ジャーナル: Nat Commun / 年: 2018 タイトル: Rational design of a triple-type human papillomavirus vaccine by compromising viral-type specificity. 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 ...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 / 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.
名称: Human papillomavirus type 33 / タイプ: virus / ID: 1 / 親要素: 0 詳細: VLP generated by recombinantly expressed; Fab Fragment generated by proteolytic cleavage of IgG antibody; NCBI-ID: 10586 / 生物種: Human papillomavirus type 33 / ウイルスタイプ: VIRUS-LIKE PARTICLE / ウイルス・単離状態: OTHER / ウイルス・エンベロープ: No / ウイルス・中空状態: Yes
Host system
生物種: Escherichia coli (大腸菌)
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実験情報
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構造解析
手法
クライオ電子顕微鏡法
解析
単粒子再構成法
試料の集合状態
particle
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試料調製
緩衝液
pH: 6.5
凍結
凍結剤: ETHANE
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電子顕微鏡法
顕微鏡
FEI TECNAI F30
撮影
フィルム・検出器のモデル: FEI FALCON II (4k x 4k) 平均電子線量: 25.0 e/Å2
電子線
加速電圧: 300 kV / 電子線源: FIELD EMISSION GUN
電子光学系
照射モード: SPOT SCAN / 撮影モード: BRIGHT FIELD
実験機器
モデル: Tecnai F30 / 画像提供: FEI Company
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画像解析
最終 再構成
解像度のタイプ: BY AUTHOR / 解像度: 12.3 Å / 解像度の算出法: OTHER / 詳細: FSC 0.3 cut-off / 使用した粒子像数: 753