Your browser doesn't support javascript.
loading
Montrer: 20 | 50 | 100
Résultats 1 - 20 de 65
Filtrer
1.
Clin Oral Investig ; 28(6): 308, 2024 May 11.
Article de Anglais | MEDLINE | ID: mdl-38733458

RÉSUMÉ

AIMS: This study aimed to evaluate the visual improvement of resin infiltration of white spot lesions (WSL) during orthodontic treatment with the multibracket appliance (MBA) compared to fluoride varnish. METHODS: Patients aged 12-17 years with at least one WSL with an International Caries Detection and Assessment System (ICDAS) score of 1-2 during an active MBA treatment were included and randomized to receive either resin infiltration (Icon) or fluoride application (Flairesse). Standardized digital images were obtained before, one-day, one-week, one-month, three-months and six-months after treatment using a DSLR camera and a matching polarization filter. A grey reference card was used for color standardization. A Matlab routine was used to measure the color difference between adjacent healthy enamel and treated WSL. The independent-samples t-test was used for intergroup and paired-samples t-test for intragroup comparison. RESULTS: Images of 116 teeth from 36 patients were analyzed. The ΔE for the "Icon" treated WSL was smaller (T1ICON = 5.0 ± 1.4) than in the fluoride group (T1Fluoride = 8.4 ± 3.2). Caries infiltration significantly improved the aesthetic appearance of WSL (p < 0.001), which remained satisfactory at six months (T5ICON = 5.2 ± 1.6). CONCLUSION: WSL infiltration management during orthodontic treatment was superior to topical fluoridation in not only arresting the enamel lesions but also significantly improving the aesthetic appearance of demineralized regions around the brackets. CLINICAL RELEVANCE: WSL treatment in orthodontic patients is usually initiated after debonding. Research has shown that the earlier WSL is treated, the better the aesthetic outcome. There is limited data on the efficacy of resin infiltration of WSL during orthodontic treatment.


Sujet(s)
Cariostatiques , Caries dentaires , Fluorures topiques , Brackets orthodontiques , Adolescent , Enfant , Femelle , Humains , Mâle , Cariostatiques/usage thérapeutique , Caries dentaires/thérapie , Caries dentaires/prévention et contrôle , Fluorures topiques/usage thérapeutique , Résines synthétiques/usage thérapeutique , Résultat thérapeutique
2.
Nat Commun ; 15(1): 4182, 2024 May 17.
Article de Anglais | MEDLINE | ID: mdl-38755157

RÉSUMÉ

Bone marrow plasma cells (BMPC) are the correlate of humoral immunity, consistently releasing antibodies into the bloodstream. It remains unclear if BMPC reflect different activation environments or maturation of their precursors. Here we define human BMPC heterogeneity and track the recruitment of antibody-secreting cells (ASC) from SARS-CoV-2 vaccine immune reactions to the bone marrow (BM). Trajectories based on single-cell transcriptomes and repertoires of peripheral and BM ASC reveal sequential colonisation of BMPC compartments. In activated B cells, IL-21 suppresses CD19 expression, indicating that CD19low-BMPC are derived from follicular, while CD19high-BMPC originate from extrafollicular immune reactions. In primary immune reactions, both CD19low- and CD19high-BMPC compartments are populated. In secondary immune reactions, most BMPC are recruited to CD19high-BMPC compartments, reflecting their origin from extrafollicular reactivations of memory B cells. A pattern also observable in vaccinated-convalescent individuals and upon diphtheria/tetanus/pertussis recall-vaccination. Thus, BMPC diversity reflects the evolution of a given humoral immune response.


