An intranasal subunit vaccine induces protective systemic and mucosal antibody immunity against respiratory viruses in mouse models

Nature Communications, Год журнала: 2025, Номер 16(1)

Опубликована: Май 1, 2025

Язык: Английский

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Determinants of humoral and cellular immune responses to three doses of mRNA SARS-CoV-2 vaccines in older adults: a longitudinal cohort study

The Lancet Healthy Longevity, Год журнала: 2023, Номер 4(5), С. e188 - e199

Опубликована: Май 1, 2023

BackgroundOlder age is associated with poorer outcomes to COVID-19 infection. The Norwegian Institute of Public Health established a longitudinal cohort adults aged 65–80 years study the effects pandemic. Here we describe characteristics in general, and specifically immune responses at baseline after primary booster vaccination subset blood samples, epidemiological factors affecting these responses.Methods4551 participants were recruited, humoral (n=299) cellular (n=90) measured before two three vaccine doses. Information on general health, infections, vaccinations obtained from questionnaires national health registries.FindingsHalf had chronic condition. 849 (18·7%) 4551 prefrail 184 (4%) frail. 483 (10·6%) activity limitations (scored Global Activity Limitation Index). After dose two, 295 (98·7%) 299 seropositive for anti-receptor binding domain IgG, 210 (100%) three. Spike-specific CD4 CD8 T cell showed high heterogeneity responded alpha (B.1.1.7), delta (B.1.617.2), omicron (B.1.1.529 or BA.1) variants concern. Cellular seasonal coronaviruses increased SARS-CoV-2 vaccination. Heterologous prime boosting mRNA vaccines was highest antibody (p=0·019) (p=0·003), hypertension lower levels doses (p=0·04).InterpretationMost older adults, including those comorbidities, generated good serological Responses further improved doses, particularly heterologous boosting. Vaccination also cross-reactive cells against concern coronaviruses. Frailty not impaired responses, but might indicate reduced responsiveness even Individual differences identified through sampling enables better prediction variability which can help guide future policy need subsequent their timing.FundingNorwegian Health, Ministry Research Council Norway, Coalition Epidemic Preparedness Innovations.

Язык: Английский

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Humoral vaccine response and breakthrough infections in kidney transplant recipients during the COVID-19 pandemic: a nationwide cohort study

EClinicalMedicine, Год журнала: 2023, Номер 60, С. 102035 - 102035

Опубликована: Июнь 1, 2023

Kidney transplant recipients (KTRs) experienced reduced SARS-CoV-2 vaccine response and were at increased risk of severe COVID-19. It is unknown if level induced anti-receptor binding domain IgG (anti-RBD IgG) correlates with protection from survival following We aimed to evaluate the effect on breakthrough infections (BTI) COVID-19 death in KTRs.We performed a nationwide study, examining competing infection, related/unrelated death, efficacy as assessed by anti-RBD 4-10 weeks after each vaccination. The study included all KTR Norway alive functioning graft February 20th, 2020, events November 11th, 2022 right-censored. A pre-pandemic reference-cohort January 1st 2019 2020 was excess mortality. conducted Oslo University Hospital, Rikshospitalet, Norway.The 3607 KTRs (59 [48-70] years) who received (median [IQR]) 4 [3-4] vaccines (range 2-6, 99% mRNA). Anti-RBD measured 12 701 serum samples provided 3213 KTRs. Vaccine 41 [31-57] days total 1090 infected SARS-CoV-2, 1005 (92%) BTI, did not protect against BTI. hazard ratio for related 40 post-infection 1.71 (95% CI: 1.14, 2.56) comparing levels (≥5 vs. ≥5000 BAU/mL). No non-COVID-19 mortality registered surviving infection compared reference.Our findings suggested that mRNA predict but prevention fatal disease progression greater further death. seen during pandemic.CEPI internal funds.

