Antibody Testing

Professor Matthias Wolf and his team have set up a blood antibody test that can be used to determine who has previously contracted COVID-19. The test could be used to screen residents in Okinawa to determine the true extent of the spread of the coronavirus.

Updated October 15, 2020

OIST Antibody test results released

In August 2020, all members of the OIST community were invited to submit a blood sample that was analyzed for COVID-19 antibodies. In total, 635 out of around 1200 people took part. The results found that none of these samples have the antibodies for COVID-19 and have been summarized in a manuscript submitted to the medRxiv pre-print server.

“This indicates, with a great level of certainty, that no one who submitted a sample had been infected with the virus,” said OIST provost and virologist, Dr Mary Collins. “My message is to keep up adherence to the COVID-19 guidelines on and off campus. “

Dr Collins emphasized that the antibody test established at OIST was very sensitive yet specific. It had reliably shown positive results when used on samples from Okinawa residents that were confirmed COVID-19 positive through PCR tests in April. It involved a two-step process, which meant that it was far more accurate than many other antibody tests conducted around the world.

Results from the OIST antibody test
In step one, which used one part of the spike protein – the receptor-binding-domain (RBD) – 63 OIST samples were above the threshold, indicating that their sera contained antibodies that recognized this antigen. All positives from step one were re-tested at various dilutions against the spike protein, but none of these were positive. The negative controls were serum collected before December 2019. The positive control was taken from a pool of samples that were PCR-positive earlier this year. The cluster case represents one of the first COVID-19 group infections on Okinawa.

“Testing volunteers has been a really useful exercise and has given us an idea of the challenges,” said Dr Collins. “The plan now is to test 6000 people in the Okinawa community over the next few months. This will give an indication of how many people in Okinawa have been infected.”

Dr. Hiroyuki Tahara, OIST’s Occupational Health and Safety Doctor, says that the results of this antibody test should not affect anyone’s behavior. “Keep adhering to the guidelines around the new normal – wear masks, wash your hands frequently, and social distance. This won’t change until a vaccine is widely available.”

Professor Matthias Wolf, from the Molecular Cryo-Electron Microscopy Unit, who supervised the project, added to this. “These results should tell everyone that we had no antibodies against this disease,” he said. “Having this knowledge is important because it emphasizes the need to follow health guidelines.”

Updated October 15, 2020

To learn about the science and interdisciplinary work that was behind the OIST antibody test, read the web article "The OIST antibody test required an interdisciplinary approach."

Updated May 8, 2020

A team of OIST scientists, led by Professor Matthias Wolf from the Molecular Cryo-Electron Microscopy Unit, have set up a blood test that can detect the presence or absence of specific antibodies against SARS-CoV-2, the coronavirus that causes COVID-19.

Unlike PCR tests that detect RNA from the virus in currently infected patients, the blood test is used to determine who has previously contracted COVID-19. The specific immune response against the disease can be detected for a longer time after the virus is gone, but it is not yet known if this results in lasting immunity.

The antibody test being used at OIST is an enzyme-linked immunosorbent assay (ELISA), which was originally developed and validated by the Krammer Lab at the Icahn School of Medicine at Mount Sinai, New York.

“The test works by using parts from the SARS-CoV-2 virus surface called spike proteins, which act as antigens,” said Prof. Wolf. “When an individual is infected with the novel coronavirus, the immune system reacts to these antigens and produces specific antibodies which can bind to them.

“In the test, we expose blood serum to bound antigens. The serum of infected individuals, containing these specific antibodies, then bind to the antigens. In a series of stages, we can detect the quantity of antibodies that bind and therefore determine whether an individual had COVID-19.”

To establish the test, staff scientist, Dr. Tae Gyun Kim, with help from staff scientist Dr. Jaekyung Hyun and PhD student, Keon Young Kim, produced and purified components of spike proteins from genetic constructs supplied by the Krammer Lab. Spike proteins, which form the characteristic “crown” shape of coronaviruses, are key to allowing the virus to enter host cells.

Researchers work on producing the spike protein antigens
Cells can be used as microscopic factories to produce the spike protein antigens for the antibody test. (Left) PhD student Keon Young Kim is preparing to introduce the spike protein genetic construct in human embryonic kidney cells. (Right) Staff scientist, Dr. Tae Gyun Kim, checks a culture of cells.

Postdoctoral researcher, Dr. Melissa Matthews, is in charge of setting up the test. Currently, the team are awaiting positive control samples in order to validate the test.

Other units at OIST are now collaborating to further improve the antibody test. Dr. Saacnicteh Toledo-Patino, a postdoctoral researcher from the Protein Engineering and Evolution Unit, led by Professor Paola Laurino, is aiming to optimize the production of antigens, by using E. coli bacterial cells.

Meanwhile, Christian Butcher, a technician from the Fluid Mechanics Unit, led by Professor Pinaki Chakraborty, is working on automating the testing process to expand the daily testing capacity. Presently, the scientists are able to manually test around 1,000 samples each day.

Researchers work on developing automation of the serological test
Christian Butcher (left) and Dr. Melissa Matthews (right) are developing a means of automating parts of the antibody testing process, using a Beckman Biomek liquid handler.

“Ultimately, we hope that the test will be used to screen communities in Okinawa to fully understand the spread of COVID-19, helping officials make more informed decisions,” said Prof. Wolf.

A dialogue with the medical community on Okinawa has been established and the Prefectural Government has requested a pilot screen of 6,000 residents.

Researchers work on developing automation of the serological test

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