Virus glycoprotein nanodisc platform for vaccine design
Rantalainen, K.; Liguori, A.; Ozorowski, G.; Flynn, C.; Steichen, J. M.; Swanson, O.; Madden, P. J.; Baboo, S.; Phulera, S.; Gharpure, A.; Lu, D.; Kalyuzhniy, O.; Skog, P.; Terada, S.; Shil, M.; Diedrich, J. K.; Georgeson, E.; Tingle, R.; Eskandarzadeh, S.; Lee, W.-H.; Goodwin, D.; Alavi, N.; Kubitz, M.; Amirzehni, S.; Himansu, S.; Sok, D.; Lee, J. H.; Yates, J. R.; Paulson, J. C.; Crotty, S.; Schiffner, T.; Ward, A. B.; Schief, W. R.
Show abstract
Transmembrane glycoproteins of enveloped viruses are the targets of neutralizing antibodies and essential vaccine antigens. mRNA-LNP technology allows in situ production of transmembrane glycoproteins upon immunization, but biophysical characterization of transmembrane antigens and in vitro analysis of post-immunization antibody responses typically rely on soluble proteins. Here, we present a methodological platform for assembling transmembrane glycoprotein vaccine candidates into lipid nanodiscs. We demonstrate the utility of the nanodiscs in HIV membrane proximal external region (MPER)-targeting vaccine development by binding assays using surface plasmon resonance (SPR), ex vivo B cell sorting with fluorescence-activated cell sorting (FACS), and by determining the structure of a prototypical HIV MPER-targeting immunogen nanodisc in complex with three broadly neutralizing antibodies (bnAbs), including the MPER bnAb 10E8, to 3.5 [A] by cryogenic electron microscopy (cryo-EM), providing a template for structure-based immunogen design for MPER. Overall, the platform offers a tool for accelerating the development of next-generation viral vaccines.
Matching journals
The top 3 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- An alpaca nanobody neutralizes SARS-CoV-2 by blocking receptor interaction 97%
- Selection, biophysical and structural analysis of synthetic nanobodies that effectively neutralize SARS-CoV-2 97%
- A stabilized MERS-CoV spike ferritin nanoparticle vaccine elicits robust and protective neutralizing antibody responses 96%
Similar papers in this journal
- Potent SARS-CoV-2 binding and neutralization through maturation of iconic SARS-CoV-1 antibodies 96%
- Protective Antibodies Against Human Parainfluenza Virus Type 3 (HPIV3) Infection 95%
- Nebulized delivery of a broadly neutralizing SARS-CoV-2 RBD-specific nanobody prevents clinical, virological and pathological disease in a Syrian hamster model of COVID-19 95%
Similar papers in this journal
Similar papers in this journal
- Targeting HIV Env immunogens to B cell follicles in non-human primates through immune complex or protein nanoparticle formulations 97%
- Antibody elicited by HIV-1 immunogen vaccination in macaques displaces Env fusion peptide and destroys a neutralizing epitope 96%
- Immunofocusing on the conserved fusion peptide of HIV envelope glycoprotein in rhesus macaques 96%
Similar papers in this journal
- Identification of a conserved neutralizing epitope present on spike proteins from all highly pathogenic coronaviruses 96%
- Mobile barrier mechanisms for Na+-coupled symport in an MFS sugar transporter 96%
- Structure-guided glyco-engineering of ACE2 for improved potency as soluble SARS-CoV-2 decoy receptor 96%
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.