The blood of a couple who contracted SARS-CoV-2 in Wuhan, China at the start of the outbreak produced powerful antibodies that neutralized the virus in the laboratory and protected the animals from some effects of infection. The researchers have also found that combining two of the antibodies can prevent the virus from developing resistance.
In January 2020, the couple traveled to Toronto, Canada, and developed one of the first confirmed cases of COVID-19 in North America.
It can take years to isolate and develop antibodies as treatments, but a team led by scientists at Vanderbilt University Medical Center in Nashville, TN took advantage of recent technological advances to speed up the process.
Before the pandemic, they developed a way to isolate antibodies and detect the ability to neutralize a virus, all within 78 days.
Driven by the health emergency posed by COVID-19, they further simplified their technique, until it took just 35 days to isolate 70 monoclonal antibodies that neutralize SARS-CoV-2 from the couple’s blood samples.
Each monoclonal antibody is produced by a different line of memory B cells, a type of immune cell that “remembers” a particular protein sequence of the virus.
The researchers reported their work earlier this month in the journal. Natural medicine.
After working with 40 of the most effective antibodies, the researchers conducted a second set of studies, described in a document now accepted for publication in Nature.
In these, they reduced the field to several antibodies that attack a part of the characteristic peaks of the coronavirus that allows it to invade host cells.
Scientists call this area the receptor binding domain. In SARS-CoV-2, it is blocked by a receptor, called ACE2, on the outer membrane of human cells.
Therefore, an antibody that blocks the receptor binding domain can prevent the virus from entering cells and replicating.
Such an antibody could be produced in large quantities and injected into patients as treatment. Alternatively, a vaccine could cause the immune system to produce the same antibody for itself, providing protection against future infections.
In their article, the researchers write:
“Our work illustrates the promise of integrating recent technological advances for antibody discovery and helps define the [receptor-binding domain of the spike protein] as an important site of vulnerability for vaccine design and therapeutic antibody development. The most powerful neutralizing human [monoclonal antibodies] Isolated here could also serve as candidate biologics to prevent or treat SARS-CoV-2 infection. “
Two of the antibodies, which the researchers have labeled COV2-2196 and COV2-2130, recognize two sections of the receptor-binding domain that do not overlap.
Scientists have shown that the two antibodies were able to simultaneously bind to the spike, neutralizing the virus “synergistically.” In other words, the antibodies were more potent in combination than individually.
The two antibodies, together and separately, protected the mice from the worst effects of SARS-CoV-2 infection. The researchers observed that compared to untreated animals, these mice showed less weight loss, produced less virus, and had less lung inflammation.
Finally, the researchers demonstrated that COV2-2196 or another neutralizing antibody they identified, labeled COV2-2381, protected rhesus macaques from SARS-CoV-2 infection.
It is important to note that these antibodies have not yet been tested in humans.
However, thanks to their recently streamlined technique for identifying the most potent neutralizing antibodies, scientists were able to share their discovery with manufacturers in a matter of weeks.
In June 2020, the pharmaceutical company AstraZeneca signed an agreement with Vanderbilt to develop two of the coronavirus neutralizing antibodies to prevent and treat COVID-19.
A Nashville-based biotechnology company called IDBiologics reached a similar agreement with the university to subject some of the other antibodies to clinical trials.
Both companies plan to conduct clinical trials this summer.
In its Nature In the article, the scientists note that other research groups have discovered that SARS-CoV-2 can develop “escape mutations” to evade a single monoclonal antibody, but not two antibodies in combination.
They write that this reinforces the need to target different parts of the virus peak simultaneously, either through a vaccine or antibody “immunotherapy”.
“Rationally selected therapeutic cocktails like the one described here probably offer greater resistance to leakage than SARS-CoV-2. These studies set the stage for preclinical evaluation and development of [monoclonal antibodies] as candidates for use as COVID-19 immunotherapeutics in humans. “
