PMID- 36609657
OWN - NLM
STAT- MEDLINE
DCOM- 20230110
LR  - 20231106
IS  - 2045-2322 (Electronic)
IS  - 2045-2322 (Linking)
VI  - 13
IP  - 1
DP  - 2023 Jan 6
TI  - A high-throughput single-particle imaging platform for antibody characterization 
      and a novel competition assay for therapeutic antibodies.
PG  - 306
LID - 10.1038/s41598-022-27281-w [doi]
LID - 306
AB  - Monoclonal antibodies (mAbs) play an important role in diagnostics and therapy of 
      infectious diseases. Here we utilize a single-particle interferometric 
      reflectance imaging sensor (SP-IRIS) for screening 30 mAbs against Ebola, Sudan, 
      and Lassa viruses (EBOV, SUDV, and LASV) to find out the ideal capture antibodies 
      for whole virus detection using recombinant vesicular stomatitis virus (rVSV) 
      models expressing surface glycoproteins (GPs) of EBOV, SUDV, and LASV. We also 
      make use of the binding properties on SP-IRIS to develop a model for mapping the 
      antibody epitopes on the GP structure. mAbs that bind to mucin-like domain or 
      glycan cap of the EBOV surface GP show the highest signal on SP-IRIS, followed by 
      mAbs that target the GP1-GP2 interface at the base domain. These antibodies were 
      shown to be highly efficacious against EBOV infection in non-human primates in 
      previous studies. For LASV detection, 8.9F antibody showed the best performance 
      on SP-IRIS. This antibody binds to a unique region on the surface GP compared to 
      other 15 mAbs tested. In addition, we demonstrate a novel antibody competition 
      assay using SP-IRIS and rVSV-EBOV models to reveal the competition between mAbs 
      in three successful therapeutic mAb cocktails against EBOV infection. We provide 
      an explanation as to why ZMapp cocktail has higher efficacy compared to the other 
      two cocktails by showing that three mAbs in this cocktail (13C6, 2G4, 4G7) do not 
      compete with each other for binding to EBOV GP. In fact, the binding of 13C6 
      enhances the binding of 2G4 and 4G7 antibodies. Our results establish SP-IRIS as 
      a versatile tool that can provide high-throughput screening of mAbs, multiplexed 
      and sensitive detection of viruses, and evaluation of therapeutic antibody 
      cocktails.
CI  - (c) 2023. The Author(s).
FAU - Seymour, Elif
AU  - Seymour E
AD  - Department of Biomedical Engineering, Boston University, Boston, MA, 02215, USA.
AD  - Lunenfeld-Tanenbaum Research Institute, Sinai Health System, Toronto, ON, M5G 
      1X5, Canada.
FAU - Unlu, M Selim
AU  - Unlu MS
AD  - Department of Biomedical Engineering, Boston University, Boston, MA, 02215, USA.
AD  - Department of Electrical and Computer Engineering, Boston University, Boston, MA, 
      02215, USA.
FAU - Connor, John H
AU  - Connor JH
AD  - Department of Microbiology, Boston University School of Medicine, Boston, MA, 
      02118, USA. jhconnor@bu.edu.
LA  - eng
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20230106
PL  - England
TA  - Sci Rep
JT  - Scientific reports
JID - 101563288
RN  - 0 (Antibodies, Viral)
RN  - 0 (Immunologic Factors)
RN  - 0 (Epitopes)
RN  - 0 (Antibodies, Neutralizing)
SB  - IM
MH  - Animals
MH  - *Ebolavirus
MH  - Antibodies, Viral
MH  - *Hemorrhagic Fever, Ebola
MH  - Immunologic Factors/metabolism
MH  - Epitopes
MH  - Antibodies, Neutralizing
PMC - PMC9821353
COIS- The authors declare no competing interests.
EDAT- 2023/01/08 06:00
MHDA- 2023/01/11 06:00
PMCR- 2023/01/06
CRDT- 2023/01/07 16:43
PHST- 2022/07/26 00:00 [received]
PHST- 2022/12/29 00:00 [accepted]
PHST- 2023/01/07 16:43 [entrez]
PHST- 2023/01/08 06:00 [pubmed]
PHST- 2023/01/11 06:00 [medline]
PHST- 2023/01/06 00:00 [pmc-release]
AID - 10.1038/s41598-022-27281-w [pii]
AID - 27281 [pii]
AID - 10.1038/s41598-022-27281-w [doi]
PST - epublish
SO  - Sci Rep. 2023 Jan 6;13(1):306. doi: 10.1038/s41598-022-27281-w.