Antibody Response to Omicron BA.4–BA.5 Bivalent Booster

New England Journal of Medicine, Год журнала: 2023, Номер 388(6), С. 567 - 569

Опубликована: Янв. 11, 2023

Язык: Английский

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Resistance of Omicron subvariants BA.2.75.2, BA.4.6, and BQ.1.1 to neutralizing antibodies

Nature Communications, Год журнала: 2023, Номер 14(1)

Опубликована: Фев. 14, 2023

Abstract Convergent evolution of SARS-CoV-2 Omicron BA.2, BA.4, and BA.5 lineages has led to the emergence several new subvariants, including BA.2.75.2, BA.4.6. BQ.1.1. The subvariant BQ.1.1 became predominant in many countries December 2022. subvariants carry an additional often redundant set mutations spike, likely responsible for increased transmissibility immune evasion. Here, we established a viral amplification procedure easily isolate strains. We examined their sensitivity 6 therapeutic monoclonal antibodies (mAbs) 72 sera from Pfizer BNT162b2-vaccinated individuals, with or without BA.1/BA.2 breakthrough infection. Ronapreve (Casirivimab Imdevimab) Evusheld (Cilgavimab Tixagevimab) lose antiviral efficacy against BA.2.75.2 BQ.1.1, whereas Xevudy (Sotrovimab) remaine weakly active. is also resistant Bebtelovimab. Neutralizing titers triply vaccinated individuals are low undetectable 4 months after boosting. A infection increases these titers, which remains about 18-fold lower than BA.1. Reciprocally, more efficiently neutralization BA.2.75.2. Thus, trajectory novel facilitates spread immunized populations raises concerns most available mAbs.

Язык: Английский

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Repeated Omicron exposures override ancestral SARS-CoV-2 immune imprinting

Nature, Год журнала: 2023, Номер 625(7993), С. 148 - 156

Опубликована: Ноя. 22, 2023

Abstract The continuing emergence of SARS-CoV-2 variants highlights the need to update COVID-19 vaccine compositions. However, immune imprinting induced by vaccination based on ancestral (hereafter referred as WT) strain would compromise antibody response Omicron-based boosters 1–5 . Vaccination strategies counter are critically needed. Here we investigated degree and dynamics in mouse models human cohorts, especially focusing role repeated Omicron stimulation. In mice, efficacy single boosting is heavily limited when using that antigenically distinct from WT—such XBB variant—and this concerning situation could be mitigated a second booster. Similarly, humans, infections alleviate WT vaccination-induced generate broad neutralization responses both plasma nasal mucosa. Notably, deep mutational scanning-based epitope characterization 781 receptor-binding domain (RBD)-targeting monoclonal antibodies isolated infection revealed double exposure induce large proportion matured Omicron-specific have RBD epitopes WT-induced antibodies. Consequently, was largely mitigated, bias towards non-neutralizing observed exposures restored. On basis scanning profiles, identified evolution hotspots XBB.1.5 demonstrated these mutations further boost immune-evasion capability while maintaining high ACE2-binding affinity. Our findings suggest component should abandoned updating vaccines, individuals without prior receive two updated boosters.

Язык: Английский

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SARS-CoV-2 Omicron boosting induces de novo B cell response in humans

Nature, Год журнала: 2023, Номер 617(7961), С. 592 - 598

Опубликована: Апрель 3, 2023

Язык: Английский

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Fc-γR-dependent antibody effector functions are required for vaccine-mediated protection against antigen-shifted variants of SARS-CoV-2

Nature Microbiology, Год журнала: 2023, Номер 8(4), С. 569 - 580

Опубликована: Апрель 3, 2023

Язык: Английский

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Evolution of SARS-CoV-2 Variants: Implications on Immune Escape, Vaccination, Therapeutic and Diagnostic Strategies

Viruses, Год журнала: 2023, Номер 15(4), С. 944 - 944

Опубликована: Апрель 10, 2023

The COVID-19 pandemic caused by SARS-CoV-2 is associated with a lower fatality rate than its SARS and MERS counterparts. However, the rapid evolution of has given rise to multiple variants varying pathogenicity transmissibility, such as Delta Omicron variants. Individuals advanced age or underlying comorbidities, including hypertension, diabetes cardiovascular diseases, are at higher risk increased disease severity. Hence, this resulted in an urgent need for development better therapeutic preventive approaches. This review describes origin human coronaviruses, particularly well sub-variants. Risk factors that contribute severity implications co-infections also considered. In addition, various antiviral strategies against COVID-19, novel repurposed drugs targeting viral host proteins, immunotherapeutic strategies, discussed. We critically evaluate current emerging vaccines their efficacy, immune evasion new impact on diagnostic testing examined. Collectively, global research public health authorities, along all sectors society, prepare upcoming future coronavirus outbreaks.

Язык: Английский

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Persistent immune imprinting occurs after vaccination with the COVID-19 XBB.1.5 mRNA booster in humans

Immunity, Год журнала: 2024, Номер 57(4), С. 904 - 911.e4

Опубликована: Март 14, 2024

Immune imprinting describes how the first exposure to a virus shapes immunological outcomes of subsequent exposures antigenically related strains. Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) Omicron breakthrough infections and bivalent COVID-19 vaccination primarily recall cross-reactive memory B cells induced by prior Wuhan-Hu-1 spike mRNA rather than priming Omicron-specific naive cells. These findings indicate that immune occurs after repeated exposures, but whether it can be overcome remains unclear. To understand persistence imprinting, we investigated plasma antibody responses administration updated XBB.1.5 vaccine booster. We showed booster elicited neutralizing against current variants were dominated pre-existing previously spike. Therefore, persists multiple spikes through infection, including post vaccination, which will need considered guide future vaccination.

