Four years have passed since the start of the Covid-19 pandemic. SARS-CoV-2 has yet to be eradicated and new variants, such asomicron, emerge continuously. Despite extensive immunization programs, breakthrough infections (infections after vaccination) due to new variants are common.
New research suggests that human immune responses are also changing to combat the continued emergence of new SARS-CoV-2 variants. Specifically, the immune system that has encountered a breakthrough infection by the omicron variant has been found to acquire enhanced immunity against future versions of the omicron.
The study was published in Science Immunology.
The immune system has been strengthened thanks to the Omicron variant
A team of South Korean scientists led by Professor Shin Eui-Cheol from the Korea Virus Research Institute Center for Viral Immunology within the Institute for Basic Science (IBS) announced that memory T cells that form during the breakthrough infection of 'Omicrons respond to subsequent strains of the virus.
Emerging in late 2021, the omicron variant of SARS-CoV-2 had dramatically increased transmissibility compared to its predecessors, which quickly allowed it to become the dominant strain in 2022. Since then, new omicron strains have continued to emerge. Starting with strains BA.1 and BA2, BA.4/BA.5, BQ.1, XBB and, more recently, strains JN.1 have been among the new strains of the omicron variant. This led to a breakthrough infection that was widespread despite vaccination.
After being infected or vaccinated, the body creates neutralizing antibodies and memory T cells against the virus. The neutralizing antibody serves to prevent host cells from being infected by the virus. Although memory T cells cannot prevent infection, they can quickly seek out and destroy infected cells, preventing the viral infection from progressing into serious disease.
The research team's goal was to discover the changes that occur in our body's immune system after suffering from a breakthrough infection post-vaccination. To answer this question, they focused on memory T cells that formed after omicron infection.
Previous studies on the omicron variant have focused primarily on vaccine efficacy or neutralizing antibodies, and research related to memory T cells has been relatively lacking.
The research team selected as subjects patients who suffered and then recovered from the breakthrough BA.2 omicron infection in early 2022 and conducted studies on their memory T cells, in particular their ability to respond to various variants of omicrons such as BA.2, BA.4/ BA/5 and others.
To do this, immune cells were separated from the subjects' peripheral blood and memory T cell cytokine production and antiviral activities were measured in response to various spike proteins of different variants.
The results showed that memory T cells from these patients showed a heightened response not only against the BA.2 strain but also against the subsequent BA.4 and BA.5 strains of omicron. By suffering from a breakthrough infection, these patients' immune systems have been strengthened to fight off future strains of the same virus.
The research team also discovered the specific part of the spike protein that is the main cause of the improvement observed in memory T cells. These findings show that once a person experiences a breakthrough infection with omicron infection, they are unlikely to ever suffer severe COVID-19 symptoms due to future emerging variants.
Researcher Jung Min Kyung who led this research said: “This discovery gives us new perspectives in the new era of the COVID endemic,” adding: “It can be understood that in response to the constant emergence of new viral variants, our bodies also they have adapted to combat future strains of the virus.”
Director Shin Eui-Cheol of the Center for Viral Immunology commented: “This new discovery can also be applied to vaccine development. By looking for common characteristics between the current dominant strain and new emerging virus strains, there may be a greater chance of inducing memory T cell defenses against subsequent variants.”
The omicron variant may partially evade the antibody response provided by vaccination or infection with previous SARS-CoV-2 variants. However, T cells still recognize the omicron.
Omicron quickly became the dominant variant of the SARS-CoV-2 virus. New data indicates that omicron is not only more contagious than previous variants, but can also infect people with previous immunity by evading so-called neutralizing antibodies.
Severe disease appears, however, to be relatively rare in vaccinated or infected people, suggesting that other components of the immune system are still able to recognize omicron. A new study by researchers from the Karolinska Institutet now shows that so-called memory T cells formed following a previous infection or mRNA vaccination also respond to the omicron variant.
“Together with viral factors, such as a lower level of viral replication in the lower airways, and other immune components, these findings give
us a clearer picture that may explain why protection against severe omicron disease remains good in individuals previously vaccinated with mRNA,” says principal investigator Marcus Buggert from the Center for Infectious Medicine at Karolinska Institutet.
The study is a collaboration with Karolinska University Hospital in Sweden and is based on blood samples from 40 vaccinated individuals, 48 individuals who had had a mild or severe SARS-CoV-2 infection, and 48 individuals who had not previously been neither vaccinated nor infected. . Samples from the vaccinated group were collected six months after the second vaccine dose and from the previously infected group nine months after confirmed infection in spring 2020, before the appearance of the new virus variants. Additional samples were collected from healthy donors in late 2020.
Memory T cells in both experimental groups showed a good ability to recognize the omicron spike protein; the best response, however, was observed in the vaccinated group.
“These findings suggest that booster immunization may provide benefits that go beyond the induction of neutralizing antibodies to improve protection against recurrent episodes of severe COVID-19,” says Dr. Buggert.
Although the memory T cell response was generally intact against omicron, some individuals did not respond as well.
“We now want to understand why the response differs between individuals and whether a third dose of vaccine can increase the T cell response to omicron even more,” he says.
A further study by researchers at the University of Liverpool finds that mice infected with Omicron lose less weight, have lower viral loads and suffer less severe pneumonia than those infected with other COVID variants.
The Liverpool team's findings, published on the preprint server bioRxiv, are part of a growing body of evidence suggesting that Omicron is more likely to infect the throat than the lungs, which could explain why it appears to be more infectious but less deadly of other versions of the virus.
Omicron is highly transmissible and partially or completely evades a spectrum of neutralizing antibodies due to the high number of substitutions in the spike glycoprotein.
An important question is the relative severity of disease caused by the Omicron variant compared to earlier and currently circulating variants of SARS-CoV-2.
To address this issue, a mouse model was used to evaluate and compare the relative severity of infection by comparing an ancestral isolate to the Delta and Omicron variants of SARS-CoV-2.
Unlike mice infected with the ancestral and Delta variant viruses, those infected with the variant had less severe clinical signs (weight loss), showed recovery, and had a lower viral load in both the lower and upper respiratory tracts. This was also reflected in less extensive inflammatory processes in the lungs.
Professor James Stewart of the University's Molecular Virology Research Group, who led the study, said: “These animal model data suggest that the clinical consequences of infection with the Omicron variant may be less severe, which links to emerging clinical data. However, Omicron's increased transmissibility could still impose a huge burden on healthcare systems, even if a lower percentage of infected patients are admitted to hospital.”
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