Format

Send to

Choose Destination
J Exp Med. 2018 Jan 2;215(1):63-75. doi: 10.1084/jem.20170869. Epub 2017 Nov 22.

Rare PfCSP C-terminal antibodies induced by live sporozoite vaccination are ineffective against malaria infection.

Author information

1
Program in Molecular Medicine, Hospital for Sick Children Research Institute, Toronto, Ontario, Canada.
2
B Cell Immunology, German Cancer Research Center, Heidelberg, Germany.
3
Vector Biology Unit, Max Planck Institute for Infection Biology, Berlin, Germany.
4
Institute of Tropical Medicine and German Center for Infection Research, University of Tübingen, Tübingen, Germany.
5
Sanaria Inc., Rockville, MD.
6
B Cell Immunology, German Cancer Research Center, Heidelberg, Germany h.wardemann@dkfz.de.
7
Program in Molecular Medicine, Hospital for Sick Children Research Institute, Toronto, Ontario, Canada jean-philippe.julien@sickkids.ca.
8
Department of Biochemistry, University of Toronto, Toronto, Ontario, Canada.
9
Department of Immunology, University of Toronto, Toronto, Ontario, Canada.

Abstract

Antibodies 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.

PMID:
29167197
PMCID:
PMC5748854
DOI:
10.1084/jem.20170869
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for HighWire Icon for PubMed Central
Loading ...
Support Center