Zabdeno (Ad26.ZEBOV) and Mvabea (MVA-BN-Filo) Ebola Vaccine Description
The new Ebola prevention vaccine therapy consists of 2 components, Zabdeno (Ad26.ZEBOV) and Mvabea (MVA-BN-Filo). Zabdeno is given first and Mvabea is administered approximately 8-weeks later as a booster. The prime-boost vaccination method is an established approach for the prevention of infectious diseases.
As protection against Ebola virus disease (EVD) is considered to be of major public health interest, Zabdeno and Mvabea were evaluated under European Medicines Agency (EMA) accelerated assessment mechanism, a tool which aims to speed up patients' access to new medicines if there is an unmet medical need.
As a precautionary measure, a Zabdeno booster vaccination should be considered for individuals at imminent risk of exposure to Ebola virus, for example, healthcare professionals and those living in or visiting areas with an ongoing Ebola virus disease outbreak, who completed the Zabdeno, Mvabea 2-dose primary vaccination regimen more than 4-months ago.
On May 29, 2020, the Europian Medicines Agency (EMA) human medicines committee (CHMP) recommended granting Zabdeno and Mvabea a positive opinion for marketing authorizations under exceptional circumstances because the applicant was able to demonstrate that it is not possible to conduct a randomized controlled study that might generate comprehensive clinical data on the efficacy of the new Ebola vaccine even after authorization.
This was considered acceptable in light of the ongoing Ebola outbreak and its high mortality rates.
Developed by Janssen, Zabdeno (Ad26.ZEBOV) is a monovalent vaccine designed to provide active specific acquired immunity to the Ebola virus. The vaccine is based on an adenovirus type 26 (Ad26) vector expressing the glycoprotein (GP) of the Ebola virus Mayinga variant. Janssen has rapidly advanced the development of the vaccine with multiple clinical Phase 1, 2, and 3 trials ongoing in parallel in healthy adults, children, elderly and immunocompromised populations across Europe, USA, and Africa with the goal of ultimately registering the vaccine.
Mvabea (MVA-BN-Filo) is a multivalent vaccine preparation designed to provide active acquired immunity to the Sudan virus, the Ebola virus, the Marburg virus, and the Tai Forest virus (formerly known as Côte d’Ivoire ebolavirus).
The initial development of the Mvabea (MVA-BN-Filo) vaccine was sponsored by the U.S. National Institutes of Health and is now managed by Janssen, a Johnson & Johnson company, who licensed MVA-BN Filo for use from Bavarian Nordic in a prime-boost vaccine regimen together with their adenovirus-based vaccine candidate, Ad26.ZEBOV.
These vaccines both use a viral vector approach, where a virus is genetically modified so that it cannot replicate but is used to safely express key proteins of the target virus, in this case, the Ebola virus.
Global partners on the vaccine program also include the Biomedical Advanced Research and Development Authority and the National Institutes of Health.
As a result of these collaborations, more than 6,500 individuals have now participated in clinical studies for the Ebola vaccine across the U.S., Europe, and Africa. So far, the data from these studies suggest that the vaccine stimulates a robust immune response and has a favorable safety profile.
Janssen has also assembled a stockpile of 1.5 million vaccine regimens for potential use in public health emergencies.
The applicant for both Zabdeno and Mvabea is Janssen-Cilag International N.V.
Zabdeno (Ad26.ZEBOV) and Mvabea (MVA-BN-Filo) Ebola Vaccine Indication
Ad26.ZEBOV / MVA-BN-Filo is indicated to provide an active acquired immunity Ebola virus. Clinical results so far reported indicate that Ad26.ZEBOV prime immunization readily induces an immune response which is enhanced further by MVA-BN-Filo boosting, inducing a durable immunity to Ebola Zaire, and that both the prime and boost are well tolerated with a good safety profile.
Janssen’s investigational Ebola vaccine regimen is specifically designed to support preventive vaccination in countries that are at risk of Ebola outbreaks, as well as for other at-risk groups such as healthcare workers, Biosafety Level 4 (BSL-4) lab workers, the military deployed from other countries, airport staff and visitors to high-risk countries.
This prophylactic 2-dose regimen is therefore not suitable for an outbreak response where immediate protection is necessary.
The most recent Ebola outbreak, the 10th outbreak of Ebola virus disease in the Democratic Republic of the Congo (DRC) has been ongoing since August 2018. This is the largest-ever outbreak reported in the country and the world's second-largest in history. It has been declared a Public Health Emergency of International Concern by the WHO on July 17, 2019.
