Jul 15, 2022 1:00 PM
This press release has been adapted from material provided by the University of Toronto.
New COVID-19 antibody test helps keep track of variant immunity
Experts agree that the pandemic is not over. Infections resume, fueled by new variants that our immune systems are ill-prepared for.
That’s according to a study that found that antibodies generated in people vaccinated and/or recovered from COVID-19 before 2022 failed to neutralize variants circulating today.
The study was conducted by Shawn Owen, Ph.D., assistant professor of pharmacy and pharmaceutical chemistry at Utah Health University and Igor Stagljar, PhD, professor of biochemistry and molecular genetics at the University of Toronto Temerty School of Medicine.
The newspaper Nature Communication published their findings.
The researchers say the antibody test they developed to measure the immunity of study participants will be a valuable tool in deciding who needs a booster and when, which will help save lives and avoid future lockdowns.
“As the pandemic spreads, we need ways to determine if people are protected from infection or reinfection,” says Owen. “Our test can help monitor a person’s level of immunity after being vaccinated or infected. It can also reveal the level of protection against new variants, which can help guide decisions about when to get a booster or if a new vaccine is needed.”
Many antibody tests have been developed over the past two years. But only a few licensed tests are designed to monitor neutralizing antibodies, which coat the viral spike protein so it can no longer bind to its receptor and enter cells.
This is an important distinction, as only a fraction of all Sars-CoV-2 antibodies generated during infection are neutralizing. And although most vaccines have been specifically designed to produce neutralizing antibodies, the degree of protection they provide against variants is unclear.
“The truth is, we don’t yet know how often our injections should be to prevent infection,” Stagljar says. “To answer these questions, we need rapid, inexpensive, 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 NOTSerological neutralization 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 are the paper’s co-first authors.
The method is as accurate, but faster and cheaper than the current gold standard, and it can be quickly adapted to new variants as they emerge, the researchers say.
“The biggest advantage of Neu-SATiN over other surrogate assays is modularity,” says Kim. “Each of the components of the Neu-SATiN test are genetically modified and recombinantly expressed, making them relatively easy to modify and produce. This allows Neu-SATiN to be a truly mix-and-read test.
The pinprick test is powered by fluorescent luciferase protein from a deep-sea shrimp. It measures the ability of the viral spike protein to bind to the human ACE2 receptor, each of which is attached to a fragment of luciferase.
The binding brings the luciferase pieces together so that they reconstitute a full-length protein, which emits a glow of light that is captured by the instrumentation. When the patient’s blood sample is added to the mix, the neutralizing antibodies bind to the spike protein, preventing it from coming into contact with ACE2. The luciferase remains in pieces, accompanied by a drop in the light signal.
The plug and play method can be adapted to different variants within weeks by creating variant mutations in the spike protein.
The researchers applied Neu-SATiN to blood samples taken from 63 patients with different histories of COVID-19 infection and vaccination up to November 2021. Their antibody neutralizing ability was assessed against the strain original from Wuhan and the variants, Alpha, Beta, Gamma, Delta and Omicron.
The neutralizing antibodies lasted about three to four months. At that time, their levels dropped by about 70%, regardless of infection or vaccination status. Hybrid immunity, acquired by both infection and vaccination, initially produced higher antibody levels, but also dropped significantly four months later.
More worryingly, infection and/or vaccination offered good protection against the previous variants, but not Omicron, nor its subvariants, BA.4 and BA.5.
The researchers point out that vaccines still provide significant protection against serious illness and death. However, the findings of Owen’s team and others call for vigilance in the coming period, given that the more transmissible BA.4 and BA.5 subvariants can evade immunity acquired during previous Omicron infections. as evidenced by the rise in reinfections.
In the future, researchers hope to expand its availability.
“We are working with a few companies to evaluate the effectiveness of their candidate vaccines against Omicron and are also negotiating a license with another company to commercialize the test,” Owen said.
The research was funded by the Office of the Vice President for Research and the University of Utah 3i Initiative, and the Toronto COVID-19 Action Fund.
COVID-19 Research News Faculty of Pharmacy Medicinal Chemistry