Sujet(s)
Antigènes CD19 , Moelle osseuse , Interleukines , Plasmocytes , Humains , Plasmocytes/immunologie , Interleukines/immunologie , Interleukines/métabolisme , Moelle osseuse/immunologie , Antigènes CD19/immunologie , Antigènes CD19/métabolisme , Immunité humorale/immunologie , COVID-19/immunologie , COVID-19/virologie , SARS-CoV-2/immunologie , Cellules de la moelle osseuse/immunologie , Cellules de la moelle osseuse/cytologie , Analyse sur cellule unique , Adulte , Lymphocytes B/immunologie , Cellules productrices d'anticorps/immunologie , Femelle , Mâle , Vaccination , Adulte d'âge moyen , Vaccin diphtérie-tétanos-coqueluche/immunologie
3.
Antiviral Res ; 226: 105891, 2024 Jun.
Article de Anglais | MEDLINE | ID: mdl-38649071

RÉSUMÉ

Zoonoses such as ZIKV and SARS-CoV-2 pose a severe risk to global health. There is urgent need for broad antiviral strategies based on host-targets filling gaps between pathogen emergence and availability of therapeutic or preventive strategies. Significant reduction of pathogen titers decreases spread of infections and thereby ensures health systems not being overloaded and public life to continue. Based on previously observed interference with FGFR1/2-signaling dependent impact on interferon stimulated gene (ISG)-expression, we identified Pim kinases as promising druggable cellular target. We therefore focused on analyzing the potential of pan-Pim kinase inhibition to trigger a broad antiviral response. The pan-Pim kinase inhibitor AZD1208 exerted an extraordinarily high antiviral effect against various ZIKV isolates, SARS-CoV-2 and HBV. This was reflected by strong reduction in viral RNA, proteins and released infectious particles. Especially in case of SARS-CoV-2, AZD1208 led to a complete removal of viral traces in cells. Kinome-analysis revealed vast changes in kinase landscape upon AZD1208 treatment, especially for inflammation and the PI3K/Akt-pathway. For ZIKV, a clear correlation between antiviral effect and increase in ISG-expression was observed. Based on a cell culture model with impaired ISG-induction, activation of the PI3K-Akt-mTOR axis, leading to major changes in the endolysosomal equilibrium, was identified as second pillar of the antiviral effect triggered by AZD1208-dependent Pim kinase inhibition, also against HBV. We identified Pim-kinases as cellular target for a broad antiviral activity. The antiviral effect exerted by inhibition of Pim kinases is based on at least two pillars: innate immunity and modulation of the endolysosomal system.


Sujet(s)
Antiviraux , Immunité innée , Protéines proto-oncogènes c-akt , Protéines proto-oncogènes c-pim-1 , SARS-CoV-2 , Transduction du signal , Sérine-thréonine kinases TOR , Humains , Immunité innée/effets des médicaments et des substances chimiques , Antiviraux/pharmacologie , Sérine-thréonine kinases TOR/métabolisme , Protéines proto-oncogènes c-pim-1/antagonistes et inhibiteurs , Protéines proto-oncogènes c-pim-1/métabolisme , SARS-CoV-2/effets des médicaments et des substances chimiques , SARS-CoV-2/immunologie , Protéines proto-oncogènes c-akt/métabolisme , Transduction du signal/effets des médicaments et des substances chimiques , Phosphatidylinositol 3-kinases/métabolisme , Lysosomes/effets des médicaments et des substances chimiques , Lysosomes/métabolisme , Virus Zika/effets des médicaments et des substances chimiques , Inhibiteurs de protéines kinases/pharmacologie , Animaux , Virus de l'hépatite B/effets des médicaments et des substances chimiques , Endosomes/effets des médicaments et des substances chimiques , Endosomes/métabolisme , Lignée cellulaire , COVID-19/immunologie , COVID-19/virologie , Traitements médicamenteux de la COVID-19 , Réplication virale/effets des médicaments et des substances chimiques , Dérivés du biphényle , Thiazolidines
4.
J Prosthet Dent ; 2023 Sep 09.
Article de Anglais | MEDLINE | ID: mdl-37696745

