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 journalArticle

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.

Original languageEnglish (US)
Pages (from-to)532-539
Number of pages8
JournalNature structural & molecular biology
Volume22
Issue number7
DOIs
StatePublished - Jul 9 2015

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Anopheles
Malaria
Epitopes
Vaccines
Culicidae
CD13 Antigens
Parasites
Plasmodium
Plasmodium falciparum
Surface Antigens
Primates
Anti-Idiotypic Antibodies
Immunoglobulin G
Monoclonal Antibodies

ASJC Scopus subject areas

  • Structural Biology
  • Molecular Biology

Cite this

Atkinson, S. C., Armistead, J. S., Mathias, D. K., Sandeu, M. M., Tao, D., Borhani-Dizaji, N., ... Borg, N. A. (2015). The Anopheles-midgut APN1 structure reveals a new malaria transmission-blocking vaccine epitope. Nature structural & molecular biology, 22(7), 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 & molecular biology, Vol. 22, No. 7, 09.07.2015, p. 532-539.

Research output: Contribution to journalArticle

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 & molecular biology, vol. 22, no. 7, pp. 532-539. https://doi.org/10.1038/nsmb.3048
Atkinson SC, Armistead JS, Mathias DK, Sandeu MM, Tao D, Borhani-Dizaji N et al. The Anopheles-midgut APN1 structure reveals a new malaria transmission-blocking vaccine epitope. Nature structural & molecular biology. 2015 Jul 9;22(7):532-539. https://doi.org/10.1038/nsmb.3048
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 & molecular biology. 2015 ; Vol. 22, No. 7. pp. 532-539.
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