How vaccination and natural immunity pack a double punch against Omicron
Researchers have outlined the pervasive ability of the Omicron variant of SARS-CoV-2 to re-infect not only those who are naturally immune, but also those who are vaccinated.
COVID-19 has been at the forefront of the news since 2020 and is an ongoing issue for every country. To date, there have been over 550 million confirmed cases and over 6 million deaths attributed to COVID-19.† The world has now largely reopened, and most people are enjoying a pre-pandemic lack of restrictions, which is largely thanks to the rapid development of vaccines. However, this does not show the whole picture. Infection rates worldwide are rising, and governments are concerned about a stress on healthcare systems akin to previous waves of the pandemic.
This rise in infections is largely attributed to the Omicron variant, the sixth variant of concern (VOC) of the original SARS-CoV-2 viral strain. Whilst it has been shown to be less severe than previous strains of the virus, it also has a spectacular rate of reinfection and is able to circumvent natural immunity acquired through a previous infection. Researchers from the Centre for Emerging Viral Diseases of the University of Geneva (UNIGE; Switzerland), led by Isabella Eckerle, in tandem with the University Hospital of Geneva (HUG; Switzerland), have shed some light on how Omicron is sneaking past our natural defenses and if vaccinations are really playing a role in bolstering immunity.
Blood samples from 120 unvaccinated or vaccinated individuals who were infected by one of the major strains of SARS-CoV-2 (the original strain as well as the Alpha, Beta, Gamma, Delta and Zeta variants) were tested for reinfection for every VOC up to and including the first Omicron subvariant (BA.1). The participants, aged between 28 and 52, presented only mild or moderate symptoms.
Across the board, the researchers found that the immune response against earlier variants was far superior to the response against later variants. According to one of the authors of the paper, Ben Meyer (UNIGE; Switzerland), “Omicron proved to be the most effective at evading pre-existing natural immunity, as well as, to a lesser extent, that induced by vaccination.” The rate of failure to successfully neutralize an Omicron BA.1 infection ranged from 40% (Delta samples) to 85% (Original SARS-CoV-2 strain samples). Homologous neutralization, a successful immune response to re-infection from the same strain, was the most pronounced in all strains compared to infection from a different strain.
The first line of defense against HIV-1 is a two-step process
The innate immune system is able to recognize HIV-1 and signal an immune response, and researchers have now discovered the molecular mechanism behind this.
Furthermore, the researchers demonstrated that vaccinated individuals, with or without natural immunity, were far superior at neutralizing an infection from Omicron than individuals with naturally derived immunity, who were unvaccinated.
Double vaccinated individuals had antibody levels up to 10-times the concentrations seen in those with natural immunity. Individuals who had a combination of vaccinations and immunity through infection, known as hybrid immunity, were even better protected against reinfection, with higher antibody concentrations and greater versatility against multiple strains.
Lastly, the researchers managed to further corroborate with other preprint papers that the Omicron VOC has the greatest antigenic escape of all the variants.
The researchers carried out antigenic mapping of the different variants, which is used to determine changes in influenza. “This computational method makes it possible to represent the characteristics of the antigens of the variants concerned’’ explained first author Meriem Bekilz (UNIGE). “It turns out that the Omicron Serotype is totally different from the others, as was the Zeta variant, which disappeared rapidly.”
Essentially, this means the mutations that make the Omicron variant distinct have rendered existing antibodies ineffective against Omicron, which were active against previous VOCs. This was also seen in the now extinct Zeta, and the less concerning Mu and Lambda variants.
Whilst the team can explain Omicron’s ability to get around antigenic responses, its increased transmissibility is still yet to be explained. Infections due to Omicron, as well as the unpredictable and easily mutated nature of coronaviruses, remain a cause for concern. As the team noted in their Nature Communications preprint, the unevenness in approaches to handling the pandemic across the world can result in several new variants.
With the evidence that Omicron continues to be a milder strain and that hybrid immunity can further bolster an antigen response, the team close their paper on a realistic yet hopeful note: that, with increased immunity, COVID-19 could be demoted from a pandemic to an epidemic. This means that if progress continues, this could spell the beginning of the end for COVID-19.
