Antibody "Cocktail" Could Offer Potent Treatment, Prevention of COVID-19

July 23, 2020

Writing in Nature, scientists found the antibodies fell into 2 distinct groups, targeting different regions of the viral spike. Thus, they say, the battle against coronavirus disease 2019 (COVID-19) could be opened on separate fronts, much like the approach Ho and others have studied in HIV and some forms of cancer.

The scientist who changed the course of the AIDS epidemic has published findings that suggest the sickest patients who battle their way back from coronavirus disease 2019 (COVID-19) could hold a key to treating and preventing the disease, especially for elderly individuals.

David Ho, MD, scientific director of the Aaron Diamond AIDS Research Center and professor of medicine at Columbia University Vagelos College of Physicians and Surgeons, directed a team that isolated 19 antibodies from 5 patients who had been extremely ill with COVID-19. In a series of experiments, both in vitro and with hamsters, they showed how the antibodies neutralized the SARS-CoV-2 virus, which causes the disease.

Writing in Nature, the scientists found the antibodies fell into 2 distinct groups, targeting different regions of the viral spike. Thus, they say, the battle against COVID-19 could be opened on separate fronts, much like the approach Ho and others have studied in HIV and some forms of cancer.

In a statement released by Columbia University, and during interviews, Ho explained that although vaccine development is moving quickly, it could be months before one is approved. In the meantime, treatments are needed. Even when a vaccine is broadly available, it may not work well in older adults, who have been especially vulnerable in the pandemic.

The antibodies isolated in these experiments could offer a solution, Ho said. "We now have a collection of antibodies that's more potent and diverse compared to other antibodies that have been found so far, and they are ready to be developed into treatments," he said.

Knowledge gained over decades of researching HIV/AIDS is bearing fruit, as Ho has shifted his team from HIV research to a nonstop effort to find treatments for COVID-19. While plasma from recovered patients was collected from the start for use as “convalescent serum,” Ho’s team realized that not all antibodies are the same.

“We think that the sicker patients saw more virus and for a longer period of time, which allowed their immune system to mount a more robust response,” Ho said. “This is similar to what we have learned from the HIV experience.”

In 1996, Ho was named TIME Man of the Year for his work developing the HIV “cocktail,” which combined multiple drugs to battle the virus that causes AIDS “early and hard,” thus rendering what had been a death sentence into a chronic condition. In the Nature article, Ho and his co-authors conceived an antibody cocktail, which would use different types of antibodies directed at different locations on the familiar “spike” on SARS-CoV-2 that gives the virus its “corona.” The most potent antibodies isolated in the research targeted 1 of 2 locations: either the receptor binding domain, which allows the virus to attach to human cells, or the N-terminal region of the spike protein.

Using a cocktail of different antibodies to hit different vulnerable spots on the spike at once lowers the risk that the virus becomes resistant to treatment, Ho said. This concept of hitting dual targets is idea behind bispecific antibodies, which Ho and others have been investigating to fight HIV and which multiple pharmaceutical companies are researching to fight treatment-resistant cancers.

After confirming that the purified antibodies provide protection against SARS-CoV-2 infection in hamsters, the research team plans additional studies in animal models and in humans. “We believe several of our monoclonal antibodies with exquisite virus-neutralizing activity are promising candidates for development as modalities to treat or prevent SARS-CoV-2 infection,” they wrote.

Reference

Liu L, Wang P, Nair MS, et al. Potent neutralizing antibodies directed to multiple epitopes on SARS-CoV-2 spike. Nature. Published online July 22, 2020. doi:10.1038/s41586-020-2571-7