Язык: Английский

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An update on lateral flow immunoassay for the rapid detection of SARS-CoV-2 antibodies

AIMS Microbiology, Год журнала: 2023, Номер 9(2), С. 375 - 401

Опубликована: Янв. 1, 2023

Over the last three years, after outbreak of COVID-19 pandemic, an unprecedented number novel diagnostic tests have been developed. Assays to evaluate immune response SARS-CoV-2 widely considered as part control strategy. The lateral flow immunoassay (LFIA), detect both IgM and IgG against SARS-CoV-2, has studied a point-of-care (POC) test. Compared laboratory tests, LFIAs are faster, cheaper user-friendly, thus available also in areas with low economic resources. Soon onset numerous kits for rapid antibody detection were put on market emergency use authorization. However, since then, scientists tried better define accuracy these their usefulness different contexts. In fact, while during first phase pandemic auxiliary molecular diagnosis COVID-19, successively became tool seroprevalence surveillance address infection policies. When 2021 massive vaccination campaign was implemented worldwide, interest LFIA reemerged due need establish extent longevity immunization vaccinated population priorities guide health policies low-income countries limited access vaccines. Here, we summarize accuracy, advantages limits POC detection, highlighting efforts that made improve this technology over few years.

Язык: Английский

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Modeling the kinetics of the neutralizing antibody response against SARS-CoV-2 variants after several administrations of Bnt162b2

PLoS Computational Biology, Год журнала: 2023, Номер 19(8), С. e1011282 - e1011282

Опубликована: Авг. 7, 2023

Because SARS-CoV-2 constantly mutates to escape from the immune response, there is a reduction of neutralizing capacity antibodies initially targeting historical strain against emerging Variants Concern (VoC)s. That why measure protection conferred by vaccination cannot solely rely on antibody levels, but also requires their neutralization capacity. Here we used mathematical model follow humoral response in 26 individuals that received up three doses Bnt162b2 vaccine, and for whom both anti-S IgG was measured longitudinally all main VoCs. Our could identify two independent mechanisms led marked increase over successive doses. In addition already known levels after each dose, identified significantly increased third vaccine administration VoCs, despite large inter-individual variability. Consequently, projects mean duration detectable non-Omicron VoC between 348 days (Beta variant, 95% Prediction Intervals PI [307; 389]) 587 (Alpha [537; 636]). Despite low doses, Omicron variants varies 173 (BA.5 [142; 200]) 256 (BA.1 [227; 286]). shows benefit incorporating follow-up patients better inform level different variants. Trial registration: This clinical trial registered with ClinicalTrials.gov, IDs NCT04750720 NCT05315583.

Язык: Английский

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Characterization of the SARS-CoV-2 antibody landscape in Norway in the late summer of 2022: high seroprevalence in all age groups with patterns of primary Omicron infection in children and hybrid immunity in adults

BMC Infectious Diseases, Год журнала: 2024, Номер 24(1)

Опубликована: Авг. 20, 2024

According to Norwegian registries, 91% of individuals ≥ 16 years had received 1 dose COVID-19 vaccine by mid-July 2022, whereas less than 2% children < 12 were vaccinated. Confirmed was reported for 27% the population, but relaxation testing lead substantial underreporting. We have characterized humoral immunity SARS-CoV-2 in Norway late summer 2022 estimating seroprevalence and identifying antibody profiles based on reactivity Wuhan or Omicron-like viruses a nationwide cross-sectional collection residual sera, validated our findings using cohort sera.

Язык: Английский

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Adaptive immune responses against common viruses are sustained and functional in end-of-life patients

iScience, Год журнала: 2025, Номер 28(3), С. 112082 - 112082

Опубликована: Фев. 21, 2025

Язык: Английский

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Dynamics of SARS-CoV-2 immunity after vaccination and breakthrough infection in rituximab-treated rheumatoid arthritis patients: a prospective cohort study

