Immunization-Elicited Broadly Protective Antibody Reveals Ebolavirus Fusion Loop as a Site of Vulnerability.

Printer-friendly versionPrinter-friendly versionPDF versionPDF version
TitleImmunization-Elicited Broadly Protective Antibody Reveals Ebolavirus Fusion Loop as a Site of Vulnerability.
Publication TypeJournal Article
Year of Publication2017
AuthorsZhao, X, Howell, KA, He, S, Brannan, JM, Wec, AZ, Davidson, E, Turner, HL, Chiang, C-I, Lei, L, J Fels, M, Vu, H, Shulenin, S, Turonis, AN, Kuehne, AI, Liu, G, Ta, M, Wang, Y, Sundling, C, Xiao, Y, Spence, JS, Doranz, BJ, Holtsberg, FW, Ward, AB, Chandran, K, Dye, JM, Qiu, X, Li, Y, M Aman, J
JournalCell
Volume169
Issue5
Pagination891-904.e15
Date Published2017 May 18
ISSN1097-4172
Abstract

While neutralizing antibodies are highly effective against ebolavirus infections, current experimental ebolavirus vaccines primarily elicit species-specific antibody responses. Here, we describe an immunization-elicited macaque antibody (CA45) that clamps the internal fusion loop with the N terminus of the ebolavirus glycoproteins (GPs) and potently neutralizes Ebola, Sudan, Bundibugyo, and Reston viruses. CA45, alone or in combination with an antibody that blocks receptor binding, provided full protection against all pathogenic ebolaviruses in mice, guinea pigs, and ferrets. Analysis of memory B cells from the immunized macaque suggests that elicitation of broadly neutralizing antibodies (bNAbs) for ebolaviruses is possible but difficult, potentially due to the rarity of bNAb clones and their precursors. Unexpectedly, germline-reverted CA45, while exhibiting negligible binding to full-length GP, bound a proteolytically remodeled GP with picomolar affinity, suggesting that engineered ebolavirus vaccines could trigger rare bNAb precursors more robustly. These findings have important implications for developing pan-ebolavirus vaccine and immunotherapeutic cocktails.

DOI10.1016/j.cell.2017.04.038
Alternate JournalCell
PubMed ID28525756