RÉSUMÉ

STATEMENT OF PROBLEM: Little is known about the effect of illuminant metamerism between natural teeth and zirconia restorations, despite their increasing clinical popularity. PURPOSE: The purpose of this in vitro study was to compare illuminant metamerism between pairs of natural teeth and layered zirconia restorations and pairs of natural teeth and monolithic zirconia restorations under 10 different illuminants and analyze their metameric potential. MATERIAL AND METHODS: Spectral reflectance factors were obtained from 10 pairs of extracted natural teeth and layered zirconia restorations and 28 pairs of extracted natural teeth and monolithic multilayer zirconia restorations. Each pair showed a color match that was within the visual threshold for clinical acceptability (CIEDE2000≤1.8). A special index of metamerism for the change of illuminant (Milm) was calculated from the CIEDE2000 color difference equation. Descriptive statistics and the one-sample t test were used to analyze the results for the Milm and for both groups of layered and monolithic zirconia restorations (α=.05). RESULTS: Layered zirconia restorations reached a mean ±standard deviation value for Milm=0.3 ±0.2 and Milm=0.5 ±0.4 for monolithic zirconia restorations (P<.01). CONCLUSIONS: The effect of illuminant metamerism between natural teeth and zirconia crowns was weak and generally within the clinical acceptability limit.

5.
J Intell ; 11(7)2023 Jul 17.
Article de Anglais | MEDLINE | ID: mdl-37504786

RÉSUMÉ

In this article, we propose that basic cognitive skills may be fostered and assessed in early childhood educational (pre-K) settings using a technology-based approach to assessment. BELLA (Bilingual English Language Learner Assessment), designed for use with both monolingual (English or Spanish speaking) and bilingual (English and Spanish speaking) children, is designed to attend to cognitive skill development in addition to (pre-)academic knowledge. Specifically, BELLA assesses analytical, creative, and practical thinking in 3-5-year-old children through unique item content and delivery. BELLA is among the first tablet-based pre-K assessments designed to assess cognitive skills needed for the era of the Anthropocene.

6.
Sci Rep ; 13(1): 10820, 2023 07 04.
Article de Anglais | MEDLINE | ID: mdl-37402816

RÉSUMÉ

Escape mutations in the spike protein of SARS-CoV-2 are a major reason for Omicron breakthrough infections. After basal vaccination only very low titers of Omicron neutralizing antibodies are present. However, booster vaccinations induce higher titers against the Omicron variant. The neutralization of the Delta and Omicron variants by sera obtained 6 months after 3rd vaccination and 2 weeks or 6 months after 4th vaccination with a monovalent RNA vaccine (Spikevax) was analyzed. It was observed for the Omicron variant that 6 months after the fourth vaccination, the titer returns to the same very low neutralizing capacity as 6 months after the third vaccination. The Delta variant neutralizing capacity wanes with a comparable kinetic although the titers are higher as compared to the Omicron variant. This indicates that the fourth vaccination with a monovalent vaccine based on the ancestral isolate neither affects the kinetic of the waning nor the breadth of the humoral response.


Sujet(s)
COVID-19 , Immunité humorale , Humains , COVID-19/prévention et contrôle , SARS-CoV-2/génétique , Vaccination , Anticorps neutralisants , Anticorps antiviraux
7.
Law Hum Behav ; 47(3): 422-435, 2023 06.
Article de Anglais | MEDLINE | ID: mdl-37326549

RÉSUMÉ

OBJECTIVE: Responding to the concern about racial/ethnic disparities (R/ED) in the use of risk assessment instruments (RAIs) in justice systems, previous research has overwhelmingly tested the extent to which RAI scores consistently predict recidivism across race and ethnicity (predictive bias). However, little is known about R/ED in the association between RAI measures and court dispositions (disparate application) for justice-involved youths. This study investigated predictive bias and disparate application of three risk measures-criminal history, social history, and the overall risk level-produced by the Positive Achievement Change Tool (PACT) for White, Black, and Hispanic justice-involved youths. HYPOTHESES: Given the mixed evidence in existing research for predictive bias and lack of evidence for disparate application, we did not make any specific hypothesis but conducted exploratory analyses. From a clinical perspective, however, we anticipated little or no evidence to support predictive bias and disparate application of the PACT among White, Black, and Hispanic youths in the jurisdiction we examined. METHOD: The sample consisted of 5,578 youths (11.4% White, 43.9% Black, and 44.7% Hispanic) who completed the PACT while in the Harris County Juvenile Probation Department, Texas. The outcome variables included recidivism (general and violent reoffending) and court dispositions (deferred adjudication, probation without placement, and probation with placement). We ran a series of moderating binary logistic regression models and moderating ordinal logistic regression models to evaluate predictive bias and disparate application. RESULTS: Race and ethnicity influenced how the criminal history score related to violent recidivism: This compromised the validity of the score as a predictor of recidivism. Moreover, evidence showed that the overall risk of reoffending was associated with harsher sanctioning decisions for Black and Hispanic youths than for White youths. CONCLUSION: Ensuring that RAI results are consistently interpreted and used in informing decisions is as important as ensuring that RAI scores function equally well in predicting recidivism regardless of race and ethnicity. (PsycInfo Database Record (c) 2023 APA, all rights reserved).


