%0 Journal Article
%9 ACL : Articles dans des revues avec comité de lecture répertoriées par l'AERES
%A Atkinson, S. C.
%A Armistead, J. S.
%A Mathias, D. K.
%A Sandeu, M. M.
%A Tao, D. Y.
%A Borhani-Dizaji, N.
%A Tarimo, B. B.
%A Morlais, Isabelle
%A Dinglasan, R. R.
%A Borg, N. A.
%T The Anopheles-midgut APN1 structure reveals a new malaria transmission-blocking vaccine epitope
%D 2015
%L fdi:010064821
%G ENG
%J Nature Structural and Molecular Biology
%@ 1545-9993
%M ISI:000357614900004
%N 7
%P 532-539
%R 10.1038/nsmb.3048
%U https://www.documentation.ird.fr/hor/fdi:010064821
%> https://www.documentation.ird.fr/intranet/publi/2015/08/010064821.pdf
%V 22
%W Horizon (IRD)
%X 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-angstrom 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.
%$ 052 ; 020