XAV-19, a novel swine glyco-humanized polyclonal antibody against SARS-CoV-2 spike, efficiently neutralizes B.1.1.7 British and B.1.351 South-African variants

Amino acid substitutions and deletions in spike (S) protein of the 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. We report on XAV-19, a swine "glyco-humanized" polyclonal antibody (GH-pAb) raised against the receptor binding domain (RBD) of the Wuhan-Hu-1 spike protein of SARS-CoV-2. XAV-19 target epitopes are distributed all over the RBD and particularly cover the receptor binding motives (RBM), on direct contact sites with the Angiotensin Converting Enzyme-2 (ACE-2). Using spike/ACE2 interaction assays, we analyzed in vitro the impact of punctual and grouped mutations in the S protein corresponding to the B.1.1.7 (British form; UK) and B.1.351 (South-African form, SA) variants and recorded that neutralization by XAV-19 exhibited little if any sensitivity to these mutations. These results were confirmed by two independent tissue culture infective doses assays (TCID) showing 100% neutralization of the variants at close concentrations. XAV-19, which is currently evaluated in patients hospitalized for coronavirus disease 2019 (Covid-19) in the phase 2a-2b of the POLYCOR study (ClinicalTrial.gov, NCT04453384), may provide a novel effective therapeutic tool to combat coronavirus disease 2019 (Covid-19), caused by the original Wuhan form and by the UK or SA variants of concern.