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torsdag 21 mars 2024

Viimeaikaisia (2024) PubMed artikkeleita Sars-Cov-2 vallitsevista varianteista ja rokotetehoista; Tilanteen hahmotusta

 HAKU:  JN.1  variant of Sars-Cov-2 

4 articles found by citation matching
 

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

Kaku Y, et al. 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.
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). 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). 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 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. Ou G, et al. 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".  Rubin R. 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.
Roederer AL, Cao Y, St Denis K, Sheehan ML, Li CJ, Lam EC, Gregory DJ, Poznansky MC, Iafrate AJ, Canaday DH, Gravenstein S, Garcia-Beltran WF, Balazs AB. 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.
Planas D, Staropoli I, Michel V, Lemoine F, Donati F, Prot M, Porrot F, Guivel-Benhassine F, Jeyarajah B, Brisebarre A, Dehan O, Avon L, Bolland WH, Hubert M, Buchrieser J, Vanhoucke T, Rosenbaum P, Veyer D, Péré H, Lina B, Trouillet-Assant S, Hocqueloux L, Prazuck T, Simon-Loriere E, Schwartz O. 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.
Li W, Xu Z, Niu T, Xie Y, Zhao Z, Li D, He Q, Sun W, Shi K, Guo W, Chang Z, Liu K, Fan Z, Qi J, Gao GF. 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.
Lasrado N, Rössler A, Rowe M, Collier AY, Barouch DH. 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.
Huiberts AJ 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 … 
 
Next-generation treatments: Immunotherapy and advanced therapies for COVID-19.
Arevalo-Romero JA 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 …
XBB.1.5 monovalent mRNA vaccine booster elicits robust neutralizing antibodies against XBB subvariants and JN.1.
Wang Q, Guo Y, Bowen A, Mellis IA, Valdez R, Gherasim C, Gordon A, Liu L, Ho DD. 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. 
 
 
XBB.1.5 monovalent booster improves antibody binding and neutralization against emerging SARS-CoV-2 Omicron variants. Jain S, Kumar S et al. . bioRxiv [Preprint]. 2024 Feb 5:2024.02.03.578771. doi: 10.1101/2024.02.03.578771. PMID: 38370837 Free PMC article. Preprint.The rapid emergence of divergent SARS-CoV-2 variants has led to an update of the COVID-19 booster vaccine to a monovalent version containing the XBB.1.5 spike. To determine the neutralization breadth following booster immunization, we collected blood samples from 24 individuals pre- and post-XBB.1.5 mRNA booster vaccination (∼1 month). The XBB.1.5 booster improved both neutralizing activity against the ancestral SARS-CoV-2 strain (WA1) and the circulating Omicron variants, including EG.5.1, HK.3, HV.1, XBB.1.5 and JN.1. Relative to the pre-boost titers, the XBB.1.5 monovalent booster induced greater total IgG and IgG subclass binding, particular IgG4, to the XBB.1.5 spike as compared to the WA1 spike. We evaluated antigen-specific memory B cells (MBCs) using either spike or receptor binding domain (RBD) probes and found that the monovalent booster largely increases non-RBD cross-reactive MBCs. These data suggest that the XBB.1.5 monovalent booster induces cross-reactive antibodies that neutralize XBB.1.5 and related Omicron variants.

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