Safety and Immunogenicity of a 2-Dose Heterologous Vaccination Regimen With Ad26.ZEBOV and MVA-BN-Filo Ebola Vaccines: 12-Month Data From a Phase 1 Randomized Clinical Trial in Uganda and Tanzania.

BACKGROUND: Ebola vaccine development was accelerated in response to the 2014 Ebola virus infection outbreak. This phase 1 study (VAC52150EBL1004) assessed safety, tolerability, and immunogenicity of heterologous 2-dose Ad26.ZEBOV, MVA-BN-Filo vaccination regimens in the Lake Victoria Basin of Tanzania and Uganda in mid-level altitude, malaria-endemic settings. METHODS: Healthy volunteers aged 18-50 years from Tanzania (n = 25) and Uganda (n = 47) were randomized to receive placebo or active vaccination with Ad26.ZEBOV or MVA-BN-Filo (first vaccination), followed by MVA-BN-Filo or Ad26.ZEBOV (second vaccination) dose 2, respectively, with intervals of 28 or 56 days. RESULTS: Seventy-two adults were randomized to receive vaccine (n = 60) or placebo (n = 12). No vaccine-related serious adverse events were reported. The most frequent solicited local and systemic adverse events were injection site pain (frequency, 70%, 66%, and 42% per dose for MVA-BN-Filo, Ad26.ZEBOV, and placebo, respectively) and headache (57%, 56%, and 46%, respectively). Adverse event patterns were similar among regimens. Twenty-one days after dose 2, 100% of volunteers demonstrated binding antibody responses against Ebola virus glycoprotein, and 87%-100% demonstrated neutralizing antibody responses. Ad26.ZEBOV dose 1 vaccination induced more-robust initial binding antibody and cellular responses than MVA-BN-Filo dose 1 vaccination. CONCLUSIONS: Heterologous 2-dose vaccination with Ad26.ZEBOV and MVA-BN-Filo against Ebola virus is well tolerated and immunogenic in healthy volunteers. CLINICAL TRIALS REGISTRATION: NCT02376400

Asymptomatic Malaria Infection and the Immune Response to the 2-Dose Ad26.ZEBOV, MVA-BN-Filo Ebola Vaccine Regimen in Adults and Children

Background Malaria infection affects the immune response to some vaccines. As Ebola virus (EBOV) outbreaks have occurred mainly in malaria-endemic countries, we have assessed whether asymptomatic malaria affects immune responses to the 2-dose Ad26.ZEBOV, MVA-BN-Filo Ebola vaccine regimen. Methods In this sub-study of the EBOVAC-Salone Ebola vaccine trial in Sierra Leone, malaria microscopy was performed at the time of Ebola vaccination. Participants with symptomatic malaria were treated before vaccination. Ebola vaccine responses were assessed post-dose 1 (day 57) and post-dose 2 (day 78) by the EBOV glycoprotein FANG enzyme-linked immunosorbent assay (ELISA), and responses expressed as geometric mean concentrations (GMCs). Geometric mean ratios (GMRs) of the GMCs in malaria-positive versus malaria-negative participants were derived with 95% confidence intervals (CIs). Results A total of 587 participants were studied, comprising 188 adults (≥18 years) and 399 children (in age groups of 12–17, 4–11, and 1–3 years). Asymptomatic malaria was observed in 47.5% of adults and 51.5% of children on day 1. Post-dose 1, GMCs were lower in 1–3-year-old malaria-positive compared with malaria-negative children (age group–specific GMR, .56; 95% CI, .39–.81) but not in older age groups. Post-dose 2, there was no consistent effect of malaria infection across the different age groups but there was a trend toward a lower response (GMR, .82; 95% CI, .67–1.02). Conclusions The Ad26.ZEBOV, MVA-BN-Filo Ebola vaccine regimen is immunogenic in participants with asymptomatic malaria. Therefore, it is not necessary to screen for asymptomatic malaria infection prior to vaccination with this regimen

Safety and immunogenicity of the two-dose heterologous Ad26.ZEBOV and MVA-BN-Filo Ebola vaccine regimen in infants: a phase 2, randomised, double-blind, active-controlled trial in Guinea and Sierra Leone.