Sujet(s)
Criminels , Délinquance juvénile , Récidivisme , Adolescent , Humains , Ethnies , Hispanique ou Latino , Appréciation des risques/méthodes , Blanc ,
8.
J Biol Chem ; 299(6): 104743, 2023 06.
Article de Anglais | MEDLINE | ID: mdl-37100283

RÉSUMÉ

Fc receptors are involved in a variety of physiologically and disease-relevant responses. Among them, FcγRIIA (CD32a) is known for its activating functions in pathogen recognition and platelet biology, and, as potential marker of T lymphocytes latently infected with HIV-1. The latter has not been without controversy due to technical challenges complicated by T-B cell conjugates and trogocytosis as well as a lack of antibodies distinguishing between the closely related isoforms of FcγRII. To generate high-affinity binders specific for FcγRIIA, libraries of designed ankyrin repeat proteins (DARPins) were screened for binding to its extracellular domains by ribosomal display. Counterselection against FcγRIIB eliminated binders cross-reacting with both isoforms. The identified DARPins bound FcγRIIA with no detectable binding for FcγRIIB. Their affinities for FcγRIIA were in the low nanomolar range and could be enhanced by cleavage of the His-tag and dimerization. Interestingly, complex formation between DARPin and FcγRIIA followed a two-state reaction model, and discrimination from FcγRIIB was based on a single amino acid residue. In flow cytometry, DARPin F11 detected FcγRIIA+ cells even when they made up less than 1% of the cell population. Image stream analysis of primary human blood cells confirmed that F11 caused dim but reliable cell surface staining of a small subpopulation of T lymphocytes. When incubated with platelets, F11 inhibited their aggregation equally efficient as antibodies unable to discriminate between both FcγRII isoforms. The selected DARPins are unique novel tools for platelet aggregation studies as well as the role of FcγRIIA for the latent HIV-1 reservoir.


Sujet(s)
Protéines conçues par répétition de motifs ankyrine , Agrégation plaquettaire , Récepteurs du fragment Fc des IgG , Humains , Anticorps/métabolisme , Plaquettes/métabolisme , Protéines conçues par répétition de motifs ankyrine/métabolisme , VIH-1 (Virus de l'Immunodéficience Humaine de type 1) , Isoformes de protéines/métabolisme , Récepteurs du fragment Fc des IgG/métabolisme , Latence virale , Lymphocytes T/virologie
9.
Children (Basel) ; 10(3)2023 Mar 10.
Article de Anglais | MEDLINE | ID: mdl-36980096

RÉSUMÉ

This study assessed the effects of a 12-week afterschool mindfulness-based diet and exercise intervention on mental and physical health in Latinx and Black youth. One hundred forty-eight boys and girls (average age = 10.1 years, SD = 1.3 years; 52% girls; 72.3% Latinx) were randomized to either the experimental group (n = 80) or the control group (n = 68). The experimental group participants engaged in fitness yoga, kickboxing, and/or spinning sessions, and mindfulness practices (e.g., breathing, meditation, and mindful eating) twice per week for 12 weeks. The control group participants engaged in a recreational play session once per week for 12 weeks. All participants completed surveys (demographics, acculturation, anxiety, emotional eating, sleep, and food intake) and had their height, weight, and percent body fat measured pre- and post-intervention. Participants wore an accelerometer for 7 days pre- and post-intervention. Repeated measures analysis of covariance indicated that the experimental group participants reported lower scores in emotional eating, anxiety, and sleep latency post-intervention compared to the control group participants. Conversely, no significant differences were observed in physical activity between the experimental and control group participants post-intervention. These findings indicate that a mindfulness-based intervention has a positive effect on emotional eating, anxiety, and sleep latency among youth of color.

