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Rational design of a triple-type human papillomavirus vaccine by compromising viral-type specificity

Author

Listed:
  • Zhihai Li

    (Xiamen University)

  • Shuo Song

    (Xiamen University)

  • Maozhou He

    (Xiamen University)

  • Daning Wang

    (Xiamen University)

  • Jingjie Shi

    (Xiamen University)

  • Xinlin Liu

    (Xiamen University)

  • Yunbing Li

    (Xiamen University)

  • Xin Chi

    (Xiamen University)

  • Shuangping Wei

    (Xiamen University)

  • Yurou Yang

    (Xiamen University)

  • Zhiping Wang

    (Xiamen University)

  • Jinjin Li

    (Xiamen University)

  • Huilian Qian

    (Xiamen University)

  • Hai Yu

    (Xiamen University)

  • Qingbing Zheng

    (Xiamen University)

  • Xiaodong Yan

    (Xiamen University
    University of California-San Diego)

  • Qinjian Zhao

    (Xiamen University)

  • Jun Zhang

    (Xiamen University)

  • Ying Gu

    (Xiamen University
    Xiamen University)

  • Shaowei Li

    (Xiamen University
    Xiamen University)

  • Ningshao Xia

    (Xiamen University
    Xiamen University)

Abstract

Sequence variability in surface-antigenic sites of pathogenic proteins is an important obstacle in vaccine development. Over 200 distinct genomic sequences have been identified for human papillomavirus (HPV), of which more than 18 are associated with cervical cancer. Here, based on the high structural similarity of L1 surface loops within a group of phylogenetically close HPV types, we design a triple-type chimera of HPV33/58/52 using loop swapping. The chimeric VLPs elicit neutralization titers comparable with a mix of the three wild-type VLPs both in mice and non-human primates. This engineered region of the chimeric protein recapitulates the conformational contours of the antigenic surfaces of the parental-type proteins, offering a basis for this high immunity. Our stratagem is equally successful in developing other triplet-type chimeras (HPV16/35/31, HPV56/66/53, HPV39/68/70, HPV18/45/59), paving the way for the development of an improved HPV prophylactic vaccine against all carcinogenic HPV strains. This technique may also be extrapolated to other microbes.

Suggested Citation

  • Zhihai Li & Shuo Song & Maozhou He & Daning Wang & Jingjie Shi & Xinlin Liu & Yunbing Li & Xin Chi & Shuangping Wei & Yurou Yang & Zhiping Wang & Jinjin Li & Huilian Qian & Hai Yu & Qingbing Zheng & X, 2018. "Rational design of a triple-type human papillomavirus vaccine by compromising viral-type specificity," Nature Communications, Nature, vol. 9(1), pages 1-15, December.
    • Handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-07199-6
    DOI: 10.1038/s41467-018-07199-6
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