Virological characteristics of the SARS-CoV-2 JN.1 variant

Virological characteristics of the SARS-CoV-2 JN.1 variant

February 2024 | Yu Kakut, Kaho Okumura, Miguel Padilla-Blanco, Yusuke Kosugi, Keiya Uriu, Alfredo A Hinay Jr, Luo Chen, Arnon Plianchaisuk, Kouji Kobiyama, Ken J Ishii
The SARS-CoV-2 BA.2.86 lineage, first identified in August 2023, is phylogenetically distinct from the current circulating omicron XBB lineages, including EG.5.1 and HK.3. BA.2.86 has more than 30 mutations in the spike protein, indicating a high potential for immune evasion. Its descendant, JN.1 (BA.2.86.1.1), emerged in late 2023. JN.1 harbours Leu455Ser and three mutations in non-spike proteins. The Leu455Ser mutation is a hallmark of JN.1, contributing to increased transmissibility and immune escape ability compared with the parental EG.5.1 variant. The virological properties of JN.1 were investigated, and the relative effective reproductive number was estimated using genomic surveillance data from France, the UK, and Spain. The reproductive number of JN.1 was higher than that of BA.2.86.1 and HK.3. These results suggest that JN.1 might soon become the dominant lineage worldwide. The in vitro ACE2 binding assay showed that the dissociation constant value of the JN.1 receptor-binding domain (RBD) was significantly higher than that of the BA.2.86 RBD, suggesting that Leu455Ser decreases binding affinity to the human ACE2 receptor. In contrast, the pseudovirus assay showed that the infectivity of JN.1 was significantly higher than that of BA.2.86. The neutralisation assay showed that the 50% neutralisation titre against JN.1 was similar to that against BA.2.86, suggesting that Leu455Ser does not affect the antigenicity of BA.2.86. On the other hand, the 50% neutralisation titre of breakthrough infection sera with XBB.1.5 and EG.5.1 against JN.1 was significantly lower than that of HK.3 and BA.2.86. JN.1 shows robust resistance to monovalent XBB.1.5 vaccine sera compared with BA.2.86. These results suggest that JN.1 is one of the most immune-evading variants to date. Our results suggest that Leu455Ser contributes to increased immune evasion, which partly explains the increased reproductive number of JN.1.The SARS-CoV-2 BA.2.86 lineage, first identified in August 2023, is phylogenetically distinct from the current circulating omicron XBB lineages, including EG.5.1 and HK.3. BA.2.86 has more than 30 mutations in the spike protein, indicating a high potential for immune evasion. Its descendant, JN.1 (BA.2.86.1.1), emerged in late 2023. JN.1 harbours Leu455Ser and three mutations in non-spike proteins. The Leu455Ser mutation is a hallmark of JN.1, contributing to increased transmissibility and immune escape ability compared with the parental EG.5.1 variant. The virological properties of JN.1 were investigated, and the relative effective reproductive number was estimated using genomic surveillance data from France, the UK, and Spain. The reproductive number of JN.1 was higher than that of BA.2.86.1 and HK.3. These results suggest that JN.1 might soon become the dominant lineage worldwide. The in vitro ACE2 binding assay showed that the dissociation constant value of the JN.1 receptor-binding domain (RBD) was significantly higher than that of the BA.2.86 RBD, suggesting that Leu455Ser decreases binding affinity to the human ACE2 receptor. In contrast, the pseudovirus assay showed that the infectivity of JN.1 was significantly higher than that of BA.2.86. The neutralisation assay showed that the 50% neutralisation titre against JN.1 was similar to that against BA.2.86, suggesting that Leu455Ser does not affect the antigenicity of BA.2.86. On the other hand, the 50% neutralisation titre of breakthrough infection sera with XBB.1.5 and EG.5.1 against JN.1 was significantly lower than that of HK.3 and BA.2.86. JN.1 shows robust resistance to monovalent XBB.1.5 vaccine sera compared with BA.2.86. These results suggest that JN.1 is one of the most immune-evading variants to date. Our results suggest that Leu455Ser contributes to increased immune evasion, which partly explains the increased reproductive number of JN.1.
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