Distinct evolution of SARS-CoV-2 Omicron XBB and BA.2.86/JN.1 lineages combining increased fitness and antibody evasion

Nature Communications, Год журнала: 2024, Номер 15(1)

Опубликована: Март 13, 2024

Abstract The unceasing circulation of SARS-CoV-2 leads to the continuous emergence 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 JN.1 variants, representing >80% circulating variants in January 2024. XBB subvariants carry few but recurrent mutations spike, whereas harbor >30 additional changes. These replicate IGROV-1 no longer Vero E6 are not markedly fusogenic. They potently infect nasal epithelial cells, with EG.5.1.3 exhibiting highest fitness. Antivirals remain active. Neutralizing antibody (NAb) responses from vaccinees BA.1/BA.2-infected individuals lower compared BA.1, without major differences between variants. An breakthrough infection enhances NAb against both BA.2.86 displays affinity ACE2 higher immune evasion properties BA.2.86.1. Thus, while distinct, evolutionary trajectory these combines increased fitness evasion.

Язык: Английский

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Post-pandemic memory T cell response to SARS-CoV-2 is durable, broadly targeted, and cross-reactive to the hypermutated BA.2.86 variant

Cell Host & Microbe, Год журнала: 2024, Номер 32(2), С. 162 - 169.e3

Опубликована: Янв. 10, 2024

Ongoing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) evolution has given rise to recombinant Omicron lineages that dominate globally (XBB.1), as well the emergence of hypermutated variants (BA.2.86). In this context, durable and cross-reactive T cell immune memory is critical for continued protection against COVID-19. We examined responses SARS-CoV-2 approximately 1.5 years since first emerged. describe sustained CD4+ CD8+ spike-specific in healthcare workers South Africa (n = 39) who were vaccinated experienced at least one infection. Spike-specific cells are highly with all tested, including BA.2.86. Abundant nucleocapsid membrane-specific detectable most participants. The bulk SARS-CoV-2-specific have an early-differentiated phenotype, explaining their persistent nature. Overall, hybrid immunity leads accumulation spike non-spike evident 3.5 after start pandemic, preserved recognition mutated variants.

Язык: Английский

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mRNA vaccines for infectious diseases — advances, challenges and opportunities

Nature Reviews Drug Discovery, Год журнала: 2024, Номер unknown

Опубликована: Окт. 4, 2024

Язык: Английский

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Distinct evolution of SARS-CoV-2 Omicron XBB and BA.2.86/JN.1 lineages combining increased fitness and antibody evasion

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2023, Номер unknown

Опубликована: Ноя. 21, 2023

The unceasing circulation of SARS-CoV-2 leads to the continuous emergence novel viral sublineages. Here, we isolated and characterized 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 JN.1 variants, representing >80% circulating variants in January 2024. XBB subvariants carry few but recurrent mutations spike, whereas harbor >30 additional changes. These replicated IGROV-1 no longer Vero E6 were not markedly fusogenic. They potently infected nasal epithelial cells, with EG.5.1.3 exhibiting highest fitness. Antivirals remained active. Neutralizing antibody (NAb) responses from vaccinees BA.1/BA.2-infected individuals lower compared BA.1, without major differences between variants. An breakthrough infection enhanced NAb against both BA.2.86 displayed affinity ACE2 higher immune evasion properties BA.2.86.1. Thus, while distinct, evolutionary trajectory these combines increased fitness evasion.

Язык: Английский

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A bivalent COVID-19 mRNA vaccine elicited broad immune responses and protection against Omicron subvariants infection

npj Vaccines, Год журнала: 2025, Номер 10(1)

Опубликована: Янв. 10, 2025

Abstract Continuously emerging SARS-CoV-2 Omicron subvariants pose a threat thwarting the effectiveness of approved COVID-19 vaccines. Especially, protection breadth and degree these vaccines against antigenically distant is unclear. Here, we report immunogenicity efficacy bivalent mRNA vaccine, PTX-COVID19-M1.2 (M1.2), which encodes native spike proteins from Wuhan-Hu-1 (D614G) BA.2.12.1, in mouse hamster models. Both primary series booster vaccination using M1.2 elicited potent broad nAbs some subvariants. Strong spike-specific T cell responses subvariants, including JN.1, were also induced. Vaccination with protected animals multiple challenges. Interestingly, XBB.1.5 lung infection did not correlate nAb levels. These results indicate that generated broadly protective immune response cells probably contributed to protection.

Язык: Английский

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Understanding the Effectiveness of the Comirnaty Monovalent and Bivalent Vaccines During the Winter Coronavirus (COVID-19) Infection Survey

