Home Pharmaceutics Plug-and-play test to track immunity to Sars-CoV-2 variants

Plug-and-play test to track immunity to Sars-CoV-2 variants

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Experts agree that the pandemic is not over. Infections resume, fueled by new variants for which our immune system is ill-prepared.

That’s according to a study by Canadian and American researchers who found that antibodies generated in people vaccinated and/or recovered from COVID-19 before 2022 failed to neutralize variants circulating today.

The study was led by Igor Stagljar, professor of biochemistry and molecular genetics, at the Donnelly Center for Cellular and Biomolecular Research, Temerty School of Medicine, and Shawn Owen, associate professor of pharmacy and pharmaceutical chemistry, at the of Utah. .

The newspaper Nature Communication published their findings.

Researchers expect the antibody test they developed to measure the immunity of study participants will become a valuable tool in deciding who needs a booster and when, which will help save lives and avoid future lockdowns.

“The truth is, we don’t yet know how often our injections should be to prevent infection,” Stagljar said. “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.”

Many antibody tests have been developed over the past two years. But only a few of the authorized ones are designed to monitor neutralizing antibodies, which coat the viral spike protein so that 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.

“Our method, which we named Neu-SATiN, is as accurate as the gold standard, but faster and cheaper, and it can be quickly adapted to new variants as they emerge,” he said. he declares.

Neu-SATiN stands for Neutralization Serology Test Based on Fractionated Three-Part Nanoluciferase, and it is a newer version of SATiN, which monitors the full pool of IgG, which they developed last year.

The development of Neu-SATiN was led by Zhong Yao, senior research associate in Stagljar’s lab, and Sun Jin Kim, postdoctoral fellow in Owen’s lab, who are co-first authors of the paper.

The first of its kind, the pinprick test is powered by a protein supplementation strategy using fluorescent protein luciferase 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 luminometer instrument. 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. Consequently, 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. The patient’s neutralizing ability was assessed against the strain original from Wuhan and the variants, Alpha, Beta, Gamma, Delta and Omicron.

“We thought it would be important to monitor people who have been vaccinated to see if they still have protection and how long it lasts,” said Owen, who did his postdoctoral training at the Donnelly Center with bio- distinguished engineer and university professor Molly Shoichet. “But we also wanted to see if you were vaccinated against one variant, does that protect you against another variant?”

Neutralizing antibodies were found to last about three to four months, when their levels would drop by about 70%, regardless of infection or vaccination status. Hybrid immunity, acquired by both infection and vaccination, initially produced higher levels of antibodies, but these 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 data matches those of a recent UK study, which showed that neutralizing antibodies and cellular immunity, a type of immunity provided by memory T cells, against infection, vaccination or both, do not offered no protection against Omicron’s capture. In a surprising twist, the British group also found that Omicron infections boosted immunity against earlier strains, but not against Omicron itself, for reasons that remain unclear.

Importantly, vaccines still provide significant protection against serious illness and death, Stagljar said. Still, he added that the findings of his team and others call for vigilance in the coming period given that the more transmissible BA4 and BA5 subvariants may evade immunity acquired from previous Omicron infections. , as evidenced by the increase in reinfections.

“There will definitely be new variants in the near future,” Stagljar said. “Monitoring and building immunity against circulating variants will become increasingly important and our method could play a key role in this regard as it is rapid, accurate, quantitative and inexpensive.”

His lab is already collaborating with Canadian vaccine maker Medicago to help determine the effectiveness of their candidate vaccines against Omicron and its subvariants. Meanwhile, the U of T is negotiating a license for Neu-SATiN to a company that will scale it up so it can be used for population immunosurveillance and in the pharmaceutical industry for vaccine development.