Zabdeno (Ad26.ZEBOV) and Mvabea (MVA-BN-Filo) Ebola Vaccine Dosage
Heterologous 2-dose vaccination with Ad26.ZEBOV and MVA-BN-Filo against the Ebola virus are well tolerated and immunogenic in healthy volunteers. The vaccine candidate is administered as an intramuscular injection.
A study published by The Lancet on November 17, 2020, found 'the two-dose heterologous regimen with Ad26.ZEBOV and MVA-BN-Filo were safe, well-tolerated, and immunogenic, with humoral and cellular immune responses persisting for 1 year after vaccination. Taken together, these data support the intended prophylactic indication for the vaccine regimen. This study was funded by the Innovative Medicines Initiative and Janssen Vaccines & Prevention BV.
Zabdeno (Ad26.ZEBOV) and Mvabea (MVA-BN-Filo) Ebola News
November 17, 2020 - Study published by The Lancet: Vaccine innovation spurred by the long wait for an Ebola virus vaccine. Currently, the rVSV-based vaccine is used to immunize at-risk individuals during the ongoing Ebola virus outbreaks to limit the spread of the disease. However, immunization of specific populations (eg, health-care workers) in endemic countries outside of outbreak epicenters could reduce the likelihood of amplification from spillover events in humans.
July 1, 2020 - The European Commission adopted the decision granting marketing authorizations to the company Janssen, a Johnson & Johnson company, for a vaccine against Ebola. The authorization was granted in one month, further demonstrating the Commission's commitment to placing the protection of public health as a priority. The new Ebola vaccine, which consists of two components, called Zabdeno and Mvabea, had been in development with the support of the Commission. This decision follows a recommendation from the European Medicines Agency, which has assessed the benefits and risks of the vaccine.
July 1, 2020 - Johnson & Johnson today announced that the European Commission has granted Marketing Authorisation for its Janssen Pharmaceutical Companies’ Ebola vaccine regimen for the prevention of Ebola Virus Disease. Janssen’s Ebola vaccine regimen is indicated for active immunization for the prevention of Ebola Virus Disease caused by the Zaire ebolavirus species in individuals aged one year and above. The regimen includes Ad26.ZEBOV as the first dose, based on Janssen’s AdVac® viral vector technology, and MVA-BN-Filo as the second dose, based on Bavarian Nordic’s MVA-BN® technology, administered approximately eight weeks later.
June 12, 2020 - Bavarian Nordic A/S announced that the Company has entered into a new supply contract with Janssen Vaccines & Prevention B.V., part of the Janssen Pharmaceutical Companies of Johnson & Johnson valued at USD 13.9 million. Under the contract, Bavarian Nordic will manufacture and deliver bulk drug substance of its MVA-BN® Filo vaccine, which Janssen has licensed as part of its Ebola vaccine regimen.
May 29, 2020 – Johnson & Johnson announced that its Janssen Pharmaceutical Companies received a positive opinion from the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) for its investigational Ebola vaccine regimen for the prevention of the Ebola Virus Disease caused by the Zaire ebolavirus species. Two Marketing Authorisation Applications (MAAs) were submitted to the EMA in support of the vaccines in the 2-dose regimen (Ad26.ZEBOV, MVA-BN-Filo).
May 29, 2020 - Pending the final approval by the European Commission of the MVA-BN Filo vaccine, Bavarian Nordic would be eligible to receive a milestone payment of USD 10 million under the license agreement with Janssen. Bavarian Nordic and Janssen entered an agreement in 2014, under which MVA-BN Filo was licensed to Janssen as part of their commitment to developing an Ebola vaccine regimen. Under the agreement, Bavarian Nordic also manufactured a significant amount of vaccines.
May 15, 2020 - Ebola outbreak in the western section of the Democratic Republic of the Congo.
November 7, 2019 - The Janssen division of Johnson & Johnson announced it had filed for two approvals from European Medicines Agency (EMA) for its 2-dose prime-boost Ebola Zaire protective vaccine regimen. In September 2019, the EMA’s Committee for Medicinal Products for Human Use (CHMP) granted an Accelerated Assessment for these applications.
October 31, 2019 - Bavarian Nordic A/S announced that its partner Janssen Pharmaceutical Companies of Johnson & Johnson will donate up to 500,000 doses of its investigational Ebola vaccine regimen to support vaccination efforts in the Democratic Republic of the Congo.
