Twofer for the Biggest Bioterror Threats?

If you ask biodefense experts to name two diseases that keep them awake at night, there's a good chance they'll mention smallpox and anthrax. Both are highly lethal, and current vaccines have major problems. Now, researchers have found a way to target both threats at the same time: a candidate vaccine that protects against the two diseases and seems to work better than the existing preventatives.

The vaccine against smallpox, a gruesome viral disease that killed 30% of its victims before it was eradicated in the 1970s, is highly effective in a single dose. But the vaccine is a living virus itself, called vaccinia, that can cause serious side effects such as brain and heart inflammation, sometimes leading to death. It is not recommended for various groups at risk—such as eczema patients and the immunocompromised—that together make up a quarter of the population. Officially, only two labs in the United States and Russia still have Variola major, the smallpox virus, but many worry about hidden stocks elsewhere.

The anthrax vaccine is also problematic. Composed of bits of a protein, called Protective Antigen (PA)—which are harvested from the anthrax bacterium, Bacillus anthracis—the vaccine is a cumbersome series of five or six shots given over 18 months that requires yearly boosters. It's also not very stable and has a shelf life of about 4 years, which makes stockpiling for emergencies expensive. And although the smallpox vaccine acts fast enough to offer protection even when given several days after exposure to the pathogen, lab data suggest that the anthrax vaccine does not. (Because anthrax is so rare, there has never been an opportunity to test this.)

Improving on these so-so shots was never a priority—until the first Gulf War, 9/11, and the 2001 anthrax attacks propelled the risk of biowarfare and bioterror onto the political agenda. Now, many researchers are trying to develop gentler smallpox vaccines and easier-to-use, more effective ones for anthrax.

Over the past decade, researchers led by Liyanage Perera of the National Cancer Institute have developed what they claim is a safer smallpox vaccine. They did so by equipping the vaccinia virus with a gene that encodes interleukin-15 (IL-15), a signal molecule that boosts the immune system and helps clear the virus more rapidly from the body while still triggering a robust reaction. In a paper recently published in Vaccine, the team showed that the new smallpox vaccine did not kill immunocompromised mice, like the standard vaccinia does; and in monkeys, it offered long-term protection from monkeypox, the best animal model for smallpox.

For the current study, the researchers went a step further: They also stitched into the vaccinia backbone a gene encoding PA, the protein subunit in the current anthrax vaccine. In a paper published online today in the Proceedings of the National Academy of Sciences (PNAS), the team shows that two doses of the resulting vaccine given 28 days apart protect rabbits from an otherwise lethal dose of inhaled anthrax spores. In additional mouse studies, the vaccine not only elicited more antibodies against PA than the conventional vaccine but also did so faster, presumably because of IL-15's boosting effects. That means it might be more useful after an anthrax attack than the current vaccine, the team writes. And unlike the existing anthrax vaccine, this one can be freeze-dried and presumably stored for decades.

In the PNAS paper, the team did not report whether the vaccine also protects against smallpox and its ilk, but additional studies suggest that it does, says Perera.

The vaccine is still a long way from being approved, notes Nir Paran, who studies poxviruses at the Israel Institute for Biological Research in Ness-Ziona. Still, he says, "it's an interesting paper that addresses several important issues."

But Les Baillie, an anthrax researcher at Cardiff University in the United Kingdom, isn't so sure that the vaccine will be very useful after a biowarfare attack. Even with a vaccine that's faster-acting, vaccinating large numbers of people rapidly would be a huge logistical challenge, he says. What's more, a dual vaccine might not make sense in that situation: "If you have an anthrax outbreak, why would you also want to vaccinate thousands of people against smallpox?"

The vaccine might be most useful before exposure, Baillie says, for instance, for military personnel and first responders, who are most likely to come into contact with either of the agents. "If you can take care of all the nasties with one jab, that's a huge logistical advantage."