Identification of early gene expression profiles governing long-lasting antibody responses to the Ebola vaccine Ad26.ZEBOV/MVA-BN-Filo
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ABSTRACT:
PROVIDER: PRJNA973064 | ENA |
REPOSITORIES: ENA
Dataset's files
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| SRR24595000.fastq.gz | Fastqsanger.gz | |||
| SRR24595100.fastq.gz | Fastqsanger.gz | |||
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| SRR24595300.fastq.gz | Fastqsanger.gz | |||
| SRR24595400.fastq.gz | Fastqsanger.gz |
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Project description:Ebolavirus disease (EVD) is a severe hemorrhagic fever with a high fatality rate. In this study, we comprehensively investigated transcriptome profiles at 0, 3 hours, 1 and 7 days after vaccination with Ad26.ZEBOV and MVA-BN-Filo. Three hours after Ad26.ZEBOV injection, we observed an increase in gene abundance related to antigen presentation, sensing, and T- and B-cell receptors. The highest response occurred one day after Ad26.ZEBOV injection, with an increase in the expression of genes for interferon-induced antiviral molecules, monocyte activation, and sensing receptors. This response was mainly shaped by the HESX1, ATF3, ANKRD22, and ETV7 transcription factors. A plasma-cell signature was observed on day 7 post-Ad26.ZEBOV vaccination, with an increase of the abundance of CD138, MZB1, CD38, and CD79A, as well as that of immunoglobulin genes. Importantly, we identified early-expressed genes correlated with the magnitude of the antibody response 21 days after the MVA-BN-Filo and 364 days after Ad26.ZEBOV vaccinations. Our results provide early gene signatures that characterize an effective vaccine antibody response against Ebola.
2024-01-11 | GSE232633 | GEO
Project description:Ebola virus disease (EVD) outbreaks are increasing in frequency — threatening health and wellbeing of affected communities. Early and effective public health measures to manage outbreaks rely on health care and frontline workers; consequently, protecting these at high-risk groups is a key pillar of EVD vaccination strategies. IgG specific to the viral glycoprotein is used as the correlate of protection in recent vaccine licensure. Here, we use contemporary cellular and transcriptomic analyses to dissect B cell responses to the heterologous Ad26.ZEBOV, MVA-BN-Filo Ebola vaccine. We reveal robust plasma cell and persistent B cell memory responses following vaccination. Using machine-learning, trained on blood gene expression post-vaccination, we were able predict the magnitude of antibody responses. Moreover, we described a B cell receptor CDRH3 sequence which was exclusively seen post-vaccination that is similar to known Ebola GP-binding antibody sequences. Single cell analysis was used to further characterise changes to plasma cell frequency, subclass usage and CDRH3 properties, following vaccination. These results demonstrate that early immune responses —captured in blood using systems immunology approaches — are delineative and predictive of B cell responses to vaccination.
2025-06-13 | GSE273114 | GEO
Project description:Phenotypic and transcriptomic characterisation of the human B cell response to a novel Ebola vaccine regimen (Ad26.ZEBOV, MVA-BN-Filo)
| PRJNA1140197 | ENA
Project description:Without clinical efficacy data, vaccine protective effect may be extrapolated from animals to humans using an immunologic marker that correlates with protection in animals. This immunobridging approach was used for the two-dose Ebola vaccine regimen Ad26.ZEBOV, MVA-BN-Filo. Ebola virus (EBOV) glycoprotein binding antibody data obtained from 764 vaccinated healthy adults in five clinical studies (NCT02416453, NCT02564523, NCT02509494, NCT02543567, NCT02543268) were used to calculate mean predicted survival probability (with preplanned 95% confidence interval [CI]). We used a logistic regression model based on EBOV glycoprotein binding antibody responses in vaccinated non-human primates (NHPs) and NHP survival after EBOV challenge. While the protective effect of the vaccine regimen in humans can be inferred in this fashion, the extrapolated survival probability cannot be directly translated into vaccine efficacy. The primary immunobridging analysis evaluated the lower limit of the CI against predefined success criterion of 20% and passed with mean predicted survival probability of 53.4% (95% CI: 36.7-67.4).
