WASHINGTON — A one-two punch of malaria DNA virus and the virus used to vaccinate against smallpox spurs the human immune system to mount a powerful defense against malaria, researchers report.
This approach might provide a basis for preventive and therapeutic vaccination in people, scientists said in a paper that appears in Monday's online issue of the journal Nature Medicine.
The research team led by Adrian V.S. Hill of the Oxford University in England tested the combination on 63 volunteers — the first human trials of this prime-boost approach — and found the body's response far surpassed either vaccine on its own.
The treatment did not induce complete immunity to malaria, but it provided partial protection. Researchers hope it will perform even better in field tests in Africa, where U.N. agencies say the mosquitoborne disease infects 300 million people a year and has become increasingly resistant to drugs.
Smallpox vaccine virus used in the tests is a modified form that researchers said is safer than one that has caused problems in recent vaccination programs.
The human tests were conducted after the idea was successfully tested in mice, Hill said.
Using a strain of the smallpox vaccine known as MVA, the researchers found it had "a rare ability to selectively boost" T-cells — critical immune cells that attack invading disease — that have been primed in advance by the malaria protein, Hill said.
Thus, Hill said, "the immunization order is critical."
The DNA vaccine induces T-cells to respond to a malaria antigen called thrombospondin-related adhesion protein, or TRAP; the modified smallpox virus also produces a response to TRAP. As a result, the T-cells react strongly to the malaria parasite, delaying its release from the liver into the bloodstream and reducing the number of released parasites.
Programs to immunize millions of Americans against smallpox have run into problems because of worries about side effects from the vaccine. Hill said the MVA strain of vaccinia is a safer strain of the smallpox vaccine.
"MVA was used in Germany in the 1970s as a smallpox vaccine," he said. Recently, he said, the United States has begun looking at it as a next-generation vaccine. The government began research in February to develop a safer vaccine.
Along with its benefits in boosting response to malaria, Hill said, "it very likely protects against smallpox to some degree." Since naturally occurring smallpox has been eliminated, no data are available to prove that.
MVA is also being used in trials in Africa in an effort to boost the immune response to AIDS.
Mark James, a professor of tropical medicine at Tulane University in New Orleans, welcomed the report.
Even though the complete immunity sought by the scientists was not achieved, they reported a 70 percent to 80 percent reduction in parasites in the bloodstream, said James, who was not part of the research team.
In addition, James said, the vaccine would be relatively cheap to produce, is stable and has been found to be safe.
Besides Oxford, the team included researchers from Imperial College, London; Walter Reed Army Institute of Medical Research in Maryland; PowderJect Pharmaceutical Plc, in Madison, Wis.; and Oxxon Pharmaccines in England.
On the Net: Nature Medicine: nature.com/nm