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TitleProminent Neutralizing Antibody Response Targeting the Glycoprotein Subunit Interface Elicited by Immunization.
Journal, issue, pagesJ Virol, Vol. 95, Issue 8, Year 2021
Publish dateMar 25, 2021
AuthorsYimeng Wang / Katie A Howell / Jennifer Brannan / Krystle N Agans / Hannah L Turner / Ariel S Wirchnianski / Shweta Kailasan / Marnie Fusco / Andrey Galkin / Chi-I Chiang / Xuelian Zhao / Erica Ollmann Saphire / Kartik Chandran / Andrew B Ward / John M Dye / M Javad Aman / Thomas W Geisbert / Yuxing Li /
PubMed AbstractThe severe death toll caused by the recent outbreak of Ebola virus disease reinforces the importance of developing ebolavirus prevention and treatment strategies. Here, we have explored the ...The severe death toll caused by the recent outbreak of Ebola virus disease reinforces the importance of developing ebolavirus prevention and treatment strategies. Here, we have explored the immunogenicity of a novel immunization regimen priming with vesicular stomatitis virus particles bearing Sudan Ebola virus (SUDV) glycoprotein (GP) that consists of GP1 & GP2 subunits and boosting with soluble SUDV GP in macaques, which developed robust neutralizing antibody (nAb) responses following immunizations. Moreover, EB46, a protective nAb isolated from one of the immune macaques, is found to target the GP1/GP2 interface, with GP-binding mode and neutralization mechanism similar to a number of ebolavirus nAbs from human and mouse, indicating that the ebolavirus GP1/GP2 interface is a common immunological target in different species. Importantly, selected immune macaque polyclonal sera showed nAb specificity similar to EB46 at substantial titers, suggesting that the GP1/GP2 interface region is a viable target for ebolavirus vaccine. The elicitation of sustained neutralizing antibody (nAb) responses against diverse ebolavirus strains remains as a high priority for the vaccine field. The most clinically advanced rVSV-ZEBOV vaccine could elicit moderate nAb responses against only one ebolavirus strain, EBOV, among the five ebolavirus strains, which last less than 6 months. Boost immunization strategies are desirable to effectively recall the rVSV vector-primed nAb responses to prevent infections in prospective epidemics, while an in-depth understanding of the specificity of immunization-elicited nAb responses is essential for improving vaccine performance. Here, using non-human primate animal model, we demonstrated that booster immunization with a stabilized trimeric soluble form of recombinant glycoprotein derived from the ebolavirus Sudan strain following the priming rVSV vector immunization led to robust nAb responses that substantially map to the subunit interface of ebolavirus glycoprotein, a common B cell repertoire target of multiple species including primates and rodents.
External linksJ Virol / PubMed:33536172 / PubMed Central
MethodsEM (single particle)
Resolution17.5 - 24.0 Å
Structure data

EMDB-22054:
Negative stain EM map of SUDV GPdMuc in complex with EA97
Method: EM (single particle) / Resolution: 24.0 Å

EMDB-22055:
Negative stain EM map of SUDV GPdMuc in complex with EB46 Fab
Method: EM (single particle) / Resolution: 17.5 Å

Source
  • Macaca mulatta (Rhesus monkey)
  • Sudan ebolavirus

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