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Aug 3, 2007

Investigators Reveal Novel Mosquito Antigen to Block Malaria Transmission

  • Johns Hopkins Malaria Research Institute scientists have created a technique to prevent the development of malaria parasites in multiple mosquito species.

    “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 transmission-blocking vaccine,” remarks Rhoel R. Dinglasan, Ph.D., lead author of the study and a postdoctoral fellow with the Malaria Research Institute.

    The team identified a previously unknown mosquito antigen that the parasite uses for entry into the mosquito midgut. They produced an antibody that acts as a blanket, preventing the parasite from accessing the mosquito midgut antigen.

    Malaria parasites must undergo development within mosquitoes to be transmitted to a new host. Antivector transmission-blocking vaccines inhibit parasite development by preventing ookinete interaction with mosquito midgut ligands. Jacalin (a lectin) inhibits ookinete attachment by masking glycan ligands on midgut epithelial surface glycoproteins. However, the identities of these midgut glycoproteins have remained unknown, according to the scientists.

    The Johns Hopkins team reports on the molecular characterization of an Anopheles gambiae aminopeptidase N (AgAPN1) as the predominant jacalin target on the mosquito midgut luminal surface and provides evidence for its role in ookinete invasion.

    “If you ‘cover’ the antigen with an antibody, parasite invasion of the midgut is inhibited, and the mosquito can't transmit the parasite,” explains Marcelo Jacobs-Lorena, Ph.D., senior author of the study and a professor in the W. Harry Feinstone Department of Molecular Microbiology and Immunology.

    alpha-AgAPN1 IgG strongly inhibited both Plasmodium berghei and Plasmodium falciparum development in different mosquito species, according to the researchers. This implies that AgAPN1 has a conserved role in ookinete invasion of the midgut. Molecules targeting single midgut antigens seldom achieve complete abrogation of parasite development, the team adds.

    Dr. Jacobs-Lorena believes that vaccines based on this antigen have the potential to block transmission of the human malaria parasites in a broad range of mosquito species, including Anopheles gambiae and Anopheles stephensi, and possibly most parasite vectors. The researchers also have preliminary data that shows that the antibody can block another human malaria parasite, Plasmodium vivax.

    They also found that the combined blocking activity of alpha-AgAPN1 IgG and an unrelated inhibitory peptide, SM1, against P. berghei was incomplete.

    “Therefore, we hypothesize that ookinetes can evade inhibition by two potent transmission-blocking molecules, presumably through the use of other ligands, and that this process further partitions murine from human parasite midgut invasion models,” the scientists write.

    Investigators caution that although their results add to the understanding of malaria parasite-mosquito host interaction and will help design transmission-blocking vaccines, more research is needed before a vaccine can be developed.

    The study was published in early edition of Proceedings of the National Academy of Sciences on August 2.



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