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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
  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
  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
  1. Rayaprolu et al., Cell Host Microbe 2023 (10.1016/j.chom.2023.01.002)
  2. 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
  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
  1. 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)
  2. West et al., mBio 2018 — GPCL crystal; N-term tail displaced, pocket binding (10.1128/mBio.01674-18; PDB 6EA7)
  3. 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
  1. Bornholdt et al., Nat Struct Mol Biol 2019 — 310 pocket, GPCL contacts, K510 / K510E (10.1038/s41594-019-0191-4; PDB 6MAM)
  2. Bornholdt et al., Cell 2017 — ADI-15946 discovery (10.1016/j.cell.2017.04.037)
  3. Wec et al., Cell Host Microbe 2019 — MBP134 cocktail (10.1016/j.chom.2018.12.004)
  4. 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
  1. Rayaprolu et al., Cell Host Microbe 2023 — REGN-EB3 escapes (10.1016/j.chom.2023.01.002)
  2. Davidson et al., J Virol 2015 — I274M, W275L (10.1128/JVI.01490-15)
  3. Rayaprolu et al., Cell Host Microbe 2023 — maftivimab escapes (10.1016/j.chom.2023.01.002)
  4. Bornholdt et al., Cell 2017 — ADI-15878 G528E/S (10.1016/j.cell.2017.04.037)
  5. 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).