Study reveals 3 variants that resist immunity – Zoo House News

Study reveals 3 variants that resist immunity – Zoo House News

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  • November 23, 2022
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Three currently circulating omicron subvariants of SARS-CoV-2 — including two that currently account for nearly 50% of reported COVID-19 infections in the US — are better at evading vaccine- and infection-generated neutralizing antibodies than previous versions of Omicron, suggests new research.

Scientists tested neutralizing antibodies in blood serum samples from vaccinated and once-boosted or recently infected healthcare professionals against several circulating subvariants. Three subvariants were characterized by their resistance to the antibody immune response: BQ.1, BQ.1.1 and BA.2.75.2.

According to the Centers for Disease Control and Prevention (CDC). BA.2.75.2, a mutant of the BA.2 omicron variant, was the best of all variants tested to evade neutralizing antibodies, but currently accounts for a very small proportion of reported diseases in the United States.

“In general, subvariants BQ.1 and BQ.1.1 are much better at bypassing the booster-mediated antibody response compared to previous variants – the neutralizing antibody titers are clearly much lower. And those two variants become dominant,” said Shan-Lu Liu, senior author of the study and professor of virology in the Department of Veterinary Biosciences at Ohio State University.

“It’s important to be aware when traveling and collecting over the holidays that SARS-CoV-2 variants are evolving,” said Liu, also a professor in the Department of Microbial Infection and Immunity. “If you were vaccinated with the first booster more than six months ago, you should consider a second booster as the antibodies from a single booster are now likely to be too low to provide protection.”

The study is published today in the journal Cell Host & Microbe.

Although the third booster shot, an updated bivalent formulation, is now being given to those who are eligible, more than 48% of the total booster-eligible population has not yet received a booster dose, according to CDC data. Liu’s lab has previously shown that a COVID-19 booster shot provides strong and broad antibody protection against a range of Omicron sublineage variants, and that a second booster shot restores dwindling antibody counts to protective levels.

For the current study, serum samples were obtained from healthcare professionals who had received two mRNA vaccine doses and a booster dose, or who had become infected during an early or late Omicron wave.

The results showed an approximately 20-fold decrease in vaccine and individual booster-generated antibodies that could neutralize BQ.1 and BQ.1.1 compared to neutralizing antibodies against the parent or parent SARS-CoV-2 virus. Similarly, neutralizing antibody levels or titers generated by infection during the BA.1 omicron wave were significantly lower against the BQ subvariants than against the parental virus, and antibody titers against the BQ subvariants generated by infection during the BA.4/5 wave generated, the detection limit was not reached.

“Our results suggest that you cannot rely on natural infection to protect against the currently circulating omicron subvariants,” said Liu, also associate director of the Ohio State Center for Retrovirus Research and co-program director of the program for Viruses and Emerging Pathogens at the Ohio State Institute for Infectious Diseases.

Liu and colleagues performed cell culture studies using pseudoviruses – a non-infectious viral core surrounded by various surface SARS-CoV-2 spike proteins patterned to correspond to known variants. The method used to detect neutralizing antibodies in the blood samples takes into account the different levels of antibodies produced by individuals.

In this study, Ohio State collaborator Kai Xu and co-author created structural models of individual amino acids that have been altered by the latest mutations in the spike protein and identified some key molecules that rearranged the subvariants to allow them to bind antibodies to the virus can block particles. This modeling showed that one of these amino acids, called N460K, also allows the BQ.1 and BQ.1.1 particles to enter host cells more efficiently and force host cells to fuse with each other, a step in viral infection that enhances pathogenesis can – what contributes to the onset of the disease, its progression to more severe symptoms and the transmissibility of the disease.

“From my perspective, this is a concern because the original Omicron variant wasn’t very pathogenic — it didn’t cause much cell fusion at all,” Liu said. “But we are now seeing a trend in these new subvariants of increased cell fusion, and this trend puts the virus in a better position to cause infection and pathogenesis.”

The studies by other labs on the bivalent booster’s neutralizing antibody production suggest that the updated booster would offer protection against the newer omicron subvariants, Liu said.

But Liu has submitted a paper for publication on another subvariant called XBB, a recombinant variant created by the exchange of genetic material between two BA.2 omicron subvariants and the one that has what he calls “extraordinary” resistance to showing neutralizing antibodies produced by vaccination and previous infections.

“This virus can do unexpected things,” he said. “We still need to do good monitoring and keep an eye on these emerging variants of concern.”

This work was supported by anonymous donor funds, grants from the National Institutes of Health, the National Center for Advancing Translational Sciences, the Glenn Barber Fellowship of the Ohio State College of Veterinary Medicine, the National Cancer Institute, the Robert J. Anthony Fund for Cardiovascular Research, and the Ohio State Comprehensive Cancer Center, the Office of Health Sciences and the Center for Clinical and Translational Science.

Additional co-authors, all from Ohio State, are Panke Qu, John Evans, Julia Faraone, Yi-Min Zheng, Claire Carlin, Mirela Anghelina, Patrick Stevens, Soledad Fernandez, Daniel Jones, Gerard Lozanski, Ashish Panchal, Linda Saif, Eugene Oltz and Richard Gumina.

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