1. The Anopheles-midgut APN1 structure reveals a new malaria transmission-blocking vaccine epitope.
- Author
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Atkinson, Sarah C, Armistead, Jennifer S, Mathias, Derrick K, Sandeu, Maurice M, Tao, Dingyin, Borhani-Dizaji, Nahid, Tarimo, Brian B, Morlais, Isabelle, Dinglasan, Rhoel R, and Borg, Natalie A
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MOSQUITO vectors ,MALARIA prevention ,VACCINES ,ANOPHELES ,AMINOPEPTIDASES ,CRYSTAL structure - Abstract
Mosquito-based malaria transmission-blocking vaccines (mTBVs) target midgut-surface antigens of the Plasmodium parasite's obligate vector, the Anopheles mosquito. The alanyl aminopeptidase N (AnAPN1) is the leading mTBV immunogen; however, AnAPN1's role in Plasmodium infection of the mosquito and how anti-AnAPN1 antibodies functionally block parasite transmission have remained elusive. Here we present the 2.65-Å crystal structure of AnAPN1 and the immunoreactivity and transmission-blocking profiles of three monoclonal antibodies (mAbs) to AnAPN1, including mAb 4H5B7, which effectively blocks transmission of natural strains of Plasmodium falciparum. Using the AnAPN1 structure, we map the conformation-dependent 4H5B7 neoepitope to a previously uncharacterized region on domain 1 and further demonstrate that nonhuman-primate neoepitope-specific IgG also blocks parasite transmission. We discuss the prospect of a new biological function of AnAPN1 as a receptor for Plasmodium in the mosquito midgut and the implications for redesigning the AnAPN1 mTBV. [ABSTRACT FROM AUTHOR]
- Published
- 2015
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