10.
Infection ; 51(4): 1093-1102, 2023 Aug.
Article de Anglais | MEDLINE | ID: mdl-36913112

RÉSUMÉ

PURPOSE: COViK, a prospective hospital-based multicenter case-control study in Germany, aims to assess the effectiveness of COVID-19 vaccines against severe disease. Here, we report vaccine effectiveness (VE) against COVID-19-caused hospitalization and intensive care treatment during the Omicron wave. METHODS: We analyzed data from 276 cases with COVID-19 and 494 control patients recruited in 13 hospitals from 1 December 2021 to 5 September 2022. We calculated crude and confounder-adjusted VE estimates. RESULTS: 21% of cases (57/276) were not vaccinated, compared to 5% of controls (26/494; p < 0.001). Confounder-adjusted VE against COVID-19-caused hospitalization was 55.4% (95% CI: 12-78%), 81.5% (95% CI: 68-90%) and 95.6% (95%CI: 88-99%) after two, three and four vaccine doses, respectively. VE against hospitalization due to COVID-19 remained stable up to one year after three vaccine doses. CONCLUSION: Three vaccine doses remained highly effective in preventing severe disease and this protection was sustained; a fourth dose further increased protection.


Sujet(s)
COVID-19 , Humains , COVID-19/épidémiologie , COVID-19/prévention et contrôle , Vaccins contre la COVID-19 , Études cas-témoins , Études prospectives , , Allemagne/épidémiologie
11.
Assessment ; 30(8): 2373-2386, 2023 12.
Article de Anglais | MEDLINE | ID: mdl-36658778

RÉSUMÉ

This study investigated item- and test-level functioning of the Structured Assessment of Violence Risk in Youth (SAVRY) and differential item functioning (DIF) across gender and race/ethnicity in justice-involved youth (JIY) using item response theory analysis. Participants were 868 JIY (23.7% female; 26.9% White, 50.9% Black, and 22.2% Hispanic) in pre-trial detention centers in Connecticut. Results obtained from the application of the graded response model showed that the SAVRY items were not equally discriminating JIY with varying levels of the latent trait, with "Poor compliance" as the most discriminating item and "History of self-harm or suicide attempts" as the least discriminating item. At the test level, the SAVRY provided precise (reliable) information about the latent trait for the majority of JIY whose latent trait between two standard deviations below and above the mean. Results of DIF revealed that six items operated inconsistently between White, Black, and Hispanic JIY, among which two items also functioned differentially across gender.


Sujet(s)
Tests psychologiques , Violence , Adolescent , Femelle , Humains , Mâle , Connecticut , Hispanique ou Latino , Blanc , , Établissements correctionnels
13.
Vaccine ; 41(2): 290-293, 2023 01 09.
Article de Anglais | MEDLINE | ID: mdl-36509640

RÉSUMÉ

We included 852 patients in a prospectively recruiting multicenter matched case-control study in Germany to assess vaccine effectiveness (VE) in preventing COVID-19-associated hospitalization during the Delta-variant dominance. The two-dose VE was 89 % (95 % CI 84-93 %) overall, 79 % in patients with more than two comorbidities and 77 % in adults aged 60-75 years. A third dose increased the VE to more than 93 % in all patient-subgroups.


Sujet(s)
COVID-19 , Vaccins , Adulte , Humains , Études cas-témoins , COVID-19/prévention et contrôle , Hospitalisation , Hôpitaux , Allemagne/épidémiologie
14.
Dent Mater ; 38(10): 1661-1668, 2022 10.
Article de Anglais | MEDLINE | ID: mdl-36085084

