New American Study Finds That SARS-CoV-2’s XEC Variant Shows Alarming Ability to Evade Immunity and Boosts Infectivity

Medical News: American Researchers Investigate the New XEC Variant
A team of scientists from The Ohio State University-USA and the University of Texas Health Science Center at Houston-USA recently examined the new SARS-CoV-2 variant known as XEC, a recombinant strain combining the properties of two other variants, KS.1.1 and KP.3.3. The study, led by Shan-Lu Liu at the Center for Retrovirus Research at Ohio State, sought to uncover the unique biological features of XEC that could potentially help it evade immunity and affect transmission rates. This Medical News report delves into how the XEC variant may impact current vaccines and infection patterns worldwide.


New American Study Finds That SARS-CoV-2’s XEC Variant Shows Alarming Ability to
Evade Immunity and Boosts Infectivity

This research is particularly significant given that XEC carries two unique mutations, T22N and F59S, within the spike protein’s N-terminal domain (NTD). These mutations alter the virus's interactions with neutralizing antibodies, potentially making it harder for the immune system to recognize and neutralize the virus. The study reports that understanding how these mutations affect viral behavior is critical to ongoing efforts to control the spread of COVID-19.
 
Key Mutations and Their Impacts on Immune Evasion and Spike Stability
The T22N mutation, akin to a mutation previously seen in other variants, introduces a new glycosylation site on the spike protein. Glycosylation is a biochemical process where sugar molecules attach to proteins, which in this case can alter how the immune system perceives the virus. Researchers found that the T22N mutation in XEC forms a glycosylation pattern that disrupts the binding sites for certain antibodies, reducing the immune system's ability to neutralize the virus. Similarly, the F59S mutation modifies local spike protein structure by disrupting hydrophobic interactions, thus increasing infectivity. The XEC variant also shows reduced cell-to-cell fusion, a factor influenced by the T22N mutation. This reduction, however, does not appear to limit the variant’s capacity to evade neutralizing antibodies.
 
Reduced Neutralization Across Different Sera Samples
Researchers studied the neutralizing antibody (nAb) response in different sera samples. These samples included those from healthcare workers vaccinated with a combination of three doses of the monovalent mRNA vaccine and one dose of the bivalent mRNA vaccine, patients infected with BA.2.86/JN.1 lineage variants, and hamsters vaccinated with a recombinant mumps vaccine expressing the XBB.1.5 spike protein. For all these groups, XEC showed a significantly reduced neutralization response compared to other SARS-CoV-2 variants. The F59S mutation was primarily responsible for this escape from immunity, while the T22N mutation had a lesser but still notable impact.
 
Notably, sera from bivalent-vaccinated healthcare workers saw a 3.8-fold reduction in neutralization for XEC, and sera from BA.2.86/JN.1-infected individuals e xhibited a 4.0-fold decrease in effectiveness. This indicates that the mutations in XEC’s spike protein enable it to evade neutralizing antibodies effectively, suggesting that current vaccination and infection-derived immunity may provide limited protection against XEC.
 
Insights from Antigenic Cartography Analysis
To further evaluate XEC’s immune escape abilities, scientists conducted an antigenic cartography analysis. This technique plots viruses and antibody responses in two-dimensional space to map antigenic distances, where each antigenic unit represents about a two-fold change in neutralization capacity. The analysis showed that XEC was the furthest variant from the original D614G and other parental lineages, reflecting a high degree of immune escape. For individuals with prior BA.2.86/JN.1 infection, XEC was the most antigenically distant variant from JN.1, demonstrating its substantial immune escape.
 
Structural Insights into the XEC Spike Protein
Molecular modeling of the spike protein revealed how the T22N and F59S mutations affect spike stability, fusion, and immune escape. The T22N mutation, which adds a glycan to the spike protein, interferes with antibody binding and makes the virus more difficult for the immune system to detect. Meanwhile, the F59S mutation disrupts hydrophobic interactions within the spike protein, leading to a more flexible spike structure that enhances its ability to bind ACE2 receptors on host cells.
 
These structural changes mean the virus can evade immune responses more effectively and increase infectivity. Although the precise mechanisms behind these structural changes require more research, these findings are crucial for predicting how variants like XEC might spread and impact immunity.
 
Experimental Findings and Future Directions
Beyond immune escape, XEC exhibited a unique balance of increased infectivity and modified cell fusion compared to other SARS-CoV-2 variants. Notably, the XEC spike protein has reduced S1 shedding, which could enhance spike stability, aiding immune escape. Importantly, when researchers removed the glycosylation caused by the T22N mutation, they observed increased cell fusion activity and partially restored antibody neutralization.
 
These findings highlight the importance of the NTD in SARS-CoV-2's ability to evade immunity and remain infective. Moreover, the study indicates that as SARS-CoV-2 evolves, future vaccines may need to target the unique features of these spike mutations to maintain efficacy.
 
Conclusion
The emergence of the XEC variant underscores the adaptive nature of SARS-CoV-2 and the continuous evolution of its spike protein to evade immune responses. This variant, with its unique mutations, presents a challenge for existing vaccines and could affect the effectiveness of antibody-based treatments. By understanding the mechanisms behind immune escape and increased infectivity in variants like XEC, researchers hope to guide the development of next-generation vaccines and therapeutic strategies.
 
The study findings were published on a preprint server and are currently being peer reviewed.
https://www.biorxiv.org/content/10.1101/2024.11.12.623078v1
 
For the latest COVID-19 News, keep on logging to Thailand Medical News.
 
Read Also:
https://www.thailandmedical.news/news/sars-cov-2-xec-variant-shows-enhanced-immune-evasion-through-ntd-glycosylation
 
https://www.thailandmedical.news/news/new-sars-cov-2-xec-2-strain-with-nsp5-mutation-v73f-detected-in-17-countries-could-be-a-potential-winter-threat
 
https://www.thailandmedical.news/news/latest-updates-show-that-a-new-sars-cov-2-variant-called-mv-1-is-likely-to-be-the-next-contender-to-xec-variant