Yellow Fever Vaccine Enters Clinical Trial

Currently, travel to and from Angola poses a threat of the spread of yellow fever to other countries. Although the infection is preventable, there is growing concern of a vaccine shortage. In light of this, the National Institute of Allergy and Infectious Diseases (NIAID) has started human clinical trials on a new yellow fever vaccine.

Angola has been experiencing an ongoing yellow fever outbreak since December 2015. In May of 2016, the first reported cases of yellow fever in China were confirmed to be originating from the Angola outbreak. Previously, health experts urged the World Health Organization (WHO) to take a stance in regards to the impending vaccine shortages. The currently available vaccine is a single-dose shot that provides life-long protection for those for whom vaccination is recommended; however, it can result in neurological impairment, multiple organ failure, and even death, for some.

In response to the growing outbreak and the escalating need for a vaccine that can be used in infants, those who are immunocompromised, and other populations in whom currently available vaccines are not to be administered, NIAID has entered a vaccine manufactured by Bavarian Nordic into Phase I trials. Anthony Fauci, MD, director of NIAID, stated in a press release, “Yellow fever has recently re-emerged as a major public health threat in parts of Africa. Although a vaccine exists to prevent this serious disease, it is currently in short supply, and it is not recommended for certain populations, such as pregnant women and people older than 60 years... We must develop new options for preventing this terrible disease.”

The clinical trial will evaluate the safety, tolerability, and efficacy of the new vaccine (MVA-BN-YF). MVA-BN-YF uses a weakened form of the Modified Vaccinia Ankara (MVA) virus to import the yellow fever virus into the human body. Bavarian Nordic has successfully vaccinated approximately 7,600 individuals, 1,000 of whom were immunocompromised. The trials will enroll a total of 90 “healthy men and women” between the ages of 18 and 45 who have never been infected with a flavivirus (including yellow fever, West Nile Virus, dengue, Zika). In the controlled, double-blinded trial, the available vaccine will be subcutaneously administrered to 15 participants, while the rest of the participants will be broken up into five groups of 15, in which the new vaccine will be administered intramuscularly either with or without an adjuvant.

According to the press release, in animal trials, “combining MVA-BN with ISA 720, an experimental immune-boosting adjuvant that has been used in prior clinical trials, induces a strong immune response after a single dose of vaccine.” The NIAID trial will compare the efficacy of two unadjuvanted doses of the vaccine to one dose of the vaccine administered with the ISA 720 adjuvant.

As of July 21, 2016, more than 3,000 suspected cases of yellow fever have been reported in Angola, with 877 being confirmed through lab testing, according to WHO. Of the confirmed cases, 117 have died of yellow fever infection. The Democratic Republic of Congo, a neighboring nation to Angola, has also reported a large number of suspected yellow fever cases. Of the more than 1,700 suspected cases in the Democratic Republic of Congo, 68 have been confirmed and 59 of those cases had been confirmed to be imported from Angola. WHO reports that “between 2007 and 2016, 14 countries have completed preventive yellow fever vaccination campaigns.”

Since 2006, a total of approximately 105 million individuals living in Africa have been vaccinated for yellow fever; nonetheless, there is a growing need for a vaccine that can be administered across all populations, without regards to age or underlying health conditions.