8EZL

Pfs25 in complex with transmission-reducing antibody AS01-50

Summary for 8EZL

• Entry DOI: 10.2210/pdb8ezl/pdb
• Descriptor: 25 kDa ookinete surface antigen, Transmission-reducing antibody AS01-50, single chain Fv, 2-acetamido-2-deoxy-beta-D-glucopyranose, ... (4 entities in total)
• Functional Keywords: pfs25, transmission-blocking vaccine, immune system
• Biological source: Plasmodium falciparum NF54; More
• Total number of polymer chains: 2
• Total formula weight: 49976.13

Authors

Shukla, N.,Tang, W.K.,Tolia, N.H. (deposition date: 2022-11-01, release date: 2023-08-16, Last modification date: 2024-10-16)

Primary citation

Shukla, N.,Tang, W.K.,Coelho, C.H.,Long, C.A.,Healy, S.A.,Sagara, I.,Miura, K.,Duffy, P.E.,Tolia, N.H.
A human antibody epitope map of the malaria vaccine antigen Pfs25.
Npj Vaccines, 8:108-108, 2023

PubMed Abstract: Pfs25 is a leading antigen for a malaria transmission-blocking vaccine and shows moderate transmission-blocking activity and induction of rapidly decreasing antibody titers in clinical trials. A comprehensive definition of all transmission-reducing epitopes of Pfs25 will inform structure-guided design to enhance Pfs25-based vaccines, leading to potent transmission-blocking activity. Here, we compiled a detailed human antibody epitope map comprising epitope binning data and structures of multiple human monoclonal antibodies, including three new crystal structures of Pfs25 in complex with transmission-reducing antibodies from Malian volunteers immunized with Pfs25 conjugated to EPA and adjuvanted with AS01. These structures revealed additional epitopes in Pfs25 capable of reducing transmission and expanded this characterization to malaria-exposed humans. This work informs immunogen design to focus the antibody response to transmission-reducing epitopes of Pfs25, enabling development of more potent transmission-blocking vaccines for malaria.

PubMed: 37542029
DOI: 10.1038/s41541-023-00712-z

Experimental method

X-RAY DIFFRACTION (2.3 Å)