Atkinson S. C., Armistead J. S., Mathias D. K., Sandeu M. M., Tao D. Y., Borhani-Dizaji N., Tarimo B. B., Morlais Isabelle, Dinglasan R. R., Borg N. A. (2015). The Anopheles-midgut APN1 structure reveals a new malaria transmission-blocking vaccine epitope. Nature Structural and Molecular Biology, 22 (7), p. 532-539. ISSN 1545-9993.
Titre du document
The Anopheles-midgut APN1 structure reveals a new malaria transmission-blocking vaccine epitope
Atkinson S. C., Armistead J. S., Mathias D. K., Sandeu M. M., Tao D. Y., Borhani-Dizaji N., Tarimo B. B., Morlais Isabelle, Dinglasan R. R., Borg N. A.
Source
Nature Structural and Molecular Biology, 2015,
22 (7), p. 532-539 ISSN 1545-9993
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-angstrom 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.
Plan de classement
Sciences fondamentales / Techniques d'analyse et de recherche [020]
;
Entomologie médicale / Parasitologie / Virologie [052]
