Researchers reveal Omicron’s exceptional ability to evade the immune system

The current wave of COVID-19 points to a particularly high risk of reinfection from the Omicron variant of SARS-CoV-2. Why is this? A team from the Center for Emerging Viral Diseases at the University of Geneva (UNIGE) and from the University Hospital of Geneva (HUG) analyzed the antibody neutralization capacity of 120 people infected with the original SARS-CoV-2 strain, or with a of its Alpha, Beta, Gamma, Delta, Zeta or Omicron (subvariant BA.1) variants. And unlike its predecessors, Omicron appears to be able to evade the antibodies generated by all other variants. In vaccinated persons, although the neutralization capacity is reduced, it remains much better than natural immunity alone. This could explain why Omicron is responsible for a net increase in vaccine breakthrough infections, but not hospital admissions. These results can be read in the magazine nature communication†

Since the start of the pandemic, the HUG Outpatient Test Center has been providing SARS-CoV-2 testing to the community. “As the National Reference Center for Emerging Viral Diseases, we have the capacity to sequence a large proportion of positive cases to monitor the appearance of new variants,” explains Isabella Eckerle, Professor in the Department of Medicine at the UNIGE Faculty of Medicine , from and head of the HUG-UNIGE Center for Emerging Viral Diseases, who led this work. “Since the beginning of 2020, we have collected samples of the original virus and all its variants that have appeared in Switzerland, even the rarest such as Gamma or Zeta. This makes it a comprehensive collection of samples from individuals with different infection backgrounds, collected according to an identical protocol.”

The research team took blood samples from 120 volunteers previously infected with one of several variants, unvaccinated, or vaccinated and infected, before or after vaccination. “With an average age of 28 to 52 years, with no major co-morbidities and a mild to moderate form of COVID-19, this cohort represents the majority of cases in the community,” explains Isabella Eckerle.

Antibody levels ten times higher with vaccination

The aim was to determine how well the antibodies generated during the initial infection could neutralize the different variants of SARS-CoV-2. “Omicron has been shown to be most effective in bypassing pre-existing natural immunity and, to a lesser extent, that caused by vaccination,” explains Benjamin Meyer, researcher at the Center for Vaccinology of the Department of Pathology and Immunology of the Faculty of Medicine at UNIGE. . Indeed, antibody levels against ancestral SARS-CoV-2 in vaccinated humans are approximately 10-fold higher than in humans who have developed immunity only after infection. In addition, the combination of the two, known as hybrid immunity, appears to maintain even higher and broader reactive antibody levels.

“For example, Omicron can evade existing immunity and cause infection, but hospitalization and death from COVID-19, even with Omicron, is still reduced after vaccination.” Nevertheless, SARS-CoV-2 retains an amazing ability to mutate, which also appears to accelerate. “Vigilance is still warranted, especially as epidemiological curves have risen sharply since the appearance of BA.5, the most recent Omicron subvariant,” adds Isabella Eckerle.

The scientists also performed antigenic mapping of the different variants, based on the same model used to determine the antigenic changes of influenza.

This computational method makes it possible to represent the distance between the characteristics of the antigens of the variants in question: the further away they are, the less effective the antibodies generated during previous infections. It turns out that the Omicron serotype is completely different from the others, as is the Zeta variant, which quickly disappeared.”

Meriem Bekliz, postdoctoral researcher in Isabella Eckerle’s lab and lead author of this study

Advances in understanding viruses

Never before has a respiratory virus been examined so closely. “This virus, belonging to the same family of coronaviruses that cause nearly a third of colds, can spread like wildfire in populations without immunity to fight it, if no measures are taken,” explains Benjamin Meyer.

“We now have tools for sequencing and molecular observation that were unknown a few years ago; the discoveries we are making today open up perspectives and insights that will be useful far beyond SARS-CoV-2.” The COVID-19 pandemic has also enabled an unprecedented acceleration in vaccine research. Several teams are now working on nasal spray vaccines, which are easier to administer and especially can work directly into the mucous membranes of the nose and throat, where they are most useful.