JYNNEOS® Mpox Smallpox Vaccine Clinical Trials, Dosage, Efficacy, Side Effects, Usage
Bavarian Nordic A/S JYNNEOS® (MVA-BN®, IMVAMUNE®, IMVANEX®) two-dose vaccine is based on a live, attenuated vaccinia virus, Modified Vaccinia Ankara (MVA). The MVA is cultured in chicken embryo fibroblast cells and is a serum-free medium, incapable of replicating in the human body yet able to elicit a potent immune response. It is purified and filtered from the cells using various methods, including benzonase digestion. JYNNEOS was codeveloped with the U.S. Government (BARDA, BioShield) to ensure adult populations can be protected from smallpox, including people with weakened immune systems or at high risk of adverse reactions to traditional smallpox vaccines based on replicating vaccinia virus strains.
On July 26, 2024, Bavarian Nordic announced that the Committee for Medicinal Products for Human Use of the European Medicines Agency (EMA) had recommended the approval of a type II variation for the IMVANEX® smallpox and mpox vaccine. B.N. confirmed that in real-world studies, vaccine effectiveness (VE) against mpox (clade 2) disease was demonstrated at least 14 days after vaccination, with adjusted VE estimates ranging from 35% (95% CI, -2-59) to 89% (95% CI, 76-95) after one MVA-BN dose and from 66% (95% CI, 47-78) to 90% (95% CI, 86-92) after two MVA-BN doses. Furthermore, a meta-analysis of 16 studies published on April 26, 2024, revealed that the VE for one preexposure prophylactic JYNNEOS vaccination ranged from 35% to 86%, and VE ranged from 66% to 90% for two doses.
The U.S. government recommends two doses to provide more robust protection, and routine immunization against mpox is not recommended for the general public. Booster doses (3rd) are not endorsed. As of September 13, 2024, JYNNEOS is commercially available in the U.S. and has been added to the World Health Organization (WHO) prequalification (P.Q.) list. WHO PQ and Emergency Use Listing are mechanisms to evaluate medical products' quality, safety, and efficacy, such as vaccines. According to estimates from the CDC, two million U.S. individuals are eligible for mpox vaccination. Recent data shows that 15% of eligible people have received only one dose of the JYNNEOS vaccine. The CDC's ACIP Immunization Schedule includes JYNNEOS for 2023-2024.
On November 11, 2024, the WHO confirmed the Mpox Vaccines Access and Allocation Mechanism endorsed an independent Technical Review Committee to allocate 899,000 MVA-BN vaccine doses to nine countries across the African region. For 2025, the Company has so far secured revenue from mpox/smallpox vaccine orders of approximately DKK 2,400 million, including previously announced deferred revenue.
Bavarian Nordic A/S, headquartered in Kvistgaard, Denmark (OTCMKTS: BVNRY) (OMX: BAVA), focuses on developing, manufacturing, and commercializing life-saving vaccines. The MVA-BN® vaccine is marketed under the brand names IMVANEX® in the European Union and IMVAMUNE® in Canada.
Bavarian Nordic JYNNEOS (MVA-BN) Production
Since 2022, Bavarian Nordic has created a vaccine inventory to provide a surge capacity for potential outbreaks. Bavarian Nordic has identified 50 million doses that could be supplied during the next 12-18 months, pending regulatory approvals and demand. The Company has informed the African CDC that it can manufacture 10 million doses in addition to current orders by the end of 2025.
Bavarian Nordic - Biomedical Advanced Research and Development Authority (BARDA) Agreements
Since 2003, Bavarian Nordic has worked with the U.S. government on developing, manufacturing, and supplying a nonreplicating smallpox vaccine. On September 24, 2024, Bavarian Nordic announced that it had received an additional order valued at $63 million from the Biomedical Advanced Research and Development Authority (BARDA) to manufacture additional bulk products and final freeze-dried doses of JYNNEOS® smallpox/mpox vaccine.
