Author(s)
Yaroslav Tsybovsky
Published 9 Projects
COVID-19 Immunology Synthetic Biology Antibody Immune Evasion
Jeffrey C Boyington
Published 2 Projects
Immunology Immune Evasion Structural Rearrangement Type 1 Cr3022
Content
Influenza vaccines targeting the highly-conserved stem of the hemagglutinin (HA) surface glycoprotein have the potential to protect against pandemic and drifted seasonal influenza viruses not covered by current vaccines. While HA stem-based immunogens derived from group 1 influenza A have been shown to induce intra-group heterosubtypic protection, HA stem-specific antibody lineages originating from group 2 may be more likely to possess broad cross-group reactivity. We report the structure-guided development of mammalian cell-expressed candidate vaccine immunogens based on influenza A group 2 H3 and H7 HA stem trimers displayed on self-assembling ferritin nanoparticles using an iterative, multipronged approach involving helix stabilization, loop optimization, disulfide bond addition, and side chain repacking. These immunogens were thermostable, formed uniform and symmetric nanoparticles, were recognized by cross-group-reactive broadly neutralizing antibodies (bNAbs) with nanomolar affinity, and elicited protective, homosubtypic antibodies in mice. Importantly, several immunogens were able to activate B cells expressing inferred unmutated common ancestor (UCA) versions of cross-group-reactive human bNAbs from two multi-donor classes, suggesting they could initiate elicitation of these bNAbs in humans.
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Yaroslav Tsybovsky. (2021, Nov 1).Design of nanoparticulate group 2 influenza hemagglutinin stem antigens that activate unmutated ancestor B cell receptors of broadly neutralizing antibody lineages[Video]. Scitok. https://scitok.com/project/p/0cd80490
S. Corbett Kizzmekia. "Design of nanoparticulate group 2 influenza hemagglutinin stem antigens that activate unmutated ancestor B cell receptors of broadly neutralizing antibody lineages" Scitok, uploaded by Tsybovsky Yaroslav, 1 Nov, 2021, https://scitok.com/project/p0cd80490
Yaroslav Tsybovsky. "Design of nanoparticulate group 2 influenza hemagglutinin stem antigens that activate unmutated ancestor B cell receptors of broadly neutralizing antibody lineages" Scitok. (Nov 1, 2021). https://scitok.com/project/p/0cd80490
Yaroslav Tsybovsky (Nov 1, 2021). Design of nanoparticulate group 2 influenza hemagglutinin stem antigens that activate unmutated ancestor B cell receptors of broadly neutralizing antibody lineages Scitok. https://scitok.com/project/p/0cd80490
Yaroslav Tsybovsky. Design of nanoparticulate group 2 influenza hemagglutinin stem antigens that activate unmutated ancestor B cell receptors of broadly neutralizing antibody lineages[video]. 2021 Nov 1. https://scitok.com/project/p/0cd80490
@online{al2006link, title={ Design of nanoparticulate group 2 influenza hemagglutinin stem antigens that activate unmutated ancestor B cell receptors of broadly neutralizing antibody lineages }, author={ Tsybovsky, Yaroslav }, organization={Scitok}, month={ Nov }, day={ 1 }, year={ 2021 }, url = {https://scitok.com/project/p/0cd80490}, }