RÉSUMÉ

OBJECTIVES: The determination of the extinction coefficient of human dental enamel to deliver further optical properties of enamel to improve the understanding of light propagation in teeth and to improve restoration materials. METHODS: The extinction coefficient was measured within a spectral range of 300-980 nm using a collimated transmission setup. 35 specimens from 16 donors were examined. The donors were categorized by age and the researched specimen were categorized by tooth type, tooth quality and lateral expansion of the enamel to clarify the influence of these parameters. RESULTS: The obtained spectrally resolved extinction coefficient was accurately described by a power law, which agrees with theoretical scattering models. The results were evaluated with regard to the influence of parameters such as subject age, tooth type, enamel sample quality and enamel width. For this purpose, both the average values of multiple measurements of a single sample in a defined spectral range as well as the curve slope of the averaged results versus wavelength were compared. SIGNIFICANCE: The results provide detailed information about the optical properties of human enamel. The wide spectrum investigated provides important information for the evaluation of the main scatterers and the optical impression under any light condition. However, the deviation of the extinction coefficient varies less between the mean values for the specimens grouped by several parameters than between the specimens themselves within a group. This indicates a unique optical behaviour for every specimen and this requires consideration in the development of artificial materials.


Sujet(s)
Émail dentaire , Dent , Émail dentaire/composition chimique , Humains , Analyse spectrale
15.
Clin Infect Dis ; 75(Suppl 1): S110-S120, 2022 08 15.
Article de Anglais | MEDLINE | ID: mdl-35749674

RÉSUMÉ

BACKGROUND: Comprehensive pathogen genomic surveillance represents a powerful tool to complement and advance precision vaccinology. The emergence of the Alpha variant in December 2020 and the resulting efforts to track the spread of this and other severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern led to an expansion of genomic sequencing activities in Germany. METHODS: At Robert Koch Institute (RKI), the German National Institute of Public Health, we established the Integrated Molecular Surveillance for SARS-CoV-2 (IMS-SC2) network to perform SARS-CoV-2 genomic surveillance at the national scale, SARS-CoV-2-positive samples from laboratories distributed across Germany regularly undergo whole-genome sequencing at RKI. RESULTS: We report analyses of 3623 SARS-CoV-2 genomes collected between December 2020 and December 2021, of which 3282 were randomly sampled. All variants of concern were identified in the sequenced sample set, at ratios equivalent to those in the 100-fold larger German GISAID sequence dataset from the same time period. Phylogenetic analysis confirmed variant assignments. Multiple mutations of concern emerged during the observation period. To model vaccine effectiveness in vitro, we employed authentic-virus neutralization assays, confirming that both the Beta and Zeta variants are capable of immune evasion. The IMS-SC2 sequence dataset facilitated an estimate of the SARS-CoV-2 incidence based on genetic evolution rates. Together with modeled vaccine efficacies, Delta-specific incidence estimation indicated that the German vaccination campaign contributed substantially to a deceleration of the nascent German Delta wave. CONCLUSIONS: SARS-CoV-2 molecular and genomic surveillance may inform public health policies including vaccination strategies and enable a proactive approach to controlling coronavirus disease 2019 spread as the virus evolves.


Sujet(s)
COVID-19 , SARS-CoV-2 , COVID-19/épidémiologie , COVID-19/prévention et contrôle , Génome viral , Génomique , Humains , Phylogenèse , SARS-CoV-2/génétique , Vaccinologie
16.
Vaccines (Basel) ; 10(5)2022 May 17.
Article de Anglais | MEDLINE | ID: mdl-35632550

RÉSUMÉ

The SARS-CoV-2 variant Omicron has spread world-wide and is responsible for rapid increases in infections, including in populations with high vaccination rates. Here, we analysed in the sera of vaccinated individuals the antibody binding to the receptor-binding domain (RBD) of the spike protein and the neutralization of wild-type (WT), Delta (B.1.617.2), and Omicron (B.1.1.529; BA.1) pseudotyped vectors. Although sera from individuals immunized with vector vaccines (Vaxzevria; AZ and COVID-19 Janssen, Ad26.COV2.S; J&J) were able to bind and neutralize WT and Delta, they showed only background levels towards Omicron. In contrast, mRNA (Comirnaty; BNT) or heterologous (AZ/BNT) vaccines induced weak, but detectable responses against Omicron. While RBD-binding antibody levels decreased significantly six months after full vaccination, the SARS-CoV-2 RBD-directed avidity remained constant. However, this still coincided with a significant decrease in neutralization activity against all variants. A third booster vaccination with BNT significantly increased the humoral immune responses against all tested variants, including Omicron. In conclusion, only vaccination schedules that included at least one dose of mRNA vaccine and especially an mRNA booster vaccination induced sufficient antibody levels with neutralization capacity against multiple variants, including Omicron.

