International Immunology, Vol 9, 1817-1824, Copyright © 1997 by Oxford University Press
M Marussig, L Renia, A Motard, F Miltgen, P Petour, V Chauhan, G Corradin and D Mazier
We previously reported the identification of a T cell epitope in the N-
terminal part of the circumsporozoite protein (CSP) of Plasmodium yoelii
yoelii (Pyy). CD4+ T cell clones derived from mice immunized with a 21-mer
peptide (amino acids 59-79, referred to as Py1) containing this epitope
confer complete protection after passive transfer in mice. These clones
proliferate in vitro in the presence of a 13-mer peptide (amino acids
59-71, referred to as Py1T). This shorter peptide was found to behave as a
Th epitope in vivo, allowing overcoming of the genetic restriction for
production of anti-repeat antibodies in BALB/c mice, when cross-linked to
three (QGPGAP) repeats of the Pyy CSP. In this study, we report protection
in BALB/c mice, against a challenge with Pyy sporozoites after immunization
with linear and multiple antigen peptides containing Py1T as T epitope and
three repeats QGPGAP (Py3) as B epitope. Multiple antigen peptide
(MAP4-Py1T- Py3)-induced immunity was shown to be more effective than
immunity induced by the linear form of the conjugate (Py1T-Py3), protecting
against challenges with higher numbers of sporozoites. In both cases,
levels of anti-repeat antibodies were strongly correlated with anti-
parasite antibodies and protection. When tested in vitro, sera from mice
immunized with the protective constructs strongly inhibited Pyy liver
stages, while lymph node T cells displayed no cytotoxicity. In vivo,
depletion of CD4+ or CD8+ T cells did not affect protection. Furthermore,
MAP4-Py1T-Py3-immunized mice were not protected against a challenge with P.
yoelii nigeriensis sporozoites, a parasite which has the same Py1T sequence
but differs from Pyy in its repeated sequence. These results demonstrate
that anti-repeat antibodies raised by immunization with the linear or the
MAP form are exclusively responsible for the protection. Furthermore, this
antibody response is boosted by a sporozoite challenge, allowing protection
against a second challenge.
ARTICLES
Linear and multiple antigen peptides containing defined T and B epitopes of the Plasmodium yoelii circumsporozoite protein: antibody- mediated protection and boosting by sporozoite infection
INSERM U313, CHU Pitie-Salpetriere, Paris, France.
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