Fusion of HPV L1 into Shigella surface IcsA: a new approach in developing live attenuated Shigella-HPV vaccine

Dan Xu, Depu Wang, Xiaofeng Yang, Meng Cao, Jun Yu, Wang Yili

Research output: Contribution to journalArticle

5 Citations (Scopus)

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.
LanguageEnglish
Pages61-69
Number of pages9
JournalAntiviral Research
Volume102
Early online date13 Dec 2013
DOIs
Publication statusPublished - Feb 2014

Fingerprint

Shigella sonnei
Papillomavirus Vaccines
Shigella
Uterine Cervical Neoplasms
Virion
Shigella Vaccines
Vaccination
Virus-Like Particle Vaccines
Bacterial Antigens
Costs and Cost Analysis
Papillomavirus Infections
Virulence Factors
Codon
Suicide
Open Reading Frames
Genes
Actins
Guinea Pigs
Cytoplasm
Vaccines

Keywords

  • Shigella-HPV vaccine
  • human papillomavirus vaccine
  • Shigella sonnei
  • autotransporter
  • genomic integration

Cite this

Xu, Dan ; Wang, Depu ; Yang, Xiaofeng ; Cao, Meng ; Yu, Jun ; Yili, Wang. / Fusion of HPV L1 into Shigella surface IcsA : a new approach in developing live attenuated Shigella-HPV vaccine. In: Antiviral Research. 2014 ; Vol. 102. pp. 61-69.
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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.",
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Fusion of HPV L1 into Shigella surface IcsA : a new approach in developing live attenuated Shigella-HPV vaccine. / Xu, Dan; Wang, Depu; Yang, Xiaofeng; Cao, Meng; Yu, Jun; Yili, Wang.

In: Antiviral Research, Vol. 102, 02.2014, p. 61-69.

Research output: Contribution to journalArticle

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