BACKGROUND: This study assessed the safety and immunogenicity of the Ad26.ZEBOV and MVA-BN-Filo Ebola virus (EBOV) vaccine regimen in infants aged 4-11 months in Guinea and Sierra Leone. METHODS: In this phase 2, randomised, double-blind, active-controlled trial, we randomly assigned healthy infants (1:1 in a sentinel cohort, 5:2 for the remaining infants via an interactive web response system) to receive Ad26.ZEBOV followed by MVA-BN-Filo (Ebola vaccine group) or two doses of meningococcal quadrivalent conjugate vaccine (control group) administered 56 days apart. Infants were recruited at two sites in west Africa: Conakry, Guinea, and Kambia, Sierra Leone. All infants received the meningococcal vaccine 8 months after being randomly assigned. The primary objective was safety. The secondary objective was immunogenicity, measured as EBOV glycoprotein-binding antibody concentration 21 days post-dose 2, using the Filovirus Animal Non-Clinical Group ELISA. This study is registered with ClinicalTrials.gov (NCT03929757) and the Pan African Clinical Trials Registry (PACTR201905827924069). FINDINGS: From Aug 20 to Nov 29, 2019, 142 infants were screened and 108 were randomly assigned (Ebola vaccine n=75; control n=33). The most common solicited local adverse event was injection-site pain (Ebola vaccine 15 [20%] of 75; control four [12%] of 33). The most common solicited systemic adverse events with the Ebola vaccine were irritability (26 [35%] of 75), decreased appetite (18 [24%] of 75), pyrexia (16 [21%] of 75), and decreased activity (15 [20%] of 75). In the control group, ten (30%) of 33 had irritability, seven (21%) of 33 had decreased appetite, three (9%) of 33 had pyrexia, and five (15%) of 33 had decreased activity. The frequency of unsolicited adverse events was 83% (62 of 75 infants) in the Ebola vaccine group and 85% (28 of 33 infants) in the control group. No serious adverse events were vaccine-related. In the Ebola vaccine group, EBOV glycoprotein-binding antibody geometric mean concentrations (GMCs) at 21 days post-dose 2 were 27 700 ELISA units (EU)/mL (95% CI 20 477-37 470) in infants aged 4-8 months and 20 481 EU/mL (15 325-27 372) in infants aged 9-11 months. The responder rate was 100% (74 of 74 responded). In the control group, GMCs for both age groups were less than the lower limit of quantification and the responder rate was 3% (one of 33 responded). INTERPRETATION: Ad26.ZEBOV and MVA-BN-Filo was well tolerated and induced strong humoral responses in infants younger than 1 year. There were no safety concerns related to vaccination. FUNDING: Janssen Vaccines & Prevention and Innovative Medicines Initiative 2 Joint Undertaking. TRANSLATION: For the French translation of the abstract see Supplementary Materials section

The effect of immigrant status on changes in student achievement and relation with teachers in secondary school: A multivariate growth curve model

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Multilevel analysis of the factors affecting mathematics achievement of First Year Secondary School students in Uganda

This study explores the sources of variability in mathematics achievement for Ugandan students at the student-, classroom- and school-level, based on the international research literature. The mathematics scores and questionnaire responses of 4819 First Year secondary students(about 14-15 years) from 78 classes of 49 schools were analyzed. A three-level multilevel linear modeling was used. The results indicate that out of the total variance in mathematics achievement, the relevant factors could explain 68.49%, 14.07% and 17.44% , respectively, of student-, classroom- and school-level differences. For student-level factors, gender, prior mathematics achievement, attitude toward mathematics were significant predictors of achievement. For classroom-level factors, class-mean of prior math achievement and of students' perception of good classroom assessment were significant predictors. For school-level factors, school-mean of students' perception of good classroom assessment and of prior math achievement had significant association with math achievement.status: publishe

The impact of coding time on the estimation of school effects

Multilevel growth curve models are becoming invaluable in educational research because they model changes in student outcomes efficiently. The coding of the time variable in these models plays a crucial role as illustrated in this study for the case of a three-level quadratic growth curve model. This paper shows clearly how the choice of a time coding affects school effects estimates and their interpretation. A new definition for school effects for growth curve models with random intercepts and slopes is proposed. This study recommends that the choice of a time coding should not only be based on the ease of interpretation and model convergence but also on its consequences on the student status and growth parameter estimates. The current application illustrates that in general the school effects for student growth in well-being and language achievement in secondary school, are greater for student growth than for student status. © 2011 Springer Science+Business Media B.V.status: publishe

Growth in reading comprehension and mathematics achievement in primary school: A bivariate transition multilevel growth curve model approach

zie ook http://medcraveonline.com/BBIJ/BBIJ-05-00137.pdfstatus: publishe

School effects in growth curve models

The objective of this study is to give an overview of the literature on the size of school effects in growth curve models. These studies have led to contradictory results. Some studies found that school effects on student growth are larger than school effects on student status, while others have found exactly the opposite. The current study will employ a structured literature review to investigate whether certain study characteristics can explain these different results.status: publishe

Double serial correlation for multilevel growth curve models

Multilevel growth curve models for repeated measures data have become increasingly popular and stand as a flexible tool for investigating longitudinal change in students’ outcome variables. In addition, these models allow the estimation of school effects on students’ outcomes though making strong assumptions about the serial independence of level-1 residuals. This paper introduces a method which takes into account the serial correlation of level-1 residuals and also introduces such serial correlation at level-2 in a complex double serial correlation (DSC) multilevel growth curve model. The results of this study from both real and simulated data show a great improvement in school effects estimates compared to those that have previously been found using multilevel growth curve models without correcting for DSC for both the students’ status and growth criteria.DOI: 10.1007/s11135-011-9598-7status: publishe

Multilevel analysis of the factors affecting mathematics achievement of first-year secondary school

This study explores the sources of variability in mathematics achievement for Ugandan students at student, classroom, and school level, inspired by international research. Mathematics scores at the beginning and at the end of school-year 2012, and questionnaire responses of 4819 first-year secondary students (grade 7, 14-15 years old) from 78 classes in 49 schools were analysed, using a three-level linear regression model. Results of a multilevel analysis show that, out of the total variance in mathematics achievement, 68.4%, 14.2%, and 17.4% is situated at student, classroom, and school level, respectively. Socio-economic status, gender, prior mathematics achievement, parental support, class mean of prior math achievement and of students' perception of good classroom assessment, and school mean of parental support were significant predictors of math achievement. The relevant factors explained 7.5%, 63.9%, and 77.4% of the student-, classroom-, and school-level differences respectively.status: publishe