Johns Hopkins
Malaria Research Institute scientists have taken one
step closer to a universal
malaria transmission-blocking vaccine by creating a new
technique for preventing the development of
malaria parasites in multiple mosquito species.
The researchers identified a previously unknown
mosquito antigen that the parasite uses for
entry into the mosquito midgut, a critical step in the
Plasmodium parasite's development. They
produced an antibody that acts as a blanket that prevents
the parasite from accessing the mosquito
midgut antigen.
The study was published in PNAS Early Edition
on Aug. 2.
Mosquitoes pick up the Plasmodium parasite from
infected hosts during a blood feeding. In
order for malaria parasites to be transmitted to a new
human host, the parasite must first penetrate
the mosquito midgut before moving on to invade other
tissues. This penetration requires recognition
of the antigen, called Anopheles gambiae aminopeptidase N
(AgAPN1), on the surface of the mosquito
midgut.
"If you 'cover' the antigen with an antibody, parasite
invasion of the midgut is inhibited, and the
mosquito can't transmit the parasite," said Marcelo
Jacobs-Lorena, senior author of the study and a
professor in the W. Harry
Feinstone Department of Molecular Microbiology and
Immunology.
Jacobs-Lorena explained that vaccines based on this
antigen have the potential to block
transmission of the deadliest human malaria parasite
— Plasmodium falciparum — in a broad range of
mosquito species, including Anopheles gambiae, Anopheles
stephensi and possibly most parasite
vectors. The researchers also have preliminary data that
show that the antibody can block another
human malaria parasite, Plasmodium vivax.
Rhoel R. Dinglasan, lead author of the study and a
postdoctoral fellow with the Malaria Research
Institute, said, "The antibodies that we have produced are
effective against multiple malaria parasites
and, therefore, this antigen may constitute the basis for a
future 'universal' malaria transmissionÐ
blocking vaccine."
Investigators caution that although their results add
to the understanding of malaria parasiteÐ
mosquito host interaction and guide in the design of
transmission-blocking vaccines, more research is
needed before a vaccine can be developed.
The current research is one of a handful of ways
Jacobs-Lorena and his team are hoping to stop
the transmission of malaria. In March, Jacobs-Lorena and
colleagues determined that genetically
engineered malaria-resistant mosquitoes fared better than
their natural counterparts when fed
malaria-infected blood. Theoretically, mosquitoes resistant
to malaria could be introduced into nature
to replace malaria-carrying mosquitoes.
In addition, in 2002, researchers from the same
laboratory identified a small protein that when
expressed in transgenic mosquitoes helps fight off
infection by the Plasmodium parasite.
The research was supported by grants from the National
Institutes of Health.
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