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.
journal_name
Nat Struct Mol Bioljournal_title
Nature structural & molecular biologyauthors
Atkinson SC,Armistead JS,Mathias DK,Sandeu MM,Tao D,Borhani-Dizaji N,Tarimo BB,Morlais I,Dinglasan RR,Borg NAdoi
10.1038/nsmb.3048subject
Has Abstractpub_date
2015-07-01 00:00:00pages
532-9issue
7eissn
1545-9993issn
1545-9985pii
nsmb.3048journal_volume
22pub_type
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