Structural Basis for Recognition of the Malaria Vaccine Candidate Pfs48/45 by a Transmission Blocking Antibody

Overview

Journal Nat Commun

Specialty Biology

Date 2018 Sep 22

PMID 30237518

Citations 29

Authors

Frank Lennartz

Florian Brod

Rebecca Dabbs

Kazutoyo Miura

David Mekhaiel

Arianna Marini

Matthijs M Jore

Max M Sogaard

Thomas Jorgensen

Willem A de Jongh

Robert W Sauerwein

Carole A Long

Sumi Biswas

Matthew K Higgins

Affiliations

Soon will be listed here.

Abstract

The quest to develop an effective malaria vaccine remains a major priority in the fight against global infectious disease. An approach with great potential is a transmission-blocking vaccine which induces antibodies that prevent establishment of a productive infection in mosquitos that feed on infected humans, thereby stopping the transmission cycle. One of the most promising targets for such a vaccine is the gamete surface protein, Pfs48/45. Here we establish a system for production of full-length Pfs48/45 and use this to raise a panel of monoclonal antibodies. We map the binding regions of these antibodies on Pfs48/45 and correlate the location of their epitopes with their transmission-blocking activity. Finally, we present the structure of the C-terminal domain of Pfs48/45 bound to the most potent transmission-blocking antibody, and provide key molecular information for future structure-guided immunogen design.

Citing Articles

Structure of endogenous Pfs230:Pfs48/45 in complex with potent malaria transmission-blocking antibodies.

Bekkering E, Yoo R, Hailemariam S, Heide F, Ivanochko D, Jackman M bioRxiv. 2025; .

PMID: 39990443 PMC: 11844449. DOI: 10.1101/2025.02.14.638310.

Targeting Bottlenecks in Malaria Transmission: Antibody-Epitope Descriptions Guide the Design of Next-Generation Biomedical Interventions.

Yoo R, Jore M, Julien J Immunol Rev. 2025; 330(1):e70001.

PMID: 39907429 PMC: 11796336. DOI: 10.1111/imr.70001.

Target-agnostic identification of human antibodies to sexual forms reveals cross-stage recognition of glutamate-rich repeats.

Amen A, Yoo R, Fabra-Garcia A, Bolscher J, Stone W, Bally I Elife. 2025; 13.

PMID: 39817720 PMC: 11737873. DOI: 10.7554/eLife.97865.

Diversity and selection analyses identify transmission-blocking antigens as the optimal vaccine candidates in Plasmodium falciparum.

Ciubotariu I, Broyles B, Xie S, Thimmapuram J, Mwenda M, Mambwe B EBioMedicine. 2024; 106:105227.

PMID: 39018754 PMC: 11663769. DOI: 10.1016/j.ebiom.2024.105227.

Diversity and selection analyses identify transmission-blocking antigens as the optimal vaccine candidates in .

Ciubotariu I, Broyles B, Xie S, Thimmapuram J, Mwenda M, Mambwe B medRxiv. 2024; .

PMID: 38766239 PMC: 11100930. DOI: 10.1101/2024.05.11.24307175.

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