Journal of Infection, Год журнала: 2025, Номер unknown, С. 106461 - 106461

Опубликована: Март 1, 2025

Highlights•The Comirnaty Omicron XBB.1.5 vaccine demonstrated moderate short-term protection against infection and symptomatic infection, reaching peak effectiveness between 2 to 5 weeks post-vaccination.•Approximately 9 12 after vaccination, the protective effect of booster declined near zero both infection.•The BA.5 bivalent showed no evidence within study period, with estimates wide confidence intervals indicating considerable uncertainty.•These findings emphasize need for adaptive strategies development variant-targeted vaccines maintain emerging SARS-CoV-2 variants.AbstractBackgroundUnderstanding over time is critical informing strategies, types, public health policies, particularly continued emergence novel variants.MethodsThe Winter Coronavirus (COVID-19) Infection Study (WCIS), conducted from November 2023 March 2024, involved approximately 150,000 participants aged 3 years older England Scotland. The WCIS tested at regular using lateral flow tests estimate prevalence incidence in real-time. Survival analysis Cox proportional hazards regression was conducted, data linked participant vaccination records, evaluate association since risk infection. Vaccine (VE) evaluated those 65 old over. model incorporated time-varying covariates counting process framework, stratified baseline by age group, region, time, included key such as sex, clinical status, ethnicity, socioeconomic indicators. VE estimated hazard ratios, penalised cubic splines were used capture nonlinear effects vaccination.ResultsWe that peaked day 14 post-vaccination, 70.63% (95% Confidence Intervals (CI): 43.33%, 84.78%) 63.62% CI: 22.69%, 82.88%) rapidly 9-12 post point close uncertainty 60 onwards. In contrast, crossing zero.ConclusionsThese provide important insights into targeted context an evolving pandemic. As continues mutate, approaches design policy will be addressing variants protecting high-risk groups.

Язык: Английский

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A decavalent composite mRNA vaccine against both influenza and COVID-19

mBio, Год журнала: 2024, Номер 15(9)

Опубликована: Авг. 6, 2024

The COVID-19 pandemic caused by SARS-CoV-2 has had a persistent and significant impact on global public health for 4 years. Recently, there been resurgence of seasonal influenza transmission worldwide. co-circulation viruses results in dual burden communities. Additionally, the potential zoonotic viruses, such as avian Influenza A/H5N1 A/H7N9, remains concern. Therefore, combined vaccine against all these respiratory diseases is urgent need. mRNA vaccines, with their superior efficacy, speed development, flexibility, cost-effectiveness, offer promising solution infectious future pandemics. In this study, we present FLUCOV-10, novel 10-valent created from our proven platform. This encodes hemagglutinin (HA) proteins four two potential, well spike variants. A two-dose immunization FLUCOV-10 elicited robust immune responses mice, producing IgG antibodies, neutralizing antigen-specific cellular vaccine-matched SARS-CoV-2. Remarkably, provided complete protection mouse models both homologous heterologous strains These highlight an effective candidate prevention COVID-19.IMPORTANCEAmidst ongoing emerging viral threats, particularly concurrent sequential spread influenza, research introduces FLUCOV-10. mRNA-based combination vaccine, designed to counteract COVID-19, incorporating genes surface glycoproteins various was highly preclinical trials, generating strong ensuring matching represents step forward ability address showcasing singular, adaptable challenges.

Язык: Английский

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SARS-CoV-2 BA.1 and BA.2 breakthrough infections boost antibody responses to early Omicron subvariants but not BQ.1.1 or XBB.1.5

Cell Reports Medicine, Год журнала: 2024, Номер 5(3), С. 101474 - 101474

Опубликована: Март 1, 2024

Subvariants of the Omicron lineage severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) efficiently escape neutralizing antibody responses induced by both vaccination and infection with antigenically distinct variants. Here, we describe potency breadth binding against a large panel variants following an BA.1 or BA.2 breakthrough in heterogeneous cohort individuals diverse exposure histories. Both infections significantly boost levels broaden reactivity. However, this broader immunity does not neutralize BQ XBB subvariants efficiently. While these are neutralized well post-breakthrough sera, suggesting escape, non-neutralizing sustained. In summary, our data suggest that while immune response to SARS-CoV-2 spike, is still outpaced viral evolution.

Язык: Английский

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Spatial Engineering of Heterotypic Antigens on a DNA Framework for the Preparation of Mosaic Nanoparticle Vaccines with Enhanced Immune Activation against SARS‐CoV‐2 Variants

Angewandte Chemie International Edition, Год журнала: 2024, Номер 63(46)

Опубликована: Июль 19, 2024

Abstract Mosaic nanoparticle vaccines with heterotypic antigens exhibit broad‐spectrum antiviral capabilities, but the impact of antigen proportions and distribution patterns on vaccine‐induced immunity remains largely unexplored. Here, we present a DNA nanotechnology‐based strategy for spatially assembling to guide rational design mosaic vaccines. By utilizing two aptamers orthogonal selectivity original SARS‐CoV‐2 spike trimer Omicron receptor‐binding domain (RBD), along soccer‐ball framework, precisely manipulate spacing, stoichiometry, overall create nanoparticles average, bipolar, unipolar distributions. Systematic in vitro vivo immunological investigations demonstrate that 30 equivalent proportions, an average distribution, lead higher production neutralizing antibodies compared bipolar Furthermore, precise assembly our developed methodology reveals mere increment five RBD (from 15 20) not only diminishes neutralization against variant also triggers excessive inflammation. This work provides unique perspective by highlighting significance spatial placement proportion their structure–activity mechanisms.

Язык: Английский

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New COVID-19 vaccination recommendations in Spain: Optimizing for next seasons

Enfermedades infecciosas y microbiologia clinica (English ed ), Год журнала: 2025, Номер 43(1), С. 36 - 46

Опубликована: Янв. 1, 2025

Despite high initial vaccination rates, Spain's current COVID-19 coverage in recommended groups does not meet WHO targets. For the upcoming season, challenges include revising age, updating risk groups, and unifying criteria with flu vaccine co-administration. European Commission's advance purchase agreements limit access to certain vaccines, need for vaccines effective against variants adds administrative complexities. recommendations should adapt these specific circumstances. Using predominant appropriate response duration is crucial protect at-risk populations. Enhancing training health education campaigns professionals general public, alongside utilizing tools simplify recommendations, can promote higher rates Spain. Addressing essential ensure adequate protection improve coverage, ultimately achieving better public outcomes face of evolving threats.

Язык: Английский

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