A recent study published in the journal Euro Surveill claims that the recent increase in cases of the JN.1 variant of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may not necessarily be due to the variant’s ability to escape immunity.
Rapid Communication: Humoral immune escape through the current SARS-CoV-2 variants BA.2.86 and JN.1, December 2023. Image Source: NIAID
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of the coronavirus disease 2019 (COVID-19) pandemic, is a respiratory virus belonging to the family of human beta coronaviruses. During the pandemic, many variants of SARS-CoV-2 with enhanced immune fitness have emerged, triggering several different pandemic waves worldwide.
The Omicron variant of SARS-CoV-2 first emerged in South Africa in late 2021. The BA.2 lineage was one of the major Omicron lineages, exhibiting significantly higher transmissibility and infectivity. BA.2.86 is a notable lineage of BA.2 that emerged in 2023, with more spike protein mutations than previously observed variants.
The recently emerged JN.1 variant is a descendant of BA.2.86, which has achieved significantly higher transmissibility. Through an additional substitution mutation (L455S) in the spike protein, the JN.1 variant has rapidly circulated worldwide compared to BA.2.86.
In this study, scientists examined the immune escape potential of the new JN.1, BA.2.86, and earlier variants.
Scientists collected serum samples from a total of 39 vaccinated and SARS-CoV-2-exposed healthy individuals and evaluated virus neutralization titers in these samples against seven different virus variants, including B.1, BA.2, BA.5, and XBB. 1.5, EG.5.1, BA.2.86, and JN.1.
The serum samples were collected in September 2023, when the SARS-CoV-2 variant EG.5.1 predominantly circulated in the study area (Berlin and surrounding areas) for at least 1.5 months. Plaque reduction neutralization tests were performed on transmembrane serine protease (TMPRSS 2)-expressing monkey kidney epithelial cells to determine neutralization titers.
Evaluation of neutralization titers revealed the highest neutralizing reactivity against the ancestral B.1 variants, followed by the BA.2 and BA.5 variants. This is attributed to pre-existing anti-SARS-CoV-2 immunity induced by COVID-19 vaccination or prior SARS-CoV-2 infection.
Compared to the B.1 variant, the XBB.1.5 and EG.5.1 variants showed about a 15-fold reduction in neutralization. Furthermore, 12 out of 39 participants showed no detectable neutralizing reactivity against these variants.
For the BA.2.86 variant, the reduction in neutralizing titers was 20-fold compared to the ancestral variant B.1. 11 out of 39 participants showed no neutralizing titers. Compared to the BA.2.86 variant, the JN.1 variant did not show a further reduction in neutralizing titers. This observation remained consistent when participants were grouped into two categories based on exposure to XBB variants or not.
The study concludes that both the BA.2.86 and JN.1 variants of SARS-CoV-2 have comparable immune escape capabilities. Both variants have a significantly higher ability to evade pre-existing anti-SARS-CoV-2 immunity compared to earlier variants, which may explain the recent dominance of the BA.2.86 and JN.1 variants.
However, higher immune fitness may not be the sole reason for the recent rise in JN.1 cases, as the variant does not exhibit additional immune escape capabilities compared to the BA.2.86 variant. There may be other factors responsible for enhanced virus transmissibility and infectivity. Future studies are required to understand the dynamics of JN.1 transmissibility.
The scientists compared their findings with existing evidence and found discrepancies with two earlier studies examining a higher proportion of individuals with XBB variant exposure history. A significant portion of participants showed no detectable neutralizing titers against the circulating virus variants, including XBB.1.5, EG.5.1, BA.2.86, and JN.1. This suggests that immunity induced by vaccines or infections may be waning at the population level, potentially increasing the frequency of new infections in the upcoming winter months in the Northern Hemisphere.
- Jeworowski Lara M, Mühlemann Barbara, Walper Felix, Schmidt Marie L, Jansen Jenny, Krumbholz Andi, Simon-Lorière Etienne, Jones Terry C, Corman Victor M, Drosten Christian. Humoral immune escape through the current SARS-CoV-2 variants BA.2.86 and JN.1, December 2023. Euro Surveill. 2024;29(2):pii=2300740. https://doi.org/10.2807/1560-7917.ES.2024.29.2.2300740, https://www.eurosurveillance.org/content/10.2807/1560-7917.ES.2024.29.2.2300740