| S-EPMC9712521 | biostudies-literature
Project description:The persistence of the long-term immune response induced by the heterologous Ad26.ZEBOV, MVA-BN-Filo two-dose vaccination regimen against Ebola has been investigated in several clinical trials. Longitudinal data on IgG-binding antibody concentrations were analyzed from 487 participants enrolled in six Phase I and Phase II clinical trials conducted by the EBOVAC1 and EBOVAC2 consortia. A model based on ordinary differential equations describing the dynamics of antibodies and short- and long-lived antibody-secreting cells (ASCs) was used to model the humoral response from 7 days after the second vaccination to a follow-up period of 2 years. Using a population-based approach, we first assessed the robustness of the model, which was originally estimated based on Phase I data, against all data. Then we assessed the longevity of the humoral response and identified factors that influence these dynamics. We estimated a half-life of the long-lived ASC of at least 15 years and found an influence of geographic region, sex, and age on the humoral response dynamics, with longer antibody persistence in Europeans and women and higher production of antibodies in younger participants.
| S-EPMC10632397 | biostudies-literature
Project description:In this prospective, observational study (ClinicalTrials.gov Identifier: NCT02661464), long-term safety information was collected from participants previously exposed to the Ebola vaccines Ad26.ZEBOV and/or MVA-BN-Filo while enrolled in phase 1, 2, or 3 clinical studies. The study was conducted at 15 sites in seven countries (Burkina Faso, France, Kenya, Tanzania, Uganda, the United Kingdom, and the United States). Adult participants and offspring from vaccinated female participants who became pregnant (estimated conception ≤28 days after vaccination with MVA-BN-Filo or ≤3 months after vaccination with Ad26.ZEBOV) were enrolled. Adults were followed for 60 months after their first vaccination, and children born to female participants were followed for 60 months after birth. In the full analysis set (n = 614 adults; median age [range]: 32.0 [18-65] years), 49 (8.0%) had ≥1 serious adverse event (SAE); the incidence rate of any SAE was 27.4 per 1000 person-years (95% confidence interval: 21.0, 35.2). The unrelated SAEs of malaria were reported in the two infants in the full analysis set, aged 11 and 18 months; both episodes were resolved. No deaths or life-threatening SAEs occurred during the study. Overall, no major safety issues were identified; one related SAE was reported. These findings support the long-term clinical safety of the Ad26.ZEBOV and MVA-BN-Filo vaccines.
| S-EPMC10892482 | biostudies-literature
Project description:BackgroundFrom 2019 to 2021, Rwandan residents of the border with the Democratic Republic of the Congo were offered the Ad26.ZEBOV (adenovirus type 26 vector vaccine encoding Ebola virus glycoprotein) and MVA-BN-Filo (modified vaccinia virus Ankara vector vaccine, encoding glycoproteins from Ebola, Sudan, Marburg, and nucleoprotein from Tai Forest viruses) Ebola vaccine regimen.MethodsNonpregnant persons aged ≥2 years were eligible. Unsolicited adverse events (UAEs) were reported through phone calls or visits, and serious adverse events (SAEs) were recorded per International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use guidelines.ResultsFollowing Ad26.ZEBOV, UAEs were reported by 0.68% of 216 113 vaccinees and were more common in younger children (aged 2-8 years, 1.2%) compared with older children (aged 9-17 years, 0.4%) and adults (aged ≥18 years, 0.7%). Fever and headache were the most reported symptoms. All 17 SAEs related to vaccine were in children aged 2-8 years (10 postvaccination febrile convulsions ± gastroenteritis and 7 fever and/or gastroenteritis). The incidence of febrile seizures was 8 of 26 062 (0.031%) prior to initiation of routine acetaminophen in December 2020 and 2 of 15 897 (0.013%) thereafter. Nonobstetric SAEs were similar in males and females. All 20 deaths were unrelated to vaccination. Young girls and adult women with UAEs were less likely to receive the second dose than those without UAEs. Seven unrelated SAEs occurred in 203 267 MVA-BN-Filo recipients.ConclusionsPostvaccination febrile convulsions in young children were rare but not previously described after Ad26.ZEBOV and were reduced with routine acetaminophen. The regimen was otherwise safe and well-tolerated.
