Today, in the leading academic journal Science, five research papers on antibodies to the new coronavirus are on the line at the same time, introducing a number of newly discovered human-sourceed neutralizing antibodies and antibody “cocktail therapy”. These new “brushing” studies are important for the design of therapeutic antibody drugs and protective vaccines. In this article, the academic team will also share these research progress.
In the first three papers, the three teams successfully isolated neutralizing antibodies from patients with RECOVERY-phase COVID-19 using high-throughput screening techniques based on a single B cell (an immune cell that produces antibodies). Some of these can effectively combine the new coronavirus (SARS-CoV-2) and have a protective effect in animal models.
The first work came from the University of Amsterdam in the Netherlands, where researchers designed a stable prefusion of the new coronavirus S protein for pre-fusion conformation. Using this as an antigen, they isolated 403 monoclonal antibodies from three recovery patients. These antibodies indicate that the body has a strong immune response to the S protein of the new coronavirus.
Cell experiments showed that there were 19 antibodies that could be combined against different antigen sites of the virus S protein, of which 2 semi-inhibition concentrations (IC50) for the new coronavirus were less than 0.01 micrograms/ml, indicating high neutrality.
In another effort, scientists at the Scripps Institute in the United States took less than seven weeks to identify and isolate powerful new coronavirus neutralizing antibodies from patients’ blood samples and experimented with animals.
The researchers first used the institute’s high-throughput antibody production platform to quickly screen more than 1,800 antibodies. Antibodies with high efficiency neutralizing and activity are isolated according to the two epitopes on the receptor binding domain (RBD) and the non-RBD epithesis on the S protein. The team then tested neutralizing antibodies using hamsters as animal models, two of which showed protective effects on the new coronavirus infection.
In the third article, a team led by Adimab identified a group of antibodies that were widely protective and cross-reactive.
The researchers isolated and identified 200 antibodies that can bind to the new coronavirus from a database of memory B cells in a SARS recoverer. Both coronaviruses rely on the S protein and enter the host cell by binding the ACE2 receptor. Nine of these antibodies have neutralizing SARS virus esccoviruses and new coronaviruses, with eight targeted receptor binding domains, and some being neutralized with a bat SARS-like coronavirus.
In two other papers, researchers at Regeneron, a biopharmaceutical company, reported on their leading development of a double-antibody “cocktail therapy.” The study authors note that, in addition to effective treatment, the use of biantibodies, as opposed to a single antibody, can prevent the virus from developing resistance through mutations at selective pressure of monoantibody therapy.
In this work, the researchers first isolated thousands of human-derived antibodies that could be combined with the new coronavirus using a genetically nativeized mouse model and B cells from patients with new coronary pneumonia during recovery. Subsequently, among these antibodies with different binding properties and different antiviral activity, the researchers looked for pairs of antibodies that met the target criteria: two antibodies at different binding sites, combined with the key receptor binding domain of the viral S protein.
“Antibodies containing these antibodies may provide better antiviral effectiveness while minimizing the likelihood of virus escape,” the study authors wrote in their paper. “
In a second article aimed at solving the problem of virus escape, researchers from Regenerative Yuan further evaluated four of the thousands of antibodies mentioned above. They tested various combinations of antibodies by preparing THE SARS-CoV-2 pseudovirus (pseudovirus) that expressed the S protein and equipped it with a series of mutations. For some combinations, virus escape still occurs; however, when two antibodies do not compete or only partially compete, i.e. bind to different or non-overlapping regions of the RBD, the virus can be prevented from producing resistance.
“These data strongly support the possibility that bi-antibody cocktail therapy could provide an effective way to minimize the possibility of sudden escape from SARS-CoV-2,” the authors of the two studies concluded.
Currently, this bi-antibody cocktail therapy has initiated clinical trials to treat and prevent COVID-19.