Abstract
| Original language | English |
|---|---|
| Pages (from-to) | 532 - 539 |
| Number of pages | 8 |
| Journal | Nature Structural and Molecular Biology |
| Volume | 22 |
| Issue number | 7 |
| DOIs | |
| Publication status | Published - 2015 |
Cite this
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The Anopheles-midgut APN1 structure reveals a new malaria transmission-blocking vaccine epitope. / 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; Borg, Natalie A.
In: Nature Structural and Molecular Biology, Vol. 22, No. 7, 2015, p. 532 - 539.Research output: Contribution to journal › Article › Research › peer-review
TY - JOUR
T1 - The Anopheles-midgut APN1 structure reveals a new malaria transmission-blocking vaccine epitope
AU - Atkinson, Sarah C
AU - Armistead, Jennifer S
AU - Mathias, Derrick K
AU - Sandeu, Maurice M
AU - Tao, Dingyin
AU - Borhani-Dizaji, Nahid
AU - Tarimo, Brian B
AU - Morlais, Isabelle
AU - Dinglasan, Rhoel R
AU - Borg, Natalie A
PY - 2015
Y1 - 2015
N2 - 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.
AB - 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.
UR - http://www.nature.com/nsmb/journal/v22/n7/pdf/nsmb.3048.pdf
U2 - 10.1038/nsmb.3048
DO - 10.1038/nsmb.3048
M3 - Article
VL - 22
SP - 532
EP - 539
JO - Nature Structural Biology
JF - Nature Structural Biology
SN - 1545-9993
IS - 7
ER -