Projects per year
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-A 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.
Original language | English |
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Pages (from-to) | 532 - 539 |
Number of pages | 8 |
Journal | Nature Structural & Molecular Biology |
Volume | 22 |
Issue number | 7 |
DOIs | |
Publication status | Published - 2015 |
Projects
- 2 Finished
-
Host-virus protein complexes in the immune system response to influenza
Atkinson, S.
National Health and Medical Research Council (NHMRC) (Australia)
1/01/14 → 31/12/17
Project: Research
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The regulation of anti-viral immunity by host and viral proteins
Australian Research Council (ARC), Monash University
1/08/12 → 31/12/18
Project: Research