Ebola Vaccine Regimen Zabdeno® and Mvabea® April 2023
The Johnson & Johnson (J&J) Janssen Ebola prevention vaccine therapy consists of two components, Zabdeno® (Ad26.ZEBOV) and Mvabea® (MVA-BN-Filo). Zabdeno is given first, and Mvabea is administered approximately 8-weeks later as a vaccine booster. This prime-boost vaccination method is an established approach for preventing infectious diseases during Ebola outbreaks for individuals at risk of exposure and preventively before episodes, says J&J.
Developed by J&J's Janssen division, 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 Ebola virus Mayinga variant's glycoprotein. Janssen has rapidly advanced the vaccine's development with multiple clinical Phase 1, 2, and 3 trials in parallel in healthy adults, children, elderly and immunocompromised populations across Europe, the U.S., and Africa.
Mvabea (MVA-BN-Filo) is a multivalent vaccine preparation designed to provide active acquired immunity to the Sudan virus, Ebola virus, Marburg virus, and the Tai Forest virus (formerly known as Côte d'Ivoire ebolavirus).
Zabdeno and Mvabea combination was evaluated under the European Medicines Agency (EMA) accelerated assessment. However, as a precautionary measure, a Zabdeno booster vaccination should be considered for individuals at imminent risk of exposure to the Ebola virus, for example, healthcare professionals and those living in or visiting areas with an ongoing Ebola virus outbreak who completed the Zabdeno, Mvabea 2-dose primary vaccination regimen.
On June 4, 2021, J&J welcomed a new recommendation by the WHO's Strategic Advisory Group of Experts on Immunization that supports the use of the Ebola vaccine regimen both during outbreaks for individuals at risk of Ebola exposure and preventively, in the absence of an outbreak, as protection against Ebola virus disease (EVD) is considered a significant public health interest. Accordingly, African countries began evaluating a single dose of Bavarian Nordic's Mvabea (MVA-BN-Filo) to treat the Marburg virus disease in August 2021.
The Lancet published a study on September 13, 2021, concluding, 'The Ad26.ZEBOV and MVA-BN-Filo Ebola vaccine regimen was well tolerated with no safety concerns in children aged 1–17 years and induced robust humoral immune responses, suggesting the suitability of this regimen for Ebola virus disease prevention in children.' ClinicalTrials.gov: NCT02509494.
Data from two papers published in The Lancet Infectious Diseases demonstrated that the Janssen Ebola vaccine regimen, Zabdno®, and Mvabea®, generated robust humoral immune responses in adults and children, with the immune responses persisting in adults for at least two years. The data also showed that booster vaccination with Ad26.ZEBOV, administered to adults two years after the initial immunization, induced a robust anamnestic response within seven days. On December 14, 2022, a study published by the New England Journal of Medicine concurred with The Lancet's findings. In addition, the JAMA Network published: Ebola Vaccines Safe and Immunogenic in Clinical Trials on January 24, 2023.
Zabdeno and Mvabea History
The U.S. NIAID, BARDA, and other funding partners supported the development and preclinical and clinical testing of this investigational vaccine regimen designed to protect against the virus responsible for the 2014-2016 Ebola outbreak in West Africa. As of June 4, 2021, J&J confirmed that more than 235,000 people had received at least the first dose of the Ebola vaccine, including 190,000 fully vaccinated with both doses.
On May 29, 2020, the European Medicines Agency (EMA) human medicines committee 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 latest Ebola vaccine even after authorization. This was accepted due to the ongoing Ebola outbreak and its high mortality rates.
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 licensed MVA-BN Filo for use from Bavarian Nordic in a prime-boost vaccine regimen together with their adenovirus-based vaccine candidate, Ad26.ZEBOV. Both vaccines use a viral vector approach, where a virus is genetically modified not to replicate but is used to express the target virus's essential proteins safely; in this case, the Ebola virus. Global partners in the vaccine program 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.
On November 17, 2020, The Lancet published a study, Safety and immunogenicity of a two-dose heterologous Ad26.ZEBOV and MVA-BN-Filo Ebola vaccine regimen in European adults (EBOVAC2): a randomized, observer-blind, participant-blind, placebo-controlled, phase 2 trial. This study concluded with 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 one year after vaccination. These data support the intended prophylactic indication for the vaccine regimen.'
Johnson & Johnson - Janssen has 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 and Mvabea Indication
The Ad26.ZEBOV / MVA-BN-Filo combination is indicated to provide an active acquired immunity Ebola virus. Clinical results suggest that Ad26.ZEBOV prime immunization readily induces an immune response enhanced by MVA-BN-Filo boosting, inducing a durable immunity to Ebola Zaire. Both the prime and boost are well tolerated with a good safety profile.
Janssen's 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. Therefore, this prophylactic 2-dose regimen is unsuitable for an outbreak response where immediate protection is necessary.
Data from two papers published in The Lancet Infectious Diseases on September 13, 2021, demonstrated that the Johnson & Johnson Ebola vaccine regimen generated robust humoral immune responses in adults and children, with the immune responses persisting in adults for at least two years.
