--- A child dies every 20 seconds from malaria. Photo courtesy of Dr. S. Lindsay, WHO
BETHESDA, Md. Scientists at the National Institutes of Health (NIH) and the Liverpool School of Tropical Medicine in England are hard at work developing a vaccine to combat malaria. But what makes the Liverpool project unusual is that researchers there plan to use the mosquitoes themselves as "airborne" inoculators.
The plan calls for creating squadrons of genetically altered Anopheles mosquitoes whose bites will carry a vaccine that will prevent transmission of the malaria parasite. When the malaria-carrying mosquitoes bite humans who have previously been bitten by the altered mosquitoes, human antibodies will attack the malaria parasite in the infected mosquito, blocking the spread of the disease, NIH officials said.
The research is still in its early stages, and the day when swarms of malaria preventing mosquitoes will bring relief to the people of Africa, Asia and South America is still some time off, but the researchers said there has been some progress.
"We were glancing at a picture of a mosquito and trying to decipher a way to deliver a [malaria] vaccine cheaply," said Robert Sinden, MD, of the Liverpool School of Tropical Medicine. "The answer was right in front of us."
According to numbers provided by the NIH, a child dies every 20 seconds from malaria. Malaria alone can kill up to 2 million people annually, mostly children, but health officials said that number is misleading because it only accounts for the number of hospital deaths. Estimates are that two to three times that number die at home. An additional 400 million people in Africa, Asia and South America will contract the disease before the end of the year.
Several drug companies have scaled back their malaria research just as strains are developing resistance to drugs like chloroquine (Aralen, Sanofi Winthrop). Historically, a vaccine can take an average of 12 years and cost in excess of $250 million from development to licensure. In 1996 alone, the NIH spent $19.2 million trying to develop a malaria vaccine.
The trouble with developing a malaria vaccine, said researchers, is that some of the parasite's genes constantly mutate, which makes it hard to target a specific protein that could elicit protective immunity. But the researchers in England think they have found one, which they dubbed Pbs21.
When the English scientists injected Pbs21 into 15 lab mice, the mice created antibodies against the malaria parasite. When several malaria-carrying mosquitoes fed on the mice, they ingested the antibodies as well. The antibodies were effective against 90% of the parasites. As a result, the next set of mice bitten by any of the inoculated mosquitoes would have a much smaller chance of contracting the disease.
The problem with developing a vaccine in the past was how to deliver it safely, cheaply and effectively. One way, of course, would be to use the mosquito itself to deliver the injection, NIH officials said.
"It could be a very effective way to deliver the vaccine without having to mobilize medical teams to tramp around jungles and swamps," said Kate Aultman, Vector Biology Program Officer at the National Institute for Allergy and Infectious Diseases (NIAID) at the NIH, who are also in the process of developing a malaria vaccine that would block the parasite's transmission.
Currently, NIAID is supporting efforts to develop a malaria vaccine, including a transmission-blocking vaccine. But NIAID is taking another tack.
Proteins from the form of the malaria parasite which exists in the mosquito are injected into people, who then generate antibodies. The mosquitoes that subsequently bite those people ingest the antibodies along with many malaria parasites.
"The differences between [the English and American vaccine research] are in the methods of inoculation and the identity of the protein being studied," Aultman said.
One great challenge to English scientists is to get the mosquito to act as the carrier of the Pbs21 protein, which means genetically altering its salivary glands so that when it bites, it passes on the protein antibody.
But the question then arises: if scientists genetically alter the mosquito, could it one day simply mutate and begin carrying a more virulent strain of the parasite?
"The mosquitoes would not be given the entire malaria parasite but only a particular surface protein. What you're doing is allowing them to carry a tiny portion of the parasite," said Aultman. "The chance that this method of inoculation could cause a terrible form of malaria is remote, but not impossible."
Aultman said the malaria protein carries various proteins on its surface that are vital to its survival. When the parasite enters the human body, the body defends itself against these proteins by producing antibodies, according to Aultman.
But the mosquito constantly mutates, altering its genomes and proteins almost at will. Many scientists have deep reservations about changing mosquitoes' genomes because people who live in malaria-ridden areas have built up an immunity to the parasite and could develop a much more virulent form of the disease.
The problem with making the mosquito a vaccine carrier is that its tiny salivary gland, where the malaria antibodies would be stored, could also be effected by mutation. However, despite the lingering questions and lack of a workable vaccine, scientists are confident that in the long run the malaria threat can be controlled.
"In theory we could someday eradicate [malaria], but practically speaking it makes more sense to think in terms of controlling severe disease," Aultman said. "But what impact could genetically altered mosquitoes have on the environment we'll just have to wait and see what develops in the lab."
For more information
- NIAID. Policy Paper. Research Plan for Malaria Vaccine Development. Washington, D.C. 1997.
- Altman K. (NIAID) Policy Paper. Research plan for malaria vaccine development. Washington, D.C. 1997.
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