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JYNNEOS Smallpox Vaccine

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December 5, 2021
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JYNNEOS (MVA-BN) Smallpox (Monkeypox) Vaccine Description

Bavarian Nordic JYNNEOS smallpox (Monkeypox) vaccine is based on a live, attenuated vaccinia virus (Modified Vaccinia Ankara, MVA-BN), incapable of replicating in the body, yet still capable of eliciting a potent immune response. The MVA is cultured in Chicken Embryo Fibroblast cells placed in a serum-free medium. It is purified and filtered from the cells using various methods, including benzonase digestion.

JYNNEOS (IMVANEX, IMVAMUNE) was initially Approved in 2019 by the U.S. Food and Drug Administration (FDA) and is indicated for preventing smallpox and monkeypox disease in adults 18 years of age and older determined to be at high risk for smallpox or monkeypox infection. JYNNEOS is the only FDA-approved non-replicating smallpox vaccine and the only FDA-approved monkeypox vaccine for non-military use.

The vaccine was developed in partnership with the U.S. Government to ensure all 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. Typical severe adverse reactions known for replicating vaccinia virus strains, such as myocarditis, encephalitis, generalized vaccinia, or eczema vaccinatum, were not observed during the clinical development program of JYNNEOS.

During 2020, positive topline results from a Phase 3 lot-consistency trial of the freeze-dried formulation of MVA-BN were reported. The three lots induced equivalent antibody responses, meeting the study's primary endpoint, while the favorable safety profile was in line with the cumulative safety experience of the approved liquid-frozen formulation.

In terms of efficacy, MVA-BN induces strong cellular activity as well as humoral (antibody) immune response and has demonstrated an ability to stimulate a response even in individuals with pre-existing immunity against vaccinia.

On June 21, 2021, the U.S. FDA issued an update for JYNNEOS - STN: BL 125678/20. The Modified Vaccinia Ankara - Bavarian Nordic (MVA-BN®) vaccine is marketed under the brand names IMVANEX® and IMVAMUNE® in the European Union and Canada. In the U.K., the Vaccination Act of 1853 made it compulsory for all children born after August 1953 to be vaccinated against smallpox during their first three months of life.

Bavarian Nordic is headquartered in Kvistgaard, Denmark (OTCMKTS: BVNRY) (OMX: BAVA) focused on developing, manufacturing, and commercializing life-saving vaccines.

JYNNEOS (MVA-BN) Smallpox (Monkeypox) Vaccine Cell Line

JYNNEOS (MVA-BN) Smallpox Vaccine (IMVANEX, IMVAMUNE) utilizes Chicken Embryo Fibroblast cells to produce the vaccine.

JYNNEOS (MVA-BN) Smallpox (Monkeypox) Vaccine Indication

The smallpox vaccine is not recommended for the general public in the USA since smallpox has been eradicated. Routine smallpox vaccination among the American public stopped in 1972 says the U.S. CDC. However, health officials are prepared to use a vaccine if there were a smallpox outbreak, says the CDC

JYNNEOS is indicated to protect people 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. Pregnant or breastfeeding women should discuss the clinical need prior to vaccination.

The WHO states, 'Vaccination against smallpox with first-generation vaccinia-virus-based smallpox vaccine was shown to be 85% effective in preventing monkeypox in the past. Therefore, family and community members, health workers, and laboratory personnel who were vaccinated against smallpox in childhood may have some remaining protection against monkeypox.' When properly administered before exposure to monkeypox, vaccines are effective at protecting people against monkeypox.

The WHO says 'Monkeypox is a sylvatic zoonosis with incidental human infections that usually occur sporadically in forested parts of Central and West Africa. It is caused by the monkeypox virus and belongs to the Orthopoxvirus family. Monkeypox can be transmitted by contact and droplet exposure via exhaled large droplets.'

