Columbia team pinpoints potent antibody cocktail for COVID-19

Columbia University scientists have identified a cocktail of potent neutralizing antibodies (blue) that can bind to various sites of SARS-CoV-2. (David Ho/Columbia University Irving Medical Center)

Scientists at Columbia University have identified a cocktail of antibodies they say could be a potent option for treating and preventing COVID-19. The team, led by renowned HIV researcher David Ho, collected neutralizing antibodies from five severely ill COVID-19 patients and picked 19 candidates that aggressively killed off the novel coronavirus in lab dishes.

What makes the findings notable is that some of the antibodies the researchers identified target areas of the virus that were not previously described, according to results published in Nature.

Most antibodies bind to the spike protein on the surface of SARS-CoV-2, the virus that causes COVID-19. The Columbia researchers showed that their antibodies target one of two locations on the S protein: either the receptor binding domain (RBD), which helps the virus latch onto and infect human cells, or the N-terminal domain (NTD).

Among nine of the most potent antibodies, four are specifically directed at the RBD and three at the NTD. But in what they believe is an unprecedented discovery, the Columbia team found two powerful neutralizing antibodies that recognize a site on the top of the S protein that crosses from one RBD to another.

Physicians are already using antibody-containing plasma from recovered COVID-19 patients to treat patients. But because convalescent serum contains a variety of antibodies, each patient may need a different plasma product with varying concentrations or strengths of neutralizing antibodies. So purified antibodies that can be mass produced by drugmakers could be a better option, the team argues.

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Ho is best known for his research that laid the groundwork for controlling HIV replication in patients with combination antiretroviral therapy. Now, he's suggesting a similar strategy for combating COVID-19.

“Using a cocktail of different antibodies that are directed to different sites in spike will help prevent the virus becoming resistant to the treatment,” Ho said in a statement.

Regeneron is currently leading the race to develop COVID-19 neutralizing antibody cocktails for potential treatment and prevention of the disease. In collaboration with the National Institute of Allergy and Infectious Diseases, the company recently started a phase 3 study testing whether a mixture of two neutralizing antibodies, dubbed REGN-COV2, can prevention infections in people who have had close contact with an infected person. The company has also advanced the candidate into two clinical trials for treating hospitalized and non-hospitalized COVID-19 patients.

Eli Lilly is testing two antibody treatments, LY-CoV555 and JS016, through separate partnerships with Canadian biotech AbCellera and Chinese company Junshi Biosciences. The Indianapolis pharma is also considering a potential combination of the two.

Ho and colleagues have validated their antibody strategy in a virus challenge study in hamsters. The researchers are now designing further studies in other animals in the hopes of eventually progressing to human trials. “[W]e 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,” the researchers wrote in the study.