HAKU: JN.1 variant of Sars-Cov-2
4
articles
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Virological characteristics of the SARS-CoV-2 JN.1 variant.
Lancet Infect Dis. 2024.
PMID: 38184005
No abstract available.
The SARS-CoV-2 BA.2.86 lineage, first
identified in August 2023, is phylogenetically distinct from the current
circulating SARS-CoV-2 omicron XBB lineages, including EG.5.1 and HK.3.
Compared with XBB and BA.2, BA.2.86 carries more than 30 mutations in
the spike 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 harbours Leu455Ser and three mutations in non-spike
proteins (appendix pp 17–18).
Spike protein mutation Leu455Ser is a hallmark mutation of JN.1: we
have recently shown that HK.3 and other flip variants carry Leu455Phe,
which contributes to increased transmissibility and immune escape
ability compared with the parental EG.5.1 variant.5
Here, we investigated the virological properties of JN.1. We estimated
the relative effective reproductive number of JN.1 using genomic
surveillance data from France, the UK, and Spain, where more than 25
sequences of JN.1 have been reported, using a Bayesian multinomial
logistic model (appendix pp 10–15, 17–18). 6
The reproductive number of JN.1 in these three countries was higher
than that of BA.2.86.1 and HK.3, one of the XBB lineages with the
highest growth advantage at the end of November, 2023 (appendix pp 17–18). 5
These results suggest that JN.1 might soon become the dominant lineage
worldwide. Indeed, by the end of November 2023, JN.1 had already
overtaken HK.3 in France and Spain (appendix pp 17–18).The in vitro ACE2 binding assay 7
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 (appendix pp 17–18),
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 (appendix pp 17–18). This discrepancy could be due to the difference between monomeric RBD and trimerised whole spike protein (appendix pp 2, 17–18).
We then performed a neutralisation assay using rodent sera infected
with BA.2.86 or immunised with BA.2.86 spike protein. In both cases, the
50% neutralisation titre (NT50) against JN.1 was similar to that against BA.2.86 (appendix 17–18), suggesting that Leu455Ser does not affect the antigenicity of BA.2.86. On the other hand, the NT50
of breakthrough infection sera with XBB.1.5 and EG.5.1 against JN.1 was
significantly lower than that of HK.3 (2·6-fold to 3·1-fold) and
BA.2.86 (3·8-fold; appendix pp 17–18). Furthermore, JN.1 shows robust resistance to monovalent XBB.1.5 vaccine sera compared with BA.2.86 (appendix 17–18).
Taken together, 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.
KJI
and KS are supported in part by AMED SCARDA Japan Initiative for
World-leading Vaccine Research and Development Centers UTOPIA and by
AMED SCARDA Program on R&D of new generation vaccine including new
modality application. The G2P-Japan Consortium and KS are supported by
AMED Research Program on Emerging and Re-emerging Infectious Diseases
and by the JSPS KAKENHI Fund for the Promotion of Joint International
Research (International Leading Research). KS received funding from the
AMED Research Program on HIV/AIDS, JST CREST, JSPS Core-to-Core Program,
The Tokyo Biochemical Research Foundation, and The Mitsubishi
Foundation; received consulting fees from Moderna Japan and Takeda
Pharmaceutical; and honoraria for lectures from Gilead Sciences, Moderna
Japan, and Shionogi & Co. JI received funding from JST PRESTO and
JSPS KAKENHI Grant-in-Aid for Early-Career Scientists; and received
consulting fees and honoraria for lectures from Takeda Pharmaceutical.
KU is a JSPS Research Fellow DC2. YKo is a JSPS Research Fellow DC1. JZ
is funded by the International Joint Research Project of the Institute
of Medical Science, the University of Tokyo and the project of National
Institute of Virology and Bacteriology, Programme EXCELES, that is
funded by the European Union, Next Generation EU. The other authors
declare no competing interests. We thank CEU Universities and Santander
Bank (Ayudas a la movilidad internacional de los investigadores en
formación de la CEINDO) and to the Federation of European Biochemical
Societies for their financial support to MP-B during the first and
second part of his internship period at BIOCEV.
Evolving immune evasion and transmissibility of SARS-CoV-2: The emergence of JN.1 variant and its global impact.
Drug Discov Ther. 2024.
PMID: 38382991 Abstract (20.3. 2024)
The continuous evolution of SARS-CoV-2 variants constitutes a
significant impediment to the public health. The World Health
Organization (WHO) has designated the SARS-CoV-2 variant JN.1, which has
evolved from its progenitor BA.2.86, as a Variant of Interest (VOI) in
light of its enhanced immune evasion and transmissibility. The
proliferating dissemination of JN.1 globally accentuates its competitive
superiority and the potential to instigate fresh surges of infection,
notably among cohorts previously infected by antecedent variants.
