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-Structure paper
タイトル | Rational design of a triple-type human papillomavirus vaccine by compromising viral-type specificity. |
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ジャーナル・号・ページ | Nat Commun, Vol. 9, Issue 1, Page 5360, Year 2018 |
掲載日 | 2018年12月18日 |
著者 | 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 / Ningshao Xia / |
PubMed 要旨 | 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 ...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. |
リンク | Nat Commun / PubMed:30560935 / PubMed Central |
手法 | EM (単粒子) / X線回折 |
解像度 | 2.5 - 12.3 Å |
構造データ | EMDB-9665: EMDB-9666: EMDB-9667: PDB-6igc: PDB-6igd: PDB-6ige: PDB-6igf: |
化合物 | ChemComp-HOH: |
由来 |
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キーワード | STRUCTURAL PROTEIN / capsid protein / Human Papillomavirus type 52 capsid protein |