Язык: Английский

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Original SARS-CoV-2 monovalent and Omicron BA.4/BA.5 bivalent COVID-19 mRNA vaccines: phase 2/3 trial interim results

Nature Medicine, Год журнала: 2023, Номер 29(9), С. 2325 - 2333

Опубликована: Авг. 31, 2023

This ongoing, open-label, phase 2/3 trial compared the safety and immunogenicity of Omicron BA.4/BA.5-containing bivalent mRNA-1273.222 vaccine with ancestral Wuhan-Hu-1 mRNA-1273 as booster doses. Two groups adults who previously received primary vaccination series doses were enrolled in a sequential, nonrandomized manner single-second boosters (n = 376) or 511). Primary objectives noninferiority superiority neutralizing antibody (nAb) responses against BA.4/BA.5 SARS-CoV-2 D614G mutation (ancestral (D614G)), 28 days post boost. Superiority based on prespecified success criteria (lower bounds 95% CI > 1 < 0.677, respectively) mRNA-1273.222:mRNA-1273 geometric mean ratios. Bivalent elicited superior nAb versus noninferior (D614G) at day 29 boost participants without detectable prior infection. Day seroresponses higher for than similar (D614G), both meeting criterion. The profile was to that reported no new concerns identified. Continued monitoring neutralization real-world effectiveness are needed additional divergent-virus variants emerge. ClinicalTrials.gov registration: NCT04927065.

Язык: Английский

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Duration of protection of ancestral-strain monovalent vaccines and effectiveness of bivalent BA.1 boosters against COVID-19 hospitalisation in England: a test-negative case-control study

The Lancet Infectious Diseases, Год журнала: 2023, Номер 23(11), С. 1235 - 1243

Опубликована: Июль 12, 2023

Bivalent BA.1 booster vaccines were offered to adults aged 50 years or older and clinically vulnerable people as part of the 2022 autumn COVID-19 vaccination programme in England. Previously, all England had been a primary course consisting two doses either ChAdOx1-S monovalent mRNA vaccine an vaccine. We aimed estimate long-term duration protection provided by vaccines, incremental effectiveness bivalent boosters.In this test-negative case-control study, cases controls 18 identified from national data for PCR tests done hospital settings Our analysis was restricted with acute respiratory infections coded diagnosis field. Data status extracted English register linked testing data. Between June 13 Dec 25, 2022, we estimated against hospitalisation three more compared being unvaccinated, stratified age (18-64 vs ≥65 years). Sept 5, Feb 2023, (ie, addition earlier vaccines) receiving at least (when last dose 6 months ago) among older. Analyses adjusted week test, gender, age, risk group, residing care home, health social worker, Index Multiple Deprivation quintile, ethnicity, recent positivity.Our included 19 841 43 410 controls. Absolute who received plateaued after around 50% those 65 30% 18-64 years. analyses boosters 9954 39 108 Incremental peaked 53·0% (95% CI 47·9-57·5) 2-4 weeks administration, before waning 35·9% (31·4-40·1) 10 weeks.Our study provides evidence that offer moderate effective preventing time when omicron lineages circulating England.None.

Язык: Английский

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Effectiveness of BNT162b2 BA.4/5 bivalent mRNA vaccine against a range of COVID-19 outcomes in a large health system in the USA: a test-negative case–control study

The Lancet Respiratory Medicine, Год журнала: 2023, Номер 11(12), С. 1089 - 1100

Опубликована: Окт. 25, 2023

BackgroundXBB-related omicron sublineages have recently replaced BA.4/5 as the predominant in USA and other regions globally. Despite preliminary signs of immune evasion XBB sublineages, few data exist describing real-world effectiveness bivalent COVID-19 vaccines, especially against XBB-related illness. We aimed to investigate Pfizer-–BioNTech BNT162b2 vaccine both BA.4/5-related disease adults aged 18 years or older.MethodsIn this test-negative case–control study, we estimated using from electronic health records Kaiser Permanente Southern California system members older who received at least two doses wild-type mRNA vaccines. Participants sought care for acute respiratory infection between Aug 31, 2022, April 15, 2023, were tested SARS-CoV-2 via PCR tests. Relative (≥2 plus a booster vs ≥2 alone) absolute (vs unvaccinated individuals) was critical illness related (intensive unit [ICU] admission, mechanical ventilation, inpatient death), hospital emergency department urgent visits, in-person outpatient encounters with odds ratios logistic regression models adjusted demographic clinical factors. stratified estimates by sublineage (ie, likely XBB-related), time since receipt, age group, number received, immunocompromised status. This study is registered ClinicalTrials.gov (NCT04848584).FindingsAnalyses conducted 123 419 (24 246 cases 99 173 controls), including 4131 episode (a subset admissions), 14 529 admissions, 63 566 45 324 visits. 20 555 infections 3691 related. In analyses, relative those compared alone an additional 50% (95% CI 23–68) illness, 39% (28–49) 35% (30–40) 28% (22–33) encounters. Waning 0–3 months 4–7 after vaccination evident outcomes but not detected outcomes. The 56% 12–78) versus 40% (27–50) admission; 34% (21–45) 36% (30–41) visits; 29% (19–38) 27% (20–33) encounters.InterpretationBy mid-April, individuals previously vaccinated only vaccines had little protection COVID-19—including admission. A restored range outcomes, most substantial observed admission illness.FundingPfizer.

Язык: Английский

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