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

Sarah C Atkinson, Jennifer S Armistead, Derrick K Mathias, Maurice M Sandeu, Dingyin Tao, Nahid Borhani-Dizaji, Brian B Tarimo, Isabelle Morlais, Rhoel R Dinglasan, Natalie A Borg

Research output: Contribution to journalArticleResearchpeer-review

21 Citations (Scopus)

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 languageEnglish
Pages (from-to)532 - 539
Number of pages8
JournalNature Structural and Molecular Biology
Volume22
Issue number7
DOIs
Publication statusPublished - 2015

Cite this

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. / The Anopheles-midgut APN1 structure reveals a new malaria transmission-blocking vaccine epitope. In: Nature Structural and Molecular Biology. 2015 ; Vol. 22, No. 7. pp. 532 - 539.
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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.",
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Atkinson, SC, Armistead, JS, Mathias, DK, Sandeu, MM, Tao, D, Borhani-Dizaji, N, Tarimo, BB, Morlais, I, Dinglasan, RR & Borg, NA 2015, 'The Anopheles-midgut APN1 structure reveals a new malaria transmission-blocking vaccine epitope', Nature Structural and Molecular Biology, vol. 22, no. 7, pp. 532 - 539. https://doi.org/10.1038/nsmb.3048

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 journalArticleResearchpeer-review

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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

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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.

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