On August 8, 2024, Bavarian Nordic announced a new order valued at $156.8 million from the BARDA to manufacture additional bulk product for JYNNEOS®. BARDA has supported the development of a freeze-dried version of the vaccine and, in 2017, awarded the Company a ten-year contract for the supply of freeze-dried vaccines. On August 3, 2023, Bavarian Nordic announced it would manufacture and supply additional liquid-frozen doses of JYNNEOS to the U.S. government in 2023, valued at $3 million. Additionally, on August 3, 2023, Bavarian Nordic announced that BARDA placed a new order valued at $120 million, primarily manufacturing a new bulk product for the JYNNEOS smallpox/mpox vaccine. Since 2003, Bavarian Nordic has worked with the U.S. government on developing, manufacturing, and supplying a nonreplicating smallpox vaccine to ensure all populations can be protected from smallpox. This includes people with weakened immune systems at a high risk of adverse reactions to traditional smallpox vaccines based on replicating vaccinia virus strains.
JYNNEOS Vaccine U.S. FDA
The U.S. Food and Drug Administration (FDA ) initially approved JYNNEOS for smallpox prevention in September 2019, based on a comprehensive development program comprising 22 clinical trials, including two Phase 3 studies. The FDA granted Bavarian Nordic a Priority Review Voucher (PRV) under the Material Threat Medical Countermeasure program, accelerating the FDA's application review. The FDA's emergFDA'suse authorization (EUA) for JYNNEOS for mpox was issued by Peter Marks, MD, Ph.D., in Application Number 28801 on August 9, 2022. JYNNEOS' apJYNNEOS'or mpox use was based on survival data from lethal mpox virus challenge studies (FDA's Rule) FDA'son-human primates. The FDA granted an Emergency Use Authorization for use in adolescents in 2022. On March 15, 2023, the U.S. FDA updated JYNNEOS - STN: BL 125678/20. As of June 2024, JYNNEOS is the only FDA-non-replicating smallpox and mpox vaccine for military and non-military use.
JYNNEOS Vaccine U.S. CDC
In November 2021, the U.S. Centers for Disease Control and Prevention (CDC) vaccine committee unanimously voted for JYNNEOS as an alternative to the ACAM2000 vaccine for primary and booster doses against smallpox. The CDC's CommiCDC'son Immunization Practices (ACIP) group leader, Pablo Sanchez, MD, led the Mpox Vaccine presentation on October 20, 2022, and February 22, 2023. The CDC announced Interim Clinical Considerations on February 22, 2023: Mpox vaccination should continue to be offered to people with the highest potential for exposure to mpox. An updated U.S. National Mpox Vaccination Strategy was published on February 6, 2023. On June 23, 2023, Agam Rao, MD CAPT, U.S. Public Health Service, presented: Considerations for long-term protection against mpox - prefers no CDC recommendation for third JYNNEOS dose, including persons with advanced HIV or other severe immunocompromised immune systems. On August 18, 2023, the CDC's WeeklCDC'sort stated that all adults at risk for mpox should receive the JYNNEOS vaccine, regardless of childhood smallpox vaccination status. On October 25, 2023, the CDC recommended using JYNNEOS routinely for people at risk of smallpox or mpox infection. Survey results published in the U.S. CDC's CDC'sCDC'snCDC'sing Diseases Volume 30, Number 5 May 2024, showed that among vaccine-eligible GBMSM, uptake was 69% (95% CI 65%–72%; 601/875) and 92% (95% CI 89%–94%; 601/655) among those offered the JYNNEOS vaccine. On April 22, 2024, the CDC published updated Mpox Vaccine Recommendations.
JYNNEOS Vaccine Availability United States
As of November 2024, healthcare providers in the U.S. can order JYNNEOS through their preferred wholesaler and distribution partners to make it available for at-risk individuals at pharmacies, physician offices, and public health clinics. This HHS operational planning guide is provided to aid state, tribal, local, and territorial health officials in their planning and response efforts. JYNNEOS became commercially available at pharmacies in the U.S. in 2024. As of April 3, 2024, Morris & Dickson became the first U.S. commercial distributor of JYNNEOS. Cities such as Austin, Texas, offer free JYNNEOS vaccination services.
