NIH-Backed Yellow Fever Vaccine Trial Announced

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The Phase I trial will test Bavarian Nordic’s vaccine, which is manufactured using a vaccine vector based on smallpox.

The recent resurgence of yellow fever incidences over the past six months has prompted health officials to ramp up the fight against the virus. Like the Zika virus, yellow fever is transmitted primarily through the bite of infected female Aedes aegypti mosquitoes.

The National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health (NIH), announced it has begun a Phase I clinical trial of an investigational vaccine to protect against yellow fever virus. The experimental vaccine is being developed by the Danish biopharmaceutical company Bavarian Nordic.

A live attenuated virus vaccine for yellow fever has actually been in existence since the 1930s, but the Centers for Disease Control and Prevention (CDC) reports that no vaccine efficacy studies have been performed with the yellow fever vaccine, also known as 17D.

Although 17D is manufactured worldwide at the Bio-Manguinhos Oswaldo Cruz Foundation in Rio de Janeiro, Brazil; the Institute of Poliomyelitis and Viral Encephalitides in Moscow, Russia; the Pasteur Institute of Dakar in Dakar, Senegal; Sanofi Pasteur in Lyon, France; and at Berna, in Berne, Switzerland (formerly produced at the Robert Koch Institute in Berlin, Germany), the only 17D yellow fever vaccine approved for use in the United States (known as YF-Vax) is manufactured by Sanofi Pasteur in Swiftwater, Pennsylvania, according to the CDC. Only four of the six vaccine manufacturers are prequalified by the World Health Organization (WHO) to distribute vaccine product internationally. At a meeting earlier this year, WHO called the recent reappearance of yellow fever a serious health concern.

Manufacturing and supply issues have limited the amount of 17D that is available on the market. Plus, because the current vaccine options are made from a live attenuated virus, the vaccine cannot be used to treat certain immunocompromised patients. Current options, such as Sanofi’s Dengvaxia (CYD-TDV) and Imojev (ChimeriVax-JE) yellow fever vaccines, are made from live attenuated versions of the virus.


The NIH-backed vaccine candidate from Bavarian Nordic (MVA-BN-YF) will also be based on a weakened version of a virus, but will use a strain of the Modified Vaccinia Ankara (MVA) virus as a vaccine vector to carry yellow fever virus genes into the body. The MVA smallpox vaccine Imvamune is a non-replicating, highly attenuated live vaccinia virus. According to Bavarian Nordic, more than 7600 people, including 1000 individuals who are immunocompromised, have been safely vaccinated with vaccines using their MVA-BN-based platform. The company is currently in a partnership with Janssen to develop an Ebola vaccine using the same vaccine model.

A separate company, PnuVax, is taking a different approach to the manufacture of a yellow fever vaccine. The company plans to make an inactivated version, which is thought to be safer than a live attenuated version of the vaccine. PnuVax will use a modular FlexFactory from GE to manufacture the product, and GE will assist with production optimization. Unlike most other existing products and future product candidates, which are produced in pathogen-free chicken embryos, PnuVax would rely on the cell culture of Vero cells for the production of its yellow fever vaccine.

Sources: NIH, Bavarian Nordic