EMD-27255
SARS-CoV-2 Spike RBD in complex with DMAb 2196
EMD-27255
Single-particle4.1 Å
Deposition: 08/06/2022Map released: 19/10/2022
Last modified: 06/11/2024
Sample Organism:
Severe acute respiratory syndrome coronavirus 2,
Homo sapiens
Sample: SARS-CoV-2 Spike RBD in complex with DMAb 2196
Fitted models: 8d8r (Avg. Q-score: 0.281)
Deposition Authors: Du J, Cui J, Pallesen J
Sample: SARS-CoV-2 Spike RBD in complex with DMAb 2196
Fitted models: 8d8r (Avg. Q-score: 0.281)
Deposition Authors: Du J, Cui J, Pallesen J
DNA-delivered antibody cocktail exhibits improved pharmacokinetics and confers prophylactic protection against SARS-CoV-2.
Parzych EM,
Du J,
Ali AR,
Schultheis K,
Frase D,
Smith TRF ,
Cui J,
Chokkalingam N,
Tursi NJ ,
Andrade VM,
Warner BM,
Gary EN ,
Li Y,
Choi J,
Eisenhauer J,
Maricic I,
Kulkarni A,
Chu JD,
Villafana G,
Rosenthal K,
Ren K,
Francica JR,
Wootton SK ,
Tebas P,
Kobasa D,
Broderick KE,
Boyer JD,
Esser MT ,
Pallesen J ,
Kulp DW ,
Patel A ,
Weiner DB
(2022) Nat Commun , 13 , 5886 - 5886
,
Cui J,
Chokkalingam N,
Tursi NJ ,
Andrade VM,
Warner BM,
Gary EN ,
Li Y,
Choi J,
Eisenhauer J,
Maricic I,
Kulkarni A,
Chu JD,
Villafana G,
Rosenthal K,
Ren K,
Francica JR,
Wootton SK ,
Tebas P,
Kobasa D,
Broderick KE,
Boyer JD,
Esser MT ,
Pallesen J ,
Kulp DW ,
Patel A ,
Weiner DB
(2022) Nat Commun , 13 , 5886 - 5886
Abstract:
Monoclonal antibody therapy has played an important role against SARS-CoV-2. Strategies to deliver functional, antibody-based therapeutics with improved in vivo durability are needed to supplement current efforts and reach underserved populations. Here, we compare recombinant mAbs COV2-2196 and COV2-2130, which compromise clinical cocktail Tixagevimab/Cilgavimab, with optimized nucleic acid-launched forms. Functional profiling of in vivo-expressed, DNA-encoded monoclonal antibodies (DMAbs) demonstrated similar specificity, broad antiviral potency and equivalent protective efficacy in multiple animal challenge models of SARS-CoV-2 prophylaxis compared to protein delivery. In PK studies, DNA-delivery drove significant serum antibody titers that were better maintained compared to protein administration. Furthermore, cryo-EM studies performed on serum-derived DMAbs provide the first high-resolution visualization of in vivo-launched antibodies, revealing new interactions that may promote cooperative binding to trimeric antigen and broad activity against VoC including Omicron lineages. These data support the further study of DMAb technology in the development and delivery of valuable biologics.
Monoclonal antibody therapy has played an important role against SARS-CoV-2. Strategies to deliver functional, antibody-based therapeutics with improved in vivo durability are needed to supplement current efforts and reach underserved populations. Here, we compare recombinant mAbs COV2-2196 and COV2-2130, which compromise clinical cocktail Tixagevimab/Cilgavimab, with optimized nucleic acid-launched forms. Functional profiling of in vivo-expressed, DNA-encoded monoclonal antibodies (DMAbs) demonstrated similar specificity, broad antiviral potency and equivalent protective efficacy in multiple animal challenge models of SARS-CoV-2 prophylaxis compared to protein delivery. In PK studies, DNA-delivery drove significant serum antibody titers that were better maintained compared to protein administration. Furthermore, cryo-EM studies performed on serum-derived DMAbs provide the first high-resolution visualization of in vivo-launched antibodies, revealing new interactions that may promote cooperative binding to trimeric antigen and broad activity against VoC including Omicron lineages. These data support the further study of DMAb technology in the development and delivery of valuable biologics.