title: Construction and evaluation of replication-defective recombinant optimized triosephosphate isomerase adenoviral vaccination in Schistosoma japonicum challenged mice.
abstract: Schistosomiasis is an endemic, zoonotic parasitic disease that remains a public health concern in China. Development of transmission blocking veterinary vaccines against Schistosoma japonicum infection is urgently needed. Replication-defective adenoviral vector is an efficient vaccine delivery system that has been widely used. Its use is associated with high levels of gene insertion and expression. It is easy to construct and prepare, and is safe. It is not known whether this delivery system can improve the protective effect of schistosome vaccination. Triosephosphate isomerase from S. japonicum (SjTPI) is a promising vaccine candidate. Thus far it has induced only partial protection in animal models and needs to be further enhanced to be effective. We constructed a replication-defective adenoviral vector-based vaccine with optimized SjTPI (rAdV-SjTPI.opt). The specific immune responses and protective efficiency in mice were evaluated. Results showed that intramuscular rAdV-SjTPI.opt induced Th1 biased immune responses in the host, while subcutaneous rAdV-SjTPI.opt induced Th2 predominant immune responses. Oral rAdV-SjTPI.opt induced low levels of immune responses and no significant protection. Intramuscular rAdV-SjTPI.opt provided a consistent and repeatable higher protective effect in mice (more than 50%). These findings may be due to the associated higher levels of specific Th1, antibody responses and partially lower level of IL-17A. This report provides a foundation for developing transmission-blocking veterinary vaccines in larger animals.
authors.affiliation: Department of Pathogen Biology and Immunology, Jiangsu Key Laboratory of Pathogen Biology, Nanjing Medical University, Nanjing 210029, Jiangsu, 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 214064, Jiangsu, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Dai
authors.affiliation: 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 214064, Jiangsu, China.
authors.forename: Xiaoting
authors.initials: X
authors.lastname: Wang
authors.affiliation: 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 214064, Jiangsu, China.
authors.forename: Song
authors.initials: S
authors.lastname: Zhao
authors.affiliation: 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 214064, Jiangsu, China.
authors.forename: Jianxia
authors.initials: J
authors.lastname: Tang
authors.affiliation: China-US Vaccine Research Center, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, Jiangsu, China.
authors.forename: Lu
authors.initials: L
authors.lastname: Zhang
authors.affiliation: 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 214064, Jiangsu, China.
authors.forename: Jianrong
authors.initials: J
authors.lastname: Dai
authors.affiliation: Department of Biomedical Sciences and Center of Excellence for Infectious Diseases, Paul L. Foster School of Medicine, Texas Tech University Health Sciences Center, El Paso, TX 79905, USA.
authors.forename: Mingtao
authors.initials: M
authors.lastname: Zeng
authors.affiliation: China-US Vaccine Research Center, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, Jiangsu, China; Laboratory of Nucleic Acid Vaccines, Department of Medicine, University of Massachusetts Medical School, Worcester, MA 01605, USA.
authors.forename: Shan
authors.initials: S
authors.lastname: Lu
authors.affiliation: 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 214064, Jiangsu, China.
authors.forename: Yinchang
authors.initials: Y
authors.lastname: Zhu
authors.affiliation: Department of Pathogen Biology and Immunology, Jiangsu Key Laboratory of Pathogen Biology, Nanjing Medical University, Nanjing 210029, Jiangsu, China. Electronic address: chuansu@njmu.edu.cn.
authors.forename: Chuan
authors.initials: C
authors.lastname: Su
mesh_terms: D000256:Adenoviridae; D000818:Animals; D000909:Antibodies, Helminth / Q000097:blood; D005260:Female; D005822:Genetic Vectors; D015801:Helminth Proteins / Q000235:genetics / Q000276:immunology*; D007273:Injections, Intramuscular; D007279:Injections, Subcutaneous; D020381:Interleukin-17 / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D012549:Schistosoma japonicum / Q000201:enzymology; D012554:Schistosomiasis japonica / Q000517:prevention & control*; D018417:Th1 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology; D014305:Triose-Phosphate Isomerase / Q000235:genetics / Q000276:immunology*; D014611:Vaccination / Q000379:methods*; D014612:Vaccines / Q000008:administration & dosage / Q000276:immunology*
chemical_list: D000909:Antibodies, Helminth; D015801:Helminth Proteins; C098680:Il17a protein, mouse; D020381:Interleukin-17; D014612:Vaccines; D014305:Triose-Phosphate Isomerase
keywords: Gene optimization; Replication-defective adenoviral vector; Schistosoma japonicum; Triosephosphate isomerase; Vaccine