Ebola, Marburg DNA Vaccines Prove Safe in Phase 1 Trial

Beth Skwarecki

September 17, 2014

A phase 1 clinical trial showed that 2 experimental vaccines, 1 against Ebola and 1 against the related Marburg virus, are well-tolerated and produce immunity after a course of 3 shots and a later booster. The results were published online September 14 in the Journal of Infectious Diseases.

Both viruses are in the Filoviridae family, both cause hemorrhagic fever, and both rely on a glycoprotein on their surface for entry into human cells. Previous studies in nonhuman primates showed that vaccines based on this glycoprotein in its natural, wild-type form are safe and provide better protection than vaccines in which the glycoprotein had been altered.

The current trial tested each vaccine in 10 healthy adults aged 18 to 60 years who were recruited in 2008 and 2009. The vaccines were made with a strand of DNA encoding the virus's wild-type glycoprotein. The DNA does not replicate in human cells, but the patient's body makes glycoproteins from the DNA instructions, triggering an immune response. The Marburg virus vaccine was based on the glycoprotein from the Angola strain, and the Ebola vaccine was based on glycoproteins from the Zaire and Sudan species. (The current Ebola outbreak in western Africa involves the Zaire species.)

Participants received the vaccine in a 3-dose priming series at 4-week intervals. An optional fourth shot was given as a booster after week 32. All but 2 participants completed the 3-dose series.

Both vaccines were well-tolerated, and there were no adverse events, the investigators report. Patients were followed until 32 weeks; those who received the booster shot were followed for an additional 12 weeks. After the 3-dose series, 8 of 10 participants who had received the Marburg vaccine had positive enzyme-linked immunosorbent assay results for the Marburg glycoprotein 4 weeks later, showing immunogenicity. Among participants who received the Ebola vaccine, 8 of 9 tested positive for immunity at the 4-week mark against the Sudan glycoprotein, and 5 of 9 for the Zaire glycoprotein.

The response declined over time, however, with only a single participant showing immunity 24 weeks after the third vaccination. The booster improved antibody and T-cell responses.

"A well tolerated, highly effective Ebola vaccine that can rapidly elicit protection following the administration of a single dose would constitute an important public health tool," write Myron M. Levine, MD, DTPH, from the Center for Vaccine Development, University of Maryland School of Medicine, Baltimore, and colleagues in an editorial. Ideally, such a vaccine could be given to healthcare workers and to contacts of an infected person to provide immediate immunity.

Field tests for Ebola vaccines are difficult, they write, in part because setting up a trial before an Ebola outbreak occurs is difficult when outbreaks are unpredictable and because controlled trials in the midst of an epidemic present ethical issues. Instead, they note that phase 2 trials could be done during an outbreak by comparing rates of disease and fatalities among high-risk groups before and after the vaccine is introduced; this is how effectiveness was shown for the Sabin polio vaccine.

The vaccine trial was funded by the National Institutes of Health Intramural Research Program. The authors have disclosed no relevant financial relationships.

When asked whether the DNA vaccines would be tested in the ongoing Ebola outbreak in West Africa, a spokesperson for the National Institute of Allergy and Infectious Diseases said, "The Ebola DNA vaccine was a precursor to the chimp adenovirus 3 vaccine that is currently being tested in clinical trials at [the National Institutes of Health]. There will be no further testing of the DNA vaccine."

J Infect Dis. Published online September 14, 2014. Full text

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