ebolaseq

mAb epitope positions (ebolaseq mab-escape-report)

Literature GP epitopes for Ebanga (mAb114), Inmazeb (REGN-EB3), and MBP134 (ADI-15878 + ADI-23774), mapped to UniProt Q05320 positions and 2014 Makona amino acids (KJ660346.2). The report watchlist is gp_epitope_watchlist.json; tables below match that file.

Pipeline steps (alignment → scoring → outputs): Methodology.

Therapies covered

Product	Monoclonal antibody(ies)
Ebanga (ansuvimab)	mAb114
Inmazeb (REGN-EB3)	mAb3470 (atoltivimab), mAb3471 (odesivimab), mAb3479 (maftivimab)
MBP134 / MBP134AF	ADI-15878, ADI-23774

Details: Coordinate system.

mAb114 (Ebanga / ansuvimab)

GP1 receptor-binding head and glycan cap.

Pos (Q05320)	Makona 2014 aa	GP subunit	Region	Proven escape mutants	Ref
112	E	GP1	GP1 head / RBS beta7-beta9	—	1
116	P	GP1	GP1 head / RBS beta7-beta9	P116H	1
118	G	GP1	GP1 head / RBS beta7-beta9	G118E, G118R	1
143	G	GP1	GP1 head / RBS beta7-beta9	—	1
144	T	GP1	GP1 head / RBS beta7-beta9	T144M	1
146	P	GP1	GP1 head / RBS beta7-beta9	—	1
270	T	GP1	Glycan cap	—	1

Misasi et al., Science 2016 — epitope (10.1126/science.aad6117; PDB 5FHC)

REGN3470 — atoltivimab (Inmazeb component 1)

GP1 glycan cap.

Pos (Q05320)	Makona 2014 aa	GP subunit	Region	Proven escape mutants	Ref
278	N	GP1	Glycan cap beta17-beta18	—	1
279	P	GP1	Glycan cap loop 279-306	—	1
280	E	GP1	Glycan cap beta17-beta18	—	1
282	D	GP1	Glycan cap beta17-beta18	—	1
296	N	GP1	Glycan cap loop 279-306	—	1

Rayaprolu et al., Cell Host Microbe 2023 — REGN-EB3 contacts and escape (10.1016/j.chom.2023.01.002; EMDB-26005)

REGN3471 — odesivimab (Inmazeb component 2)

GP1 head + glycan cap.

Pos (Q05320)	Makona 2014 aa	GP subunit	Region	Proven escape mutants	Ref
111	L	GP1	GP1 head / RBS beta7-beta9	—	1
112	E	GP1	GP1 head / RBS beta7-beta9	—	1
116	P	GP1	GP1 head / RBS beta7-beta9	P116H	1
118	G	GP1	GP1 head / RBS beta7-beta9	G118E, G118R	1
143	G	GP1	GP1 head / RBS beta7-beta9	—	1
144	T	GP1	GP1 head / RBS beta7-beta9	T144M	1
146	P	GP1	GP1 head / RBS beta7-beta9	—	1
270	T	GP1	Glycan cap	—	1
272	K	GP1	Glycan cap	—	1
274	I	GP1	Glycan cap	I274M	1
275	W	GP1	Glycan cap	W275L	1

Rayaprolu et al., Cell Host Microbe 2023 (10.1016/j.chom.2023.01.002)
Davidson et al., J Virol 2015 — I274M, W275L (10.1128/JVI.01490-15)

REGN3479 — maftivimab (Inmazeb component 3)

GP base / fusion loop (quaternary).

