They claim that this small-sized biological molecule can completely neutralize the SARS-Cov-2 virus that causes Covid-19.
The UPMC and Pitt researchers are collaborating with scientists at the University of North Carolina, University of Texas Medical Branch, the University of British Columbia and University of Saskatchewan.
University of Pittsburgh and UPMC researchers plan to start human trials early next year for an antibody therapy that might both prevent and treat COVID-19. It also makes it possible to administer the drug by alternative routes, including inhalation, the researchers said.
One of the world's largest efforts to find effective COVID-19 treatments will evaluate the impact of REGN-COV2, an investigational antibody cocktail, on mortality, hospital stays, and the need for ventilation.
Wei Li, assistant director of Pitt's Center for Therapeutic Antibodies and co-lead author of the research, sifted through antibody components and found multiple therapeutic antibody candidates in record time. In a membrane protein array assay, the team found that ab8 did not bind to any of the 5,300 human membrane-associated proteins, suggesting that it is highly specific and therefore has a low potential for off-target toxicities in vivo. The tiny antibody component is the variable in the heavy chain (VH) of an immunoglobulin.
When the VH component of an antibody fuses with the tail region of the immunoglobulin, the drug Ab8 produced.
Ab8 could have its worldwide development since it was already licensed by Abound Bio, a newly formed UPMC-backed company. This corresponds to the specificity of an antibody molecule towards a particular virus. REGN-COV2 is now being studied in two Phase 2/3 clinical trials for the treatment of COVID-19 and in a Phase 3 trial for the prevention of COVID-19 in household contacts of infected individuals. They found that ab8 blocked the virus from entering cells, outperforming the angiotensin converting enzyme 2 (ACE2) receptor for binding to the RBD.
With these results in hand, Ralph Baric, PhD, and his UNC colleagues tested ab8 at varying concentrations in mice using a modified version of SARS-CoV-2.
During initial tests, even at the lowest dose, Ab8 decreased by 10-fold the amount of infectious virus in those mice compared to those who were untreated.
Ab8 also showed prophylactic and therapeutic efficacy against SARS-CoV-2 infection in hamsters, as evaluated by Darryl Falzarano, PhD, and colleagues at the University of Saskatchewan.
John Mellors, who co-authored the report with Xianglei Liu of Pitt, said Ab8 could be useful to prevent COVID-19 infection in humans.
"The new trial will tell us whether antibodies that attack the virus can be an effective treatment for COVID-19", she said.