17.
Vaccines (Basel) ; 10(5)2022 May 17.
Article de Anglais | MEDLINE | ID: mdl-35632552

RÉSUMÉ

Waning immunity against SARS-CoV-2 and the emergence of variants, especially of the most distant variant, Omicron, affect titers of neutralizing antibodies in the sera of vaccinated individuals. Thus, two vaccinations with the mRNA vaccine BNT162b fail to induce neutralizing antibodies against the Omicron variant. A first booster vaccination increases Omicron-RBD-binding IgG and IgA and neutralizing capacity. In comparison, the Wuhan isolate titers of the Omicron variant binding antibodies are 8.5 lower. After a third vaccination, induction of Omicron-RBD- and Wuhan-RBD-binding antibodies follows the same kinetic. Five to six months after the third vaccination, there are still Omicron-RBD-binding antibodies detectable, but 35.9 percent of the analyzed sera fail to neutralize the Omicron variant, while all sera efficiently neutralize the Delta isolate. In the case of the Wuhan-RBD, a significantly larger number of stable antigen-antibody complexes is formed than in Omicron-RBD. A fourth vaccination with mRNA-1273 temporarily restores levels of Omicron-, Delta- and Wuhan-specific antibodies. Comparing different booster strategies revealed that the breadth of the immune response is not affected by the vaccination regimen. Taken together, these data indicate that booster vaccinations (third and fourth dose) increase the breadth of the immune response, but there is a qualitative difference of antibodies with respect to the stability of antigen-antibody complexes and persistence of antibody titers.

18.
Viruses ; 14(2)2022 02 17.
Article de Anglais | MEDLINE | ID: mdl-35216003

RÉSUMÉ

In light of an increasing number of vaccinated and convalescent individuals, there is a major need for the development of robust methods for the quantification of neutralizing antibodies; although, a defined correlate of protection is still missing. Sera from hospitalized COVID-19 patients suffering or not suffering from acute respiratory distress syndrome (ARDS) were comparatively analyzed by plaque reduction neutralization test (PRNT) and pseudotype-based neutralization assays to quantify their neutralizing capacity. The two neutralization assays showed comparable data. In case of the non-ARDS sera, there was a distinct correlation between the data from the neutralization assays on the one hand, and enzyme-linked immune sorbent assay (ELISA), as well as biophysical analyses, on the other hand. As such, surface plasmon resonance (SPR)-based assays for quantification of binding antibodies or analysis of the stability of the antigen-antibody interaction and inhibition of syncytium formation, determined by cell fusion assays, were performed. In the case of ARDS sera, which are characterized by a significantly higher fraction of RBD-binding IgA antibodies, there is a clear correlation between the neutralization assays and the ELISA data. In contrast to this, a less clear correlation between the biophysical analyses on the one hand and ELISAs and neutralization assays on the other hand was observed, which might be explained by the heterogeneity of the antibodies. To conclude, for less complex immune sera-as in cases of non-ARDS sera-combinations of titer quantification by ELISA with inhibition of syncytium formation, SPR-based analysis of antibody binding, determination of the stability of the antigen-antibody complex, and competition of the RBD-ACE2 binding represent alternatives to the classic PRNT for analysis of the neutralizing potential of SARS-CoV-2-specific sera, without the requirement for a BSL3 facility.