Pos (Q05320)	Makona 2014 aa	GP subunit	Region	Proven escape mutants	Ref
34	P	GP1	GP1 quaternary 2nd protomer	—	1
43	L	GP1	GP1 quaternary 2nd protomer	—	1
45	V	GP1	GP1 quaternary 2nd protomer	—	1
504	I	GP2	Fusion loop / GP base	—	1
505	V	GP2	Fusion loop / GP base	—	1
506	N	GP2	Fusion loop / GP base	—	1
507	A	GP2	Fusion loop / GP base	—	1
527	I	GP2	Fusion loop / GP base	—	1
528	G	GP2	Fusion loop / GP base	G528R	1
529	L	GP2	Fusion loop / GP base	—	1
530	A	GP2	Fusion loop / GP base	—	1
535	F	GP2	Fusion loop / GP base	—	1
536	G	GP2	Fusion loop / GP base	—	1
560	Q	GP2	HR1	—	1
563	N	GP2	HR1 N-linked glycan	N563Y	1
564	E	GP2	HR1	—	1
567	Q	GP2	HR1	—	1

Rayaprolu et al., Cell Host Microbe 2023 (10.1016/j.chom.2023.01.002)

ADI-15878 (MBP134 component 1)

Pan-ebolavirus GP-base mAb; quaternary IFL / HR1 epitope spanning two protomers (overlaps REGN3479 IFL; escape G528E/S not G528R). Binds the conserved N-term pocket beneath the GP2 N-terminal tail (502–510); tail residues 504–507 are displaced and disordered in the ADI-15878–GP complex and are not contact residues (1, 2).

Pos (Q05320)	Makona 2014 aa	GP subunit	Region	Proven escape mutants	Ref
34	P	GP1	GP1 base, 2nd protomer	—	1, 2
45	V	GP1	GP1 base, 2nd protomer	—	1, 2
47	D	GP1	GP1 base, 2nd protomer	—	1, 2
526	A	GP2	IFL, adjacent protomer	—	1, 2
527	I	GP2	IFL, adjacent protomer	—	1, 2
528	G	GP2	IFL, adjacent protomer	G528E, G528S	1, 2, 3
529	L	GP2	IFL, adjacent protomer	—	1, 2
530	A	GP2	IFL, adjacent protomer	—	1, 2
535	F	GP2	IFL, adjacent protomer	—	1, 2
537	P	GP2	IFL, adjacent protomer	—	1, 2
560	Q	GP2	HR1, adjacent protomer	—	1, 2
561	L	GP2	HR1, adjacent protomer	—	1, 2
563	N	GP2	HR1 glycan (NAG563)	N563Y	1, 2
564	E	GP2	HR1, adjacent protomer	—	1, 2
567	Q	GP2	HR1, adjacent protomer	—	1, 2

Murin et al., Cell Rep 2018 — GP–ADI-15878 contacts ≤4 Å, Table S2; EBOV/Mak cryo-EM (10.1016/j.celrep.2018.08.009; EMD-8935)
West et al., mBio 2018 — GPCL crystal; N-term tail displaced, pocket binding (10.1128/mBio.01674-18; PDB 6EA7)
Bornholdt et al., Cell 2017 — G528E/S escape (10.1016/j.cell.2017.04.037)

ADI-23774 (MBP134 component 2)

310-pocket mAb. Same GP epitope as parental ADI-15946. ADI-23774 is affinity-matured from ADI-15946 (yeast display) to improve SUDV GP binding—not a new GP footprint. MBP134 = ADI-15878 + ADI-23774 (non-overlapping sites).

K510: HC contacts K510; K510E abolishes binding/neutralization (escape catalogue).

Pos (Q05320)	Makona 2014 aa	GP subunit	Region	Proven escape mutants	Ref
71	E	GP1	GP1 base / 310 helix (310 pocket)	—	1
72	G	GP1	GP1 base / 310 helix (310 pocket)	—	1
73	N	GP1	GP1 base / 310 helix (310 pocket)	—	1
74	G	GP1	GP1 base / 310 helix (310 pocket)	—	1
75	V	GP1	GP1 base / 310 helix (310 pocket)	—	1
287	E	GP1	Glycan cap loop 279-306	—	1
288	W	GP1	Glycan cap loop 279-306	—	1
289	A	GP1	Glycan cap loop 279-306	—	1
290	F	GP1	Glycan cap loop 279-306	—	1
291	W	GP1	Glycan cap loop 279-306	W291R	1
292	E	GP1	Glycan cap loop 279-306	—	1
510	K	GP2	GP2 N-terminus / 310 pocket interface	K510E	1

