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9CJ8

Lineage IV Lassa virus glycoprotein (Josiah) in complex with rabbit polyclonal antibody (LAVA01-like epitope)

Summary for 9CJ8
Entry DOI10.2210/pdb9cj8/pdb
EMDB information45625
DescriptorRabbit polyclonal Fv heavy chain, Rabbit polyclonal Fv light chain, Glycoprotein G1, ... (9 entities in total)
Functional Keywordslassa, polyclonal antibody, ll-1, glycoprotein, viral protein, viral protein-immune system complex, viral protein/immune system
Biological sourceLassa virus Josiah
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Total number of polymer chains8
Total formula weight250198.80
Authors
Brouwer, P.J.M.,Perrett, H.R.,Ward, A.B. (deposition date: 2024-07-05, release date: 2024-09-25, Last modification date: 2024-10-09)
Primary citationBrouwer, P.J.M.,Perrett, H.R.,Beaumont, T.,Nijhuis, H.,Kruijer, S.,Burger, J.A.,Bontjer, I.,Lee, W.H.,Ferguson, J.A.,Schauflinger, M.,Muller-Krauter, H.,Sanders, R.W.,Strecker, T.,van Gils, M.J.,Ward, A.B.
Defining bottlenecks and opportunities for Lassa virus neutralization by structural profiling of vaccine-induced polyclonal antibody responses.
Cell Rep, 43:114708-114708, 2024
Cited by
PubMed Abstract: Lassa fever continues to be a major public health burden in West Africa, yet effective therapies or vaccines are lacking. The isolation of protective neutralizing antibodies against the Lassa virus glycoprotein complex (GPC) justifies the development of vaccines that can elicit strong neutralizing antibody responses. However, Lassa vaccine candidates have generally been unsuccessful at doing so, and the associated antibody responses to these vaccines remain poorly characterized. Here, we establish an electron microscopy-based epitope mapping workflow that enables high-resolution structural characterization of polyclonal antibodies to the GPC. By applying this method to rabbits vaccinated with a recombinant GPC vaccine and a GPC-derived virus-like particle, we reveal determinants of neutralization that involve epitopes of the GPC-A competition cluster. Furthermore, by identifying undescribed immunogenic off-target epitopes, we expose the challenges that recombinant GPC vaccines face. By enabling detailed polyclonal antibody characterization, our work ushers in a next generation of more rational Lassa vaccine design.
PubMed: 39243373
DOI: 10.1016/j.celrep.2024.114708
PDB entries with the same primary citation
Experimental method
ELECTRON MICROSCOPY (3.74 Å)
Structure validation

227111

数据于2024-11-06公开中

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