Monkeypox disease was discovered in 1958 and is caused by infection with monkeypox virus and belongs to the Orthopoxvirus genus in the family Poxviridae. The Orthopoxvirus genus also includes variola virus (the cause of smallpox), vaccinia virus (used in the smallpox vaccine), and cowpox virus, says the U.S. CDC. Human monkeypox (MPX) is a zoonotic viral disease caused by the Monkeypox virus

The clinical presentation is similar to smallpox. Human monkeypox was recognized as a human disease in 1970. Persons exposed to the monkeypox virus and who have not received the smallpox vaccine within the last 3 years, should consider getting vaccinated. The sooner the person receives the vaccine, the more effective it will be in protecting against the monkeypox virus, says the CDC.

JYNNEOS (MVA-BN) Smallpox (Monkeypox) Vaccine U.S. CDC Presentations

During the U.S. CDC's ACIP Meeting on September 29, 2021, Agam Rao, M.D. CAPT, U.S. Public Health Service, presented: Background information to interpret GRADE tables and Evidence to Recommendations framework about JYNNEOS vaccine. The Demographic Subgroup Information - JYNNEOS - Refer to Section 1.1 of the Clinical Review Memo for information about participation in the clinical trials and any analysis of demographic subgroup outcomes that is notable.

On November 3, 2021, Pablo Sanchez, MD Chair, ACIP Orthopoxvirus WG, led an update discussion, followed by Brett Petersen, MD, MPH, who presented Clinical Guidance for the use of JYNNEOS. Then, Agam Rao, MD CAPT, US Public Health Service, presented a Summary of Evidence to Recommendations Frameworks for Use of JYNNEOS.

JYNNEOS (MVA-BN) Smallpox (Monkeypox) Vaccine Dosage

JYNNEOS is for subcutaneous injection only. Administer 2-doses (0.5 mL each) 28 days apart. JYNNEOS is administered as a live virus that is non-replicating. People who receive JYNNEOS are not considered vaccinated until they receive both doses of the vaccine.

JYNNEOS (MVA-BN) Smallpox (Monkeypox) Vaccine Side Effects

There is no visible “take” and as a result, no risk for spread to other parts of the body or other people. A major advantage of MVA-BN is the virus’ inability to replicate in a vaccinated individual, in contrast to the original smallpox vaccines.

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%). (6.1). In healthy adults previously vaccinated with a smallpox vaccine, the most common (> 10%) solicited injection site reactions were redness (80.9%), pain (79.5%), induration (70.4%), swelling (67.2%), and itching (32.0%); the most common solicited systemic adverse reactions were fatigue (33.5%), headache (27.6%), and muscle pain (21.5%).

The frequencies of solicited local and systemic adverse reactions among adults with HIV infection and adults with atopic dermatitis were generally similar to those observed in healthy adults.

To report SUSPECTED ADVERSE REACTIONS, contact Bavarian Nordic at toll-free phone 1-800-675-9596 or VAERS, a passive reporting system, meaning it relies on individuals to send in reports of their experiences. Anyone can submit a report to VAERS, including parents and patients. Healthcare providers are required by law to report to VAERS.

Smallpox Vaccines

ACAM200 and JYNNEOS are the two currently licensed vaccines in the United States to prevent smallpox. JYNNEOS is also licensed specifically to prevent monkeypox. ACAM2000 is administered as a live virus preparation that is inoculated into the skin by pricking the skin surface. Following a successful inoculation, a lesion will develop at the site of the vaccination. The virus growing at the site of this inoculation lesion can be spread to other parts of the body or even to other people. Individuals who receive vaccination with ACAM2000 must take precautions to prevent the spread of the vaccine virus.

The U.S. CDC says 'at this time, vaccination with ACAM2000 is recommended for laboratorians working with certain orthopoxviruses and military personnel. The ACIP is currently evaluating JYNNEOS for the protection of people at risk of occupational exposure to orthopoxviruses in a pre-event setting.'

