Virus World

The ongoing evolution of SARS-CoV-2 continues to challenge the global immune barrier established by infections and vaccine boosters. Recently, the emergence and dominance of the JN.1 lineage over XBB variants have prompted a reevaluation of current vaccine strategies. Despite the demonstrated effectiveness of XBB-based vaccines against JN.1, concerns persist regarding the durability of neutralizing antibody (NAb) responses against evolving JN.1 subvariants. In this study, we compared the humoral immunogenicity of XBB and JN.1 lineage infections in human subjects with diverse immune histories to understand the antigenic and immunogenic distinctions between these variants. Similar to observations in naive mice, priming with XBB and JN.1 in humans without prior SARS-CoV-2 exposure results in distinct NAb responses, exhibiting minimal cross-reactivity.

Importantly, breakthrough infections (BTI) with the JN.1 lineage induce 5.9-fold higher neutralization titers against JN.1 compared to those induced by XBB BTI. We also observed notable immune evasion of recently emerged JN.1 sublineages, including JN.1+R346T+F456L, with KP.3 showing the most pronounced decrease in neutralization titers by both XBB and JN.1 BTI sera. These results underscore the challenge posed by the continuously evolving SARS-CoV-2 JN.1 and support the consideration of switching the focus of future SARS-CoV-2 vaccine updates to the JN.1 lineage.

Preprint in bioRxiv (April 22, 2024):

https://doi.org/10.1101/2024.04.19.590276 

Effectiveness of the 2023-2024 vaccine lands at 54% for symptomatic cases. The updated 2023-2024 COVID-19 vaccine was approximately 54% effective against symptomatic SARS-CoV-2 infection in adults, and was also effective against the JN.1 variant, which became predominant in January, CDC researchers said. Overall, vaccine effectiveness against symptomatic COVID was 57% for people ages 18 to 49 years and 46% for people ages 50 and older, reported Ruth Link-Gelles, PhD, of the CDC's National Center for Immunization and Respiratory Diseases, and colleagues in the Morbidity and Mortality Weekly Reportopens in a new tab or window.

The updated vaccine is a monovalent XBB.1.5-derived vaccine, and there have been few estimates regarding its effectiveness, the authors noted. This study is the first to look at the vaccine's effectiveness against symptomatic COVID caused by the JN.1 variantopens in a new tab or window, a derivative of BA.2.86. The data came from the CDC's Increasing Community Access to Testing program that provided no-cost SARS-CoV-2 nucleic acid amplification tests (NAAT) to uninsured people at participating CVS and Walgreens pharmacies from Sept. 21, 2023 to Jan. 14, 2024. Vaccine effectiveness was 58% among those who received testing 7 to 59 days after receiving the updated vaccine, and 49% among those who received testing 60 to 119 days after receipt.

The SARS-CoV-2 BA.2.86 lineage, first identified in August 2023, is phylogenetically distinct from the currently circulating SARS-CoV-2 Omicron XBB lineages, including EG.5.1 and HK.3. Comparing to XBB and BA.2, BA.2.86 carries more than 30 mutations in the spike (S) protein, indicating a high potential for immune evasion. BA.2.86 has evolved and its descendant, JN.1 (BA.2.86.1.1), emerged in late 2023. JN.1 harbors S:L455S and three mutations in non-S proteins. S:L455S is a hallmark mutation of JN.1: we have recently shown that HK.3 and other "FLip" variants carry S:L455F, which contributes to increased transmissibility and immune escape ability compared to the parental EG.5.1 variant. Here, we investigated the virological properties of JN.1.

Preprint in bioRxiv (Dec. 9, 2023):

 https://doi.org/10.1101/2023.12.08.570782 

tThe SARS-CoV-2 saltation variant BA.2.86, which was quickly designated as a variant under monitoring after its emergence, has garnered global attention. Although BA.2.86 did not show substantial humoral immune escape and growth advantage compared with current dominant variants, such as EG.5.1 and HK.3, it showed remarkably high ACE2 binding affinity. This increased binding affinity, coupled with its distinct antigenicity, could enable BA.2.86 to accumulate immune-evasive mutations during low-level populational transmission, akin to the previous evolution from BA.2.75 to CH.1.1 and XBB.

With just one additional receptor binding domain mutation (L455S) compared to its predecessor BA.2.86, the JN.1 variant rapidly became predominant in France (figure A; appendix 1 p 12), surpassing both BA.2.86 and the so-called FLip (L455F+F456L) strains. A thorough investigation into the immune evasion capability of JN.1, particularly given its few additional mutations, is imperative.

Published in The Lancet Infectious Diseases (Dec. 15, 2023):

https://doi.org/10.1016/S1473-3099(23)00744-2

COVID-19 vaccines have recently been updated with the spike protein of SARS-Co-V-2 XBB.1.5 subvariant alone, but their immunogenicity in humans has yet to be fully evaluated and reported, particularly against emergent viruses that are rapidly expanding. We now report that administration of an updated monovalent mRNA vaccine (XBB.1.5 MV) to uninfected individuals boosted serum virus-neutralization antibodies significantly against not only XBB.1.5 (27.0-fold) and the currently dominant EG.5.1 (27.6-fold) but also key emergent viruses like HV.1, HK.3, JD.1.1, and JN.1 (13.3-to-27.4-fold). In individuals previously infected by an Omicron subvariant, serum neutralizing titers were boosted to highest levels (1,764-to-22,978) against all viral variants tested. While immunological imprinting was still evident with the updated vaccines, it was not nearly as severe as the previously authorized bivalent BA.5 vaccine. Our findings strongly support the official recommendation to widely apply the updated COVID-19 vaccines to further protect the public.

Preprint in bioRxiv (Nov. 27, 2023): 

 https://doi.org/10.1101/2023.11.26.568730