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A small antibody component that is very effective against SARS-COV-2 in animal experiments

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A small antibody component that is very effective against SARS-COV-2 in animal experiments

Wei Li, Ph.D. from Pitt. Shows a step in the process of obtaining potential drugs for COVID-19. Credit: UPMC

Scientists at the University of Pittsburgh School of Medicine have isolated the smallest biomolecule to date that completely and specifically neutralizes the SARS-CoV-2 virus responsible for COVID-19. This antibody component is one-tenth that of full-size antibodies and is used to build a drug called Ab8 that could be used as a therapeutic and prophylactic agent for SARS-CoV-2.

Researchers report in the journal today cell Ab8 is very effective in preventing and treating SARS-CoV-2 infection in mice and hamsters. Its small size not only increases the chances of diffusion within the tissue Not only does it allow the drug to be administered by other routes, including inhalation. Importantly, it doesn’t bind — A good sign that it doesn’t hurt people.

Ab8 was evaluated in collaboration with scientists from the University of North Carolina at Chapel Hill (UNC) and the University of Texas School of Medicine (UTMB) at Galveston, as well as scientists from the University of British Columbia and the University of Saskatchewan.

“Ab8 has potential as a treatment for COVID-19, but can also be used to prevent SARS-CoV-2 infections,” said Dr. John Mellors, MD, Head of Infectious Diseases at UPMC. Stated. And the pit. “Large size antibodies are available for other Well tolerated and it is To protect patients with COVID-19 and those who have never been infected and are not immune. “

The small antibody component is the variable heavy chain (VH) domain of immunoglobulins. This is a type of antibody found in the blood. Discovered by “fishing” in a pool of over 100 billion potential candidates using the SARS-CoV-2 spike protein as bait. Ab8 is created when the VH domain is fused to part of the tail region of an immunoglobulin, adding to the immune function of a bulk-free, full-sized antibody.

UPMC and Dr. John Mellors, MD, Head of Infectious Diseases at the University of Pittsburgh, talks about scientific advances that are a major step towards drugs that have the potential to treat and prevent COVID-19. Credit: UPMC

Abound Bio, a newly established UPMC-backed company, is licensed to develop Ab8 on a global scale.

Dimiter Dimitrov, Ph.D., cell The publisher and director of the Pit Center for Antibody Treatment was one of the first to discover neutralizing antibodies for the original SARS. Over the next few years, his team discovered strong antibodies against many other infections, including those caused by MERS-CoV, dengue, Hendra, and Nipah virus. Antibodies to Hendra virus and Nipah virus have been evaluated in humans and approved for clinical use in Australia on compassionate criteria.

Clinical trials are testing convalescent plasma (including antibodies from people who already have COVID-19) as a treatment for people fighting infections, but those who may need it. Does not have enough plasma and has proven to be ineffective.

As a result, Dimitrov and his team set out to isolate the genes for one or more antibodies that block the SARS-CoV-2 virus, which allows mass production. In February, Wei Li, Ph.D., assistant director and co-author of the study at the Pit Center for Therapeutic Antibodies. Examined a large library of antibody components created using human blood samples and found multiple therapeutic antibody candidates, including Ab8, at record speed.

The team at UTMB’s Center for Biodefense and Emerging Diseases and the Galveston National Laboratory, led by Dr. Chien-Te Kent Tseng, then tested Ab8 with the SARS-CoV-2 virus. At very low concentrations, Ab8 completely blocked the virus from entering the cells. With these results in hand, Ralph Baric, Ph.D. and his UNC colleagues tested Ab8 at various concentrations in mice using a modified version of SARS-CoV-2. Even at the lowest dose, Ab8 was reduced by a factor of 10 in these mice compared to the untreated one. Ab8 was also effective in treating and preventing SARS-CoV-2 infection in hamsters, as evaluated by Dr. Darryl Falzarano and colleagues at the University of Saskatchewan. Dr. Sriram Subramaniam of the University of British Columbia and his colleagues have revealed a unique way in which Ab8 uses sophisticated electron microscopy techniques to neutralize the virus very effectively.

“The COVID-19 pandemic is a global challenge facing humanity, but biomedicine and human ingenuity are likely to overcome it,” said Pitt for the global eradication of HIV and AIDS. Mellors, an emeritus professor of medicine, said that he is hosting a donation course. “We We have found that it contributes to that victory. ”


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For more information:
Wei Li et al, High potency of divalent human VH domain in SARS-CoV-2 animal model, cell (2020). DOI: 10.1016 / j.cell.2020.09.007

Journal information:
cell

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