Structure of the Malaria Vaccine Candidate Pfs48/45 and Its Recognition by Transmission Blocking Antibodies

Overview

Journal Nat Commun

Specialty Biology

Date 2022 Sep 24

PMID 36153317

Authors

Kuang-Ting Ko

Frank Lennartz

David Mekhaiel

Bora Guloglu

Arianna Marini

Danielle J Deuker

Carole A Long

Matthijs M Jore

Kazutoyo Miura

Sumi Biswas

Matthew K Higgins

Affiliations

Soon will be listed here.

Abstract

An effective malaria vaccine remains a global health priority and vaccine immunogens which prevent transmission of the parasite will have important roles in multi-component vaccines. One of the most promising candidates for inclusion in a transmission-blocking malaria vaccine is the gamete surface protein Pfs48/45, which is essential for development of the parasite in the mosquito midgut. Indeed, antibodies which bind Pfs48/45 can prevent transmission if ingested with the parasite as part of the mosquito bloodmeal. Here we present the structure of full-length Pfs48/45, showing its three domains to form a dynamic, planar, triangular arrangement. We reveal where transmission-blocking and non-blocking antibodies bind on Pfs48/45. Finally, we demonstrate that antibodies which bind across this molecule can be transmission-blocking. These studies will guide the development of future Pfs48/45-based vaccine immunogens.

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