IMVAMUNE® Vaccine Europe
The European Commission issued marketing authorization for smallpox prevention for MVA-BN (Imvanex) in 2013. It extended it to include mpox for adults in 2022, based on efficacy data in non-human primates and immunogenicity data from numerous studies involving more than 4,000 healthy and immune-compromised individuals. On September 19, 2024, the EMA recommended extending the indication of the smallpox and mpox vaccine Imvanex to adolescents from 12 to 17 years of age. It is inferred that the vaccine will provide similar protection in adolescents to that expected in adults.
MVA-BN® Vaccine
On September 26, 2024, Bavarian Nordic announced an agreement with UNICEF to supply 1 million doses of the MVA-BN® mpox vaccine for African countries. In the agreement, UNICEF has negotiated a price of up to $65 per vaccine dose, the lowest price in the market. On August 20, 2024, the USAID confirmed donating 50,000 Jynneos vaccines to the DRC. On August 13, 2024, Bavarian Nordic announced a new order from the European Health Emergency Preparedness and Response Authority (HERA) for the MVA-BN® vaccine. HERA will procure 175,420 vaccine doses for donation to the Africa Centres for Disease Control and Prevention.
Additionally, Bavarian Nordic will donate 40,000 doses to HERA. This more significant donation follows a recent pledge from the Company for 15,000 doses as part of a coordinated response in the African region by Gavi, WHO, and UNICEF. Bavarian Nordic was awarded a contract on September 13, 2023, to supply its MVA-BN smallpox vaccine to rescEU, a strategic reserve within the European Union.
MVA-BN® Vaccine For Children
Bavarian Nordic announced on October 29, 2024, the initiation of phase 2 clinical study (NCT06549530) of the MVA-BN® mpox/smallpox vaccine in children 2 to 11 years of age in the Democratic Republic of Congo (DRC) with plans also to include sites in Uganda. The study is partially funded by the Coalition for Epidemic Preparedness Innovations, which announced on May 30, 2024, that it awarded B.N. $6.5 million to support phase 2 clinical trials.
As of October 2024, a National Institutes of Health-funded phase 2 clinical trial of JYNNEOS in 229 adolescents found it was safe and generated an antibody response equivalent to that seen in adults. A peer-reviewed study funded by the U.K. Health Security Agency, published on June 15, 2023, concluded a single dose of MVA–BN for post-exposure prophylaxis was well-tolerated in children and induced robust antibody and cellular responses up to 15 weeks after vaccination. On September 15, 2022, the U.S. CDC confirmed that children and adolescents exposed to people with suspected or confirmed mpox infections might be eligible for post-exposure prophylaxis with vaccination. In addition, the CDC published interim Clinical guidance for Healthcare Providers in September 2022.
JYNNEOS Vaccine Efficacy
The JAMA Network published results from a study on October 3, 2024, that concluded two doses provided 66% effectiveness and one dose provided 36% effectiveness at peak immunity during the 2022 mpox outbreak. The findings of a study conducted in the context of a targeted vaccination program in Canada suggested on September 11, 2024, that one dose of MVA-BN is moderately (58% (95% CI 31% to 75%)) effective in preventing clade 2 mpox infection. The study showed that the MVA-BN vaccine generated mpox serum antibody responses that largely waned after 6-12 months. High titers of mpox NAbs (median titer 965) were detected at three months. MVA-BN provided 66% efficacy as a 2-dose regimen and 36% as a 1-dose regimen at peak immunity during the 2022 mpox outbreak in the U.S.
