Temporal associations of B and T cell immunity with robust vaccine responsiveness in a 16-week interval BNT162b2 regimen.
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ABSTRACT:
SUBMITTER: Nayrac M
PROVIDER: S-EPMC8722583 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:The standard regimen of the BNT162b2 mRNA vaccine for SARS-CoV-2 includes two doses administered three weeks apart. However, some public health authorities spaced these doses, raising questions about efficacy. We analyzed longitudinal humoral responses against the D614G strain and variants of concern for SARS-CoV-2 in a cohort of SARS-CoV-2-naive and previously infected individuals who received the BNT162b2 mRNA vaccine with sixteen weeks between doses. While administering a second dose to previously infected individuals did not significantly improve humoral responses, these responses significantly increased in naive individuals after a 16-week spaced second dose, achieving similar levels as in previously infected individuals. Comparing these responses to those elicited in individuals receiving a short (4-week) dose interval showed that a 16-week interval induced more robust responses among naive vaccinees. These findings suggest that a longer interval between vaccine doses does not compromise efficacy and may allow greater flexibility in vaccine administration.
| S-EPMC8639412 | biostudies-literature
Project description:Continuous emergence of SARS-CoV-2 variants of concern (VOCs) is fueling the COVID-19 pandemic. Omicron (B.1.1.529) rapidly spread worldwide. The large number of mutations in its Spike raise concerns about a major antigenic drift that could significantly decrease vaccine efficacy and infection-induced immunity. A long interval between BNT162b2 mRNA doses elicits antibodies that efficiently recognize Spikes from different VOCs. Here, we evaluate the recognition of Omicron Spike by plasma from a cohort of SARS-CoV-2 naive and previously infected individuals who received their BNT162b2 mRNA vaccine 16 weeks apart. Omicron Spike is recognized less efficiently than D614G, Alpha, Beta, Gamma, and Delta Spikes. We compare with plasma activity from participants receiving a short (4 weeks) interval regimen. Plasma from individuals of the long-interval cohort recognize and neutralize better the Omicron Spike compared with those who received a short interval. Whether this difference confers any clinical benefit against Omicron remains unknown.
| S-EPMC8823958 | biostudies-literature
Project description:The BNT162b2 vaccine is highly effective against COVID-19 infection and was delivered with a 3-week time interval in registration studies1. However, many countries extended this interval to accelerate population coverage with a single vaccine. It is not known how immune responses are influenced by delaying the second dose. We provide the assessment of immune responses in the first 14 weeks after standard or extended-interval BNT162b2 vaccination and show that delaying the second dose strongly boosts the peak antibody response by 3.5-fold in older people. This enhanced antibody response may offer a longer period of clinical protection and delay the need for booster vaccination. In contrast, peak cellular-specific responses were the strongest in those vaccinated on a standard 3-week vaccine interval. As such, the timing of the second dose has a marked influence on the kinetics and magnitude of the adaptive immune response after mRNA vaccination in older people.
| S-EPMC8795435 | biostudies-literature
Project description:BackgroundComparative analyses of SARS-CoV-2-specific immune responses elicited by diverse prime-boost regimens are required to establish efficient regimens for the control of COVID-19.MethodIn this prospective observational cohort study, spike-specific immunoglobulin G (IgG) and neutralizing antibodies (nAbs) alongside spike-specific T-cell responses in age-matched groups of homologous BNT162b2/BNT162b2 or AZD1222/AZD1222 vaccination, heterologous AZD1222/BNT162b2 vaccination, and prior wild-type SARS-CoV-2 infection/vaccination were evaluated.ResultsPeak immune responses were achieved after the second vaccine dose in the naïve vaccinated groups and after the first dose in the prior infection/vaccination group. Peak titers of anti-spike IgG and nAb were significantly higher in the AZD1222/BNT162b2 vaccination and prior infection/vaccination groups than in the BNT162b2/BNT162b2 or AZD1222/AZD1222 groups. However, the frequency of interferon-γ-producing CD4+ T cells was highest in the BNT162b2/BNT162b2 vaccination group. Similar results were observed in the analysis of polyfunctional T cells. When nAb and CD4+T-cell responses against the Delta variant were analyzed, the prior infection/vaccination group exhibited higher responses than the groups of other homologous or heterologous vaccination regimens.ConclusionnAbs are efficiently elicited by heterologous AZD1222/BNT162b2 vaccination, as well as prior infection/vaccination, whereas spike-specific CD4+T-cell responses are efficiently elicited by homologous BNT162b2 vaccination. Variant-recognizing immunity is more efficiently generated by prior infection/vaccination than the other homologous or heterologous vaccination regimens.
| S-EPMC9901539 | biostudies-literature
Project description:We use our sense of time to identify temporal relationships between events and to anticipate actions. The degree to which we can exploit temporal contingencies depends on the variability of our measurements of time. We asked humans to reproduce time intervals drawn from different underlying distributions. As expected, production times were more variable for longer intervals. However, production times exhibited a systematic regression toward the mean. Consequently, estimates for a sample interval differed depending on the distribution from which it was drawn. A performance-optimizing Bayesian model that takes the underlying distribution of samples into account provided an accurate description of subjects' performance, variability and bias. This finding suggests that the CNS incorporates knowledge about temporal uncertainty to adapt internal timing mechanisms to the temporal statistics of the environment.