Notably, prevailing evidence does not corroborate an increase in
pathogenicity associated with JN.1, and antiviral agents retain their
antiviral activity against both BA.2.86 and JN.1. The sustained
effectiveness of antiviral agents offers a beacon of hope. Nonetheless,
the variant's adeptness at eluding the immunoprotective effects
conferred by extant vaccines highlights the imperative for the
development of more effective vaccines and therapeutic approaches.
Overall, the distinct evolutionary trajectories of BA.2.86 and JN.1
underscore the necessity for ongoing surveillance and scholarly inquiry
to elucidate their implications for the pandemic's evolution, which
requires the international communities to foster collaboration through
the sharing of data, exchange of insights, and collective scientific
endeavors.
As COVID-19 Cases Surge, Here's What to Know About JN.1, the Latest SARS-CoV-2 "Variant of Interest".
JAMA. 2024.
PMID: 38214935
Parents often bask in the glow of their children’s accomplishments, so if SARS-CoV-2 variants were like people, BA.2.86 would be busting its buttons right about now. BA.2.86’s spawn, JN.1, has become the dominant SARS-CoV-2 variant in the US, status its parent variant never achieved. Fortunately, although COVID-19 cases have surged, hospitalizations and deaths from the disease are still considerably lower than they were the same time a year earlier. When BA.2.86 joined the SARS-CoV-2 Omicron family last summer, it grabbed pandemic trackers’ attention because it was so different from its progenitor, BA.2. Compared with BA.2, BA.2.86’s spike protein carries more than 30 mutations, suggesting that it might spread more easily than its predecessors
Ongoing evolution of SARS-CoV-2 drives escape from mRNA vaccine-induced humoral immunity.
medRxiv [Preprint]. 2024 Mar 7:2024.03.05.24303815. doi: 10.1101/2024.03.05.24303815.
PMID: 38496628
Free PMC article.
Preprint.Since the COVID-19 pandemic began in 2020, viral sequencing has
documented 131 individual mutations in the viral spike protein across 48
named variants. To determine the ability of vaccine-mediated humoral
immunity to keep pace with continued SARS-CoV-2 evolution, we assessed
the neutralization potency of sera from 76 vaccine recipients collected
after 2 to 6 immunizations against a comprehensive panel of mutations
observed during the pandemic. Remarkably, while many individual
mutations that emerged between 2020 and 2022 exhibit escape from sera
following primary vaccination, few escape boosted sera. However, progressive loss of neutralization was observed across newer variants, irrespective of vaccine doses. Importantly, an updated XBB.1.5 booster significantly increased titers against newer variants but not JN.1. These findings demonstrate that seasonal boosters improve titers against contemporaneous strains,
but novel variants continue to evade updated mRNA vaccines,
demonstrating the need for novel approaches to adequately control
SARS-CoV-2 transmission.
Distinct evolution of SARS-CoV-2 Omicron XBB and BA.2.86/JN.1 lineages combining increased fitness and antibody evasion.
Nat Commun. 2024 Mar 13;15(1):2254. doi: 10.1038/s41467-024-46490-7.
PMID: 38480689
Free PMC article. The unceasing circulation of SARS-CoV-2 leads to the continuous
emergence of novel viral sublineages. Here, we isolate and characterize
XBB.1, XBB.1.5, XBB.1.9.1, XBB.1.16.1, EG.5.1.1, EG.5.1.3, XBF,
BA.2.86.1 and JN.1 variants, representing >80% of circulating
variants in January 2024. The XBB subvariants carry few but recurrent
mutations in the spike, whereas BA.2.86.1 and JN.1 harbor >30
additional changes. These variants replicate in IGROV-1 but no longer in
Vero E6 and are not markedly fusogenic. They potently infect nasal
epithelial cells, with EG.5.1.3 exhibiting the highest fitness.
Antivirals remain active. Neutralizing antibody (NAb) responses from
vaccinees and BA.1/BA.2-infected individuals are markedly lower compared
to BA.1, without major differences between variants. An XBB
breakthrough infection enhances NAb responses against both XBB and
BA.2.86 variants. JN.1 displays lower affinity to ACE2 and higher immune
evasion properties compared to BA.2.86.1. Thus, while distinct, the
evolutionary trajectory of these variants combines increased fitness and
antibody evasion.
Key mechanistic features of the trade-off between antibody escape and host cell binding in the SARS-CoV-2 Omicron variant spike proteins.
EMBO J. 2024 Mar 11. doi: 10.1038/s44318-024-00062-z. Online ahead of print.
PMID: 38467833
Since SARS-CoV-2 Omicron variant emerged, it is constantly evolving into
multiple sub-variants, including BF.7, BQ.1, BQ.1.1, XBB, XBB.1.5 and
the recently emerged BA.2.86 and JN.1. Receptor binding and immune
evasion are recognized as two major drivers for evolution of the
receptor binding domain (RBD) of the SARS-CoV-2 spike (S) protein.
