tetano
Editor, Senior Moderator
iScience
. 2023 Apr 21;26(4):106323.
doi: 10.1016/j.isci.2023.106323. Epub 2023 Mar 2.
Preclinical safety and efficacy of a therapeutic antibody that targets SARS-CoV-2 at the sotrovimab face but is escaped by Omicron
Jakob Kreye[SUP] 1 2 3 4 5 [/SUP], S Momsen Reincke[SUP] 1 2 3 5 [/SUP], Stefan Edelburg[SUP] 6 [/SUP], Lara M Jeworowski[SUP] 7 8 [/SUP], Hans-Christian Kornau[SUP] 1 9 [/SUP], Jakob Trimpert[SUP] 10 [/SUP], Peter Hombach[SUP] 6 [/SUP], Sophia Halbe[SUP] 6 [/SUP], Volker Nölle[SUP] 6 [/SUP], Martin Meyer[SUP] 6 [/SUP], Stefanie Kattenbach[SUP] 6 [/SUP], Elisa Sánchez-Sendin[SUP] 1 2 3 [/SUP], Marie L Schmidt[SUP] 7 8 [/SUP], Tatjana Schwarz[SUP] 7 8 [/SUP], Ruben Rose[SUP] 11 [/SUP], Andi Krumbholz[SUP] 11 12 [/SUP], Sophie Merz[SUP] 13 [/SUP], Julia M Adler[SUP] 10 [/SUP], Kathrin Eschke[SUP] 10 [/SUP], Azza Abdelgawad[SUP] 10 [/SUP], Dietmar Schmitz[SUP] 1 9 14 15 16 [/SUP], Leif E Sander[SUP] 17 [/SUP], Uwe Janssen[SUP] 6 [/SUP], Victor M Corman[SUP] 5 7 8 18 [/SUP], Harald Prüss[SUP] 1 2 3 [/SUP]
Affiliations
Abstract
The recurrent emerging of novel viral variants of concern (VOCs) with evasion of preexisting antibody immunity upholds severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) case numbers and maintains a persistent demand for updated therapies. We selected the patient-derived antibody CV38-142 based on its potency and breadth against the VOCs Alpha, Beta, Gamma, and Delta for preclinical development into a therapeutic. CV38-142 showed in vivo efficacy in a Syrian hamster VOC infection model after post-exposure and therapeutic application and revealed a favorable safety profile in a human protein library screen and tissue cross-reactivity study. Although CV38-142 targets the same viral surface as sotrovimab, which maintains activity against Omicron, CV38-142 did not neutralize the Omicron lineages BA.1 and BA.2. These results highlight the contingencies of developing antibody therapeutics in the context of antigenic drift and reinforce the need to develop broadly neutralizing variant-proof antibodies against SARS-CoV-2.
Keywords: Immunology; Virology.
. 2023 Apr 21;26(4):106323.
doi: 10.1016/j.isci.2023.106323. Epub 2023 Mar 2.
Preclinical safety and efficacy of a therapeutic antibody that targets SARS-CoV-2 at the sotrovimab face but is escaped by Omicron
Jakob Kreye[SUP] 1 2 3 4 5 [/SUP], S Momsen Reincke[SUP] 1 2 3 5 [/SUP], Stefan Edelburg[SUP] 6 [/SUP], Lara M Jeworowski[SUP] 7 8 [/SUP], Hans-Christian Kornau[SUP] 1 9 [/SUP], Jakob Trimpert[SUP] 10 [/SUP], Peter Hombach[SUP] 6 [/SUP], Sophia Halbe[SUP] 6 [/SUP], Volker Nölle[SUP] 6 [/SUP], Martin Meyer[SUP] 6 [/SUP], Stefanie Kattenbach[SUP] 6 [/SUP], Elisa Sánchez-Sendin[SUP] 1 2 3 [/SUP], Marie L Schmidt[SUP] 7 8 [/SUP], Tatjana Schwarz[SUP] 7 8 [/SUP], Ruben Rose[SUP] 11 [/SUP], Andi Krumbholz[SUP] 11 12 [/SUP], Sophie Merz[SUP] 13 [/SUP], Julia M Adler[SUP] 10 [/SUP], Kathrin Eschke[SUP] 10 [/SUP], Azza Abdelgawad[SUP] 10 [/SUP], Dietmar Schmitz[SUP] 1 9 14 15 16 [/SUP], Leif E Sander[SUP] 17 [/SUP], Uwe Janssen[SUP] 6 [/SUP], Victor M Corman[SUP] 5 7 8 18 [/SUP], Harald Prüss[SUP] 1 2 3 [/SUP]
Affiliations
- PMID: 36925720
- PMCID: PMC9979625
- DOI: 10.1016/j.isci.2023.106323
Abstract
The recurrent emerging of novel viral variants of concern (VOCs) with evasion of preexisting antibody immunity upholds severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) case numbers and maintains a persistent demand for updated therapies. We selected the patient-derived antibody CV38-142 based on its potency and breadth against the VOCs Alpha, Beta, Gamma, and Delta for preclinical development into a therapeutic. CV38-142 showed in vivo efficacy in a Syrian hamster VOC infection model after post-exposure and therapeutic application and revealed a favorable safety profile in a human protein library screen and tissue cross-reactivity study. Although CV38-142 targets the same viral surface as sotrovimab, which maintains activity against Omicron, CV38-142 did not neutralize the Omicron lineages BA.1 and BA.2. These results highlight the contingencies of developing antibody therapeutics in the context of antigenic drift and reinforce the need to develop broadly neutralizing variant-proof antibodies against SARS-CoV-2.
Keywords: Immunology; Virology.