– University of Pittsburgh School of Medicine
scientists have isolated the smallest biological molecule to date that completely and specifically neutralizes the SARS-CoV-2 virus, which is the cause of COVID-19. This antibody component, which is 10 times smaller than a full-sized antibody, has been used to construct a drug—known as Ab8—for potential use as a therapeutic and prophylactic against SARS-CoV-2.
The researchers report today in the journal Cell
that Ab8 is highly effective in preventing and treating SARS-CoV-2 infection in mice and hamsters. Its tiny size not only increases its potential for diffusion in tissues to better neutralize the virus, but also makes it possible to administer the drug by alternative routes, including inhalation. Importantly, it does not bind to human cells—a good sign that it won’t have negative side-effects in people.
“Ab8 not only has potential as therapy for COVID-19, but it also could be used to keep people from getting SARS-CoV-2 infections,” said co-author John Mellors, M.D.
, chief of the Division of Infectious Diseases at UPMC
“Antibodies of larger size have worked against other infectious diseases and have been well tolerated, giving us hope that it could be an effective treatment for patients with COVID-19 and for protection of those who have never had the infection and are not immune.”
The tiny antibody component is the variable, heavy chain (VH) domain of an immunoglobulin, which is a type of antibody found in the blood. It was found by “fishing” in a pool of more than 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 immunoglobulin tail region, adding the immune functions of a full-size antibody without the bulk.
Like the Pitt and UPMC vaccine candidate PittCoVacc that delivers an immunization through a spiky Band-Aid-like patch and overcomes the need for needles and refrigeration, the researchers are “thinking outside the box” when it comes to how Ab8 could be administered. Its small size might allow it to be given as an inhaled drug or intradermally, rather than intravenously through an IV drip, like most monoclonal antibodies currently in development.
, a newly formed UPMC-backed company, has licensed Ab8 for worldwide development.