| S-EPMC2916084 | biostudies-literature
Project description:BACKGROUND:Sleep is intricately tied to emotional well-being, yet little is known about the reciprocal links between sleep and psychosocial experiences in the context of daily life. PURPOSE:The aim of this study is to evaluate daily psychosocial experiences (positive and negative affect, positive events, and stressors) as predictors of same-night sleep quality and duration, in addition to the reversed associations of nightly sleep predicting next-day experiences. METHODS:Daily experiences and self-reported sleep were assessed via telephone interviews for eight consecutive evenings in two replicate samples of US employees (131 higher-income professionals and 181 lower-income hourly workers). Multilevel models evaluated within-person associations of daily experiences with sleep quality and duration. Analyses controlled for demographics, insomnia symptoms, the previous day's experiences and sleep measures, and additional day-level covariates. RESULTS:Daily positive experiences were associated with improved as well as disrupted subsequent sleep. Specifically, positive events at home predicted better sleep quality in both samples, whereas greater positive affect was associated with shorter sleep duration among the higher-income professionals. Negative affect and stressors were unrelated to subsequent sleep. Results for the reversed direction revealed that better sleep quality (and, to a lesser degree, longer sleep duration) predicted emotional well-being and lower odds of encountering stressors on the following day. CONCLUSIONS:Given the reciprocal relationships between sleep and daily experiences, efforts to improve well-being in daily life should reflect the importance of sleep.
| S-EPMC5739917 | biostudies-literature
Project description:Interval mapping approaches have been playing significant role for quantitative trait locus (QTL) mapping to discover genetic architecture of diseases or traits with molecular markers. Composite interval mapping (CIM) is one of the superior approaches of the interval mapping for discovering both linked and unlinked putative QTL positions. However, estimators of this approach are not robust against phenotypic outliers. As a result, it fails to detect true QTL positions in presence of outliers. In this study, we investigated the performance of ?-Composite Interval Mapping (BetaCIM) for detecting both linked and unlinked important QTLs positions from the robustness points of views. Performance of this approach depends on the value of tuning parameter ?. It reduces to the classical CIM approach for ? ?0. We described and formulated the cross-validation procedure for selecting trait specific optimum value of ?. It was observed that the optimum value of ? depends on both amount of contaminated observations and their scatteredness. BetaCIM approach discover similar QTL positions as classical IM/CIM in absence of phenotypic outliers, but gives better results in presence of phenotypic outliers in terms of detecting true QTLs and effects estimation. We formulated the generalized forms of robust QTL analysis and developed an R-package named "BetaCIM" by implementing this robust approach. Left and right kidney weight data sets of mouse intercross population (129 S1/SvlmJ × A/J) were analyzed by using BetaCIM, CIM, and IM approaches. For right kidney weight (RKW) CIM and BetaCIM provided similar LOD score profile, and both approaches identified 3 QTL positions. IM approach also identified 3 QTL positions. For left kidney weight (LKW), there was evidence of one outlying observation; and in this case the BetaCIM approach identified 2 QTL positions. However, none of the QTLs were significant by CIM and IM approaches at 5% level of significance. Gene expression ontology (GEO) search showed that the candidate genes (Otof and A330033J07Rik) of the identified QTLs for LKW were expressed in kidney. Both simulation and real data analysis results showed that BetaCIM approach improves the performance over the existing methods in presence of phenotypic outliers. Otherwise, it keeps almost equal performance.