However, the underlying mechanism of interplay between two factors
remains incompletely understood. Herein, we determined the structures of
human ACE2 complexed with BF.7, BQ.1, BQ.1.1, XBB and XBB.1.5 RBDs.
Based on the ACE2/RBD structures of these sub-variants and a comparison
with the known complex structures, we found that R346T substitution in
the RBD enhanced ACE2 binding upon an interaction with the residue R493,
but not Q493, via a mechanism involving long-range conformation
changes. Furthermore, we found that R493Q and F486V exert a balanced
impact, through which immune evasion capability was somewhat compromised
to achieve an optimal receptor binding. We propose a "two-steps-forward
and one-step-backward" model to describe such a compromise between
receptor binding affinity and immune evasion during RBD evolution of
Omicron sub-variants.
Neutralization of SARS-CoV-2 Omicron subvariant BA.2.87.1.
Vaccine. 2024 Mar 7:S0264-410X(24)00292-5. doi: 10.1016/j.vaccine.2024.03.007. Online ahead of print.
PMID: 38458874
Free article.
A new highly mutated Omicron subvariant BA.2.87.1 has recently been
identified with over 30 amino acid mutations in the Spike protein
compared with BA.2, BA.5, XBB.1.5, and JN.1 variants. Multiple mutations
in BA.2.87.1 are located in the N-terminal domain (NTD) rather than in
the receptor binding domain (RBD) of the Spike protein. We evaluated
neutralizing antibody (NAb) responses to BA.2.87.1 because of its highly
mutated sequence and its unique NTD region. Our data show that NAb
responses to BA.2.87.1 were lower than to BA.2 but higher than to JN.1,
suggesting that BA.2.87.1 is not a further antibody escape variant
compared with other currently circulating variants. Moreover, XBB.1.5
mRNA boosting increased NAb titers to all variants tested including
BA.2.87.1.
Effectiveness of Omicron XBB.1.5 vaccine against infection with SARS-CoV-2 Omicron XBB and JN.1 variants, prospective cohort study, the Netherlands, October 2023 to January 2024.
et al. 2024 Mar;29(10). doi: 10.2807/1560-7917.ES.2024.29.10.2400109.
PMID: 38456217
Free article. We estimated vaccine effectiveness (VE) of SARS-CoV-2
Omicron XBB.1.5 vaccination against self-reported infection between 9
October 2023 and 9 January 2024 in 23,895 XBB.1.5 vaccine-eligible
adults who had previously received at least one booster. ...Sequenci …
Wastewater-based epidemiological surveillance of SARS-CoV-2 new variants BA.2.86 and offspring JN.1 in south and Southeast Asia.
Travel Med. 2024 Mar 4:taae040. doi: 10.1093/jtm/taae040. Online ahead of print.
PMID: 38438141
No abstract available.
Next-generation treatments: Immunotherapy and advanced therapies for COVID-19.
et al. 2024 Feb 19;10(5):e26423. doi: 10.1016/j.heliyon.2024.e26423. eCollection 2024 Mar 15.
PMID: 38434363
Free PMC article.
Review.
The emergence of new SARS-CoV-2
lineages, shaped by mutation and recombination processes, has led to
successive waves of infections. ...Moreover, the detrimental
consequences of the novel emergence of SARS-CoV-2 lineages bear a particular …
Evolving immune evasion and transmissibility of SARS-CoV-2: The emergence of JN.1 variant and its global impact.
Drug Discov Ther. 2024 Mar 20;18(1):67-70. doi: 10.5582/ddt.2024.01008. Epub 2024 Feb 22.
PMID: 38382991
Free article.
The continuous evolution of SARS-CoV-2 variants constitutes a significant impediment to the public health. The World Health Organization (WHO) has designated the SARS-CoV-2 variant JN.1, which has evolved from …
XBB.1.5 monovalent mRNA vaccine booster elicits robust neutralizing antibodies against XBB subvariants and JN.1.
Cell Host Microbe. 2024 Mar 13;32(3):315-321.e3. doi: 10.1016/j.chom.2024.01.014. Epub 2024 Feb 19.
PMID: 38377995
Free article. COVID-19 vaccines have recently been updated to specifically encode or
contain the spike protein of the SARS-CoV-2 XBB.1.5 subvariant, 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 booster (XBB.1.5 MV) to previously uninfected individuals
boosted serum virus-neutralizing antibodies significantly against not
only XBB.1.5 (27.0-fold increase) and EG.5.1 (27.6-fold increase) but
also key emerging viruses such as HV.1, HK.3, JD.1.1, and JN.1 (13.3- to
27.4-fold increase). Individuals previously infected by an Omicron
subvariant had the highest overall serum neutralizing titers (ID50
1,504-22,978) against all viral variants tested. While immunological
imprinting was still evident with the updated vaccines, it was not
nearly as severe as observed with the previously authorized bivalent
BA.5 vaccine. Our findings strongly support the official recommendation
to widely apply the updated COVID-19 vaccines.
