Experimental Vaccine Protects Against Multiple Ebolavirus Species

Created by CDC microbiologist Cynthia Goldsmith, this colorized transmission electron micrograph (TEM) revealed some of the ultrastructural morphology displayed by an Ebola virus virion.Ebolavirus, also known simply as Ebola, gained notoriety in the United States in 1989 and 1990, when imported monkeys infected with a subtype of the virus were introduced to quarantine facilities in Virginia, Pennsylvania, and Texas. The viral species isolated from the infected monkeys at a Reston, Virginia lab was eventually named Ebola-Reston, and the incident was documented in Richard Preston’s best-selling 1994 book The Hot Zone. Yet while Ebola-Reston proved quite dangerous to monkeys, it did not cause illness in humans: though some humans exposed to it developed antibodies, none experienced any symptoms.

Other species of Ebola, however, are far more dangerous. Ebola-Reston is only one of five known species of Ebola, and is the only one of the five that has never caused serious human illness. Of the others–Ebola-Zaire, Ebola-Sudan, Ebola-Ivory Coast, and Ebola-Bundibugyo–all but Ebola-Ivory Coast have led to varying rates of fatalities since the first known outbreak of Ebola-Zaire killed 88% of infected patients in 1976.

When the Ebola-Bundibugyo species was identified in 2007, researchers at the National Institutes of Health decided to try to develop a vaccine that could provide broad protection against Ebola as a whole (as opposed to a vaccine that would protect against only one species). The team was led by Nancy J. Sullivan, PhD (Vaccine Research Center at the National Institute of Allergy and Infectious Diseases) and included researchers from the Centers for Disease Control and Prevention as well as the U.S. Army Medical Research Institute for Infectious Diseases. In the May 2010 issue of PLoS Pathogens, the team published their results: a vaccine that provided protection against not only the two oldest and most lethal species (Ebola-Zaire and Ebola-Sudan) but against the emerging Ebola-Bundibugyo species as well.

The experimental vaccine is of the “prime-boost” type, wherein one vaccine component is designed to prime the immune system, and another to boost its response. In this case, the prime component is a DNA vaccine containing genetic material that codes for both Ebola-Zaire and Ebola-Sudan surface proteins; meanwhile, the boost component is an attenuated virus delivering an actual surface protein of Ebola-Zaire.

The experimental prime-boost vaccine generates a strong response, not only in the production of antibodies, but also in the response of T cells. This is particularly significant, as DNA vaccines alone cannot provoke a killer T cell response–only live, attenuated vaccines can. In this case, the researchers were able to provoke a T cell response without having to use an attenuated form of Ebolavirus.

Perhaps most importantly, T cells are the immune system component that are capable of generating broad immunity–that is, protection against more than one species of Ebola. Antibodies against Ebola are typically specific to a given species, so that antibodies generated against Ebola-Zaire may not be effective against Ebola-Sudan. T cells, however, can react to different species of Ebola, and in fact did during the researchers’ tests on macaque monkeys.

Four monkeys were given the vaccine, while four remained unvaccinated. All eight monkeys were then exposed to lethal levels of Ebola-Bundibugyo. The unvaccinated monkeys all fell ill, and three of the four died; meanwhile, none of the vaccinated monkeys experienced symptoms at all. Further analysis showed that the vaccinated monkeys were protected by T cell responses to Ebola-Bundibugyo, even though the vaccine components contained no Ebola-Bundibugyo material. In fact, the monkeys’ immune systems produced no Ebola-Bundibugyo-specific antibodies at all: they were entirely protected by their T cell responses.

The researchers are continuing their work by studying the T cell response in order to optimize the design of future vaccines. Their findings offer hope that a single vaccine against all species of Ebola may be possible.

Sources and additional reading:

Hensley LE, Mulangu S, Asiedu C, Johnson J, Honko AN, et al. 2010 Demonstration of Cross-Protective Vaccine Immunity against an Emerging Pathogenic Ebolavirus Species. PLoS Pathog 6(5): e1000904. doi:10.1371/journal.ppat.1000904
http://www.plospathogens.org/article/info%3Adoi%2F10.1371%2Fjournal.ppat.1000904

Known Cases and Outbreaks of Ebola Hemorrhagic Fever, in Chronological Order. CDC Special Pathogens Branch, created August 25, 2006.
http://www.cdc.gov/ncidod/dvrd/spb/mnpages/dispages/ebola/ebolatable.htm