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Antibodies Could Be the Key to COVID-19 Immunity

By: Sai Srihaas Potu

During the COVID-19 pandemic, SARS-CoV-2 infected millions of people and claimed hundreds of thousands of lives. Virus entry into cells depends on the receptor-binding domain of the SARS-CoV-2 spike protein. Although there is no vaccine, antibodies will likely be essential for protection. However, little is known about the body’s production of antibodies in response to SARS-CoV-2.


As coronavirus spreads across the globe, a crucial question has emerged: After recovering from an infection, are people immune due to the creation of antibodies by their immune system?


This question is important for understanding who can safely go back to work, as well as for understanding how long the worst impacts of the pandemic are likely to last. Because the virus is so new, the answer isn't fully understood. But so far, scientists say, it looks like SARS-CoV-2 probably induces immunity like other coronaviruses. That means that the human body will probably retain a memory of the virus for at least a few years and should be protected from reinfection, at least in the short-term.

When infected by a virus-like SARS-CoV-2, the cause of COVID-19, the body initially produces antibodies known as IgM (immunoglobulin-M), in an attempt to neutralize the virus. Later, as the body’s adaptive immune system revs up, IgM levels go down, and the body ramps up production of IgG, which more specifically targets the viral invader. However, as the days go by the body will start to run out of antibodies which is why the memorization of the virus physiology by the immune system is integral for immunity.


In a recent study, scientists found out that people who have recovered from COVID-19 had generated at least some level of antibodies that were intrinsically capable of neutralizing the SARS-CoV-2 virus. Antibodies vary widely in their efficacy. While many may latch on to the virus, only some are truly “neutralizing,” meaning that they block the virus from entering the cells.


For the research project, 200 people who had recovered from COVID-19 donated plasma, the portion of the blood that contains the antibodies, and the immune B-cells that produce them. The participants had experienced symptoms for an average of 3 weeks and had their first symptoms on average 6 weeks before plasma donation.


The research team used an essay they had developed to test the neutralizing activity of the plasma samples. This involved mixing the plasma with a pseudo-SARS-CoV-2 virus and measuring how well this mixture could still infect human cells in a dish.


In 33 percent of donors, the neutralizing activity of plasma was below detectable levels. This shows that for most of the people in this group the immune system’s first line of defense was able to quickly resolve the infection before the body was able to create any antibody-producing cells.


Based on the results, the majority of the plasma samples showed poor to modest neutralizing activity. And for 1 percent of donors, it was remarkably high. Everyone responds to an infection differently. Based on their body and their immune system, some people have a poor or average response whereas others have an exceptional response to any viral infections.


Those exceptional responders are crucial to the team’s plans. The high numbers of neutralizing antibodies in their serum make it possible for researchers to catch the rare B cells that can make the antibodies. They can then clone the antibodies from those cells, and use them to emulate the same strong defense in other people.


Out of the numerous antibodies generated by elite responders who had the best performing plasma, the team identified 40 that neutralized the virus and zeroed in on three that could do so even at very low concentrations. The team has cloned these most potent antibodies and is now working to develop them for clinical use.


Neutralizing antibodies found in this study bind to at least three distinct sites on the receptor-binding domain subunit of the spike protein, which is what SARS-CoV-2 uses to gain entry to host cells. A second look at the low-performing plasma samples revealed they also contained these RBD-binding antibodies, albeit in small quantities.


Ultimately, researchers are still uncertain about what level of long-term immune memory is sufficient to protect against future coronavirus infection, and how long it takes for the immune system to drop below that level. With the help of subsequent research, scientists will be able to use these antibodies to not only replicate the rare B cells that produce these fighting agents but also create viral proteins that are integral for the creation of a vaccine that will help trigger an effective immune response.


References:

1. Davide F. Robbiani, Christian Gaebler, Frauke Muecksch, Julio C. C. Lorenzi. Convergent Antibody Responses to Sars-CoV-2 Infection in Convalescent Individuals. BioRxiv. 2020.

2. Gurwitz D. Angiotensin receptor blockers as tentative SARS-CoV-2 therapeutics. Drug Development Research. 2020.

3. Walker L.M., Burton D.R. Passive immunotherapy of viral infections: ‘super-antibodies’ enter the fray. Nature Reviews Immunology. 2020.

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