prevention & control*; D014162:Transfection; D014611:Vaccination / Q000379:methods; D019444:Vaccines, DNA / Q000008:administration & dosage* / Q000276:immunology*
chemical_list: D016207:Cytokines; D019444:Vaccines, DNA; D015847:Interleukin-4; D007371:Interferon-gamma; D005982:Glutathione Transferase
keywords: Anti-fecundity; DNA vaccine; Gene delivery; Glutathione S-transferase (GST); Nanoparticle; Schistosoma japonicum