Contracts With the U.S. Government

Since 2010, Bavarian Nordic has manufactured its liquid-frozen MVA-BN smallpox vaccine and has supplied 28 million doses to the U.S. Strategic National Stockpile (SNS) for emergency use. Concurrently, BARDA has supported the development of a freeze-dried version of the vaccine with a longer shelf-life to replace the current stockpile that has expired. The manufacturing of bulk vaccines to support this transition was initiated in 2016 and by end of 2019, the Company will have manufactured and invoiced bulk vaccines worth USD 333 million. The fill-finish of this bulk will trigger additional contract options valued at USD 299 million. The ten-year contract, awarded in 2017, also includes pricing for additional orders of vaccine bulk and vaccine doses of either liquid-frozen or freeze-dried MVA-BN.

On April 30, 2020, the company confirmed a contract expansion that covers two years of performance and includes the manufacturing of additional bulk vaccines and the supply of up to 1.4 million doses of liquid frozen JYNNEOS. This is the first order from the U.S. following the approval of JYNNEOS by the FDA in September 2019, which will ensure the availability of a smallpox vaccine in the U.S. Strategic National Stockpile for potential use by first-line responders. 

JYNNEOS (MVA-BN) Smallpox (Monkeypox) Vaccine News

November 18, 2021 - Laboratory testing at the Centers for Disease Control and Prevention showed that recently discovered vials marked as “smallpox” contain vaccinia, the virus used in the smallpox vaccine. There is no evidence that the vials contain the variola virus, the cause of smallpox. Revenue in the third quarter totaled DKK 449 million comprised of DKK 214 million from sales of MVA-BN smallpox vaccine.

November 16, 2021 - The Maryland Department of Health, in collaboration with the U.S. CDC, confirmed a single case of monkeypox virus infection in a Maryland resident who recently returned from Nigeria. The individual is currently recovering in isolation and is not hospitalized. No special precautions are recommended at this time for the general public.

November 12, 2021 - Bavarian Nordic A/S announced today its interim financial results for the first nine months of 2021 and business progress for the third quarter of 2021.

November 4, 2021 - Mr. Bill Gates, founder of Microsoft in a meeting with Jeremy Hunt, chair of the UK Health Select Committee, warned of future pandemics as well as smallpox terror attacks.

September 30, 2021 - The U.S. CDC issued a Travel Alert regarding the Monkeypox outbreak in the Democratic Republic of the Congo. People infected with monkeypox can spread the virus to others through the air when they cough, sneeze or talk. The body fluids and skin sores of a person infected with monkeypox are also infectious.

September 15, 2021 - Guinea declared the end of the Marburg virus disease outbreak having recorded no new cases over the past 42 days, two incubation periods, or the time between infection and the onset of symptoms. The virus was confirmed on 9 August, marking the first time the disease emerged in the country and in West Africa. Only one case—the index patient who was diagnosed with the virus posthumously—was recorded and more than 170 high-risk contacts were monitored for 21 days. 

September 12, 2021 - The WHO reported nine suspected monkeypox cases were reported in Nigeria in August 2021, which was a substantial increase from the previous month. Overall, seventy-nine suspected cases have been reported this year with no deaths recorded. In mid-July 2021, a case of monkeypox from Nigeria was reported to have been imported into the United States highlighting the risk of cross-border spread and the need for collaboration to disease management and response.

July 16, 2021 - The Centers for Disease Control and Prevention and the Texas Department of State Health Services confirmed a case of human monkeypox in a U.S. resident who recently traveled from Nigeria to the U.S.

June 24, 2021 - Local media reported Public Health Wales and Public Health England have confirmed they are monitoring three cases of imported monkeypox identified in North Wales.

June 11, 2021 - Bavarian Nordic A/S announced the company was recently engaged by Public Health England (PHE) and the Medicines and Health Products Regulatory Agency (MHRA) to supply its IMVANEX® smallpox vaccine in response to new cases of monkeypox in the U.K. Two related cases were confirmed and admitted to a hospital in Liverpool, England. Bavarian Nordic previously delivered IMVANEX to PHE in connection with the first human cases of monkeypox in the U.K. in 2018 and later in 2019, when several unrelated human cases were imported from Nigeria with subsequent infection of a healthcare worker in the U.K. The U.S. trade name is JYNNEOS.

June 9, 2021 - Public Health Wales confirmed it is monitoring two cases of imported monkeypox after their discovery in north Wales.