| S-EPMC9833427 | biostudies-literature
Project description:BackgroundMalaria 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.MethodsIn 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).ResultsA 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).ConclusionsThe 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.
| S-EPMC9617582 | biostudies-literature
Project description:This phase-3, double-blind, placebo-controlled study (NCT04228783) evaluated lot-to-lot consistency of the Ad26.ZEBOV, MVA-BN-Filo Ebola vaccine regimen. Participants were randomized (6:6:6:1) to receive the two-dose regimen from three consecutively manufactured lots of Ad26.ZEBOV on Day 1 paired with three consecutively manufactured lots of MVA-BN-Filo on Day 57 (Groups 1-3) or two doses of placebo (Group 4). An additional cohort also received an Ad26.ZEBOV booster or placebo 4 months post-dose 2. Equivalence of the immunogenicity at 21 days post-dose 2 between any two groups was demonstrated if the 95% confidence interval (CI) of the Ebola virus glycoprotein (EBOV GP)-binding antibody geometric mean concentration (GMC) ratio was entirely within the prespecified margin of 0.5-2.0. Lot-to-lot consistency (i.e., consecutive lots can be consistently manufactured) was accomplished if equivalence was shown for all three pairwise comparisons. Results showed that the primary objective in the per-protocol immunogenicity subset (n = 549) was established for each pairwise comparison (Group 1 vs 2: GMC ratio = 0.9 [95% CI: 0.8, 1.1], Group 1 vs 3: 0.9 [0.8, 1.1], Group 2 vs 3: 1.0 [0.9, 1.2]). Equivalence of the three groups for the Ad26.ZEBOV component only was also demonstrated at 56 days post-dose 1. EBOV GP-binding antibody responses (post-vaccination concentrations >2.5-fold from baseline) were observed in 419/421 (99.5%) vaccine recipients at 21 days post-dose 2 and 445/460 (96.7%) at 56 days post-dose 1. In the booster cohort (n = 39), GMCs increased 9.0- and 11.8-fold at 7 and 21 days post-booster, respectively, versus pre-booster. Ad26.ZEBOV, MVA-BN-Filo was well tolerated, and no safety issues were identified.
| S-EPMC10965106 | biostudies-literature
Project description:During the 2018-2020 Ebola virus disease outbreak in Democratic Republic of the Congo, a phase 3 trial of the Ad26.ZEBOV, MVA-BN-Filo Ebola vaccine (DRC-EB-001) commenced in Goma, with participants being offered the two-dose regimen given 56 days apart. Suspension of trial activities in 2020 due to the COVID-19 pandemic led to some participants receiving a late dose 2 outside the planned interval. Blood samples were collected from adults, adolescents, and children prior to their delayed dose 2 vaccination and 21 days after, and tested for IgG binding antibodies against Ebola virus glycoprotein using the Filovirus Animal Nonclinical Group (FANG) ELISA. Results from 133 participants showed a median two-dose interval of 9.3 months. The pre-dose 2 antibody geometric mean concentration (GMC) was 217 ELISA Units (EU)/mL (95% CI 157; 301) in adults, 378 EU/mL (281; 510) in adolescents, and 558 EU/mL (471; 661) in children. At 21 days post-dose 2, the GMC increased to 22,194 EU/mL (16,726; 29,449) in adults, 37,896 EU/mL (29,985; 47,893) in adolescents, and 34,652 EU/mL (27,906; 43,028) in children. Participants receiving a delayed dose 2 had a higher GMC at 21 days post-dose 2 than those who received a standard 56-day regimen in other African trials, but similar to those who received the regimen with an extended interval.
| S-EPMC11359010 | biostudies-literature