Immune evasion, infectivity, and fusogenicity of SARS-CoV-2 BA.2.86 and FLip variants

The study titled “Immune evasion, infectivity, and fusogenicity of SARS-CoV-2 BA.2.86 and FLip variants” published in Cell (2024) by Qu et al. explored the immune response and biological characteristics of two emerging SARS-CoV-2 variants: BA.2.86 and FLip. This study is particularly relevant in the context of the ongoing evolution of SARS-CoV-2 and the challenges it presents in vaccine effectiveness.

Key Findings and Analyses of the Study:

  1. Characterization of Variants: The study characterized the BA.2.86 and FLip variants in terms of their ability to evade immune responses and their biological properties. BA.2.86 was shown to be less immune evasive compared to FLip and other XBB variants, with distinct properties in terms of neutralizing antibody resistance and viral infectivity​​.
  2. Viral Infectivity and Cell Fusion: BA.2.86 exhibited unique infectivity and fusogenicity patterns compared to other Omicron variants. In HEK293T cells expressing human ACE2 (293T-ACE2), BA.2.86 showed lower infectivity than other Omicron variants. However, in human lung cell-derived epithelial CaLu-3 cells, BA.2.86 demonstrated higher infectivity and cell-cell fusion capacity​​.
  3. Neutralizing Antibody Response: The study found that BA.2.86 was less resistant to neutralization by bivalent vaccine-induced antibodies compared to other XBB variants. Individuals vaccinated with bivalent vaccines showed higher neutralizing antibody (nAb) titers against BA.2.86 than against other XBB variants, including FLip. However, sera from individuals vaccinated with three doses of monovalent vaccines showed limited effectiveness in neutralizing BA.2.86, similar to other XBB variants​​.
  4. Efficacy of Monoclonal Antibodies: The monoclonal antibody S309, effective against most Omicron variants, was unable to neutralize BA.2.86, highlighting a distinct resistance pattern of this variant. This resistance was attributed to specific mutations in the spike protein of BA.2.86 that affect antibody binding​​.
  5. Antigenic Mapping: Antigenic mapping revealed that BA.2.86 is more similar to early Omicron subvariants (BA.1, BA.2, BA.4/5) and distinct from the FLip variant. This suggests differences in the immune response elicited by these variants​​.
  6. Molecular Modeling: Molecular modeling showed how specific mutations in the BA.2.86 spike protein affect its neutralization and infectivity. These mutations may impact the spike protein’s binding to the ACE2 receptor, influencing how the virus enters cells​​.
  7. Study Limitations: The study acknowledged limitations, including the small sample sizes of cohorts and the use of pseudotyped lentivirus rather than authentic virus. It highlighted the need for further research to fully understand the impact of key mutations in BA.2.86 and FLip on antibody and ACE2 interactions​​.

Summary:

The study by Qu et al. is crucial in understanding the evolving landscape of SARS-CoV-2 variants, particularly BA.2.86 and FLip. It highlights the need for continuous surveillance and adaptation of vaccines and treatments in response to new variants. The distinct biological characteristics of BA.2.86, such as its unique infectivity profile and resistance to certain monoclonal antibodies, underscore the complexities in managing the ongoing pandemic. The findings emphasize the importance of updated vaccination strategies and the need for ongoing research to keep pace with the virus’s evolution.

Read More: https://www.cell.com/action/showPdf?pii=S0092-8674%2823%2901400-9

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