Research ensures that Ab8 is very effective in preventing and treating coronavirus infection in mice and hamsters
Scientists at the University of Pittsburgh School of Medicine have isolated a smaller biological molecule that “completely and specifically neutralizes” the SARS-CoV-2 virus, which causes Covid-19. This antibody component, which is 10 times smaller than a full-size antibody, has been used to make a drug, known as Ab8, for potential preventive and therapeutic use against coronavirus.
The study, published this Monday in the journal Cell, ensures that Ab8 is very effective in preventing and treating coronavirus infection in mice and hamsters. Its small size not only increases its potential for diffusion into tissues to better neutralize the virus but also allows the drug to be administered by alternative routes, including inhalation. Importantly, it doesn’t bind to human cells, a good sign that it won’t have negative side effects on people.
Ab8 was evaluated in conjunction with scientists from the University of North Carolina at Chapel Hill (UNC) and the Medical Branch of the University of Texas (UTMB) at Galveston, as well as from British Columbia University and the University of Saskatchewan. ” Ab8 not only has potential as a therapy for Covid-19, but it could also be used to prevent people from contracting coronavirus infections” explains one of the study scientists, John Mellors, chief of the Division of Infectious Diseases at Pitt and UPMC.” The larger antibodies have worked against other infectious diseases and have been well-tolerated, giving us hope that which could be an effective treatment for Covid-19 patients and for the protection of those who have never had the infection and are not immune, “adds lead researcher Xianglei Liu.
The small 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 “fishing” in a pool of more than 100 billion candidates using the SARS-CoV-2 spike protein as bait. Ab8 is created when the VH domain fuses with part of the tail region of the immunoglobulin, adding the immune functions of a full-size, massless antibody.
Dimiter Dimitrov, the lead author of the Cell post and director of the Pitt Center for Antibody Therapy, was one of the first to discover neutralizing antibodies to the original SARS coronavirus in 2003. In the years that followed, his team discovered potent antibodies against many other infectious diseases, including those caused by the MERS-CoV, dengue, Hendra, and Nipah viruses. The antibody against Hendra and Nipah viruses has been evaluated in humans and approved for clinical use in Australia.
Clinical trials are testing plasma containing antibodies from people who already had Covid-19, as a treatment for those fighting the infection, but there is not enough plasma for those who might need it and it has not been shown to work. That is why Dimitrov and his team set out to isolate the gene for one or more antibodies that block the SARS-CoV-2 virus, allowing mass production. In February, Wei Li, deputy director of the Pitt Center for Therapeutic Antibodies and a co-lead author on the research, began examining large libraries of antibody components made from human blood samples and found multiple therapeutic antibody candidates, including Ab8, at one time. record.
Next, a team from the UTMB Center for Biodefense and Emerging Diseases and the Galveston National Laboratory tested Ab8 using the live SARS-CoV-2 virus. At very low concentrations, Ab8 completely blocked the entry of the virus into cells. With those results in hand, a team from UNC tested Ab8 at different concentrations in mice using a modified version of SARS-CoV-2. Even with the lowest dose, Ab8 decreased the amount of infectious virus in these mice 10 times.
“The coronavirus pandemic is a global challenge facing humanity, but science and human ingenuity are likely to overcome it,” said Mellors, also a Professor of Medicine, who holds the Endowed for Global Elimination of HIV and AIDS Chair. in Pitt. “We hope that the antibodies we have discovered will contribute to that success.”