Scientists develop 'elite' antibodies capable of defeating coronavirus variants at extremely low dosage

Japanese scientists created "elite" antibodies that defeat various coronavirus variants even at an extremely low dose through a new method that accelerated the months-long process of finding such extraordinary antibody candidates to just ten days.

Our bodies produce specific antibodies to thwart invading pathogens. Some of these antibodies are the neutralizing kind that latches onto the virus' spike protein, preventing it from hijacking and reprogramming a cell into a virus-making factory. So-called "elite" antibodies, known as broadly neutralizing antibodies, are rare immune molecules capable of keeping up with disguises used by a virus' different variants to mask its spike protein.

Monoclonal antibodies that neutralize the SARS-CoV-2 virus are so far the most promising therapeutic intervention."

Tomoharu Yasuda, Study Lead, Professor, Hiroshima University

"Mutant viruses resistant to current vaccines are a potential but realistic risk in the near future. To prepare to fight against such viruses and to save people from those infectious diseases, we need to hurry in developing effective drugs against broad SARS-CoV-2 mutant strains."

But these life-saving molecules are laborious to locate. Researchers have to screen hundreds to hundreds of millions of B cells from patient blood samples to find the most potent candidates they can enhance and grow in laboratories as therapeutic monoclonal antibodies.

By clarifying the typical characteristics of patients likely to carry "elite" antibodies and optimizing the discovery process, Yasuda and his colleagues have dramatically cut down the number of cells needed to be screened and sped up the identification of winning antibody candidates.

Eighteen recovered patients were enrolled as blood donors for the study from April 2020 to January 2021. The patients aged 23-93 years old experienced COVID-19 at different severities. Blood samples were taken over two weeks after the patients tested positive for SARS-CoV-2 — the virus that causes COVID-19 — based on the germinal center reaction theory on neutralizing antibodies production.

"Getting blood samples from severe COVID-19 patients over four weeks, ideally around eight weeks, after the primary infection obtains effective elite antibodies efficiently," Yasuda explained.

After analyzing the patients' samples, they found that even though all carried neutralizing antibodies, about 40% of those had weak or no activity to beat SARS-CoV-2.

Their findings also showed that 80% of participants with severe COVID-19 made a high level of "elite" antibodies, while only 20-30% of those with mild cases did.

The new method successfully obtained five "elite" antibody candidates out of 51 cells from two donor patients. They manufactured engineered versions of these antibodies and found that four work against more dangerous strains of SARS-CoV-2 even at a low dose.

All four antibodies quelled the Alpha and Delta variants, which are more infectious than the original strain of the novel coronavirus. Two of them also neutralized the Beta variant known to reduce the effectiveness of some vaccines.

The antibodies showed IC50 potency at 3-20 ng/mL. A widely used measure of medicine effectivity, IC50 determines how much drug is needed to stop a biological process from happening by half. The researchers said that antibody treatments currently progressing in clinical trials worldwide reached IC50 potency at 15-95 ng/mL.

According to them, this technology is the first in Japan to obtain "elite" antibodies that bind to multiple threatening strains of SARS-CoV-2.

"Our approach could be useful to develop antibody drugs even in other future pandemics, not only SARS-CoV-2 mutants," Yasuda said.

Their novel technique and the four "elite" antibodies they engineered are now awaiting patent approval. The next step for the research team is to develop a technology that accelerates at a pandemic pace the manufacture of monoclonal antibody therapies effective against future SARS-CoV-2 strains. The entire manufacturing process usually takes one to three years, from discovering viable candidates to mass production for medical use.

Comments

  1. ZaCloud StriFair ZaCloud StriFair United States says:

    Cool!
    But, I wonder... shouldn't they have been going for the antibodies of those who had MILD symptoms instead of severe? Because whatever antibodies THEY'VE got protected THEM from getting so badly ill in the first place...

    Plus, there's basically two classes of severely infected patients (if I understand right, please correct me if I'm wrong)... 1) People who are being badly attacked by the virus itself. And 2) People whose immune systems are fighting the virus so hard, that the cytokine storm is what ends up causing severe system-wide inflammatory damage (blood clots, heart kidney lung and brain damage, etc).

    So, when the elite antibodies were extracted, was the patient type (of those two) taken into account? And if so, there's definitely caution as to whether you actually WANT an over-strong immune system in the patients. (Sadly I don't know what the ratio is when it comes to mortality, so that'd give us a better picture...)

    This is why there's mixed results on using certain treatments for Covid-19; some may be on the right track for one class of patient, but terrible for the other. So it has to be figured out: If the virus itself is causing poor condition in the patient, then an immune boost is DEFINITELY the best approach.

    But, if the virus is overshadowed by the body's own hyperactive flood of immune cells, then immunosuppressants are the way to go (as is being studied and used in many hospitals, last I've seen at least). I just hope the distinction and timing is being weighed with increasing wisdom as time goes on.

    So yeah, realizing this is just a layman's article, thus it likely simplifies or omits details... I just hope that both sides of the coin are being investigated. That the antibodies of people whose Covid infections were mild (or even better, by people who tested positive yet had no symptoms at all!) should be just as important to study. I really hope they are.

    Sometimes, looking for the strongest warriors to protect your city results in a lot more death and destruction... than managing to make peace via calm negotiations.

The opinions expressed here are the views of the writer and do not necessarily reflect the views and opinions of News Medical.
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