Zabdeno and Mvabea Dosage
Heterologous 2-dose vaccination with Ad26.ZEBOV and MVA-BN-Filo against the Ebola virus were well tolerated and immunogenic in healthy volunteers. The vaccine is administered as an intramuscular injection. A study published in 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 one year after vaccination.
The EMA recommends a Zabdeno booster for individuals at high risk of Ebola virus exposure if their 2-dose vaccine regimen was completed more than four months ago. And, if four weeks have passed, the Johnson & Johnson Ebola vaccine can be administered to an individual vaccinated with a COVID-19 vaccine.
Zabdeno and Mvabea Side Effects
The most common side effects found in participants in the clinical trials were injection-site reactions (pain, warmth, and swelling), fatigue, headache, myalgia, arthralgia, and chills reported by the EMA.
In a phase 1 study, the reporting of A.E.s was identical to that described for the VAC52150EBL1003 trial. Briefly, solicited A.E.s were recorded in a diary by participants for seven days following each vaccination, and unsolicited A.E.s were collected at all visits until 21 days after dose 2.
Zabdeno and Mvabea News For 2014 - 2023
January 31, 2023 - The JAMA Network published a review of three vaccine regimens against Zaire Ebola virus disease that safely produced immune responses for up to 12 months, according to two clinical trials of adults and children reported in the New England Journal of Medicine.
October 3, 2022 - The U.S. CDC published a Watch - Level 1 Practice Usual Precations regarding the Sudan Ebolavirus outbreak in Uganda.
September 26, 2022 - The WHO published: Ebola Disease caused by Sudan virus - Uganda.
December 9, 2021 - The peer-reviewed journal PLOS Pathogens published: Current state of Ebola virus vaccines: A snapshot.
November 6, 2021 - The WHo Africa total of 11 EVD cases, including eight confirmed cases (with four community deaths) and three probes reported in the Beni HZ in the DRC. Additional three deaths were notified as probable cases after in-depth investigations established epidemiological links to confirmed cases on the 13, 16, and 22 October 2021, respectively.
October 4, 2021 - The journal PLOS Medicine published a RESEARCH ARTICLE: Safety and immunogenicity of 2-dose heterologous Ad26.ZEBOV, MVA-BN-Filo Ebola vaccination in healthy and HIV-infected adults: A randomized, placebo-controlled Phase II clinical trial in Africa. Conclusions - Ad26.ZEBOV, MVA-BN-Filo vaccination was well tolerated and immunogenic in healthy and HIV-infected African adults. Increasing the interval between vaccinations from 28 to 56 days improved the magnitude of humoral immune response; however, antibody body levels persisted for at least one year and Ad26. In addition, ZEBOV booster vaccination demonstrated the presence of vaccination-induced immune memory. These data supported the approval by the European Union for prophylaxis against EBOV disease in adults and children ≥1 year of age.
September 13, 2021 - A new study published by the journal The Lancet assessed the Safety and immunogenicity of a two-dose heterologous vaccine regimen comprising the adenovirus type 26 vector-based vaccine encoding the Ebola virus glycoprotein (Ad26.ZEBOV) and the modified vaccinia Ankara vector-based vaccine, encoding glycoproteins from the Ebola virus, Sudan virus, and Marburg virus, and the nucleoprotein from the Tai Forest virus (MVA-BN-Filo), in a pediatric population in Sierra Leone, Africa. Ebola virus glycoprotein-specific binding antibody responses at 21 days after the second dose of the Ebola virus vaccine were observed in about 97% of the children. And there were no treatment-related deaths.
August 31, 2021 - The WHO announced the new tests by the Institut Pasteur in Lyon, France, following tests conducted by the Institut Pasteur of Cote d'Ivoire, considering that the patient did not have Ebola virus disease and further analysis on the cause of her illness is ongoing. After Cote d'Ivoire announced the Ebola case, in line with the no-regrets policy followed by WHO, immediate actions were implemented in both Cote d'Ivoire and GuinIn addition, around a dozen WHO experts were mobilized to support the country's vaccination efforts with 5,000 Ebola vaccine doses.
August 23, 2021 - The WHO Africa announced frontline health workers, practitioners of traditional medicines or traditional healers, and commercial motorbike riders in Sierra Leone who received the first dose a being given their second jab to maximize their protection against the disease. There were 8,583 people vaccinated with the first dose who would receive their second dose of the vaccine as the full regimen. In addition, health workers who had not been vaccinated with the first dose of the Ebola vaccine because of difficulty exigency for their second COVID-19 vaccine dose will now have the chance to be vaccinated with the first dose of the Ebola vaccine and then wait for their second dose six weeks later.
August 17, 2021 - The World Health Organization Africa confirmed it helped the vaccine deployment from Guinea to Cote d'Ivoire of about 3,000 vaccine doses manufactured by Johnson & Johnson, which are to be used to boost the vaccination in areas not experiencing active Ebola transmission.
August 14, 2021 - The Guardian reported that the Ivory Coast confirmed an 18-year-old woman is the first occurrence of Ebola in the country in nearly 30 years.