U.S. CDC research published in the journal Emerging Infectious Diseases, Volume 30, Number 10—October 2024, concluded the estimated effectiveness of the 2-dose JYNNEOS vaccine was about 80%. Results from a study announced in March 2024 showed mpox antibodies waned within a year of JYNNEOS vaccination. Among individuals with childhood smallpox vaccination, most people had detectable IgG after one year, and the GMT reduction between 4 weeks after the last vaccine dose in 2022 and the one-year follow-up visit was 2.5-fold for those vaccinated with two doses of JYNNEOS, and 1.9-fold for those vaccinated with one dose of JYNNEOS.
On March 14, 2024, the U.S. CDC staff stated, 'JYNNEOS vaccination is expected to be effective regardless of mpox clade. Mpox virus Clade I is divided into lineages 1–5, while Clade II is divided into subclades IIa and IIb. Clade IIb is responsible for the global mpox outbreak that began in May 2022. On December 7, 2023, the CDC published a Health Alert Network Health Advisory stating that mpox vaccines are expected to be effective for both Clade I and Clade II MPXV infections. However, the ECDC reported in 2023 that real-world data regarding JYNNEOS effectiveness against clade 1 is lacking.
The Lancet Infectious Diseases reported on December 7, 2023, that 12% of vaccinated individuals were non-antibody responders, whereas all people with mpox infection developed a neutralizing antibody response. A case-series (67) study published by The Lancet Infectious Diseases on September 4, 2023, confirmed natural immunity and vaccine-induced immunity are not fully protective against mpox infection. Demographic subgroup information is available in Section 1.1 of the Clinical Review Memo for information about participation in the clinical trials and any notable analysis of demographic subgroup outcomes. And Section 6.2 (Postmarketing Experience) to the Package Insert.
The CDC's CDC reported in October 2023 that JYNNEOS Vaccine Effectiveness (VE) against mpox ranges from 36%–75% for 1-dose vaccination and 66%–89% for 2-dose vaccination. VE trended higher for immunocompetent participants compared to self-reported immunocompromised participants. The Lancet Infectious Disease reported that the JYNNEOS vaccine showed an effectiveness of 66–78%, and second episodes of mpox and cases of breakthrough infections among fully vaccinated individuals have been reported. On June 29, 2023, Orginal Research estimated adjusted vaccine effectiveness was 66% (95% confidence interval [CI], 47.4 to 78.1), and 146 case patients and 1000 control patients received one dose, among whom the estimated adjusted vaccine effectiveness was 35.8% (95% CI, 22.1 to 47.1).
On May 18, 2023, the NEJM published data from Cosmos, a nationwide Epic EHR database, to assess the effectiveness of JYNNEOS vaccination in preventing mpox disease among adults who received two doses. The estimated adjusted vaccine effectiveness was 66% (95% confidence interval [CI], 47.4 to 78.1), and those who received one dose, among whom the estimated adjusted VE was 35.8% (95% CI, 22.1 to 47.1).
JYNNEOS Breakthrough Mpox Infections
The CDC published a Morbidity and Mortality Weekly Report (MMWR, 73(20);460–466) in May 2024 that highlighted among 32,819 U.S. mpox cases reported from May 2022 to May 2024, only 0.8% occurred among people who had received two doses of JYNNEOS. From May 2022 to May 2024, 271 mpox cases among fully vaccinated persons from 27 U.S. jurisdictions. The CDC issued an MMWR on June 23, 2023, and the Clinician Outreach and Communication Activity (COCA) call on May 18, 2023, confirmed that a cluster of mpox cases was reported in Chicago, Illinois. During March 18–June 12, 2023, 40 laboratory-confirmed mpox cases were identified in Chicago, including 22 (55%), five (13%), and 13 (33%), respectively, among patients who had received two doses of JYNNEOS or one dose of ACAM2000 vaccine, those who had received one vaccine dose of JYNNEOS vaccine, and those who had not received any vaccines for mpox.
JYNNEOS Vaccine Coadministration
As of 2024, the CDC says limited clinical trial data has been presented on administering the JYNNEOS vaccine simultaneously with other vaccines.
