PMID- 38540255
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20240330
IS  - 2227-9059 (Print)
IS  - 2227-9059 (Electronic)
IS  - 2227-9059 (Linking)
VI  - 12
IP  - 3
DP  - 2024 Mar 13
TI  - Broad Epitope Coverage of Therapeutic Multi-Antibody Combinations Targeting 
      SARS-CoV-2 Boosts In Vivo Protection and Neutralization Potency to Corner an 
      Immune-Evading Virus.
LID - 10.3390/biomedicines12030642 [doi]
LID - 642
AB  - Therapeutic antibodies (Abs) which act on a broader range of epitopes may provide 
      more durable protection against the genetic drift of a target, typical of viruses 
      or tumors. When these Abs exist concurrently on the targeted antigen, several 
      mechanisms of action (MoAs) can be engaged, boosting therapeutic potency. This 
      study selected combinations of four and five Abs with non- or partially 
      overlapping epitopes to the SARS-CoV-2 spike glycoprotein, on or outside the 
      crucial receptor binding domain (RBD), to offer resilience to emerging variants 
      and trigger multiple MoAs. The combinations were derived from a pool of 
      unique-sequence scFv Ab fragments retrieved from two SARS-CoV-2-naive human phage 
      display libraries. Following recombinant expression to full-length human IgG(1) 
      candidates, a biolayer interferometric analysis mapped epitopes to bins and 
      confirmed that up to four Abs from across the bins can exist simultaneously on 
      the spike glycoprotein trimer. Not all the bins of Abs interfered with the spike 
      protein binding to angiotensin converting enzyme 2 (ACE2) in competitive binding 
      assays, nor neutralized the pseudovirus or authentic virus in vitro, but when 
      combined in vivo, their inclusion resulted in a much stronger viral clearance in 
      the lungs of intranasally challenged hamsters, compared to that of those treated 
      with mono ACE2 blockers. In addition, the Ab mixtures activated in vitro reporter 
      cells expressing Fc-gamma receptors (FcgammaRs) involved in antibody-dependent 
      cellular cytotoxicity (ADCC) and phagocytosis (ADCP). The best four-Ab 
      combination neutralized seventeen variants of concern from Wuhan-Hu1 to Omicron 
      BA.4/BA.5 in vitro.
FAU - Roodink, Ilse
AU  - Roodink I
AD  - ImmunoPrecise Antibodies Ltd., 4837 Amber Valley Parkway, Suite 11, Fargo, ND 
      58104, USA.
FAU - van Erp, Maartje
AU  - van Erp M
AD  - ImmunoPrecise Antibodies Ltd., 4837 Amber Valley Parkway, Suite 11, Fargo, ND 
      58104, USA.
FAU - Li, Andra
AU  - Li A
AD  - ImmunoPrecise Antibodies Ltd., 4837 Amber Valley Parkway, Suite 11, Fargo, ND 
      58104, USA.
FAU - Potter, Sheila
AU  - Potter S
AD  - ImmunoPrecise Antibodies Ltd., 4837 Amber Valley Parkway, Suite 11, Fargo, ND 
      58104, USA.
FAU - van Duijnhoven, Sander M J
AU  - van Duijnhoven SMJ
AD  - ImmunoPrecise Antibodies Ltd., 4837 Amber Valley Parkway, Suite 11, Fargo, ND 
      58104, USA.
FAU - Smits, Milou
AU  - Smits M
AD  - ImmunoPrecise Antibodies Ltd., 4837 Amber Valley Parkway, Suite 11, Fargo, ND 
      58104, USA.
FAU - Kuipers, Arthur J
AU  - Kuipers AJ
AUID- ORCID: 0009-0005-4430-3120
AD  - ImmunoPrecise Antibodies Ltd., 4837 Amber Valley Parkway, Suite 11, Fargo, ND 
      58104, USA.
FAU - Kazemier, Bert
AU  - Kazemier B
AD  - ImmunoPrecise Antibodies Ltd., 4837 Amber Valley Parkway, Suite 11, Fargo, ND 
      58104, USA.
FAU - Berkeveld, Bob
AU  - Berkeveld B
AD  - ImmunoPrecise Antibodies Ltd., 4837 Amber Valley Parkway, Suite 11, Fargo, ND 
      58104, USA.
