July 15, 2022 1:00 p.m
A newly developed blood test that measures immunity to COVID-19 could be a valuable tool for deciding who needs a booster and when, according to an international team of researchers. Photo credit: Getty Images
This press release was adapted from material provided by the University of Toronto.
New antibody test for COVID-19 helps track immunity to variants
Experts agree – the pandemic is not over. Infections grow again, fueled by new variants for which our immune system is not prepared.
That’s according to a study that found antibodies generated in people who were vaccinated and/or contracted COVID-19 before 2022 failed to neutralize the variants circulating today.
The study was led by Dr. Sean Owen, assistant professor of pharmaceutics and pharmaceutical chemistry at the University of Utah Health and Dr. Igor Staglar, professor of biochemistry and molecular genetics, at the University of Toronto’s Temerty School of Medicine.
The journal Nature Communications published their findings.
The researchers say the antibody test they developed to measure the immunity of study participants will be a valuable tool for deciding who needs a booster and when, helping to save lives and avoid future blockages.
“As the pandemic continues, we need ways to determine whether people are protected from infection or re-infection,” says Owen. “Our analysis can help monitor the level of immunity a person has after being vaccinated or infected. It can also reveal the level of protection against new variants, which can help in making decisions about when to get a booster or whether a new vaccine is needed.”
Sean Owen, MD, assistant professor of pharmacy and pharmaceutical chemistry at University of Utah Health.
Many antibody tests have been developed in the past two years. But only a few approved tests are designed to look for neutralizing antibodies that coat the viral spike protein so that it can no longer bind to its receptor and enter cells.
This is an important distinction because only a fraction of all Sars-CoV-2 antibodies generated during infection are neutralizing. And although most vaccines are specifically designed to produce neutralizing antibodies, it’s unclear how well they protect against variants
“The truth is, we still don’t know how frequent our shots need to be to prevent infection,” Staglar says. “To answer these questions, we need rapid, cheap and quantitative tests that specifically measure Sars-CoV-2 neutralizing antibodies, which are the ones that prevent infection.”
To meet this need, the research team developed Neu-SATiN, which stands for nneutralization Serological Asay. The effort was led by Sun Jin Kim, a postdoctoral fellow in Owen’s lab, and Zhong Yao, a senior research associate in Stagljar’s lab, who co-authored the paper.
The method is as accurate as, but faster and cheaper than, the current gold-standard assay, and can be quickly adapted for new variants as they emerge, according to the researchers.
“The biggest advantage of Neu-SATiN over other surrogate assays is modularity,” says Kim. “Each of the Neu-SATiN assay components is genetically engineered and recombinantly expressed, making them relatively easy to modify and manufacture. This allows Neu-SATiN to be a truly mix-and-read analysis.
The prick test is powered by the fluorescent luciferase protein from a deep-sea shrimp. It measures the ability of the viral spike protein to bind the human ACE2 receptor, each of which is attached to a luciferase fragment.
The binding brings the luciferase parts together so that they reconstitute a full-length protein that emits light from light that is picked up by the instruments. When the patient’s blood sample is added to the mixture, the neutralizing antibodies will bind the spike protein, preventing it from contacting ACE2. Luciferase remains fragmented, with a concomitant drop in light signal.
The plug and play method can be adapted to different variants within a few weeks by engineering mutations of variants in the spike protein.
The researchers applied Neu-SATiN to blood samples collected from 63 patients with varying histories of COVID-19 infection and vaccination up to November 2021. Their capacity to neutralize antibodies was assessed against the original Wuhan strain and the variants, Alpha, Beta, Gamma , Delta and Omicron.
Neutralizing antibodies have been found to last about three to four months. During that time, their levels dropped by about 70 percent, regardless of infection or vaccination status. Hybrid immunity, acquired through both infection and vaccination, produced higher levels of antibodies at first, but also declined significantly four months later.
Most worryingly, infection and/or vaccination provided good protection against the previous variants, but not against Omicron or its sub-variants BA.4 and BA.5.
The researchers emphasize that vaccines still provide significant protection against severe disease and death. However, the findings from Owen’s team and others call for vigilance in the next period, given that the more transmissible BA.4 and BA.5 subvariants may escape immunity acquired from earlier Omicron infections. as evidenced by increasing re-infections.
Moving forward, the researchers hope to expand its availability.
“We are working with several companies to evaluate the efficacy of their Omicron vaccine candidates and are also negotiating a license with another company to commercialize the assay,” says Owen.
The research was supported by funding from the Office of the Vice President for Research and the 3i Initiative at the University of Utah and the Toronto COVID-19 Action Fund.
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