- EMDB-72064: Polyclonal immune complex of Fab from mice sera binding the ester... -
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基本情報
登録情報
データベース: EMDB / ID: EMD-72064
タイトル
Polyclonal immune complex of Fab from mice sera binding the esterase of H5 HA after immunization with inactivated split A/bald eagle/FL/W22-134-OP/2022 Influenza virus vaccine adjuvanted with CpG
マップデータ
Negative stain map of polyclonal Fab from mice sera binding the esterase of H5 HA after immunization with inactivated split A/bald eagle/FL/W22-134-OP/2022 Influenza virus vaccine adjuvanted with CpG
試料
複合体: Polyclonal immune complex of Fab from mice sera binding H5 HA after immunization with inactivated split A/bald eagle/FL/W22-134-OP/2022 Influenza virus vaccine adjuvanted with CpG
キーワード
influenza / hemagglutinin / Flu A / polyclonal / complex / fab complex / VIRAL PROTEIN
National Institutes of Health/National Institute Of Allergy and Infectious Diseases (NIH/NIAID)
75N39019C00051
米国
引用
ジャーナル: bioRxiv / 年: 2025 タイトル: A clade 2.3.4.4b H5N1 virus vaccine that elicits cross-protective antibodies against conserved domains of H5 and N1 glycoproteins. 著者: Eduard Puente-Massaguer / Thales Galdino Andrade / Michael J Scherm / Kirill Vasilev / Hassanein Abozeid / Alesandra J Rodriguez / Josh Yueh / Disha Bhavsar / John D Campbell / Dong Yu / ...著者: Eduard Puente-Massaguer / Thales Galdino Andrade / Michael J Scherm / Kirill Vasilev / Hassanein Abozeid / Alesandra J Rodriguez / Josh Yueh / Disha Bhavsar / John D Campbell / Dong Yu / Richard J Webby / Yoshihiro Kawaoka / Gabriele Neumann / Julianna Han / Andrew B Ward / Florian Krammer / 要旨: The continuous evolution and widespread dissemination of highly pathogenic avian influenza (HPAI) H5N1 viruses, particularly clade 2.3.4.4b, pose critical challenges to global pandemic preparedness. ...The continuous evolution and widespread dissemination of highly pathogenic avian influenza (HPAI) H5N1 viruses, particularly clade 2.3.4.4b, pose critical challenges to global pandemic preparedness. In this study, we assessed a low-dose inactivated split virus vaccine derived from clade 2.3.4.4b H5N1, formulated with an Alum/CpG adjuvant, using a preclinical mouse model. This vaccine induced potent humoral and cellular immune responses, generating high titers of cross-reactive antibodies targeting both hemagglutinin (HA) and neuraminidase (NA) glycoproteins across homologous and heterologous H5 clades. The Alum/CpG adjuvant enabled significant antigen dose-sparing while promoting a balanced Th1/Th2 immune profile. Functional analyses demonstrated strong virus neutralization, neuraminidase inhibition, and potent antibody-dependent cellular cytotoxicity activity. Additionally, the vaccine elicited robust antigen-specific CD4 and CD8 T cell responses and effectively controlled viral replication in the lungs, accompanied by reduced lung inflammation. Importantly, vaccinated mice were fully protected against lethal challenges with both the homologous clade 2.3.4.4b and heterologous clade 1 H5N1 viruses, despite low hemagglutination inhibition titers. Electron microscopy polyclonal epitope mapping revealed serum antibodies targeting multiple epitopes on homologous HA and NA, with some cross-reacting to conserved epitopes on heterologous proteins, underscoring broad immune recognition. Collectively, these results highlight the potential of this vaccine candidate to provide broad, multifunctional, and durable immunity against both current and emerging H5N1 threats, supporting its further development for pandemic preparedness.
ダウンロード / ファイル: emd_72064.map.gz / 形式: CCP4 / 大きさ: 34.3 MB / タイプ: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
注釈
Negative stain map of polyclonal Fab from mice sera binding the esterase of H5 HA after immunization with inactivated split A/bald eagle/FL/W22-134-OP/2022 Influenza virus vaccine adjuvanted with CpG
全体 : Polyclonal immune complex of Fab from mice sera binding H5 HA aft...
全体
名称: Polyclonal immune complex of Fab from mice sera binding H5 HA after immunization with inactivated split A/bald eagle/FL/W22-134-OP/2022 Influenza virus vaccine adjuvanted with CpG
要素
複合体: Polyclonal immune complex of Fab from mice sera binding H5 HA after immunization with inactivated split A/bald eagle/FL/W22-134-OP/2022 Influenza virus vaccine adjuvanted with CpG
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超分子 #1: Polyclonal immune complex of Fab from mice sera binding H5 HA aft...
超分子
名称: Polyclonal immune complex of Fab from mice sera binding H5 HA after immunization with inactivated split A/bald eagle/FL/W22-134-OP/2022 Influenza virus vaccine adjuvanted with CpG タイプ: complex / ID: 1 / 親要素: 0
由来(天然)
生物種: Mus musculus (ハツカネズミ)
分子量
理論値: 280 KDa
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実験情報
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構造解析
手法
ネガティブ染色法
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
濃度
0.015 mg/mL
緩衝液
pH: 7.4
染色
タイプ: NEGATIVE / 材質: 2% w/v uranyl formate
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電子顕微鏡法
顕微鏡
TFS TALOS F200C
撮影
フィルム・検出器のモデル: FEI CETA (4k x 4k) / 平均電子線量: 25.0 e/Å2
電子線
加速電圧: 200 kV / 電子線源: FIELD EMISSION GUN
電子光学系
照射モード: FLOOD BEAM / 撮影モード: DARK FIELD / 最大 デフォーカス(公称値): 2.0 µm / 最小 デフォーカス(公称値): 0.5 µm
試料ステージ
試料ホルダーモデル: SIDE ENTRY, EUCENTRIC / ホルダー冷却材: NITROGEN