Cheap, Convenient DNA Vaccine May Short-Circuit Malaria Parasite

Researchers from the Johns Hopkins School of Public Health have fashioned a DNA-based vaccine, tailor-made from bits of nucleic acid that match a segment of the malaria parasite's own DNA, which short-circuits the parasite's development and blocks malaria transmission. The study appeared in the April 1999 issue of Infection and Immunity.

Despite intensive mosquito-control campaigns and a range of drug treatments, malaria continues to devastate the health of 300 to 500 million people each year. Senior author Nirbhay Kumar, PhD, associate professor, Molecular Microbiology and Immunology, Johns Hopkins School of Public Health, said, "DNA technology may allow us to develop vaccines that reduce or even eliminate parasite infectivity in the mosquito, thus blocking malaria transmission." Lead author Cheryl Lobo, PhD, postdoctoral fellow, Molecular Microbiology and Immunology, Johns Hopkins School of Public Health, noted that the DNA vaccines have several advantages over those made from conventional proteins: they are easy to produce and inexpensive, don't need refrigeration, and are responsive to genetic manipulation.

Malaria is caused by a parasite, Plasmodium falciparum, the sexual form of which is taken in by the mosquito when it bites an infected human. The parasite incubates in the insect's midgut until maturing into an infective form, which is reintroduced into humans when the mosquito feeds again.

The researchers injected mice with the DNA vaccine both intramuscularly and intradermally, in order to force the immune system to make antibodies that would seek out and neutralize infectivity of sexual forms to mosquitoes. Both before immunization and four weeks after, serum samples were collected from the mice and then fed along with P. falciparum sexual forms to Anopheles mosquitoes. Eight days after this feeding, the mosquitoes were dissected and their midguts examined for the presence of oocysts of Plasmodium. The mosquitoes that had ingested sera from immunized mice showed a 75 percent decrease in the rates of infection, and up to a 97 percent decrease in the numbers of oocysts. Although all mice developed antibody responses to the DNA vaccines, antibodies levels were as much as 30 times higher with the intramuscular route than with the intradermal route.

Before human vaccine trials are contemplated, studies are in progress to demonstrate comparable antibody development in nonhuman primates immunized with the DNA vaccine.

Support for this study was provided by grants from the National Institutes of Health and from the United Nations Development Program/World Bank/World Health Organization.