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Scientists develop Covid-19 antibody measuring tech

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Ha-CoV-2 pseudovirus was used against the Covid-19 virus and its variants including Alpha, Delta and Omicron

Do a person’s antibodies work to block the Covid-19 virus from infecting their system? Are these antibodies also capable of blocking emerging variants such as the Omicrons?

These are the questions that researchers at George Mason University have set out to answer.

A cross-disciplinary team, coordinated by scientists at the university’s Center for Infectious Disease Research, has developed Ha-CoV-2.

The non-replicating rapid SARS-CoV-2 pseudovirus system robustly expresses reporter genes in cells within hours, to rapidly measure neutralising antibodies – and the ability of a person to block the virus.

The technology, published in detail in the journal Cell Reports Methods on March 8, reduces a typical two-day process down to a few hours.

It was used against the Covid-19 virus and its variants including Alpha, Delta, and Omicron, as well as the currently emerging omicron BA.2 variant.

The discovery

Dr Yuntao Wu, a professor and virologist in Mason’s College of Science and team’s primary investigator, said: “The lab leveraged learnings from our prior HIV and polio virus research and Mason’s extensive, high-level and integrated infectious disease facilities, just as the SARS CoV-2 virus emerged.”

Brian Hetrick, who performed novel viral vector-based research with Wu, co-invented the pseudo virus system while pursuing his PhD.

“I attempted to make a hybrid alphavirus vector-based pseudovirus for SARS-CoV-2. We hoped to have a more robust and rapid system for screening and measuring antiviral drugs and antibodies. We luckily got it after a few failed attempts.”

The team came up with the new pseudovirus technology in the summer of 2020.

“We learned from previous SARS-CoV-2 pseudoviruse technology that we could get a superior technology with both higher precision and faster speed to quantify neutralisation antibodies,” Wu said.

Wu’s lab then collaborated with researchers from Mason’s Center for Proteomics and Molecular Medicine and the CAP/CLIA certified laboratory whose saliva testing method to monitor Covid-19 spread provided the large amount samples required to dilute the serum and confirm the technology’s powerful impact.

By October of 2020, Wu and his team at Mason had filed for a provisional patent.

Mechanics

The science underpinning the discovery reviews the concentration of antibodies in a person’s blood at various levels of dilution to determine what is the minimal level required to block the virus particle getting into the cell.

“People are different, and so are their neutralising antibodies produced from vaccination,” Wu said.

This Ha-CoV-2 system can tell a person their antibodies’ strength to neutralise SARS-CoV-2 or a particular variant.

Some have stronger antibodies due to prior infection, and whether a person received one or more vaccine. Vaccination and repeated exposure can trigger stronger antibody response.

The future

The technology has a multitude of virus monitoring applications in the public and private sector. For example, within the first few weeks it emerged, this team quickly understood how much more infectious the Omicron virus would be.

“This rapid pseudovirus technology could identify antibody levels and their efficacy to determine if one should need additional protection and could become part of an organisation’s or person’s structured antibody assessment process,” Wu said.

The team’s findings could have significant impacts for pandemic control strategies.

“Just think of it,” Hetrick said, “rather than the now prevalent ‘back to school uncertainty,’ imagine if members of the Mason community could go through an antibody screening at the beginning of an academic year and receive a report detailing their antibody protection levels.

“You’d have the peace of mind to know you are physically protected so you should be fine to come to class or to work.

“Or conversely, based on the antibody levels, if one might not be protected, so a booster would be available to strengthen the antibody response.”

The CDC has not yet published acceptable levels of neutralising antibody, and there is no FDA-approved quantitative kit to measure blood neutralising antibody levels.

Currently, the Mason team and their collaborators from George Washington University and University of Toledo are applying the technology to measure neutralising antibodies from immune-compromised people after their vaccination.

They hope this will enable them to gain detailed information so that educated decisions can be made on the need for booster shots.

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