| S-EPMC6277098 | biostudies-literature
Project description:BackgroundAripiprazole lauroxil (AL) is a long-acting injectable antipsychotic approved for treatment of schizophrenia in adults. Approved AL doses and dosing regimens include 441 mg monthly, 662 mg monthly, and 882 mg monthly or every 6 weeks (q6wk), as well as the most recently approved dose, 1064 mg, administered every 2 months.ObjectivePharmacokinetics, safety, and tolerability of an AL regimen with a dose interval of every 2 months (1064 mg) were compared with two other regimens available as monthly and q6wk options.MethodsThis study evaluated pharmacokinetics of AL given at a higher dosage strength (1064 mg) and at a longer dose interval (every 8 weeks [q8wk]) than previously studied. Patients with schizophrenia or schizoaffective disorder entering this 44-week, phase I, open-label, multicenter study had no recent exposure to aripiprazole and were maintained on other oral antipsychotics throughout the study. Patients were randomized to one of three AL dose regimens for 24 weeks (four 1064-mg injections [q8wk], five 882-mg injections [q6wk], or seven 441-mg injections [q4wk], with the last AL exposure at week 24). Oral aripiprazole was prohibited. Patients were followed for an additional 20 weeks to assess terminal aripiprazole plasma concentrations and ongoing safety. Plasma concentration samples were obtained at regular intervals to provide pharmacokinetic data for the duration of AL exposure and to measure persistence of plasma aripiprazole concentrations after AL discontinuation.ResultsEligible patients received AL 1064 mg q8wk (n = 35), 882 mg q6wk (n = 34), or 441 mg q4wk (n = 35). Overall, 103/104 (99.0%) patients were taking concomitant non-aripiprazole oral antipsychotic medications during the study. All three AL dose regimens provided continuous exposure to aripiprazole. Mean aripiprazole concentrations from the 1064-mg q8wk regimen were comparable to the 882-mg q6wk regimen and higher than the 441-mg q4wk regimen. Overall incidence by group of any adverse events (AEs) throughout the study was 68.6% (1064 mg q8wk), 50.0% (882 mg q6wk), and 65.7% (441 mg q4wk). The most common AE across regimens was injection-site pain (range 8.6%-11.4%). Serious AEs were reported by eight patients (all but one [increased psychosis in one patient, 441-mg q4wk group] considered unrelated to study drug). Discontinuations due to AEs were reported for 2.9%, 11.8%, and 5.7% of patients receiving the 8-, 6-, and 4-week regimens, respectively. AEs of akathisia, dyskinesia, and dystonia occurred in 2.9%, 8.6%, and 5.7% of patients in the 1064-mg q8wk group, 8.8%, 0%, and 2.9% in the 882-mg q6wk group, and 8.6%, 0%, and 0% in the 441-mg q4wk group, respectively.ConclusionsAL 1064 mg q8wk provided continuous exposure to aripiprazole throughout the 8-week dosing interval and had a safety profile consistent with the 4- and 6-week regimens. These findings were used to support FDA approval of the 1064-mg dose administered every 2 months.RegistrationClinicaltrials.gov: NCT02320032.
| S-EPMC7447659 | biostudies-literature
Project description:COVID-19 mRNA vaccines generate high concentrations of circulating anti-Spike antibodies and Spike-specific CD4+ T cells following prime-boost vaccination. It is not yet clear if vaccine-induced CD4+ T cell responses in the draining lymph node contribute to this outstanding immunogenicity. Using fine needle aspiration of draining axillary lymph nodes from individuals who received the BNT162b2 mRNA vaccine, we found large populations of Spike-specific CD4+ T follicular helper cells in the draining lymph node. A broadly immunodominant HLA-DPB1*04-restricted response to Spike166-180 composes one of the largest populations of T follicular helper cells in individuals with this allele, which is itself among the most common HLA alleles in the human population. Spike-specific T follicular helper cells are present in the lymph node 30 days after vaccine boost and persist in some individuals more than 170 days. Collectively, our results underscore the key role that robust T follicular helper cell responses play in the establishment of long-term immunity in this very efficacious human vaccine.
2022-01-04 | GSE183393 | GEO
Project description:BackgroundIn December 2020, Israel began a mass vaccination campaign against coronavirus disease 2019 (Covid-19) by administering the BNT162b2 vaccine, which led to a sharp curtailing of the outbreak. After a period with almost no cases of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, a resurgent Covid-19 outbreak began in mid-June 2021. Possible reasons for the resurgence were reduced vaccine effectiveness against the delta (B.1.617.2) variant and waning immunity. The extent of waning immunity of the vaccine against the delta variant in Israel is unclear.MethodsWe used data on confirmed infection and severe disease collected from an Israeli national database for the period of July 11 to 31, 2021, for all Israeli residents who had been fully vaccinated before June 2021. We used a Poisson regression model to compare rates of confirmed SARS-CoV-2 infection and severe Covid-19 among persons vaccinated during different time periods, with stratification according to age group and with adjustment for possible confounding factors.ResultsAmong persons 60 years of age or older, the rate of infection in the July 11-31 period was higher among persons who became fully vaccinated in January 2021 (when they were first eligible) than among those fully vaccinated 2 months later, in March (rate ratio, 1.6; 95% confidence interval [CI], 1.3 to 2.0). Among persons 40 to 59 years of age, the rate ratio for infection among those fully vaccinated in February (when they were first eligible), as compared with 2 months later, in April, was 1.7 (95% CI, 1.4 to 2.1). Among persons 16 to 39 years of age, the rate ratio for infection among those fully vaccinated in March (when they were first eligible), as compared with 2 months later, in May, was 1.6 (95% CI, 1.3 to 2.0). The rate ratio for severe disease among persons fully vaccinated in the month when they were first eligible, as compared with those fully vaccinated in March, was 1.8 (95% CI, 1.1 to 2.9) among persons 60 years of age or older and 2.2 (95% CI, 0.6 to 7.7) among those 40 to 59 years of age; owing to small numbers, the rate ratio could not be calculated among persons 16 to 39 years of age.ConclusionsThese findings indicate that immunity against the delta variant of SARS-CoV-2 waned in all age groups a few months after receipt of the second dose of vaccine.
| S-EPMC8609604 | biostudies-literature