PAMAM-Lys, a novel vaccine delivery vector, enhances the protective effects of the SjC23 DNA vaccine against Schistosoma japonicum infection.
BACKGROUND
Schistosomiasis japonica remains a major public-health concern in China. Praziquantel-based chemotherapy effectively reduces both infections and intensity; however, it can not prevent re-infection. Furthermore, there is an increasing concern about praziquantel resistance following long-term repeated use of the drug in endemic areas. Therefore, development of a schistosomiasis vaccine, as a strategy to prevent and control schistosomiasis japonica, has been given high priority. The present study was conducted to develop PAMAM dendrimers as a novel vaccine delivery vector for a schistosomiasis japonica DNA vaccine and evaluate its ability to enhance protective effects against Schistosoma japonicum infection.


RESULTS
Lysine was used to modify 4.0G PAMAM, and the modified product PAMAM-Lys was synthesized. PAMAM-Lys showed both high transfection and low cytotocity for gene delivery in vitro. DNA vaccines combined with PAMAM-Lys produced higher level of protection compare with naked DNA vaccines against S. japonicum infection in a mouse model. Futhermore,antibodies from mice immunized with PAMAM-Lys combined DNA vaccines were significantly higher than those of mice immunized with the naked DNA vaccines. The PAMAM-Lys vector elicited a predominantly IgG2a antibody response and a tremendously increase in the production of IL-2 and IFN-γ.


CONCLUSIONS
Lysine-modified PAMAM-Lys is an excellent vector. PAMAM-Lys may enhance the immunoreactivity of DNA vaccine and increase the protective effect of the SjC23 DNA vaccine against S. japonicum infection.
Jiangsu Stem Cell Key Laboratory, Institute of Medical Biotechnology, Medical College of Soochow University; Jiangsu Institute of Clinical Immunology, The First Affiliated Hospital of Soochow University, Suzhou, China ; Jiangsu Institute of Parasitic Diseases, Key Laboratory on Technology for Parasitic Disease Prevention and Control, Ministry of Health, Jiangsu Provincial Key Laboratory on Molecular Biology of Parasites, Wuxi, Jiangsu, China.
Xiaoting
X
Wang
Jiangsu Institute of Parasitic Diseases, Key Laboratory on Technology for Parasitic Disease Prevention and Control, Ministry of Health, Jiangsu Provincial Key Laboratory on Molecular Biology of Parasites, Wuxi, Jiangsu, China.
Yang
Y
Dai
Jiangsu Institute of Parasitic Diseases, Key Laboratory on Technology for Parasitic Disease Prevention and Control, Ministry of Health, Jiangsu Provincial Key Laboratory on Molecular Biology of Parasites, Wuxi, Jiangsu, China.
Song
S
Zhao
Jiangsu Institute of Parasitic Diseases, Key Laboratory on Technology for Parasitic Disease Prevention and Control, Ministry of Health, Jiangsu Provincial Key Laboratory on Molecular Biology of Parasites, Wuxi, Jiangsu, China.
Jianxia
J
Tang
Jiangsu Institute of Parasitic Diseases, Key Laboratory on Technology for Parasitic Disease Prevention and Control, Ministry of Health, Jiangsu Provincial Key Laboratory on Molecular Biology of Parasites, Wuxi, Jiangsu, China.
Hongjun
H
Li
Jiangsu Institute of Parasitic Diseases, Key Laboratory on Technology for Parasitic Disease Prevention and Control, Ministry of Health, Jiangsu Provincial Key Laboratory on Molecular Biology of Parasites, Wuxi, Jiangsu, China.
Yuntian
Y
Xing
Jiangsu Institute of Parasitic Diseases, Key Laboratory on Technology for Parasitic Disease Prevention and Control, Ministry of Health, Jiangsu Provincial Key Laboratory on Molecular Biology of Parasites, Wuxi, Jiangsu, China.
Guoli
G
Qu
Biomaterials and Drug Delivery Laboratories, School of Chemistry and Chemical Engineering, Southeast University, Nanjing, China.
Xinsong
X
Li
Jiangsu Institute of Parasitic Diseases, Key Laboratory on Technology for Parasitic Disease Prevention and Control, Ministry of Health, Jiangsu Provincial Key Laboratory on Molecular Biology of Parasites, Wuxi, Jiangsu, China.
Jianrong
J
Dai
Jiangsu Institute of Parasitic Diseases, Key Laboratory on Technology for Parasitic Disease Prevention and Control, Ministry of Health, Jiangsu Provincial Key Laboratory on Molecular Biology of Parasites, Wuxi, Jiangsu, China.
Yinchang
Y
Zhu
Jiangsu Stem Cell Key Laboratory, Institute of Medical Biotechnology, Medical College of Soochow University; Jiangsu Institute of Clinical Immunology, The First Affiliated Hospital of Soochow University, Suzhou, China.
Xueguang
X
Zhang
D000276:Adjuvants, Immunologic / Q000737:chemistry* / Q000494:pharmacology; D000818:Animals; D000909:Antibodies, Helminth / Q000097:blood; D050091:Dendrimers / Q000737:chemistry* / Q000494:pharmacology; D005260:Female; D057809:HEK293 Cells; D006801:Humans; D056724:Immunity, Humoral; D008099:Liver / Q000469:parasitology; D008239:Lysine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D008807:Mice, Inbred BALB C; D010957:Plasmids; D012549:Schistosoma japonicum / Q000276:immunology*; D012554:Schistosomiasis japonica / Q000276:immunology / Q000469:parasitology / Q000517:prevention & control; D012908:Snails / Q000469:parasitology; D019444:Vaccines, DNA / Q000235:genetics / Q000276:immunology*
D000276:Adjuvants, Immunologic; D000909:Antibodies, Helminth; D050091:Dendrimers; D019444:Vaccines, DNA; D008239:Lysine