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

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, Xiaodong Yan, Qinjian Zhao, Jun Zhang, Ying Gu (), Shaowei Li () and Ningshao Xia ()
Additional contact information
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
Qinjian Zhao: Xiamen University
Jun Zhang: Xiamen University
Ying Gu: Xiamen University
Shaowei Li: Xiamen University
Ningshao Xia: Xiamen University

Nature Communications, 2018, vol. 9, issue 1, 1-15

Abstract: 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.

Date: 2018
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DOI: 10.1038/s41467-018-07199-6

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