Prominent Neutralizing Antibody Response Targeting the Ebolavirus Glycoprotein Subunit Interface Elicited by Immunization.

Autor:	Wang Y; Institute for Bioscience and Biotechnology Research, Rockville, MD., Howell KA; Integrated BioTherapeutics, Inc., Rockville, MD., Brannan J; US Army Medical Research Institute of Infectious Diseases, Frederick, MD., Agans KN; Galveston National Laboratory and Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX.; Galveston National Laboratory and Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX., Turner HL; Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA., Wirchnianski AS; Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, NY., Kailasan S; Integrated BioTherapeutics, Inc., Rockville, MD., Fusco M; Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA., Galkin A; Institute for Bioscience and Biotechnology Research, Rockville, MD.; La Jolla Institute for Immunology, La Jolla, CA., Chiang CI; Institute for Bioscience and Biotechnology Research, Rockville, MD., Zhao X; Institute for Bioscience and Biotechnology Research, Rockville, MD., Saphire EO; La Jolla Institute for Immunology, La Jolla, CA., Chandran K; Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, NY., Ward AB; Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA., Dye JM; US Army Medical Research Institute of Infectious Diseases, Frederick, MD., Aman MJ; Integrated BioTherapeutics, Inc., Rockville, MD., Geisbert TW; Galveston National Laboratory and Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX.; Galveston National Laboratory and Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX., Li Y; Institute for Bioscience and Biotechnology Research, Rockville, MD yuxingli@umd.edu.; Department of Microbiology and Immunology and Center of Biomolecular Therapeutics, University of Maryland School of Medicine, Baltimore, MD.; Department of Microbiology and Immunology and Center of Biomolecular Therapeutics, University of Maryland School of Medicine, Baltimore, MD.
Jazyk:	angličtina
Zdroj:	Journal of virology [J Virol] 2021 Mar 25; Vol. 95 (8). Date of Electronic Publication: 2021 Feb 03.
DOI:	10.1128/JVI.01907-20
Abstrakt:	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. Importance: 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. (Copyright © 2021 American Society for Microbiology.)
Databáze:	MEDLINE
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