Researchers working in various labs in Israel and the rest of the world have reported some success in recent days in isolating antibodies that neutralize the coronavirus’ ability to infect human cells. The use of antibodies has significant potential as a therapy for COVID-19 patients at high risk of complications from the disease, and also as a preventative treatment against infection for people exposed to the virus.
In the long run, the research may also speed up the development of effective vaccines against the illness.
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The first article presenting success in identifying and isolating an effective antibody for SARS-CoV-2 was published on Monday in a scientific journal called Nature Communications, by researchers from Utrecht University, the Erasmus University Medical Center in Rotterdam and Leinbiz University Hannover in Germany.
Defense Minister Naftali Bennett said on Monday that researchers at the Israel Institute for Biological Research have also successfully isolated an antibody that neutralizes the virus, but did not provide any further details, and no scientific studies have thus far been published examining the significance of these findings.
A second Defense Ministry statement released Tuesday said that the institute's researchers have tested the antibody on the live virus, but it also clarified that further research and experimentation is needed to turn the scientific advancement into a medical treatment, and that process will take at least a few months.
Haaretz asked the ministry and the research institute how the antibody was developed and how it has been tested to show its usefulness in stopping the virus. But the ministry declined to provide further details, even though Bennett has said that the institute plans to try to partner with global companies to develop the treatment.
Blocking the virus's key
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At Dr. Natalia Freund’s laboratory at Tel Aviv University, researchers have isolated antibodies from the blood of recovered patients. Two of these antibodies, Freund says, effectively neutralized the protein used by the virus to attach itself to human cells. The coronavirus uses a spike to link up with a human cell’s receptors, allowing it to insert its genetic material into that cell.
“The spike’s protein is like the key through which the virus opens a lock to get into the cells and infect them,” Freund says. The antibodies her team has isolated link up with this key and prevent it from breaking into the cell, she explains.
Freund says she now plans to check the antibodies’ effectiveness against a live virus through animal testing. The only labs in Israel that work with live viruses are those at the Institute for Biological Research, resulting in high demand for their services. This is why, Freund says, she collaborated with researchers at a lab in San Diego to test the antibodies isolated in her lab on animals. The experiments are due to begin next month. If this step is successful, the antibodies will undergo clinical testing to examine their safety and effectiveness on humans.
If effective, the antibodies could be used to help the elderly or people with underlying conditions overcome the virus, she says. Recent studies have shown that some people with the illness do not develop a quick immune response to the virus, so providing them with antibodies could hasten their recovery. The antibodies remain active in the bloodstream for many weeks or even months. Therefore, injecting antibodies can also provide a measure of temporary defense for medical staff and other population groups liable to be exposed to the virus.
Of hybrid mice and men
The use of antibodies is an accepted treatment for various diseases. One main way to create and isolate these antibodies is by exposing mice to the virus, identifying the antibodies in the mouse’s immune system and isolating the most effective ones. The mice used for these studies – called "hybrid mice" – have human genes mixed into their DNA, and produce antibodies more similar to those of humans. This is the system used by the Dutch and German researchers who published their findings. The Israel Institute for Biological Research hasn’t revealed the method it used to isolate the antibody.
Freund explains that using mice has limitations. Even if these are hybrid animals, whose antibodies more closely resemble those of humans, the introduction of an antibody originating in a mouse may trigger the human immune system to attack it. Freund’s lab uses antibodies that have been isolated from the blood of humans who have recovered from COVID-19. Her lab sequences the antibody’s genes and incorporates them into cultured human cells, which later produce the new antibodies. The result of this method is antibodies that are effective against the virus and which are completely human, which do not elicit a negative immune reaction.
Isolating antibodies from human cells can also have long-term benefits for research. The identification of antibodies enables an understanding of where they bind, allowing for a more effective neutralization of the virus. This method can reveal the coronavirus’ vulnerable spots, the specific site on that spike, which, when targeted, can prevent infection. This discovery will enable the development of an effective vaccine, by exposing the immune system to a stretch of a specific protein, which will “teach” the body to produce an effective immune response against this stretch.
Another treatment linked to antibodies which has received recent attention is the infusion of plasma from recovered patients to patients who are in serious condition. This method has two significant drawbacks. The first is that plasma (blood without red blood cells but with antibodies) cannot be produced commercially, and its availability is limited to plasma donations by recovered patients. Antibodies, in contrast, can be produced in unlimited quantities by existing drug companies. The second drawback is that plasma contains a large number of antibodies, some of them effective against the virus, others not, so the treatment is less active and may entail negative side effects.