Mvabea (MVA-mBN226B) / Bavarian Nordic - LARVOL DELTA

Immunogenicity and safety of Ebola vaccines in children: a systematic review and meta-analysis. (PubMed, Int J Infect Dis) - "Ebola vaccines are safe and immunogenic in children. Findings support including children in vaccination campaigns, tailoring protocols to vaccine profiles and outbreak contexts."

Journal • Retrospective data • Ebola Virus Disease • Hematological Disorders • Infectious Disease • Pediatrics

Within-host mathematical models to study antibody kinetics after the prophylactic Ebola vaccine in the Democratic Republic of the Congo. (PubMed, Vaccine) - "While vaccines like Ad26.ZEBOV and MVA-BN-Filo are safe and immunogenic, the dynamics of antibody responses after the two-dose regimen and booster vaccination are not fully understood. This study highlights critical considerations for implementing within-host mechanistic models and the need for robust data to accurately estimate model parameters. Further research is essential to elucidate the decay dynamics of memory B cells and long-lived plasma cells, as these processes play a pivotal role in sustaining antibody-mediated immunity."

Journal • Ebola Virus Disease • Infectious Disease

Heterologous two-dose Ebola vaccine regimen in pregnant women in Rwanda: a randomized controlled phase 3 trial. (PubMed, Nat Med) - P3 | "Ad26.ZEBOV, MVA-BN-Filo did not raise concerns regarding adverse maternal/fetal or neonatal/infant outcomes, had no unexpected safety issues, and induced binding antibody responses in women and offspring through passive transfer. ClinicalTrials.gov registration: NCT04556526 ."

Journal • P3 data • Ebola Virus Disease • Infectious Disease • Small for Gestational Age

Prediction and characterisation of the human B cell response to a heterologous two-dose Ebola vaccine. (PubMed, Nat Commun) - "Using advanced cellular and transcriptomic analyses, we examined B cell responses to the Ad26.ZEBOV, MVA-BN-Filo EVD vaccine. Single-cell analyses further detailed changes in plasma cell frequency, subclass usage, and CDRH3 properties. These results highlight the predictive power of early immune responses, captured through systems immunology, in shaping vaccine-induced B cell immunity."

Journal • Ebola Virus Disease • Infectious Disease

Ad26.ZEBOV, MVA-BN-Filo Vaccination in Children and Adults Previously Vaccinated With Control in the EBOVAC-Salone Study (clinicaltrials.gov) - P2 | N=133 | Completed | Sponsor: London School of Hygiene and Tropical Medicine | Active, not recruiting ➔ Completed | Trial completion date: May 2024 ➔ Oct 2024

Trial completion • Trial completion date • Ebola Virus Disease • Hematological Disorders • Infectious Disease

Therapeutic advances in Marburg virus disease: from experimental treatments to vaccine development. (PubMed, Ann Med Surg (Lond)) - "This work explored ongoing studies on the recent vaccine developments and experimental therapies, such as a recombinant vesicular stomatitis virus (VSV)-based vaccine and MVA-BN-Filo, aiming to combat this deadly infection...MVD has been recently reported in Rwanda in 2024, an African country, and nearly 15 outbreaks of MVD have been reported. This review describes the nature of the MVD, key outbreaks, the virus's pathogenesis, mode of transmission, clinical and laboratory diagnosis, and control and prevention measures to advance MVD treatment, drug development, vaccine creation, and prevention of MVD."

Journal • Review • Hematological Disorders • Infectious Disease

Ebola virus vaccination elicits Ebola virus-specific immune responses without substantial cross-reactivity to other filoviruses. (PubMed, Sci Transl Med) - "The Janssen Ebola virus (EBOV) vaccine consists of the adenovirus type 26 vector encoding the EBOV glycoprotein (GP) (Ad26.ZEBOV) and the modified vaccinia Ankara (MVA) vector encoding GP from EBOV, Sudan virus, and Marburg virus and nucleoprotein from Tai Forest virus (MVA-BN-Filo) administered 8 weeks later. Samples from 48 survivors and 121 contacts from the 2007 Ugandan Bundibugyo virus epidemic also showed minimal cross-reactivity to other filovirus proteins after infection and exposure. The lack of cross-reactivity suggests that different multivalent vaccine candidates are required to provide broad protection across filoviruses."

