SARS-CoV-2 neutralization and protection of hamsters via nasal administration of a humanized neutralizing antibody
Listed in
This article is not in any list yet, why not save it to one of your lists.Abstract
Monoclonal antibodies are widely used for the treatment of infectious human diseases, including COVID-19. Since the start of the pandemic, eight monoclonal antibodies against SARS-CoV-2 were granted emergency use authorization. High mutation rate of the SARS-CoV-2 virus has led to the emergence of highly transmissible variants efficiently evading vaccine-induced immunity. This highlights the importance of identifying broadly neutralizing antibodies with therapeutic potential. In this study, we used a panel of murine monoclonal antibodies (mAb) to identify a subset that bound and neutralized a broad spectrum of SARS-CoV-2 variants. Intranasal delivery of XR10, the most promising murine mAb, protected hamsters against infection by Alpha and Delta variants. We next humanized XR10 mAb using a combination of CDR-grafting and Vernier zones preservation approaches (CRVZ) to create a panel of humanized antibody variants. We ranked the variants based on their spike binding ability and virus neutralization. Of these, XR10v48 demonstrated the best ability to neutralize SARS-CoV-2 variants. XR10v48 was protective in hamsters when given as a single 50 µg/kg intranasal dose at the time of viral challenge. XR10v48 features 34 key amino acid residues retained from the murine progenitor. Our work introduces a potent humanized antibody that demonstrates neutralizing activity in vivo at a low dose.