The Anopheles-midgut APN1 structure reveals a new malaria transmission-blocking vaccine epitope.

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 Biol

authors

Atkinson SC,Armistead JS,Mathias DK,Sandeu MM,Tao D,Borhani-Dizaji N,Tarimo BB,Morlais I,Dinglasan RR,Borg NA

doi

10.1038/nsmb.3048

subject

Has Abstract

pub_date

2015-07-01 00:00:00

pages

532-9

issue

7

eissn

1545-9993

issn

1545-9985

pii

nsmb.3048

journal_volume

22

pub_type

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