Despite the familiarity of the immune system with the virus, new variants continue to present challenges.
Two recent studies from Dr. Klein’s group have shed light on the evolution of the antibody response to SARS-CoV-2 and the immune system’s proactive strategies against emerging variants.
One of the key processes in this battle is “affinity maturation,” where antibodies mature over time through mutations of individual amino acids. This maturation enhances the detection and neutralization of infectious pathogens.
The researchers found that an infection with the Omicron variant triggers a renewed immune response in vaccinated individuals, primarily through the reactivation of memory B cells.
Interestingly, the antibodies produced by these cells had matured even before the emergence of Omicron, suggesting that the immune system was preemptively prepared.
“Our first goal was to investigate how the antibody response in healthy subjects changes through a third vaccination against the original SARS-CoV-2 strain,” said study first author and doctoral candidate Svea Rose.
“We were initially surprised by the results. Although the third vaccination significantly increased the SARS-CoV-2 immune response overall, there was hardly any further maturation at the level of individual antibodies.”
Further analysis, particularly in individuals infected with Omicron variants BA.1 and BA.2 post-vaccination, revealed that memory B cells that were capable of forming antibodies to neutralize the Omicron variant had proliferated.
According to the study’s first author Dr. Timm Weber, these immune cells were already in existence prior to contact with the Omicron variant.
“Interestingly, the immune cells directed against the Omicron variant were already present before contact with Omicron and were not induced by Omicron,” said Dr. Weber.
Furthermore, the team discovered broad neutralizing antibodies – which had appeared early on in the pandemic – that were effective against all tested new variants.
The working group also looked at the molecular mechanism of affinity maturation. The clock was turned back and individual antibodies, which were isolated throughout the world in the first year of the pandemic, were restored to their original state, explained study lead authors Michael Korenkov and Dr Matthias Zehner.
The analysis revealed that some modifications during affinity maturation occur randomly, and surprisingly, these random modifications were crucial for neutralizing the Omicron variants.
“The immune system expands the arsenal of existing antibodies by inserting arbitrary mutations and thus increases the likelihood of having a suitable antibody in the repertoire when a new virus variant appears,” explained Dr. Christoph Kreer, who led the study together with Professor Klein.
This insight led to the modification of a therapeutic antibody, previously ineffective against Omicron, to effectively neutralize Omicron variants.
Ultimately, these studies not only illuminate how the human immune system reacts to a new virus and its evolving variants but also highlight the potential therapeutic and preventive applications of the newly isolated broad neutralizing antibodies against newer Omicron variants.
The research marks a significant advancement in our understanding of the immune system’s adaptability and resilience in the face of emerging viral threats.
The study is published in the journal Immunity.
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