TY - JOUR
T1 - Immunization-Elicited Broadly Protective Antibody Reveals Ebolavirus Fusion Loop as a Site of Vulnerability
AU - Zhao, Xuelian
AU - Howell, Katie A.
AU - He, Shihua
AU - Brannan, Jennifer M.
AU - Wec, Anna Z.
AU - Davidson, Edgar
AU - Turner, Hannah L.
AU - Chiang, Chi I.
AU - Lei, Lin
AU - Fels, J. Maximilian
AU - Vu, Hong
AU - Shulenin, Sergey
AU - Turonis, Ashley N.
AU - Kuehne, Ana I.
AU - Liu, Guodong
AU - Ta, Mi
AU - Wang, Yimeng
AU - Sundling, Christopher
AU - Xiao, Yongli
AU - Spence, Jennifer S.
AU - Doranz, Benjamin J.
AU - Holtsberg, Frederick W.
AU - Ward, Andrew B.
AU - Chandran, Kartik
AU - Dye, John M.
AU - Qiu, Xiangguo
AU - Li, Yuxing
AU - Aman, M. Javad
N1 - Publisher Copyright:
© 2017 Elsevier Inc.
PY - 2017/5/18
Y1 - 2017/5/18
N2 - 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.
AB - 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.
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U2 - 10.1016/j.cell.2017.04.038
DO - 10.1016/j.cell.2017.04.038
M3 - Article
C2 - 28525756
AN - SCOPUS:85019650530
SN - 0092-8674
VL - 169
SP - 891-904.e15
JO - Cell
JF - Cell
IS - 5
ER -