EMD-40798

Single-particle
16.8 Å
EMD-40798 Deposition: 17/05/2023
Map released: 27/12/2023
Last modified: 27/12/2023
Overview 3D View Sample Experiment Validation Volume Browser Additional data Links
Overview 3D View Sample Experiment Validation Volume Browser Additional data Links

EMD-40798

Negative stain EM map 1 of polyclonal serum from rabbit immunized with Trihead-Hyperglycosylated-Mosaic-I53_dn5 in complex with MI15 HA-foldon

EMD-40798

Single-particle
16.8 Å
EMD-40798 Deposition: 17/05/2023
Map released: 27/12/2023
Last modified: 27/12/2023
Overview 3D View Sample Experiment Validation Volume Browser Additional data Links
Sample Organism: Oryctolagus cuniculus, Influenza A virus
Sample: polyclonal serum cleaved to Fabs from rabbit immunized with Trihead-Hyperglycosylated-Mosaic-I53_dn5 in complex with MI15 HA-foldon

Deposition Authors: Dosey A , King NP
Combinatorial immune refocusing within the influenza hemagglutinin RBD improves cross-neutralizing antibody responses.
PUBMED: 38096052
DOI: doi:10.1016/j.celrep.2023.113553
ISSN: 2211-1247
Abstract:
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.