Frontiers in Immunology, Год журнала: 2024, Номер 15

Опубликована: Фев. 22, 2024

SARS-CoV-2 vaccination in rheumatoid arthritis (RA) patients treated with B cell-depleting drugs induced limited seroconversion but robust cellular response. We aimed to document specific T and cell immunity response vaccine booster doses breakthrough infection (BTI). included 76 RA rituximab who received up four or three plus BTI, addition vaccinated healthy donors (HD) control tumor necrosis factor inhibitor (TNFi). quantified anti-SARS-CoV-2 receptor-binding domain (RBD) Spike IgG, anti-nucleocapsid (NC) 92 circulating inflammatory proteins, Spike-binding cells, Spike-specific cells along comprehensive high-dimensional phenotyping functional assays. The time since the last infusion, persistent inflammation, age were associated RBD IgG seroconversion. vaccine-elicited serological was accompanied by an incomplete induction of peripheral memory occurred independently responses. Vaccine- BTI-elicited similar between HD ex vivo terms frequency phenotype cytotoxic vitro functionality differentiation profile cells. can induce effector T-cell responses that are reactivated BTI. Paused medication allowed after a dose (D4), especially lower enabling efficient humoral contributed overall development potential durable immunity.

Язык: Английский

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Incidence and outcome of COVID-19 following vaccine and hybrid immunity in patients on immunosuppressive therapy: identification of protective post-immunisation anti-RBD antibody levels in a prospective cohort study

RMD Open, Год журнала: 2024, Номер 10(2), С. e003545 - e003545

Опубликована: Апрель 1, 2024

Objectives To assess incidence, severity and predictors of COVID-19, including protective post-vaccination levels antibodies to the receptor-binding domain SARS-CoV-2 spike protein (anti-RBD), informing further vaccine strategies for patients with immune-mediated inflammatory diseases (IMIDs) on immunosuppressive medication. Methods IMIDs immunosuppressives healthy controls (HC) receiving vaccines were included in this prospective observational study. COVID-19 outcome registered anti-RBD measured 2–5 weeks post-immunisation. Results Between 15 February 2021 2023, 1729 350 HC provided blood samples self-reported COVID-19. The incidence was 66% 67% HC, re-infection occurring 12% patients. Severe recorded 22 (2%) no HC. No COVID-19-related deaths occurred. Vaccine-induced immunity gave higher risk (HR 5.89 (95% CI 4.45 7.80)) than hybrid immunity. Post-immunisation <6000 binding antibody units/mL associated an increased following three 1.37 1.08 1.74)) four doses 1.28 1.02 1.62)), 4.47 1.87 10.67)). Conclusion Vaccinated IMID have a low severe Hybrid lowers infection. High post-immunisation protect against These results suggest that knowledge history, assessment can help individualise vaccination programme series high-risk individuals. Trial registration number NCT04798625 .

Язык: Английский

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Immune Modulation and Efficacy of Tixagevimab/Cilgavimab Pre-Exposure Prophylaxis in Lung Transplant Recipients During the Omicron Wave

International Journal of Molecular Sciences, Год журнала: 2025, Номер 26(8), С. 3696 - 3696

Опубликована: Апрель 14, 2025

Lung transplant recipients are at increased risk of severe COVID-19 due to lifelong immunosuppressive therapy, which impairs both innate and adaptive immune responses. Identifying effective supportive therapies is essential for mitigating the heightened vulnerability this population. This study investigated effects tixagevimab/cilgavimab, a monoclonal antibody as pre-exposure prophylaxis (PrEP) in A prospective was conducted on 19 lung Padua University Hospital, Italy, during Omicron variant wave (May–June 2022). Participants received tixagevimab/cilgavimab intramuscularly were monitored 180 days. SARS-CoV-2-specific levels measured baseline (T0), one month (T1), three months (T3) post-treatment. Cytokine profiles clinical outcomes, including SARS-CoV-2 infections, also assessed. At baseline, 50% patients had negative responses, but one-month post-treatment, all exceeded 700 kBAU/mL (median 3870 kBAU/mL), with decreasing remaining positive 1670 kBAU/mL). Remarkably, higher level circulating IL-18 found T3 comparison T0 who did not experience after PrEP. finding aligns IL-18’s primary role stimulating type-1 T helper (Th1) cell necessary induction virus-specific cytotoxic lymphocytes (CTLs). These results suggest that may induce systemic signature could contribute priming response against SARS-CoV-2, potentially mediated by interactions subsets.

Язык: Английский

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