Cornering an Ever-Evolving Coronavirus: TATX-03, a fully human synergistic multi-antibody cocktail targeting the SARS-CoV-2 Spike Protein with in vivo efficacy

Roodink, I.; van Erp, M.; Li, A.; Potter, S.; van Duijnhoven, S. M. J.; Kuipers, A. J.; Kazemier, B.; van Geffen, E.; Hemrika, W.; Berkeveld, B.; Sonnemans, G.; de Vries, B. S.; Boers, B.; Smits, M.; Meurs, S.; de Pooter, M.; Thom, A.; Duplantis, B. N.; Romijn, R. A.; Houser, J. S.; Bath, J.; Abdiche, Y. N.

doi:10.1101/2021.07.20.452858

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bioRxiv · 10.1101/2021.07.20.452858

Cornering an Ever-Evolving Coronavirus: TATX-03, a fully human synergistic multi-antibody cocktail targeting the SARS-CoV-2 Spike Protein with in vivo efficacy

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Abstract

The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has created an ongoing global human health crisis and will likely become endemic, requiring novel sustainable therapeutic strategies. We report on the discovery of a fully human multi-antibody cocktail (TATX-03) targeting diversified non-overlapping epitopes on the SARS-CoV-2 spike protein that suppressed replication-competent viral titers to undetectable levels in the lungs of SARS-CoV-2 challenged hamsters upon both prophylactic and therapeutic administration. While monotherapy with two of the individual cocktail components also showed clear in vivo protection, neither recapitulated the efficacy of TATX-03. This synergistic effect was further supported by examining in vivo efficacy of these individual antibodies and corresponding combination therapy at a lower dose. Furthermore, in vitro screenings using VSV-particles pseudo-typed with spike proteins representing the SARS-CoV-2 variants of concern Alpha, Beta, and Delta showed that TATX-03 maintained its neutralization potency. These results merit further development of TATX-03 as a potential therapy for SARS-CoV-2 infection with resistance to mutagenic escape.

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Roodink, I., van Erp, M., Li, A., Potter, S., van Duijnhoven, S. M. J., Kuipers, A. J., Kazemier, B., van Geffen, E., Hemrika, W., Berkeveld, B., Sonnemans, G., de Vries, B. S., Boers, B., Smits, M., Meurs, S., de Pooter, M., Thom, A., Duplantis, B. N., Romijn, R. A., Houser, J. S., Bath, J., Abdiche, Y. N.. 2021-07-21. Cornering an Ever-Evolving Coronavirus: TATX-03, a fully human synergistic multi-antibody cocktail targeting the SARS-CoV-2 Spike Protein with in vivo efficacy. https://doi.org/10.1101/2021.07.20.452858

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