ジャーナル: Cell Rep / 年: 2023 タイトル: Combinatorial immune refocusing within the influenza hemagglutinin RBD improves cross-neutralizing antibody responses. 著者: Annie Dosey / Daniel Ellis / Seyhan Boyoglu-Barnum / Hubza Syeda / Mason Saunders / Michael J Watson / John C Kraft / Minh N Pham / Miklos Guttman / Kelly K Lee / Masaru Kanekiyo / Neil P King / 要旨: The receptor-binding domain (RBD) of influenza virus hemagglutinin (HA) elicits potently neutralizing yet mostly strain-specific antibodies. Here, we evaluate the ability of several immunofocusing ...The receptor-binding domain (RBD) of influenza virus hemagglutinin (HA) elicits potently neutralizing yet mostly strain-specific antibodies. Here, we evaluate the ability of several immunofocusing techniques to enhance the functional breadth of vaccine-elicited immune responses against the HA RBD. We present a series of "trihead" nanoparticle immunogens that display native-like closed trimeric RBDs from the HAs of several H1N1 influenza viruses. The series includes hyperglycosylated and hypervariable variants that incorporate natural and designed sequence diversity at key positions in the receptor-binding site periphery. Nanoparticle immunogens displaying triheads or hyperglycosylated triheads elicit higher hemagglutination inhibition (HAI) and neutralizing activity than the corresponding immunogens lacking either trimer-stabilizing mutations or hyperglycosylation. By contrast, mosaic nanoparticle display and antigen hypervariation do not significantly alter the magnitude or breadth of vaccine-elicited antibodies. Our results yield important insights into antibody responses against the RBD and the ability of several structure-based immunofocusing techniques to influence vaccine-elicited antibody responses.
全体 : polyclonal serum cleaved to Fabs from rabbit immunized with Trihe...
全体
名称: polyclonal serum cleaved to Fabs from rabbit immunized with Trihead-Hyperglycosylated-Mosaic-I53_dn5 in complex with MI15 HA-foldon
要素
複合体: polyclonal serum cleaved to Fabs from rabbit immunized with Trihead-Hyperglycosylated-Mosaic-I53_dn5 in complex with MI15 HA-foldon
複合体: polyclonal serum cleaved to Fabs from rabbit immunized with Trihead-Hyperglycosylated-Mosaic-I53_dn5
複合体: MI15 HA-foldon
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超分子 #1: polyclonal serum cleaved to Fabs from rabbit immunized with Trihe...
超分子
名称: polyclonal serum cleaved to Fabs from rabbit immunized with Trihead-Hyperglycosylated-Mosaic-I53_dn5 in complex with MI15 HA-foldon タイプ: complex / ID: 1 / 親要素: 0
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超分子 #2: polyclonal serum cleaved to Fabs from rabbit immunized with Trihe...
超分子
名称: polyclonal serum cleaved to Fabs from rabbit immunized with Trihead-Hyperglycosylated-Mosaic-I53_dn5 タイプ: complex / ID: 2 / 親要素: 1