ジャーナル: Mol Ther / 年: 2022 タイトル: Modular capsid decoration boosts adenovirus vaccine-induced humoral immunity against SARS-CoV-2. 著者: Matthew D J Dicks / Louisa M Rose / Rebecca A Russell / Lesley A H Bowman / Carl Graham / Jose M Jimenez-Guardeño / Katie J Doores / Michael H Malim / Simon J Draper / Mark Howarth / Sumi Biswas / 要旨: Adenovirus vector vaccines have been widely and successfully deployed in response to coronavirus disease 2019 (COVID-19). However, despite inducing potent T cell immunity, improvement of vaccine- ...Adenovirus vector vaccines have been widely and successfully deployed in response to coronavirus disease 2019 (COVID-19). However, despite inducing potent T cell immunity, improvement of vaccine-specific antibody responses upon homologous boosting is modest compared with other technologies. Here, we describe a system enabling modular decoration of adenovirus capsid surfaces with antigens and demonstrate potent induction of humoral immunity against these displayed antigens. Ligand attachment via a covalent bond was achieved using a protein superglue, DogTag/DogCatcher (similar to SpyTag/SpyCatcher), in a rapid and spontaneous reaction requiring only co-incubation of ligand and vector components. DogTag was inserted into surface-exposed loops in the adenovirus hexon protein to allow attachment of DogCatcher-fused ligands on virus particles. Efficient coverage of the capsid surface was achieved using various ligands, with vector infectivity retained in each case. Capsid decoration shielded particles from vector neutralizing antibodies. In prime-boost regimens, adenovirus vectors decorated with the receptor-binding domain of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) spike induced >10-fold higher SARS-CoV-2 neutralization titers compared with an undecorated vector encoding spike. Importantly, decorated vectors achieved equivalent or superior T cell immunogenicity against encoded antigens compared with undecorated vectors. We propose capsid decoration using protein superglues as a novel strategy to improve efficacy and boostability of adenovirus-based vaccines and therapeutics.
名称: Human adenovirus 5 / タイプ: virus / ID: 1 / 親要素: 0 詳細: Human adenovirus 5 particle displaying the receptor binding domain (RBD) of SARS CoV-2 spike on the surface of the adenovirus capsid. Adenovirus component produced in HEK293 cells, RBD ...詳細: Human adenovirus 5 particle displaying the receptor binding domain (RBD) of SARS CoV-2 spike on the surface of the adenovirus capsid. Adenovirus component produced in HEK293 cells, RBD component produced in CHO-S cells. Components conjugated in vitro using DogTag/DogCatcher protein superglue. NCBI-ID: 28285 / 生物種: Human adenovirus 5 / ウイルスタイプ: VIRION / ウイルス・単離状態: SEROTYPE / ウイルス・エンベロープ: No / ウイルス・中空状態: No
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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: 7.8
凍結
凍結剤: ETHANE
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電子顕微鏡法
顕微鏡
TFS GLACIOS
撮影
フィルム・検出器のモデル: FEI FALCON III (4k x 4k) 平均電子線量: 10.0 e/Å2