Journal • Ebola Virus Disease • Human Immunodeficiency Virus • Infectious Disease • CD4

EBO-BOOST: Safety and Immunogenicity of Ervebo® and Zabdeno® Booster Vaccines Against Ebola Virus Following Previous Vaccination with the Zabdeno/Mvabea® or Ervebo® Vaccine Schedules in DRC (clinicaltrials.gov) - P3 | N=624 | Recruiting | Sponsor: Institute of Tropical Medicine, Belgium | Not yet recruiting ➔ Recruiting | Trial primary completion date: Oct 2025 ➔ Oct 2026

Enrollment open • Trial primary completion date • Ebola Virus Disease • Infectious Disease

Contraception use and pregnancy in women receiving a 2-dose Ebola vaccine in Rwanda: A retrospective analysis of UMURINZI vaccination campaign data. (PubMed, PLoS Med) - "Many fertile and sexually active women who sought vaccination during UMURINZI were not using contraception prior to vaccination, and contraceptive method uptake after family planning counseling and method provision was low. Most women who became pregnant after the first vaccination dose did not receive the second dose, thus potentially reducing protection against Ebola. Family planning messaging for this context should be developed and pilot-tested. The estimated risk of spontaneous abortion was similar to previous estimates from Rwanda and other African countries."

Journal • Retrospective data • Cardiovascular • CNS Disorders • Diabetes • Ebola Virus Disease • Epilepsy • Hypertension • Infectious Disease • Long-acting Reversible Contraceptives • Metabolic Disorders • Novel Coronavirus Disease • Obstetrics

Evaluation of waning of IgG antibody responses after rVSVΔG-ZEBOV-GP and Ad26.ZEBOV, MVA-BN-Filo Ebola virus disease vaccines: a modelling study from the PREVAC randomized trial. (PubMed, Emerg Microbes Infect) - P2 | "One year after administration of the vaccine, antibody concentrations were higher in children compared to adults for both vaccines, although with different effect sizes: 1.74-fold higher concentrations (95% confidence interval [CI] [1.48; 2.02]) for children 12-17 years old to 3.10-fold higher concentrations (95% CI [2.58; 3.69]) for those 1-4 years old compared to adults for Ad26.ZEBOV, MVA-BN-Filo versus 1.36-fold (95% CI [1.12; 1.61]) to 1.41-fold (95% CI [1.21; 1.62]) higher at month 12 higher than these values for adults, with relatively small changes from one age category of children to another for rVSVΔG-ZEBOV-GP. Antibody concentrations also differed according to geographical location, pre-vaccination antibody concentration, and sex.In combination with knowledge on memory response, characterization of the major determinants of immune response durability of both vaccinations may guide future EVD control protocols.Trial registration: ClinicalTrials.gov..."

Journal • Ebola Virus Disease • Infectious Disease

Long-term cellular immunity of vaccines for Zaire Ebola Virus Diseases. (PubMed, Nat Commun) - P2 | "Authorized vaccines include Merck's Ervebo (rVSV-ZEBOV) and Johnson & Johnson's two-dose combination (Ad26.ZEBOV/MVA-BN-Filo). Finally, we establish a correlation between EBOV-specific T-cell responses and anti-EBOV IgG responses. Our findings can guide booster vaccination recommendations and help identify populations likely to benefit from revaccination."