September 21, 2019 – Authorities in the Democratic Republic of Congo said ‘they plan to introduce a 2nd experimental vaccine to counter the ongoing Ebola Zaire outbreak.
April 19, 2019 - A phase 1 study of healthy volunteers, immunization with Ad26.ZEBOV or MVA-BN-Filo did not result in any vaccine-related serious adverse events. An immune response was observed after primary immunization with Ad26.ZEBOV; boosting by MVA-BN-Filo resulted in sustained elevation of specific immunity.
March 14, 2017 - Immune Responses to Novel Adenovirus Type 26 and Modified Vaccinia Virus Ankara–Vectored Ebola Vaccines at 1 Year.
September 12, 2016 – Bavarian Nordic A/S announced that Janssen Vaccines & Prevention B.V. (Janssen) has completed a submission to the World Health Organization (WHO) for Emergency Use Assessment and Listing (EUAL) for its investigational preventive Ebola prime-boost vaccine regimen, which includes Bavarian Nordic’s MVA-BN® Filo vaccine.
October 22, 2014 – Bavarian Nordic A/S announced a global license and supply agreement for its MVA-BN Filovirus (Ebola and Marburg) vaccine candidate with Crucell Holland B.V., one of the Janssen Pharmaceutical Companies of Johnson & Johnson.
Zabdeno (Ad26.ZEBOV) and Mvabea (MVA-BN-Filo) Ebola Vaccine Clinical Trials
The ability to make the immune system respond to the virus after vaccination with Zabdeno and Mvabea was studied in a total of 3,367 adults, adolescents and children who participated in five clinical studies conducted in Europe, Africa, and the USA. These studies demonstrated that the vaccine regimen is safe and could induce an immune response against the Ebola virus.
Efficacy data in humans has been extrapolated from animal studies. The exact level of protection provided by the vaccine regimen is however unknown.
Clinical Trial NCT04028349: Ebola Vaccine Trial (Ad26.ZEBOV/MVA-BN-Filo) (Recruiting)
- This is an interventional, single-arm, open-label, non-randomized, phase II study to accumulate additional data on immunogenicity and safety of Ad26.ZEBOV/MVA-BN®-Filo against Ebola virus disease.
- It also has a qualitative component to better understand knowledge about Ebola virus disease and the perception and attitudes towards the vaccine amongst participants (Healthcare and Frontline workers).
Clinical Trial NCT02376426: A Phase 1 Study to Evaluate the Safety and Immunogenicity of Heterologous Prime-Boost Ebola Vaccine Regimens in Healthy Participants
- This is a randomized placebo-controlled, double-blind study evaluating the safety, tolerability, and immunogenicity of MVA-BN-Filo and Ad26.ZEBOV administered in different sequences and schedules to healthy adult participants.
- The study consists of a screening period of up to 28 days, a vaccination period in which participants will be vaccinated at Baseline [Day 1] followed by a boost on Day 29 or 57 and a post-boost follow-up until all participants have had their 21-day post-boost visit (Day 50 or Day 78).
- The participants who received the active vaccine will enter a long-term follow-up.
- The total duration of the study will be about 1 year for participants who received the vaccine and about 3 months for participants who received a placebo. Immunogenicity and safety will be monitored during the study.
Clinical Trial NCT03929757: A Phase 2 Study of 2-dose Vaccination Regimen of Ad26.ZEBOV and MVA-BN-Filo in Infants
- The purpose of this study is to assess the safety and reactogenicity of a heterologous 2-dose regimen utilizing Ad26.ZEBOV (first vaccination; Dose 1) and MVA-BN-Filo (second vaccination; Dose 2) administered intramuscularly (IM) on Days 1 and 57, respectively.
Clinical Trial NCT02543567: A Phase 3 Study to Evaluate A Range of Dose Levels of Ad26.ZEBOV and MVA‐BN‐Filo in Healthy Adult Participants
- This is a randomized, double‐blind, placebo‐controlled, parallel‐group, multicenter study to evaluate the safety and immunogenicity of Ad26.ZEBOV and MVA‐BN‐Filo at different dose levels, administered to healthy adult participants.
- The study consists of a screening period of up to 6 weeks, vaccinations on Day 1 and Day 57, and a post‐vaccination phase until the 6 months post‐boost visit (Day 237).
- The participants will be randomized at baseline (on Day 1) in a 2:2:2:1 ratio to Groups 1, 2, 3, and 4. Safety will be monitored throughout the study.