A newly developed blood test that measures immunity to COVID-19 could be a valuable tool in deciding who needs a booster and when, according to an international team of researchers. Photo: Getty Images
This press release was adapted from material provided by the University of Toronto. New antibody test for COVID-19 helps monitor variant immunity Experts agree – the pandemic is not over. Infections get worse again, fueled by new variants for which our immune systems are ill-prepared. This is according to a study that found that antibodies created in people who had been vaccinated and/or recovered from COVID-19 before 2022 failed to neutralize the variants circulating today. The study was led by Shawn Owen, PhD, assistant professor of pharmaceutical and medicinal chemistry at University of Utah Health, and Igor Stagljar, PhD, professor of biochemistry and molecular genetics at the University of Toronto Temerty School of Medicine. The journal Nature Communications published their findings. The researchers say the antibody test they developed to measure immunity in study participants will be a valuable tool in deciding who needs a booster and when, helping to save lives and avoid future lockdowns. “As the pandemic expands, we need ways to determine whether people are protected from infection or reinfection,” 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 make decisions about when to get a booster or whether a new vaccine is needed.” Shawn Owen, PhD, assistant professor of pharmaceutical and medicinal chemistry at University of Utah Health. Several antibody tests have been developed in the past two years. However, only a few licensed tests are designed to monitor neutralizing antibodies, which coat the virus’s spike protein so that it can no longer bind to its receptor and enter cells. It’s an important distinction, as only a fraction of all Sars-CoV-2 antibodies generated during infection are neutralizing. And while most vaccines were specifically designed to produce neutralizing antibodies, it’s unclear how much protection they provide against the variants “The truth is, we don’t yet know how often our shots should be to prevent infection,” says Stagljar. “To answer these questions, we need quick, cheap and quantitative tests that specifically measure Sars-CoV-2 neutralizing antibodies, which are what prevent infection.” To meet this need, the research team developed Neu-SATiN, which stands for NSerological indexing ONEsay. 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 are first authors of the paper. The method is as accurate as, but faster and cheaper than, the current gold standard test, and can be quickly adapted for new variants that appear, according to the researchers. “The biggest advantage of Neu-SATiN over other surrogate assays is modularity,” says Kim. “Each of the components of the Neu-SATiN assay is genetically engineered and recombinantly expressed, making them relatively easy to modify and produce. This allows Neu-SATiN to be a truly ‘mix and read’ assay.” The pin prick test is powered by the fluorescent protein luciferase 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 pieces of luciferase into proximity so that they reconstitute a full-length protein, which emits a flash of light that is picked up by organs. When a patient’s blood sample is added to the mixture, the neutralizing antibodies will bind to the spike protein, preventing it from contacting ACE2. Luciferase remains in fragments, with an accompanying drop in light signal. The plug and play method can be adapted to different variants within a few weeks, creating variant mutations in the spike protein. The researchers applied Neu-SATiN to blood samples collected from 63 patients with different histories of COVID-19 infection and vaccination through November 2021. The neutralizing ability of their antibodies was evaluated against the original Wuhan strain and the variants, Alpha, Beta, Gamma, Delta and Omicron. Neutralizing antibodies were found to last about three to four months. At 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 dropped significantly four months later. Most worryingly, infection and/or vaccination provided good protection against the previous variants, but not Omicron or its sub-variants, BA.4 and BA.5. The researchers stress that vaccines still provide significant protection against serious illness and death. However, the findings of Owen et al.’s group call for vigilance in the coming period, given that the more contagious BA.4 and BA.5 subvariants can escape immunity acquired from previous Omicron infections. as evidenced by increasing reinfections. Moving forward, researchers hope to expand its availability. “We are working with a few companies to evaluate the efficacy of their vaccine candidates against Omicron 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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