The EG.5 strain of SARS-CoV-2, known as Eris, has been spreading around the world since May 2023 and was listed as a "variant of concern" by the World Health Organization (WHO) in early August. However, the reasons for the increasing spread of "Eris" are still unclear.
The SARS-CoV-2EG.5.1 strain has an advantage in evading neutralizing antibodies. When vaccinated or infected, our immune systems produce antibodies against the SARS-CoV-2 spike protein, preventing the virus from entering and multiplying within cells. In turn, the virus mutates, reducing the ability of these antibodies to bind effectively to its spike protein.
Scientists at the German Primate Center - Leibniz Institute for Primate Research in Göttingen have now investigated the characteristics of the Erythian lineage EG.5.1.
The researchers found that EG.5.1 was no more infectious than its predecessor, meaning it could not infect host cells more efficiently. However, EG.5.1 is better able to evade neutralizing antibodies than other currently circulating SARS-CoV-2 substrains, giving it an advantage when infecting individuals who have been vaccinated or whose immune systems produce neutralizing antibodies after infection.
The situation is a marked improvement after years of a pandemic that saw multiple waves of infections and corresponding hospitalizations driven by changing virus variants. Large waves of infection no longer occur outside of cold and wet seasons. This success is largely due to the rapid development of vaccines.
Many people have already been vaccinated against SARS-CoV-2. Booster vaccinations using modified vaccines (i.e. booster shots), and infection of vaccinated people with currently circulating virus variants, further train our immune systems to deal with emerging virus variants as well.
Virus variants: Spike protein mutations can 'escape' neutralizing antibodies and increase infectivity
Part of immune protection relies on neutralizing antibodies produced by immune system cells following vaccination or infection. Neutralizing antibodies attach to SARS-CoV-2's spike protein and prevent the virus from entering our cells. This mechanism is also known as neutralization.
However, even with neutralizing antibodies, there is no guarantee of 100% protection against SARS-CoV-2 infection because SARS-CoV-2 can still change. This has led to the emergence of mutated viruses that can acquire the ability to partially evade neutralizing antibodies.
This process, also known as antibody escape, is based on mutations in the spike protein that render neutralizing antibodies unable to bind to it.
"In addition, mutations may increase the transmissibility of SARS-CoV-2 variants by improving the binding of the spike protein to the cellular receptor ACE2," said Markus Hoffmann, the lead scientist on the study.
Spike protein mutations in Eris sublineage EG.5.1 enhance the ability to evade neutralizing antibodies
Since May 2023, the SARS-CoV-2 EG.5 substrain (including its descendant EG.5.1) has been on the rise in many countries. The virus, listed as a "variant of concern" by the World Health Organization (WHO), is also known as "Eris", named after the Greek goddess of chaos and discord. Although the name sounds dangerous, there is currently no evidence that infection with EG.5 and EG.5.1 causes more severe disease.
However, the reasons for the increasing proliferation of EG.5 and EG.5.1 are unclear. The Eris sublineage EG.5.1 was studied by a research team composed of scientists from the German Primate Center - Leibniz Institute for Primate Research in Göttingen, the Medical School of Hannover and the Friedrich-Alexander University of Erlangen-Nuremberg. Markus Hoffmann said: "We found evidence that an increase in the ability of antibodies to evade is likely to be responsible for the increased transmissibility of the Pill of Eris."
"We tested the efficiency with which Eris substrain EG.5.1 enters host cells and how efficiently it is neutralized by antibodies in the blood of vaccinees uninfected with SARS-CoV-2 and infected with SARS-CoV-2. In the process, we found that EG.5.1 does not have an advantage in infecting host cells compared with other SARS-CoV-2 strains currently circulating."
Infection biologist Dr. Markus Hoffmann (left) and Professor Stefan Pöhlmann, head of the Infection Biology Group at the German Primate Center (DPZ)-Leibniz Institute for Primate Research. Photo credit: KarinTilch
Zhang Lu, the first author of the study, explained: "However, further research found that EG.5.1 was less effective at being neutralized by antibodies in the blood of vaccinated people or vaccinated and infected people. For safety reasons, the experiment used a laboratory-produced virus without replication capabilities, that is, a pseudovirus."
"Our results show that the spread of EG.5 and its substrains relies mainly on antibody escape rather than an increase in the ability to infect host cells. However, the increase in antibody escape is modest and by no means sufficient to completely destroy the immunity we have established through vaccination or previous infection," Markus Hoffmann commented on the findings.
Modified vaccines based on the SARS-CoV-2 XBB.1.5 strain should also be effective against EG.5 and its substrains
This fall, new and improved SARS-CoV-2/COVID-19 vaccines based on the widely circulating XBB.1.5 lineage of SARS-CoV-2 will become available. Now the question arises: are these vaccines also effective against EG.5 and its substrains?
"Since Eris is a descendant of the closely related XBB.1.9 lineage, and the various XBB sublineages have only subtle differences between them, it can be assumed that the newly modified vaccine will also be effective against EG.5 and its sublineages." Stefan Pöhlmann, head of the Infection Biology Group at the Leibniz Institute for Primate Research at the German Primate Center, concluded: "We therefore recommend primary and booster vaccination, especially for high-risk groups and their close contacts."