JYNNEOS Vaccine Dosage
In the U.S., the standard U.S. FDA regimen for JYNNEOS involves subcutaneous administration with two injections of 0.5mL four weeks apart.
JYNNEOS Vaccine Booster
On October 3, 2024, the JAMA published a Research Letter that concluded data suggest that protective immunity may be waning in individuals vaccinated with MVA-BN in 2022 and that boosting may be required to maintain robust levels of protective immunity. The U.S. CDC wrote on September 12, 2024, that JYNNEOS booster doses are not recommended.
JYNNEOS Pre and Post-Exposure Vaccination
On July 29, 2024, a phase 4 clinical study was launched to assess whether a mpox vaccine can protect people against the disease after coming into contact with the potentially deadly infection. A study published in January 2024 concluded that the time to PEP and the observed incubation period resulted in overestimating PEP effectiveness using a conventional method. The WHO confirmed on October 10, 2022, that post-exposure vaccination (PEPV) is recommended for close contact with MPX cases, ideally within four days of first exposure and up to 14 days without symptoms.
JYNNEOS Cell Line
JYNNEOS (MVA-BN) vaccine utilizes Chicken Embryo Fibroblast cells to produce the vaccine. Replication-competent poxvirus strains can cause clinical infection in humans and have an infectious virus that can be transmitted to others. However, replication-deficient poxvirus strains, including MVA, do not produce contagious viruses in humans and, therefore, do not cause infection. As such, replication-deficient poxvirus strains pose a substantially lower risk of adverse events than replication-competent strains.
JYNNEOS For Pregnant Women
The U.S. FDA says available human data on JYNNEOS administered to pregnant women are insufficient to inform vaccine-associated risks in pregnancy. Four developmental toxicity studies conducted in female rats and rabbits evaluated the effect of JYNNEOS on embryo-fetal and post-natal development. As of October 27, 2022, the CDC confirmed no clinical efficacy data regarding pregnant or breastfeeding women.
JYNNEOS Vaccine HIV
The European AIDS Clinical Society also recommends the vaccine for adults infected with HIV or on preexposure prophylaxis treatment, and it may support additional national recommendations for the vaccine in the future. On August 5, 2022, the early release of the CDC Report - Interim Guidance - confirmed the JYNNEOS vaccine can be safely given to people who are living with HIV infection and those who are taking preexposure prophylaxis (PrEP).
JYNNEOS Vaccine Myocarditis Risk
According to the U.S. CDC, myocarditis and pericarditis have occurred following either primary vaccination or revaccination with live vaccinia virus smallpox vaccines and is a known health risk for military forces (2003). The CDC reported on October 25, 2023, that VAERS and VSD data suggest an increased risk for myocarditis or pericarditis following JYNNEOS. Similar to smallpox vaccination, the possibility of a negligible risk cannot be excluded.
JYNNEOS Side Effects
The risk of a severe allergic reaction should be weighed against the risk of disease due to smallpox or mpox. A Research Letter on May 5, 2023, reviewed a phase 4 clinical study of adverse events following Jynneos vaccination and found that local negative event rates were highest following intradermal administration. The adverse event rate was highest following dose 1 of intradermal vaccination (53%) and low immunization dose 2 of subcutaneous vaccination (31%). The adverse effects of immunization were local redness, itching, and swelling following intradermal vaccination and local pain, swelling, and redness following subcutaneous vaccination.
Jonathan Dufimmunization, Immunization Safety Office, CDC Advisory Committee on Immunization Practices, presented JYNNEOS Vaccine Safety Monitoring During the 2022 Mpox Outbreak on February 22, 2023. According to VAERS, the number of serious adverse events reported after JYNNEOS was 26. The CDC said on December 8, 2022, that the vaccine safety profile was consistent with prelicensure studies. The most common adverse health events reported were nonserious, including injection site reactions. Serious adverse events were rare among adults.
