عرض بسيط للتسجيلة

المؤلفBoyoglu-Barnum, Seyhan
المؤلفHutchinson, Geoffrey B
المؤلفBoyington, Jeffrey C
المؤلفMoin, Syed M
المؤلفGillespie, Rebecca A
المؤلفTsybovsky, Yaroslav
المؤلفStephens, Tyler
المؤلفVaile, John R
المؤلفLederhofer, Julia
المؤلفCorbett, Kizzmekia S
المؤلفFisher, Brian E
المؤلفYassine, Hadi M
المؤلفAndrews, Sarah F
المؤلفCrank, Michelle C
المؤلفMcDermott, Adrian B
المؤلفMascola, John R
المؤلفGraham, Barney S
المؤلفKanekiyo, Masaru
تاريخ الإتاحة2020-08-30T05:29:37Z
تاريخ النشر2020-02-07
اسم المنشورNature Communications
المعرّفhttp://dx.doi.org/10.1038/s41467-020-14579-4
الاقتباسBoyoglu-Barnum, S., Hutchinson, G.B., Boyington, J.C. et al. Glycan repositioning of influenza hemagglutinin stem facilitates the elicitation of protective cross-group antibody responses. Nat Commun 11, 791 (2020). https://doi.org/10.1038/s41467-020-14579-4
معرّف المصادر الموحدhttp://hdl.handle.net/10576/15855
الملخصThe conserved hemagglutinin (HA) stem has been a focus of universal influenza vaccine efforts. Influenza A group 1 HA stem-nanoparticles have been demonstrated to confer heterosubtypic protection in animals; however, the protection does not extend to group 2 viruses, due in part to differences in glycosylation between group 1 and 2 stems. Here, we show that introducing the group 2 glycan at Asn38 to a group 1 stem-nanoparticle (gN38 variant) based on A/New Caledonia/20/99 (H1N1) broadens antibody responses to cross-react with group 2 HAs. Immunoglobulins elicited by the gN38 variant provide complete protection against group 2 H7N9 virus infection, while the variant loses protection against a group 1 H5N1 virus. The N38 glycan thus is pivotal in directing antibody responses by controlling access to group-determining stem epitopes. Precise targeting of stem-directed antibody responses to the site of vulnerability by glycan repositioning may be a step towards achieving cross-group influenza protection.
راعي المشروعWe thank D. Scorpio, A. Taylor, H. Bao, C. Chiedi, M. Dillon, L. Gilliam, and G. Sarbador (VRC) for help with animal studies; H. Andersen (Bioqual, Inc.) for mouse challenge studies; C. Case (Frederick National Laboratory for Cancer Research, Leidos Biomedical Research, Inc.) for help with challenge study coordination; A. Kumar (VRC) for producing RSV proteins; and members of Viral Pathogenesis Laboratory and Universal Influenza Vaccine Program (VRC) for helpful discussion. Support for this work was provided by the Intramural Research Program of the Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health. Electron microscopy data collection and analyses were funded by federal funds from the Frederick National Laboratory for Cancer Research, National Institutes of Health, under contract number HHSN261200800001E, and by Leidos Biomedical Research, Inc. (Y.T. and T.S.).
اللغةen
الناشرNature Research
الموضوعGlycoproteins
Humoral immunity
Influenza virus
Vaccines
العنوانGlycan repositioning of influenza hemagglutinin stem facilitates the elicitation of protective cross-group antibody responses.
النوعArticle
رقم العدد2
رقم المجلد11
ESSN2041-1723
dc.accessType Open Access


الملفات في هذه التسجيلة

Thumbnail

هذه التسجيلة تظهر في المجموعات التالية

عرض بسيط للتسجيلة