August 9, 2021 - The WHO reported, 'this is the first time Marburg Virus Disease has been reported in Guinea. Based on the current risk assessment and prior evidence on Ebola outbreaks, WHO advises against any restriction of travel and trade to and from Guinea.
June 4, 2021 - Johnson & Johnson announced it 'welcomes the recommendation by the Strategic Advisory Group of Experts on Immunization for the World Health Organization in support of the use of Johnson & Johnson's two-dose Ebola vaccine regimen, Zabdeno® (Ad26.ZEBOV) and Mvabea® (MVA-BN-Filo), both during outbreaks for individuals at some risk of Ebola exposure and preventively, before outbreaks, for national and international first responders.
May 13, 2021 - Johnson & Johnson announced the World Health Organization and the government of Sierra Leone have begun administering the Company's Ebola vaccine regimen as part of a WHO early access clinical program to the event's further spread of Ebola in West Africa.
May 11, 2021 - The vaccination was launched in Kambia District, a primary international entry point by road crossing and significant economic and commercial importance for Guinea and Sierra Leone. This preventive Ebola vaccination will continue in eight other districts sharing borders with Gu over the coming dyspnea. About 16 000 people have been targeted for vaccination in the selected border districts, and individuals will receive two doses of the vaccine given approximately eight weeks apart.
April 10, 2021 - The government of Sierra Leone and the World Health Organisation announced Johnson & Johnson; Janssen has donated about 4,500 Ebola vaccines to prevent Ebola in e country.
April 6, 2021 - Denmark-based Bavarian Nordic A/S announced the Company had received a new supply order from Janssen Pharmaceutica NV, part of the Janssen Pharmaceutical Companies of Johnson & Johnson, valued at approximately USD 28 million. Under the contract, Bavarian Nordic will manufacture and deliver bulk drug substances of the MVA-BN® Filo vaccine, licensed to Janssen as part of its Ebola vaccine regimen, Zabdeno® (Ad26.ZEBOV) and Mvabea® (MVA-BN Filo), which the European Commission approved in 2020.
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 disease's spread. However, immunization of specific populations (e.g., healthcare workers) in endemic countries outside of outbreak epicenters could reduce the likelihood of amplifying spillover events in humans. Study Interpretation - The two-dose heterologous regimen with Ad26.ZEBOV and MVA-BN-Filo were safe, well-tolerated, and immunogenic, with humoral and cellular immune responses persistingonefor one year after vaccinatTogetherether, these data support the intended prophylactic indication for the vaccine regimen.
July 1, 2020 - The European Commission adopted the decision granting marketing authorizations to Janssen, a Johnson & Johnson company, for a vaccine against Ebola. In one month, the approval was more significant, demonstrating the Commission's commitmeprioritizing public health protectioniority. The recent Ebola vaccine, which consists of two components, called Zabdeno and Mvabea, was developed with the Commission's support. This decision follows the European Medici Agency's recommendation, which has assessed the vaccine's benefits and risks.
July 1, 2020 - Johnson & Johnson announced that the European Commission had granted Marketing Authorisation for its Janssen Pharmaceutical Companies' Ebola vaccine regimen to prevent Ebola Virus Disease. Janssen's Ebola vaccine regimen is indicated for active immunization to prevent 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, administered based on Bavarian Nordic's MVA-BN® technology 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 agreement, Bavarian Nordic will manufacture and deliver bulk drug substances 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 to support the vaccines in the 2-dose regimen (Ad26.ZEBOV, MVA-BN-Filo).
May 29, 2020 - Pending the European Commission of the MVA-BN Filo vaccine's final approval, Bavarian Nordic would be eligible to receive a milestone payment of USD 10 million under Janssen's license agreement. 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 contract, 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, J&J Janssen Pharmaceutical Companies of Johnson & Johnson, would donate up to 500,000 doses of its investigational Ebola vaccine regimen to support vaccination efforts in the Democratic Republic of the Congo. Alex Gorsky, Chairman and CEO of Johnson & Johnson, commented in a press release, "The fact that we're in a position to help the people of the DRC protect their communities from such a serious threat—just a few years after we pledged to accelerate vaccine development efforts—is a testament to both the ingenuity of Janssen's scientists and the power of close collaboration between partners committed to working for the greater good of all."
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.ZE,OV; 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) had 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. Paul Stoffels, M.D., Chief Scientific Officer, Johnson & Johnson, commented in a press statement, "We must take action now so that a tragedy on the scale of West Africa never happens again. Having an Ebola vaccine available is critical for global preparedness. If the WHO grants an emergency use listing, this will accelerate the availability of Janssen's investigational vaccine regimen to the international communicant another Ebola crisis occurs."
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 response 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.
ClinicalTrials.gov: NCT02509494 - Phase 3 Study to Assess the Safety and Immunogenicity of Ebola Candidate Vaccines Ad26.ZEBOV and MVA-BN-Filo (EBOVAC-Salone). Last Update Posted: June 29, 2020.
