A small biological drug to fight COVID-19 shows promise in animal models

Neutralizing monoclonal antibodies are a promising tool in the fight against COVID-19, but their large size usually limits the route of administration to intravenous infusion.

A research team now led by scientists at the University of Pittsburgh School of Medicine has identified antibody components that are 10 times smaller than full-size antibodies. In mice and hamsters, the drug based on it was found to be very effective in preventing and treating SARS-CoV-2, the novel coronavirus behind COVID-19. cell..

Some members of the team have set up a startup called Abound Bio with the goal of introducing a candidate called Ab8 into clinical trials, perhaps as an inhaler for COVID-19.

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“Not only is Ab8 a potential treatment for COVID-19, but it can also be used to prevent people from getting SARS-CoV-2 infection,” said research author John Mellors, MD. Said In the statement. “Large size antibodies are effective against other infections and are well tolerated. Effective treatments to protect patients with COVID-19 and those who have never been infected and have no immunity. I hope it will be. “

Researchers screen a library of approximately 100 billion antibody fragments for candidates that strongly bind to spike proteins on the surface of SARS-CoV-2, in order for the virus to invade and infect human cells. To use.

The selected molecule is the variable domain of the heavy chain of immunoglobulin, a type of antibody. A typical antibody consists of two heavy chains and two light chains. The heavy chain variable domain is essential for binding to the antigen.

Ab8 is created by fusing a variable heavy chain domain with part of the immunoglobulin tail region to provide immune function, but uses molecules that are about half the size of a complete immunoglobulin.

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The small size “may improve the therapeutic effect of infectious diseases such as COVID-19 due to its high penetration into the site of infection,” the researchers wrote in the study. In addition, they added that it can be delivered directly via inhalation, as it penetrates tissues efficiently, which is another advantage for treating respiratory illness.

Ab8 completely neutralized SARS-CoV-2 in the laboratory dish. In the adaptive mouse model, SARS-CoV-2 was administered to animals that acquired Ab8. The drug effectively suppressed the virus in lung tissue in a dose-dependent manner, and researchers found that even at the lowest dose of 2 mg / kg, the virus titer was significantly reduced by a factor of 10 compared to untreated controls. I am reporting.

The team also tested the effectiveness of the drug in hamsters. Hamsters have recently been shown to better represent the clinical features of COVID-19. Ab8 treatment has successfully reduced pulmonary viral load and viral shedding through the nose and mouth in both prophylactic and therapeutic situations. And the hamsters who got the drug did not show more severe pneumonia than the control animals.

In addition, scientists argued that Ab8 does not appear to bind to human cells and may be a good sign that it does not adversely affect people.

Drugs of alternative routes of administration are considered to have added value to the first wave of COVID-19 therapy and vaccines. Another team from the University of Pittsburgh recently Developed A vaccine candidate called PittCoVacc that provides vaccination through band-aid-like patches with sugar-made microneedles.

Multiple neutralizing antibodies against SARS-CoV-2 are already in clinical trials. The pit-led team could offer a more convenient option when the small Ab8 is given as an inhaler rather than intravenously, like most antibodies under development, thanks to increased diffusion through tissues. I think there is sex.