title: Fusion of HPV L1 into Shigella surface IcsA: a new approach in developing live attenuated Shigella-HPV vaccine.
abstract: Despite the success of L1 virus-like particles (VLPs) vaccines in prevention of high-risk human papillomavirus (HPV) infection and cervical cancer, extraordinary high cost for the complete vaccination has impeded widespread use of the vaccine in resource-poor countries, where cervical cancers impose greater challenge. Presentation of HPV L1 protein by attenuated pathogenic bacteria through natural infection provides a promising low-cost and convenient alternative. Here, we describe the construction and characterization of attenuated L1-expressing Shigella vaccine candidate, by fusion of L1 into the autotransporter of Shigella sonnei, IcsA, an essential virulence factor responsible for actin-based motility. The functional α domain of IcsA was replaced by codon-optimized L1 gene with independent open reading frames (ORFs) facilitated by suicide vector pJCB12. The L1 gene was stabilized in the genome of recombinant S. sonnei with protein expression and assembly of VLPs in the bacterial cytoplasm. Through conjunctival route vaccination in guinea pigs, L1-containing S. sonnei was able to elicit specific immune response to HPV16 L1 VLP as well as bacterial antigens. The results demonstrated the feasibility of the novel stratagem to develop prophylactic Shigella-HPV vaccines.
authors: Institute of Cancer Research, School of Life Sciences and Technology, Xi'an Jiaotong University, Xi'an 710061, China; Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, Glasgow, UK.
authors: Dan
authors: D
authors: Xu
authors: Institute of Cancer Research, School of Life Sciences and Technology, Xi'an Jiaotong University, Xi'an 710061, China.
authors: Depu
authors: D
authors: Wang
authors: The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.
authors: Xiaofeng
authors: X
authors: Yang
authors: Institute of Cancer Research, School of Life Sciences and Technology, Xi'an Jiaotong University, Xi'an 710061, China.
authors: Meng
authors: M
authors: Cao
authors: Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, Glasgow, UK.
authors: Jun
authors: J
authors: Yu
authors: Institute of Cancer Research, School of Life Sciences and Technology, Xi'an Jiaotong University, Xi'an 710061, China. Electronic address: wangyili@mail.xjtu.edu.cn.
authors: Yili
authors: Y
authors: Wang
mesh_terms: D000818:Animals; D000907:Antibodies, Bacterial / Q000032:analysis / Q000097:blood; D000914:Antibodies, Viral / Q000032:analysis / Q000097:blood; D001426:Bacterial Proteins / Q000235:genetics / Q000276:immunology; D036022:Capsid Proteins / Q000235:genetics / Q000276:immunology; D061505:Cell Surface Display Techniques / Q000379:methods*; D004337:Drug Carriers; D005822:Genetic Vectors; D006168:Guinea Pigs; D007963:Leukocytes, Mononuclear / Q000276:immunology; D009856:Oncogene Proteins, Viral / Q000235:genetics / Q000276:immunology; D053918:Papillomavirus Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000276:immunology; D022281:Shigella Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D012764:Shigella sonnei / Q000235:genetics / Q000276:immunology*; D014611:Vaccination / Q000379:methods*; D014613:Vaccines, Attenuated / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology
chemical_list: D000907:Antibodies, Bacterial; D000914:Antibodies, Viral; D001426:Bacterial Proteins; D036022:Capsid Proteins; D004337:Drug Carriers; D009856:Oncogene Proteins, Viral; D053918:Papillomavirus Vaccines; D011993:Recombinant Fusion Proteins; D022281:Shigella Vaccines; D014613:Vaccines, Attenuated; D014614:Vaccines, Synthetic; C063317:L1 protein, Human papillomavirus type 16
keywords: Autotransporter; Genomic integration; Human papillomavirus vaccine; Shigella sonnei