Team discovers antigen that blocks transmission of a deadly malaria parasite in the midgut of a mosquito
A novel finding by a Johns Hopkins University researcher may constitute the basis for a future “universal” malaria vaccine. Marcelo Jacobs-Lorena, Ph.D., W. Harry Feinstone Department of Molecular Microbiology and Immunology, and his team seek to increase understanding of how the malaria parasite Plasmodium falciparum interacts with its primary mosquito host, Anopheles gambiae.
Dr. Jacobs-Lorena and his colleagues identified a previously unknown mosquito antigen that the parasite uses to enter into the mosquito midgut, a critical step in the parasite’s development. Mosquitoes pick up P. falciparum parasites when they feed on the blood of infected humans. However, before these parasites can transmit malaria infection to a new human host, they must first penetrate the mosquito midgut. This penetration requires recognition of the antigen, called Anopheles gambiae aminopeptidase N (AgAPN1), on the surface of the mosquito midgut. Dr. Jacobs-Lorena team produced an antibody that prevents the parasite from accessing the mosquito midgut antigen.
Vaccines based on this antigen have the potential to block transmission of P. 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 the antibody can block another human malaria parasite, Plasmodium vivax.
In other NIAID-funded work, Dr. Jacobs-Lorena and his team created genetically modified mosquitoes resistant to Plasmodium. This finding raises the possibility of one day stopping the spread of the disease. The research team combined equal numbers of genetically engineered and natural mosquitoes in the laboratory and let them feed on malaria-infected mice. The genetically engineered mosquitoes out bred the natural mosquitoes, raising the possibility that they might be able to replace them if released into the wild.
The study suggests that when transgenic, malaria-resistant mosquitoes feed on malaria-infected blood, they have a selective advantage over non-transgenic mosquitoes. The lab-altered mosquitoes competed equally well with natural insects when fed noninfected blood but did not outbreed their natural counterparts in that case.
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