Sujet(s)
Anticorps antiviraux/sang , Convalescence , Sérums immuns/analyse , SARS-CoV-2/immunologie , Glycoprotéine de spicule des coronavirus/sang , Glycoprotéine de spicule des coronavirus/immunologie , Adulte , Sujet âgé , Sujet âgé de 80 ans ou plus , Anticorps neutralisants/immunologie , COVID-19/immunologie , Test ELISA , Femelle , Hospitalisation/statistiques et données numériques , Humains , Sérums immuns/immunologie , Immunité humorale , Mâle , Adulte d'âge moyen , Tests de neutralisation
19.
Allergy ; 77(7): 2053-2066, 2022 07.
Article de Anglais | MEDLINE | ID: mdl-34637150

RÉSUMÉ

BACKGROUND: People suffering from COVID-19 are typically considered non-infectious 14 days after diagnosis if symptoms have disappeared for at least 48 h. We describe three patients who independently acquired their infection. These three patients experienced mild COVID-19 and completely recovered symptomatically within 10 days, but remained PCR-positive in deep pharyngeal samples for at least 38 days. We attempted to isolate virus from pharyngeal swabs to investigate whether these patients still carried infectious virus. METHODS: Infectious virus was amplified in Vero E6 cells and characterized by electron microscopy and WGS. The immune response was investigated by ELISA and peptide arrays. RESULTS: In all three cases, infectious and replication-competent virus was isolated and amplified in Vero E6 cells. Virus replication was detected by RT-PCR and immunofluorescence microscopy. Electron microscopy confirmed the formation of intact SARS-CoV-2 particles. For a more detailed analysis, all three isolates were characterized by whole-genome sequencing (WGS). The sequence data revealed that the isolates belonged to the 20A or 20C clade, and two mutations in ORF8 were identified among other mutations that could be relevant for establishing a long-term infection. Characterization of the humoral immune response in comparison to patients that had fully recovered from mild COVID-19 revealed a lack of antibodies binding to sequential epitopes of the receptor-binding domain (RBD) for the long-term infected patients. CONCLUSION: Thus, a small portion of COVID-19 patients displays long-term infectivity and termination of quarantine periods after 14 days, without PCR-based testing, should be reconsidered critically.


Sujet(s)
COVID-19 , SARS-CoV-2 , Humains , Réplication virale
20.
Allergy ; 77(7): 2080-2089, 2022 07.
Article de Anglais | MEDLINE | ID: mdl-34820854

RÉSUMÉ

BACKGROUND: The mRNA vaccine BNT162b2 (Comirnaty, BioNTech/Pfizer) and the vaccine candidate CVnCoV (Curevac) each encode a stabilized spike protein of SARS-CoV2 as antigen but differ with respect to the nature of the mRNA (modified versus unmodified nucleotides) and the mRNA amount (30 µg versus 12 µg RNA). This study characterizes antisera elicited by these two vaccines in comparison to convalescent sera. METHODS: Sera from BNT162b2 vaccinated healthcare workers, and sera from participants of a phase I trial vaccinated with 2, 4, 6, 8, or 12 µg CVnCoV and convalescent sera from hospitalized patients were analyzed by ELISA, neutralization tests, surface plasmon resonance (SPR), and peptide arrays. RESULTS: BNT162b2-elicited sera and convalescent sera have a higher titer of spike-RBD-specific antibodies and neutralizing antibodies as compared to the CVnCoV-elicited sera. For all analyzed sera a reduction in binding and neutralizing antibodies was found for the lineage B.1.351 variant of concern. SPR analyses revealed that the CVnCoV-elicited sera have a lower fraction of slow-dissociating antibodies. Accordingly, the CVnCoV sera almost fail to compete with the spike-ACE2 interaction. The significance of common VOC mutations K417N, E484K, or N501Y focused on linear epitopes was analyzed using a peptide array approach. The peptide arrays showed a strong difference between convalescent sera and vaccine-elicited sera. Specifically, the linear epitope at position N501 was affected by the mutation and elucidates the escape of viral variants to antibodies against this linear epitope. CONCLUSION: These data reveal differences in titer, neutralizing capacity, and affinity of the antibodies between BNT162b2- and CVnCoV-elicited sera, which could contribute to the apparent differences in vaccine efficacy.


Sujet(s)
COVID-19 , SARS-CoV-2 , Anticorps neutralisants , Anticorps antiviraux , Vaccin BNT162 , COVID-19/thérapie , Essais cliniques de phase I comme sujet , Épitopes , Humains , Immunisation passive , Peptides , ARN messager , ARN viral , Vaccins synthétiques , Vaccins à ARNm , Sérothérapie COVID-19
SÉLECTION CITATIONS
DÉTAIL DE RECHERCHE
...