6B0S

Crystal structure of circumsporozoite protein aTSR domain in complex with 1710 antibody

Summary for 6B0S

• Entry DOI: 10.2210/pdb6b0s/pdb
• Descriptor: 1710 antibody, heavy chain, 1710 antibody, light chain, Circumsporozoite protein, ... (6 entities in total)
• Functional Keywords: malaria, circumsporozoite protein, alpha thrombospondin type-1 repeat, immune system
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 3
• Total formula weight: 56522.85

Authors

Scally, S.W.,Murugan, R.,Bosch, A.,Triller, G.,Wardemann, H.,Julien, J.P. (deposition date: 2017-09-15, release date: 2017-11-08, Last modification date: 2023-10-04)

Primary citation

Scally, S.W.,Murugan, R.,Bosch, A.,Triller, G.,Costa, G.,Mordmuller, B.,Kremsner, P.G.,Sim, B.K.L.,Hoffman, S.L.,Levashina, E.A.,Wardemann, H.,Julien, J.P.
Rare PfCSP C-terminal antibodies induced by live sporozoite vaccination are ineffective against malaria infection.
J. Exp. Med., 215:63-75, 2018

PubMed Abstract: Antibodies against the central repeat of the (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 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.

PubMed: 29167197
DOI: 10.1084/jem.20170869

Experimental method

X-RAY DIFFRACTION (1.95 Å)