Structural highlights
FunctionCSP_PLAFO The circumsporozoite protein is the immunodominant surface antigen on the sporozoite (the infective stage of the malaria parasite that is transmitted from the mosquito to the vertebrate host). Publication Abstract from PubMedAntibodies against the central repeat of the Plasmodium falciparum (Pf) circumsporozoite protein (CSP) inhibit parasite activity and correlate with protection from malaria. However, the humoral response to the PfCSP C terminus (C-PfCSP) is less well characterized. Here, we describe B cell responses to C-PfCSP from European donors who underwent immunization with live Pf sporozoites (PfSPZ Challenge) under chloroquine prophylaxis (PfSPZ-CVac), and were protected against controlled human malaria infection. Out of 215 PfCSP-reactive monoclonal antibodies, only two unique antibodies were specific for C-PfCSP, highlighting the rare occurrence of C-PfCSP-reactive B cells in PfSPZ-CVac-induced protective immunity. These two antibodies showed poor sporozoite binding and weak inhibition of parasite traversal and development, and did not protect mice from infection with PfCSP transgenic Plasmodium berghei sporozoites. Structural analyses demonstrated that one antibody interacts with a polymorphic region overlapping two T cell epitopes, suggesting that variability in C-PfCSP may benefit parasite escape from humoral and cellular immunity. Our data identify important features underlying C-PfCSP shortcomings as a vaccine target. Rare PfCSP C-terminal antibodies induced by live sporozoite vaccination are ineffective against malaria infection.,Scally SW, Murugan R, Bosch A, Triller G, Costa G, Mordmuller B, Kremsner PG, Sim BKL, Hoffman SL, Levashina EA, Wardemann H, Julien JP J Exp Med. 2017 Nov 22. pii: jem.20170869. doi: 10.1084/jem.20170869. PMID:29167197[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
| ||||||||||||||||||||
This page was last modified 14:29, 4 October 2023.