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  • XAV-19, a Swine Glyco-Humanized Polyclonal Antibody Against SARS-CoV-2 Spike Receptor-Binding Domain, Targets Multiple Epitopes and Broadly Neutralizes Variants #MMPMID34868003
  • Vanhove B; Marot S; So RT; Gaborit B; Evanno G; Malet I; Lafrogne G; Mevel E; Ciron C; Royer PJ; Lheriteau E; Raffi F; Bruzzone R; Mok CKP; Duvaux O; Marcelin AG; Calvez V
  • Front Immunol 2021[]; 12 (ä): 761250 PMID34868003show ga
  • Amino acid substitutions and deletions in the Spike protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants can reduce the effectiveness of monoclonal antibodies (mAbs). In contrast, heterologous polyclonal antibodies raised against S protein, through the recognition of multiple target epitopes, have the potential to maintain neutralization capacities. XAV-19 is a swine glyco-humanized polyclonal neutralizing antibody raised against the receptor binding domain (RBD) of the Wuhan-Hu-1 Spike protein of SARS-CoV-2. XAV-19 target epitopes were found distributed all over the RBD and particularly cover the receptor binding motives (RBMs), in direct contact sites with the angiotensin converting enzyme-2 (ACE-2). Therefore, in Spike/ACE-2 interaction assays, XAV-19 showed potent neutralization capacities of the original Wuhan Spike and of the United Kingdom (Alpha/B.1.1.7) and South African (Beta/B.1.351) variants. These results were confirmed by cytopathogenic assays using Vero E6 and live virus variants including the Brazil (Gamma/P.1) and the Indian (Delta/B.1.617.2) variants. In a selective pressure study on Vero E6 cells conducted over 1 month, no mutation was associated with the addition of increasing doses of XAV-19. The potential to reduce viral load in lungs was confirmed in a human ACE-2 transduced mouse model. XAV-19 is currently evaluated in patients hospitalized for COVID-19-induced moderate pneumonia in phase 2a-2b (NCT04453384) where safety was already demonstrated and in an ongoing 2/3 trial (NCT04928430) to evaluate the efficacy and safety of XAV-19 in patients with moderate-to-severe COVID-19. Owing to its polyclonal nature and its glyco-humanization, XAV-19 may provide a novel safe and effective therapeutic tool to mitigate the severity of coronavirus disease 2019 (COVID-19) including the different variants of concern identified so far.
  • |Animals[MESH]
  • |Antibodies, Heterophile/*immunology/therapeutic use[MESH]
  • |Antibodies, Viral/*immunology/therapeutic use[MESH]
  • |Antigenic Variation[MESH]
  • |Broadly Neutralizing Antibodies/*immunology/therapeutic use[MESH]
  • |COVID-19/therapy/virology[MESH]
  • |Disease Models, Animal[MESH]
  • |Epitopes[MESH]
  • |Humans[MESH]
  • |Immunization, Passive[MESH]
  • |Lung/drug effects/virology[MESH]
  • |Mice[MESH]
  • |Protein Interaction Domains and Motifs[MESH]
  • |SARS-CoV-2/*immunology[MESH]
  • |Spike Glycoprotein, Coronavirus/genetics/*immunology[MESH]
  • |Swine[MESH]
  • |Viral Load/drug effects[MESH]

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  • suck abstract from ncbi

    761250 ä.12 2021