Scientists at the U.S. Food and Drug Administration (FDA) have demonstrated novel immune system targets on Ebola virus and identified the major type of vaccine-triggered antibodies that neutralize the virus.

The findings also demonstrate that selection of the appropriate assay may be important for evaluating effective vaccines against the Ebola virus.

Ebola virus causes severe and often fatal disease in humans and is considered a global public health priority. The 2014 Ebola virus epidemic in Western Africa caused more than 28,652 human cases and 11,325 deaths as of mid-April 2016—a fatality rate of about 40%. Moreover, since small outbreaks occasionally occur in Western Africa and the virus might persist in some survivors, public health experts fear that severe epidemics could recur.

The FDA scientists tracked the immune responses in 39 healthy adult volunteers who received one of three doses of an investigational Ebola vaccine (3 million, 20 million, or 100 million pfu-plaque-forming units, a method of measuring virus concentration) during a clinical trial at the National Institutes of Health.  The initial vaccination was followed later by a boost (second dose of the vaccine). The vaccine was a genetically modified virus called vesicular stomatitis virus (rVSV). The modified virus carried on its surface a molecule, called a glycoprotein (GP) that was identical to the GP of a strain of Ebola that caused the 1995 disease outbreak in Africa, which closely matches the 2014 African Ebola strain.

The scientists found novel targets on Ebola GP that could be considered in new vaccine designs. In addition, individuals who had received the mid-range dose vaccines produced a higher diversity of antibodies against various targets on GP than did individuals who received either the lower or higher dose. One variety (isotype) of antibody, called IgM, was the main isotype that appeared after both the first and second vaccinations (also referred to as “prime-boost”).  The discovery was unexpected, since another type of antibody, IgG, is generally the major subtype to appear after prime-boost vaccination.  Even though IgM antibodies disappeared rapidly, they were shown to neutralize Ebola virus in test tubes studies.

The study’s findings also suggest that the rate of decay of vaccine-generated antibodies may be important to determine the timing and type of a second vaccine dose to generate more durable antibody responses.

Title

“Human antibody repertoire following VSV-Ebola vaccination identifies novel targets and virus neutralizing IgM antibodies.”

Nature Medicine; Published online October 31, 2016

Authors

Surender Khurana¹, Sandra Fuentes¹, Elizabeth M. Coyle¹, Supriya Ravichandram¹, Richard T. Davey Jr.², and John H. Beigel³

¹Division of Viral Products, Center for Biologics Evaluation and Research (CBER), FDA, Silver Spring, Maryland, USA,
²National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.
³Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research, Frederick, Maryland, USA.