Bornholdt et al., Nat Struct Mol Biol 2019 — 310 pocket, GPCL contacts, K510 / K510E (10.1038/s41594-019-0191-4; PDB 6MAM)
Bornholdt et al., Cell 2017 — ADI-15946 discovery (10.1016/j.cell.2017.04.037)
Wec et al., Cell Host Microbe 2019 — MBP134 cocktail (10.1016/j.chom.2018.12.004)
Bornholdt et al., Cell Host Microbe 2019 — MBP134AF (10.1016/j.chom.2018.12.005)

Refs 3–4: product names for the two-mAb mix, not extra epitope sites. Positions 287–292: full-length GP / GPFL competition (contact=false in watchlist).

Catalogued escape mutations

Mutation	Pos	Change	GP subunit	Linked mAb	Product(s)	Region	Ref
P116H	116	P→H	GP1	mAb114, REGN3471	Ebanga, Inmazeb	GP1 head / RBS beta7-beta9	1
G118E	118	G→E	GP1	mAb114, REGN3471	Ebanga, Inmazeb	GP1 head / RBS beta7-beta9	1
G118R	118	G→R	GP1	mAb114, REGN3471	Ebanga, Inmazeb	GP1 head / RBS beta7-beta9	1
T144M	144	T→M	GP1	mAb114, REGN3471	Ebanga, Inmazeb	GP1 head / RBS beta7-beta9	1
I274M	274	I→M	GP1	REGN3471	Inmazeb	Glycan cap	2
W275L	275	W→L	GP1	REGN3471	Inmazeb	Glycan cap	2
W291R	291	W→R	GP1	ADI-23774	MBP134	Glycan cap loop 279-306	1
K510E	510	K→E	GP2	ADI-23774	MBP134	GP2 N-terminus / 310 pocket interface	5
G528E	528	G→E	GP2	ADI-15878	MBP134	Fusion loop / GP base	4
G528R	528	G→R	GP2	REGN3479	Inmazeb	Fusion loop / GP base	3
G528S	528	G→S	GP2	ADI-15878	MBP134	Fusion loop / GP base	4
N563Y	563	N→Y	GP2	REGN3479	Inmazeb	HR1 N-linked glycan	3

Rayaprolu et al., Cell Host Microbe 2023 — REGN-EB3 escapes (10.1016/j.chom.2023.01.002)
Davidson et al., J Virol 2015 — I274M, W275L (10.1128/JVI.01490-15)
Rayaprolu et al., Cell Host Microbe 2023 — maftivimab escapes (10.1016/j.chom.2023.01.002)
Bornholdt et al., Cell 2017 — ADI-15878 G528E/S (10.1016/j.cell.2017.04.037)
Bornholdt et al., Nat Struct Mol Biol 2019 — K510E, W291R (10.1038/s41594-019-0191-4)

Used by ebolaseq mab-escape-report vs Makona reference. Antibody links follow escape_mab_map in the watchlist.

Coordinate system

Pos: UniProt Q05320 (mature GP = residues 33–676). GP subunit: GP1 (33–501) or GP2 (502–676).
Makona 2014 aa: KJ660346.2 / AHX24649.2. At all listed sites, Makona matches Mayinga-76 (Q05320).
Literature residues are cross-matched to this scheme (no offset for antibodies here). If a source uses mature-only numbering, add 32 for Q05320.
Primary structures: REGN-EB3 escape on Makona; mAb114 / ADI-15946 crystals on Mayinga (= same indices); ADI-15878 contacts from Murin 2018 Table S2 on EBOV/Mak cryo-EM; ADI-23774 / ADI-15946 310 pocket from Bornholdt 2019 (PDB 6MAM).

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