New SARS-CoV-2 variant JN.1 shows increased transmissibility and immune resistance

By Dr. Sanchari Sinha Dutta, Ph.D.Dec 11 2023

A team of scientists in Japan has recently conducted a study to investigate virological characteristics of the JN.1 variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).

The study is currently available on the BioRxiv preprint* server.

Study: Virological characteristics of the SARS-CoV-2 JN.1 variant. Image Credit: Kateryna Kon / Shutterstock 

*Important notice: bioRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.

Background

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative pathogen of the most recent coronavirus disease 2019 (COVID-19) pandemic, is a positive-sense, single-stranded RNA virus with a genome size of around 30 kb. Many variants of SARS-CoV-2 with distinct mutational signatures have emerged throughout the pandemic. Depending on their spike protein mutational landscape, some variants have shown higher transmissibility, infectivity, and virulence.

The BA.2.86 lineage of SARS-CoV-2, which was first identified in August 2023, is phylogenetically distinct from the currently circulating Omicron XBB lineages, including EG.5.1 and HK.3. The BA.2.86 lineage contains more than 30 mutations in the spike protein, indicating that this lineage is highly capable of evading the pre-existing anti-SARS-CoV-2 immunity.

The JN.1 (BA.2.86.1.1) is the most recently emerged variant of SARS-CoV-2 that descended from the BA.2.86 lineage. The JN.1 contains a hallmark mutation L455S in the spike protein and three other mutations in the non-spike proteins. Studies investigating HK.3 and other "FLip" variants have shown that acquiring L455F mutation in the spike protein is associated with increased viral transmissibility and immune evasion ability. The L455F and F456L mutations are nicknamed "Flip" mutations because they switch the positions of two amino acids, labeled F and L, on the spike protein.  

In this study, scientists investigated the virological characteristics of the JN.1 variant. This Omicron subvariant has been identified for the first time in the United States. More than 25 sequences of JN.1 have now been reported in France, Spain, and the United Kingdom.

Important observations

The scientists analyzed genomic surveillance data from these countries using a Bayesian multinomial logistic model to estimate the relative effective reproductive number of JN.1. The effective reproductive number (R_e) is the expected number of new infections caused by an infectious individual in a population where some individuals may no longer be susceptible.

The findings revealed that the R_e of the JN.1 variant is higher in these countries compared to the R_e of BA.2.86.1 and HK.3 variants. This indicates that JN.1 has the ability to become a dominant variant worldwide in the future. In this context, existing evidence indicates that this variant has already dominated HK.3 in France and Spain.    

The spike protein of SARS-CoV-2 binds to human angiotensin-converting enzyme 2 (ACE2) to infect human cells. The in vitro ACE2 binding and pseudovirus assays are standard methods for investigating viral infectivity and transmissibility.

While the ACE2 binding assay indicated that the spike receptor binding domain (RBD) of JN.1 has a lower affinity for ACE2 compared to BA.2.86 spike RBD, the pseudovirus assay showed that JN.1 has significantly higher infectivity than BA.2.86.

As explained by the scientists, this discrepancy between the two assay findings could be due to the difference between monomeric RBD and trimerized whole spike protein used in these two assays, respectively.

Furthermore, the scientists conducted a virus neutralization assay using rodent sera infected with BA.2.86 or immunized with BA.2.86 spike protein. The findings indicated that the L455S spike mutation of JN.1 does not alter the antigenicity of BA.2.86.

The scientists also conducted separate virus neutralization assays using XBB.1.5 and EG.5.1 breakthrough infection sera and monovalent XBB.1.5 vaccine sera. The findings revealed that JN.1 is highly resistant to XBB.1.5- and EG.5.1-induced immunity.

Study significance

The study evaluated the virological characteristics of the omicron subvariant JN.1, which shows robust immune evasion ability against other co-circulating SARS-CoV-2 variants. This increased immune fitness of JN.1 could be due to the acquisition of the L455S mutation in the spike protein.

However, the study could not conclusively find out if this mutation can affect the transmissibility and infectivity of JN.1.

*Important notice: bioRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.