Table 2.

Top performing pan-Ebola mAbs from human survivors.

	Antibody and Source	Target	Competes with	Cross-Binds	Cross Neutralizes	Protection	Reference
CA45	Macaque; Immunized macaque against EBOV, SUDV and MARV GPs	Conserved epitope in the internal fusion loop. Binds to the native GP but binds with way higher potency to the cleaved GP. Does not bind soluble GP (sGP)	KZ52, 2G4 and 4G7	EBOV, SUDV and BDBV (does not bind MARV, Tai Forest or LLOV)	Potently neutralizes EBOV, SUDV, and BDBV and moderately neutralizes Reston. IC50 for EBOV and cleaved core ectodomain of EBOV (EBOV GPcl) was 4.63 and 0.05 nM, BDBV and GPcl was 4.24 and 0.007 nM, and SUDV and GPcl was 9.16 and 0.05 nM	In mice (n = 20), protection was as good as against EBOV and 80% against SUDV. In guinea pigs (n = 6) it was 100% protective against EBOV and SUDV. 100% protection in ferret model (n = 4) of BDBV. FVM04 + CA45 in mice against SUDV was 100% effective, mirrored in guinea pigs for EBOV	[100]
BDBV223	Human IgG3; Human survivor of 2007 Uganda BDBV outbreak	GP2 stalk (canonical heptad repeat 2 (HR2) domain near the MPER) (71% conserved amongst the five first Ebolaviruses, and 90% conserved amongst EBOV, BDBV, and SUDV), does not recognize BDBV sGP	BDBV317, BDBV340	rVSV-GP of EBOV, BDBV, and SUDV	rVSV-GP of EBOV, BDBV, and SUDV	100% in mice (n = 5), post-exposure (1 day) was 20% protection against lethal EBOV (Mayinga) challenge in guinea pigs (n = 5) and 50% effective in ferret models (n = 4), 3- and 6-days post-challenge	[104,105,106]
FVM04	Cloned as human IgG1 with kappa light chain; Macaque vaccinated with EBOV, SUDV, and MARV GP	The exposed tip of the receptor binding domain crest at the apex of the GP trimer and blocks interaction of GP with NPC1 in the late endosome. Glycans may moderately interfere with optimal binding. The RBD crest is highly conserved	M13C6, partially KZ52	EBOV, SUDV, and BDBV (Binds WT, cleaved and sGP of all Ebola species), low affinity binding to MARV and Reston	EBOV and SUDV but not really BDBV or MARV. It is a weaker neutralization than some others: EC50 of 4.3 and 4.3 ug/mL for SUDV and EBOV	100% in mice against EBOV and 75% in mice against SUDV. 100% protective in guinea pigs against SUDV and 40% protective against EBOV	[101,107]
ADI-15742	Human IgG; Human survivor of 2014 West Africa outbreak	A highly conserved region of GP2 within the internal fusion loop. Locks the GP into a pre-fusion state whether free or bound to NPC1. Does not bind sGP	ADI-15878, 100, KZ52, CA45	Everything but MARV/LLOV (rVSV-GP for each Ebolavirus and Marburgvirus)	Potently neutralizes all five Ebola virus with IC50 of <2 nM for rVSV pseudotypes	100% protection in lethal mouse model (100 μg against 100 pfu MA-EBOV) The two ADIs are clonal siblings with 90% and 95% chain identity. *	[102]
ADI-15878	Human IgG; Human survivor of 2014 West Africa outbreak	A highly conserved region of GP2 within the internal fusion loop. Locks the GP into a pre-fusion state whether free or bound to NPC1. Does not bind sGP. Seems to target a cleaved intermediate in endosomes while first generation base binders act further upstream	100, KZ52, CA45	Everything but MARV/LLOV	Potently neutralizes all five Ebola virus with IC50 of <2 nM for rVSV pseudotypes	80% protective in mice (n = 10) against EBOV and 100% protective in mice (n = 20) against SUDV. 75% protective against BDBV in ferrets (n = 4)	[102]
ADI-23374	Derived from affinity maturation of a human mAb (Human survivor of 2014 West Africa outbreak ADI-15946) using yeast resulting in enhanced potency against SUDV.	ADI-15946 binds a highly conserved epitope shielded by the mobile β17–β18 loop of the glycan cap, which is where ADI-23774 binds, does not bind sGP of EBOV	EBOV, BDBV, SUDV	EBOV, BDBV, SUDV	rVSV-SUDV GP	90% protective against EBOV in mice (n = 10) 3 days post exposure and was 100% protective against wt-SUDV in mice (IFNR-/- mice) (n = 10) at 1- and 4-days post exposure	[108]

* They appear to bind the exact same location, although ADI-15878 engenders viral neutralization escape to a lesser extent than ADI-15742.