In the October 2020 issue of Cell, a University of Pittsburgh group led by Dr. Dimiter S. Dimitrov reports on a novel high affinity human antibody domain with the potential to be used as a SARS-CoV-2 therapeutic and prophylactic and likely to enter clinical trials in humans by the beginning of next year.
Dr. Dimitrov’s group has been at the forefront of monoclonal antibody development with ready translation to in-human antiviral therapy for decades, including for other coronaviruses such as SARS-CoV and MERS-CoV. Building on this extensive experience, the team promptly discovered some of the first anti-SARS-CoV-2 antibodies in February by querying a diverse phage-displayed library with viral protein antigen to identify various antibodies of potential utility. The most promising antibody, named ab8, was investigated further with more detailed mapping of its epitope, and competition with angiotensin-converting enzyme 2 (ACE2), which mediates SARS-CoV-2 entry into host cells, was confirmed, along with in vitro neutralization of virus.
Efficacy studies performed in animals showed neutralization or reduction of virus in mouse lungs, depending on the dose used. In hamsters, ab8 administration reduced lung damage in infected animals and reduced viral loads in the lung, nasopharynx, and oropharynx both when given prophylactically and post-infection.
Importantly, ab8 does not aggregate or bind to any of 5,300 human membrane proteins tested, suggesting that undesirable effects such as tissue deposition or off target cross reactivity would be limited in a human recipient.
These early experimental results set the stage for further evaluation and development of highly neutralizing antibodies targeting the newly identified, unique epitope. In addition to transfer of passive immunity via antibody infusion as prophylaxis or treatment, the findings may hold implications for SARS-CoV-2 vaccine generation in the coming months.
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