Year: 2023
Type: article
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.
Source: npj Vaccines
Authors: Niharika Shukla, Wai Kwan Tang, Camila H. Coelho, Carole A. Long, Sara A. Healy, Issaka Sagara, Kazutoyo Miura, Patrick E. Duffy, Niraj H. Tolia
Language: English
Topic: Malaria Research and Control
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $3,490
Funders: U.S. Department of Energy, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Office of Science, National Cancer Institute, National Institute of General Medical Sciences, National Institute of Allergy and Infectious Diseases, Argonne National Laboratory
Awards: G102163711, G107546177, G1313983767, G1505794299, G1633006425, G1664757510, G1699008898, G1800737955, Phase II SER-CAT Optimization: Acquisition of a next generation area detector, G2101401529, G2287611682, G2302316395, G262962599, G2887060908, G3039663548, G3075337988, G3127483976, G3152346458, G3338542329, G3359596609, G340565428, G3424175725, Acquisition of a High Precision Micro Diffractometer to Support NIH funded Research at SER-CAT, G3727249409, High-Speed High-Sensitivity Detector for X-ray Micro-Crystallography at GM/CA@APS, G3913106684, G409777406, G434509735, G4356617607, G498139845, G5106849484, G5607048534, G6072549038, G6153725424, G6800544485, G6848031779, G6918803902, G7368700025, G7932540327, G8473838722, G8500532866, G9000014584, UC San Diego Raising Advancement and Parity for Infectious Disease Researchers (RAPID) Faculty Development Program, Acquition of a microdiffractometer for SER-CAT, G969889393, G993149817
OpenAlex ID: W4385582254