Dutch biotechnology company, Crucell, is to collaborate with the US National Institute of Allergy and Infectious Diseases (NIAID) to develop the first vaccine against the Ebola virus. Although Ebola kills far fewer people worldwide than scourges like malaria and AIDS, new concerns about bioterrorism—and the possibility that Ebola could eventually blossom into a global pandemic—have inspired a new effort to develop vaccines.
Live Ebola virus must be handled in a high-level 'P4' containment laboratory, and the virus does not seem susceptible to a straightforward vaccination strategy. The new vaccine, which was developed at NIAID, uses DNA encoding three Ebola glycoproteins and one nucleoprotein, followed by a boost with a replication-defective adenovirus expressing Ebola antigens (Nature408, 605; 2000). It is the first vaccine to generate protective immunity against Ebola in non-human primates.
Gary Nabel, director of the Vaccine Research Center at NIAID and senior researcher on the project, says, "DNA is very good at [inducing] cell-mediated immunity, but not so good at inducing an antibody response. We actually think ... that you need both cell-mediated and some degree of humoral immunity," which is induced by the adenoviral booster.
Unfortunately, "lots of people have adenovirus antibodies, which hampers its use [as a vector for vaccine antigens]," according to virology expert Jaap Goudsmit, head of vaccine research at Crucell. To address this problem, Crucell is developing a version of the NIAID Ebola vaccine that will use the rare serotype of adenovirus 35. Less than 5% of the population has antibodies against this serotype. Crucell has also developed a cell line that will produce replication-defective adenovirus 35, and is in the process of adapting Nabel's strategy to this platform. Goudsmit estimates that the new vaccine system will be entering nonhuman primate trials at the NIH in 3 to 4 months.
Considering the relative rarity and small size of Ebola outbreaks, the vaccine may appear to be headed for a tiny market. As Goudsmit points out, however, "since 9/11 the world changed dramatically in terms of markets. Did you or did I ever believe there would be a smallpox vaccine market ever again? That market is now big. So this makes [the Ebola vaccine] a very attractive way of validating the quality of our vectors and cell lines."
Because the etiology of Ebola is still poorly understood, the availability of a vaccine might also be a boon to public health in the future. "Obviously today Ebola is not a raging epidemic ... on the other hand it takes years to develop a vaccine, so if something should ever break out and we have a product that works, then obviously that's a very good approach for public health," says Nabel.
Before the vaccine can be made available, however, it must gain government approval. Traditional efficacy trials would be both unethical and impractical, so Crucell and NIAID are planning to use an alternative approval process recently introduced by the FDA (see box).
