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Broad Neutralization of Ebolaviruses via a Fusion Loop Epitope Elicited by Immunization

Corporate Author:

USAMRIID Frederick United States

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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 GP 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 ebola viruses in mice, guinea pigs, and ferrets. Analysis of memory B cells from the immunized macaque suggests that elicitation of broadly neutralizing antibodies bNAbs for ebola viruses is possible but difficult, potentially due to the rarity of bNAb clones and their precursors. Unexpectedly, germlinerevertedCA45, 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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Technical Report



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Approved For Public Release;

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