Antibodies Identified That Best Neutralize the Coronavirus in COVID-19 Patients

Scientists are trying to unravel the mysteries of antibodies specific to SARS-CoV-2, the virus that causes COVID-19, in search of better tests and possible cures. Credit: Fujita Health University

Scientists conduct the first detailed analysis of different antibodies produced by COVID patients against different parts of SARS-CoV-2.

Blood tests to detect antibodies to SARS-CoV-2, the virus that causes COVID-19, are an important tool for diagnosing the disease, developing possible treatments and monitoring vaccine efficacy. While such tests are available, we have very little understanding of how different antibodies interact with virus antigens. Scientists from Fujita Health University looked for several antigen-specific antibodies and determined which of them had the strongest neutralizing activity against SARS-CoV-2.

The COVID-19 pandemic has now claimed more than 2 million deaths worldwide, and this number is only increasing. In response, health authorities have rolled out tests to diagnose and understand the disease. In addition to the well-known PCR test, there is interest in serological (blood) tests that detect ‘antibodies’ against SARS-CoV-2, the virus that causes COVID-19. These blood tests have significant applications, from identifying blood donors with high levels of anti-SARS-CoV-2 antibodies, whose blood can be used for restorative plasma therapy, to measuring the effectiveness of vaccines.

So, what are antibodies? These are proteins produced by the body’s immune system to fight foreign proteins, such as the SARS-CoV-2 virus. Antibodies work by binding to a specific part of the virus that the immune system recognizes, called “antigens.” SARS-CoV-2 is composed of four major proteins, two of which are highly immunogenic (able to produce an immune response). These immunogenic proteins are called spike (S) and nucleocapsid (N) proteins. The presence of antibodies specific for the S protein means that there is a higher amount of virus neutralizing activity, while antibodies specific for the N protein indicate the presence of a previous SARS-CoV-2 infection.

Despite this general awareness, we actually have only a vague understanding of how different antibodies (or antibody isotypes) interact with the different antigens produced by SARS-CoV-2. Therefore, a team of scientists led by Senior Assistant Professor Hidetsugu Fujigaki and Professor Yohei Doi of Fujita Health University, in collaboration with the National Institute of Infectious Diseases, Japan, FUJIFILM Wako Pure Chemical Corporation and FUJIFILM Corporation, conducted the first detailed study of performed these interactions. “Our goal was to quantify the neutralizing activity of these different antibodies against SARS-CoV-2,” explains Dr. Fujigaki explains, “We looked at antibodies specific for different parts of the S protein and N protein to determine which of them is the best predictor of virus stopping.”

They did this by analyzing blood samples from 41 COVID-19 patients at Fujita Health University Hospital. The team developed assays using three common antibodies (IgG, IgM and IgA), each split into isotypes that specifically bind to five antigens (three parts of the S protein, including the receptor binding domain). [RBD], the complete S protein and the complete N protein).

The results of their experiments showed that all the antibody isotypes binding to the S protein (complete and parts) were highly specific, but antibody isotypes binding to the N protein were less. With minor variations, all antibodies are detectable in patients approximately 2 weeks after the onset of symptoms, and the detection sensitivity was greater than 90% (except in the case of IgM binding to N protein). Importantly, the researchers showed that IgG specific to the RBD of S protein had the highest correlation with virus neutralizing activity and disease severity. In other words, measuring RBD-specific IgG levels could tell us a lot about the immune response of COVID-19 patients and could be the basis for improving COVID-19 blood tests.

“We’re also very excited about our findings because of their implications for restorative serum/plasma therapy, a type of treatment where you transfuse blood from people who have recovered from COVID and have high levels of antibodies to SARS-CoV-2,” said Dr. Fujigaki adds, “By demonstrating that the IgG antibody to RBD is highly correlated with neutralizing activity, we can identify suitable blood donors for this treatment.”

The world is hopefully entering the final stages of the pandemic, and this information may be the tools needed to take the last few steps towards a safe post-pandemic world.

Reference: “Comparative Analysis of Antigen-Specific Anti-SARS-CoV-2 Antibody Isotypes in COVID-19 Patients” by Hidetsugu Fujigaki, Masato Inaba, Michiko Osawa, Saya Moriyama, Yoshimasa Takahashi, Tadaki Suzuki, Kenya Yamase, Yukihiro Yoshida, Yo Yagura , Takayoshi Oyamada, Masao Takemura, Yohei Doi and Kuniaki Saito, May 15, 2021, Journal of Immunology.
DOI: 10.4049 / jimmunol.2001369

Funding: Japan Agency for Medical Research and Development (AMED), FUJIFILM Wako Pure Chemical Corporation