Severe adverse reactions known for replicating vaccinia virus strains, such as myocarditis, encephalitis, generalized vaccinia, or eczema vaccinatum, were not observed during the Jynneos development program. The U.S. FDA reports in smallpox vaccine-naïve healthy adults, the most common (> 10%) solicited injection site reactions were pain (84.9%), redness (60.8%), swelling (51.6%), induration (45.4%), and itching (43.1%); the most common solicited systemic adverse reactions were muscle pain (42.8%), headache (34.8%), fatigue (30.4%), nausea (17.3%) and chills (10.4%).
JYNNEOS Contraindication
According to the CDC, JYNNEOS is contraindicated in persons with allergies to any vaccine component.
JYNNEOS Immunocompromised
Immunocompromised persons, including those receiving immunosuppressive therapy, may have a diminished immune response to JYNNEOS.
JYNNEOS Storage Requirement
JYNNEOS must be safely stored at negative 20 degrees Celsius (-20°C).
JYNNEOS MVA-BN® Vaccine News
November 22, 2024 - The WHO Director-General, agreeing with the advice of the IHR Emergency Committee, has determined that the upsurge of mpox continues to constitute a public health emergency of international concern.
November 15, 2024 - Paul Chaplin, President & Chief Executive Officer of Bavarian Nordic, said: “We have had a busy but highly purposeful and rewarding third quarter, where we have worked intensively to support the efforts to curb the ongoing mpox outbreak in Africa."
October 23, 2024 - A study reported a distinct clade I sequence from Sudan, suggesting local MPXV circulation in Eastern Africa over the past four decades.
October 14, 2024 - The WHO approved JYNNEOS for people aged 12 to 17.
September 26, 2024 - Bavarian Nordic A/S announced an agreement with UNICEF to supply 1 million doses of the MVA-BN® mpox vaccine for African countries.
August 27, 2024 - Germany intends to donate 100,000 mpox vaccine doses to African countries.
August 16, 2024 - "Children and adolescents are disproportionally affected by mpox in the ongoing outbreak in Africa, highlighting the importance and urgency to broaden the access to vaccines and therapies for this vulnerable population. We applaud the NIH for their work on this study and are pleased to report data that support the use of our vaccine in adolescents, adding to the growing pool of evidence that MVA-BN is well tolerated and able to generate a relevant immune response in adolescents and adult populations," said Paul Chapel, President, and Chief Executive Officer of Bavarian Nordic.
April 2, 2024 - Brian Hujdich, Executive Director of the National Coalition for LGBTQ Health, commented: "JYNNEOS is a vital step toward ensuring equitable access to healthcare for the LGBTQ+ community and marks a significant stride in preventing the spread of mpox."
JYNNEOS Vaccine Clinical Trial
A phase 2 study results posted as a preprint on September 9, 2022, concluded priming with either 1 or 2 doses of MVA-BN induced a durable immune memory, similar to that of older generation replicating smallpox vaccines. When the MVA-BN vaccine was administered as a booster to individuals either primed two years earlier with MVA-BN or an older generation replicating smallpox vaccine in the distant past, it elicited a similarly rapid and durable immune response that was generally safe and well-tolerated. One-dose priming with MVA induced a long-term B-cell memory that resulted in robust anamnestic responses following an MVA booster two years later, suggesting that a single dose may offer protection against future exposure.
The FDA approval of JYNNEOS for smallpox comes from a development program comprising 22 clinical trials, including two phase III trials. The program enrolled 7,871 individuals aged between 18 and 80 years who received at least one dose of the vaccine. Approval for monkeypox indication comes from survival data from studies conducted in non-human primates. The survival rate ranged from 80%-100% in animals vaccinated with JYNNEOS compared to 0%-40% in the control group.
Upon successful completion of the current study, expected in 2021, the Company plans to submit a supplement to the BLA to extend the approval for both formulations of MVA-BN, anticipated in 2022.