May 25, 2021 - The United Kingdom and Northern Ireland notified the WHO of one laboratory-confirmed case of monkeypox. The patient arrived in the United Kingdom on 8 May 2021. Before travel, the patient had lived and worked in Delta State, Nigeria.

May 7, 2021 - Bavarian Nordic A/S announced today that the U.S. Biomedical Advanced Research and Development Authority, part of the Office of the Assistant Secretary for Preparedness and Response, has exercised the final $12 million option under the $202 million order for JYNNEOS awarded in April 2020. This project has been supported in part with federal funds from the Department of Health and Human Services; Office of the Assistant Secretary for Preparedness and Response; Biomedical Advanced Research and Development Authority, under Contract No. HHSO100201700019C.

March 22, 2021 - Bavarian Nordic A/S announced that the Public Health Agency of Canada had ordered the IMVAMUNE® smallpox vaccine to the national stockpile at a total value of $31.2 million. Deliveries of the vaccines are expected to occur from the first quarter of 2022, with anticipated completion in 2023. Hence this order, made under an existing contract with PHAC, will have no impact on the Company's financial guidance for 2021.    

December 16, 2020 - Bavarian Nordic A/S announced the U.S. BARDA exercised an option covering the majority of the second year of performance under the USD 200 million order for JYNNEOS awarded in April 2020. The first USD 106 million covered both manufacturings of bulk vaccine and supply of liquid-frozen JYNNEOS doses and was secured upon contract award last April. BARDA is committing to an additional USD 83 million with the current option to procure more bulk smallpox vaccines manufactured and invoiced in 2021. The last option of the order, amounting to USD 12 million, is to supply additional liquid-frozen JYNNEOS doses that will be manufactured in the Company's new fill and finish facility and is expected to be awarded and invoiced during 2021.

November 12, 2020 - Bavarian Nordic A/S announced that Health Canada had expanded the approval of the Company's non-replicating smallpox vaccine, IMVAMUNE®, to include additional indications – specifically, monkeypox and related orthopoxvirus infections and disease in adults 18 years of age and older determined to be at high risk for exposure.

October 1, 2020 - The WHO announced from 1 January through 13 September 2020, a total of 4,594 suspected cases of monkeypox, including 171 deaths (case fatality ratio 3.7%), have been reported in 127 health zones from 17 out of 26 provinces in the Democratic Republic of the Congo.

September 23, 2020 - Phase 3 study: IMVAMUNE® Smallpox Vaccine in Adult Healthcare Personnel at Risk for Monkeypox in the Democratic Republic of the Congo.

April 30, 2020 - Bavarian Nordic A/S announced that the U.S. Biomedical Advanced Research and Development Authority had placed a new order under the contract, awarded in 2017, for the manufacturing and supply of JYNNEOS® at a total value of U.S. $202 million. This new order is also the option to manufacture approximately 13 million freeze-dried doses worth USD 299 million. The Company expects to start manufacturing in 2022, and revenue is recognized following approval by the U.S. FDA of this vaccine formulation.

September 30, 2019 - "In addition to its public health importance, this vaccine will have a direct impact on improving force health protection for U.S. service members who are required to be immunized against smallpox," said Col. E. Darrin Cox, commander of the U.S. Army Medical Research Institute of Infectious Diseases. The USAMRIID-led Phase 3 clinical trial was funded in full by a Cooperative Research and Development Agreement with Bavarian Nordic.

September 24, 2019 - The U.S. Food and Drug Administration announced the approval of Jynneos Smallpox and Monkeypox Vaccine, Live, Non-Replicating, to prevent smallpox and monkeypox disease in adults 18 years of age and older determined to be at high risk for smallpox or monkeypox infection. This is the only currently FDA-approved vaccine for the prevention of monkeypox disease. Summary Basis for Regulatory Action.

JYNNEOS Smallpox Vaccine Clinical Trial

The FDA approval of JYNNEOS for smallpox comes from a development program comprising 22 clinical trials, including two phase III trials. The program enrolled a total of 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 gathered 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.