Clinical • Journal • Ebola Virus Disease • Infectious Disease • CD4

Delivery and Safety of a Two-Dose Preventive Ebola Virus Disease Vaccine in Pregnant and Non-Pregnant Participants during an Outbreak in the Democratic Republic of the Congo. (PubMed, Vaccines (Basel)) - "Adults, including pregnant women, and children aged ≥1 year old were offered the Ad26.ZEBOV (day 0; dose 1), MVA-BN-Filo (day 56; dose 2) EVD vaccine through an open-label clinical trial. The uptake of the two-dose regimen was high: 15,328/20,408 (75.1%). The vaccine regimen was well-tolerated among the study participants, including pregnant women, although further data, ideally from controlled trials, are needed in this crucial group."

Journal • Ebola Virus Disease • Infectious Disease

Immunogenicity of an Extended Dose Interval for the Ad26.ZEBOV, MVA-BN-Filo Ebola Vaccine Regimen in Adults and Children in the Democratic Republic of the Congo. (PubMed, Vaccines (Basel)) - "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."

Journal • Ebola Virus Disease • Infectious Disease • Novel Coronavirus Disease

Computational mining of B cell receptor repertoires reveals antigen-specific and convergent responses to Ebola vaccination. (PubMed, Front Immunol) - "In response to recent outbreaks, the two dose, heterologous Ad26.ZEBOV/MVA-BN-Filo vaccine regimen was developed and was tested in a large phase II clinical trial (EBL2001) as part of the EBOVAC2 consortium. Our results show striking convergence in VH germline gene usage across participants following the MVA-BN-Filo dose, and provide further evidence of the role of IGHV3-15 and IGHV3-13 antibodies in the B cell response to Ebolavirus glycoprotein. Furthermore, we found that previously described Ebola-specific mAb sequences present in EBOV-AbDab were sufficient to describe at least one of the ten most expanded BCR clonotypes in more than two thirds of our cohort of vaccinees following the boost, providing proof of principle for the utility of computational mining of immune repertoires."

Journal • Ebola Virus Disease • Infectious Disease

Innate and cellular immune response to the Ebola vaccine Ad26.ZEBOV, MVA-BN-Filo: an ancillary study of the EBL2001 phase II trial. (PubMed, J Infect Dis) - "This study provides unique insights into the in vivo contribution of proliferation/cytotoxic CD8+ T cells and inflammation to the Ad26.ZEBOV, MVA-BN-Filo vaccine-induced potency."

Journal • P2 data • Ebola Virus Disease • Infectious Disease • Inflammation • CD8 • CXCL8

Partnership for Research on Ebola VACcinations (clinicaltrials.gov) - P2 | N=4789 | Completed | Sponsor: National Institute of Allergy and Infectious Diseases (NIAID) | Active, not recruiting ➔ Completed | Trial completion date: Jun 2024 ➔ Dec 2023

Trial completion • Trial completion date • Ebola Virus Disease • Infectious Disease

EBO-BOOST: Safety and Immunogenicity of Ervebo® and Zabdeno® Booster Vaccines Against Ebola Virus Following Previous Vaccination With the Zabdeno/Mvabea® or Ervebo® Vaccine Schedules in DRC (clinicaltrials.gov) - P3 | N=624 | Not yet recruiting | Sponsor: Institute of Tropical Medicine, Belgium

Trial completion date • Trial initiation date • Trial primary completion date • Ebola Virus Disease • Infectious Disease

INFANT SAFETY IN A PHASE 3, OPEN-LABEL, RANDOMIZED CLINICAL TRIAL OF A 2-DOSE EBOLA VACCINE IN HEALTHY PREGNANT WOMEN (ESPID 2024) - "Conclusions/Learning Points The Ad26.ZEBOV, MVA-BN-Filo vaccine regimen was considered safe in offspring, with no major safety issues observed. Passive transfer of anti-Ebola virus glycoprotein-specific binding antibodies from mother to offspring was observed, as quantifiable binding antibodies in offspring."

