The SARS-CoV-2 JN.1 variant, derived from the BA.2.86 lineage, emerged in late 2023 and is phylogenetically distinct from the current omicron XBB lineages. JN.1 carries over 30 mutations in the spike protein, particularly the Leu455Ser mutation, which enhances immune evasion. Virological studies using genomic surveillance data from France, the UK, and Spain indicate that JN.1 has a higher reproductive number compared to BA.2.86 and HK.3, suggesting it may soon become the dominant lineage globally. In vitro assays show that JN.1 has increased infectivity but decreased binding affinity to human ACE2 receptors due to the Leu455Ser mutation. Neutralization assays reveal that JN.1 is resistant to monovalent XBB.1.5 vaccine sera, further highlighting its immune evasion capabilities. These findings suggest that the Leu455Ser mutation contributes significantly to JN.1's increased reproductive advantage and immune resistance.The SARS-CoV-2 JN.1 variant, derived from the BA.2.86 lineage, emerged in late 2023 and is phylogenetically distinct from the current omicron XBB lineages. JN.1 carries over 30 mutations in the spike protein, particularly the Leu455Ser mutation, which enhances immune evasion. Virological studies using genomic surveillance data from France, the UK, and Spain indicate that JN.1 has a higher reproductive number compared to BA.2.86 and HK.3, suggesting it may soon become the dominant lineage globally. In vitro assays show that JN.1 has increased infectivity but decreased binding affinity to human ACE2 receptors due to the Leu455Ser mutation. Neutralization assays reveal that JN.1 is resistant to monovalent XBB.1.5 vaccine sera, further highlighting its immune evasion capabilities. These findings suggest that the Leu455Ser mutation contributes significantly to JN.1's increased reproductive advantage and immune resistance.