FAU - van Geffen, Ellen
AU  - van Geffen E
AD  - ImmunoPrecise Antibodies Ltd., 4837 Amber Valley Parkway, Suite 11, Fargo, ND 
      58104, USA.
FAU - Vries, Britte S de
AU  - Vries BS
AD  - ImmunoPrecise Antibodies Ltd., 4837 Amber Valley Parkway, Suite 11, Fargo, ND 
      58104, USA.
FAU - Rijbroek, Danielle
AU  - Rijbroek D
AD  - ImmunoPrecise Antibodies Ltd., 4837 Amber Valley Parkway, Suite 11, Fargo, ND 
      58104, USA.
FAU - Boers, Bianca
AU  - Boers B
AD  - ImmunoPrecise Antibodies Ltd., 4837 Amber Valley Parkway, Suite 11, Fargo, ND 
      58104, USA.
FAU - Meurs, Sanne
AU  - Meurs S
AD  - ImmunoPrecise Antibodies Ltd., 4837 Amber Valley Parkway, Suite 11, Fargo, ND 
      58104, USA.
FAU - Hemrika, Wieger
AU  - Hemrika W
AD  - ImmunoPrecise Antibodies Ltd., 4837 Amber Valley Parkway, Suite 11, Fargo, ND 
      58104, USA.
FAU - Thom, Alexandra
AU  - Thom A
AD  - ImmunoPrecise Antibodies Ltd., 4837 Amber Valley Parkway, Suite 11, Fargo, ND 
      58104, USA.
FAU - Duplantis, Barry N
AU  - Duplantis BN
AD  - ImmunoPrecise Antibodies Ltd., 4837 Amber Valley Parkway, Suite 11, Fargo, ND 
      58104, USA.
FAU - Romijn, Roland A
AU  - Romijn RA
AD  - ImmunoPrecise Antibodies Ltd., 4837 Amber Valley Parkway, Suite 11, Fargo, ND 
      58104, USA.
FAU - Houser, Jeremy S
AU  - Houser JS
AD  - ImmunoPrecise Antibodies Ltd., 4837 Amber Valley Parkway, Suite 11, Fargo, ND 
      58104, USA.
FAU - Bath, Jennifer L
AU  - Bath JL
AD  - ImmunoPrecise Antibodies Ltd., 4837 Amber Valley Parkway, Suite 11, Fargo, ND 
      58104, USA.
FAU - Abdiche, Yasmina N
AU  - Abdiche YN
AD  - ImmunoPrecise Antibodies Ltd., 4837 Amber Valley Parkway, Suite 11, Fargo, ND 
      58104, USA.
LA  - eng
GR  - 20-341/North Dakota Department of Agriculture/
GR  - 20-188/BioScience Innovation Grant/
PT  - Journal Article
DEP - 20240313
PL  - Switzerland
TA  - Biomedicines
JT  - Biomedicines
JID - 101691304
PMC - PMC10968570
OTO - NOTNLM
OT  - COVID-19
OT  - SARS-CoV-2
OT  - antibody-dependent cellular effects
OT  - bio-engineering
OT  - multi-antibody combination
OT  - neutralizing antibodies
OT  - resilient efficacy
COIS- All the authors are (former) employees (and shareholders) of ImmunoPrecise 
      Antibodies Ltd. IR, JLB, and YNA are listed as inventors of the patents 
      "Anti-spike glycoprotein antibodies and the therapeutic use thereof" 
      (PCT/US2022/014103; pending) and US-11623949-B2 (issued 11 April 2023). These 
      associations do not alter the authors' adherence to all the Biomedicines policies 
      on sharing data and materials. The authors declare no other conflict of interest.
EDAT- 2024/03/28 06:45
MHDA- 2024/03/28 06:46
PMCR- 2024/03/13
CRDT- 2024/03/28 01:06
PHST- 2023/06/22 00:00 [received]
PHST- 2024/03/05 00:00 [revised]
PHST- 2024/03/08 00:00 [accepted]
PHST- 2024/03/28 06:46 [medline]
PHST- 2024/03/28 06:45 [pubmed]
PHST- 2024/03/28 01:06 [entrez]
PHST- 2024/03/13 00:00 [pmc-release]
AID - biomedicines12030642 [pii]
AID - biomedicines-12-00642 [pii]
AID - 10.3390/biomedicines12030642 [doi]
PST - epublish
SO  - Biomedicines. 2024 Mar 13;12(3):642. doi: 10.3390/biomedicines12030642.