Clinical • P3 data • Ebola Virus Disease • Infectious Disease • Small for Gestational Age

Safety and Immunogenicity of an Accelerated Ebola Vaccination Schedule in People with and without Human Immunodeficiency Virus: A Randomized Clinical Trial. (PubMed, Vaccines (Basel)) - P2 | "The safety and immunogenicity of the two-dose Ebola vaccine regimen MVA-BN-Filo, Ad26.ZEBOV, 14 days apart, was evaluated in people without HIV (PWOH) and living with HIV (PLWH). Findings support continued evaluation of accelerated vaccine schedules for rapid deployment in populations at immediate risk. Trial registration: NCT02598388 (submitted 14 November 2015)."

Clinical • Journal • Ebola Virus Disease • Human Immunodeficiency Virus • Infectious Disease • CD4 • CD8

Use of Ebola Vaccines - Worldwide, 2021-2023. (PubMed, MMWR Morb Mortal Wkly Rep) - "Two licensed vaccines are currently available against Orthoebolavirus zairense, the virus that causes Ebola: the 1-dose rVSVΔG-ZEBOV-GP (ERVEBO [Merck]) and the 2-dose regimen of Ad26.ZEBOV and MVA-BN-Filo (Zabdeno/Mvabea [Johnson & Johnson]). However, because outbreaks since 2021 have been limited and rapidly contained, most doses (139,120; 95%) shipped from the ICG stockpile have been repurposed for preventive vaccination of high-risk groups, compared with 6,570 (5%) used for outbreak response. Repurposing doses for preventive vaccination could be prioritized in the absence of Ebola outbreaks to prevent transmission and maximize the cost-efficiency and benefits of the stockpile."

Journal • Ebola Virus Disease • Infectious Disease

Safety and Immunogenicity of Accelerated Heterologous Two-dose Ebola Vaccine Regimens in Adults With and Without HIV in Africa. (PubMed, Clin Infect Dis) - P2 | "Accelerated 14- and 28-day Ebola vaccine regimens were safe and immunogenic in PWOH and PLWH in Africa."

Journal • Ebola Virus Disease • Human Immunodeficiency Virus • Infectious Disease • CD4

Helminth exposure and immune response to the two-dose heterologous Ad26.ZEBOV, MVA-BN-Filo Ebola vaccine regimen. (PubMed, PLoS Negl Trop Dis) - P2, P3 | "No clear association was found between immune markers of helminth exposure as measured by ELISA and post-vaccination response to the Ebola Ad26.ZEBOV/ MVA-BN-Filo vaccine regimen."

Journal • Ebola Virus Disease • Infectious Disease • CCL11 • CCL2 • IL13 • IL7

Ad26.ZEBOV, MVA-BN-Filo Ebola virus disease vaccine regimen plus Ad26.ZEBOV booster at 1 year versus 2 years in health-care and front-line workers in the Democratic Republic of the Congo: secondary and exploratory outcomes of an open-label, randomised, phase 2 trial. (PubMed, Lancet Infect Dis) - P2 | "Overall, the vaccine regimen and booster dose were well tolerated. A similar and robust humoral immune response was observed for participants boosted 1 year and 2 years after the first dose, supporting the use of the regimen and flexibility of booster dose administration for prophylactic vaccination in at-risk populations."

Journal • P2 data • Ebola Virus Disease • Infectious Disease • Pain

Lot-to-lot consistency, immunogenicity, and safety of the Ad26.ZEBOV, MVA-BN-Filo Ebola virus vaccine regimen: A phase 3, randomized, double-blind, placebo-controlled trial. (PubMed, Hum Vaccin Immunother) - P3 | "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."

Clinical • Journal • P3 data • Ebola Virus Disease • Infectious Disease

Effects of Shock and Vibration on Product Quality during Last-Mile Transportation of Ebola Vaccine under Refrigerated Conditions1. (PubMed, Emerg Infect Dis) - "Analyzing vaccine stability under different storage and transportation conditions is critical to ensure that effectiveness and safety are not affected by distribution. In a simulation of the last mile in the supply chain, we found that shock and vibration had no effect on Ad26.ZEBOV/MVA-BN-Filo Ebola vaccine regimen quality under refrigerated conditions."

Journal • Ebola Virus Disease • Infectious Disease