by Emerging variants of the SARS-CoV-2 virus continue to pose challenges for the immune system, despite its growing familiarity with the virus. Professor Dr. Florian Klein and his team at the Institute of Virology at the University Hospital Cologne and the Faculty of Medicine have recently published two groundbreaking studies that shed light on the evolution of the antibody response to SARS-CoV-2 over time and how the immune system adapts to new variants.
The first study, entitled “Enhanced SARS-CoV-2 humoral immunity following breakthrough infection builds upon the preexisting memory B cell pool,” has been published in Science Immunology. The second study, titled “Somatic hypermutation introduces bystander mutations that prepare SARS-CoV-2 antibodies for emerging variants,” is published in Immunity.
Antibodies can undergo a process known as affinity maturation, where individual amino acids are exchanged (mutated) over time to enhance their ability to detect and neutralize infectious pathogens. Professor Klein’s team has discovered that infection with the omicron variant triggers a renewed immune response in vaccinated individuals by reactivating memory B cells.
Remarkably, the maturation process of the antibodies produced by these cells had already occurred long before the emergence of omicron, suggesting that the immune system was already primed and prepared. The findings from both studies highlight the importance of the initial contact with SARS-CoV-2 in influencing the immune system and suggest that it may be equipped to tackle future variants.
The primary objective of the research was to examine how the antibody response changes in healthy individuals after receiving a third vaccination against the original SARS-CoV-2 strain. “We were initially surprised by the results,” says Svea Rose, a doctoral candidate and first author of the study. While the third vaccination significantly boosted the overall immune response to SARS-CoV-2, there was minimal further maturation at the individual antibody level.
However, the study also analyzed individuals who had received vaccinations but subsequently became infected with the omicron variants BA.1 and BA.2. The re-analysis revealed that memory B cells capable of producing antibodies that neutralize SARS-CoV-2 omicron were now proliferating.
Dr. Timm Weber, another first author of the study, adds an interesting observation: the immune cells targeting the omicron variant were already present before exposure to omicron, and their presence was not induced by the variant itself. Moreover, the researchers discovered broad neutralizing antibodies early on that could effectively neutralize all tested new variants.
Simultaneously, the research team examined the molecular mechanism of affinity maturation. By reverting individual antibodies isolated during the first year of the pandemic to their original state, the team identified that some of the modifications that occur during affinity maturation are random. Surprisingly, these random modifications were crucial for neutralizing the omicron variants, as reported by lead authors Michael Korenkov and Dr. Matthias Zehner in their study published in Immunity.
Dr. Christoph Kreer, who co-led the study with Professor Klein, explains, “The immune system expands the arsenal of existing antibodies by inserting arbitrary mutations, thereby increasing the likelihood of having a suitable antibody in the repertoire when a new virus variant appears.” Furthermore, the researchers were able to modify a therapeutic antibody that was initially ineffective against omicron to effectively neutralize omicron variants once again, leveraging their new biological insights.
In summary, these studies offer valuable insights into how the human immune system responds to new viruses and their emerging variants. The discovery of broad neutralizing antibodies with such high efficacy raises the possibility of their therapeutic and preventive use against future omicron variants.
*Note:
1. Source: Coherent Market Insights, Public sources, Desk research
2. We have leveraged AI tools to mine information and compile it
