LINEAR AND MULTIPLE ANTIGEN PEPTIDES CONTAINING DEFINED T-EPITOPE ANDB-EPITOPE OF THE PLASMODIUM-YOELII CIRCUMSPOROZOITE PROTEIN - ANTIBODY-MEDIATED PROTECTION AND BOOSTING BY SPOROZOITE INFECTION
M. Marussig et al., LINEAR AND MULTIPLE ANTIGEN PEPTIDES CONTAINING DEFINED T-EPITOPE ANDB-EPITOPE OF THE PLASMODIUM-YOELII CIRCUMSPOROZOITE PROTEIN - ANTIBODY-MEDIATED PROTECTION AND BOOSTING BY SPOROZOITE INFECTION, International immunology, 9(12), 1997, pp. 1817-1824
We previously reported the identification of a T cell epitope in the N
-terminal part of the circumsporozoite protein (CSP) of Plasmodium yoe
lii yoelii (Pyy), CD4(+) T cell clones derived from mice immunized wit
h 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 peptid
e (amino acids 59-71, referred to as Py1T), This shorter peptide was f
ound to behave as a T-h epitope in vivo, allowing overcoming of the ge
netic restriction for production of anti-repeat antibodies in BALB/c m
ice, when cross-linked to three (QGPGAP) repeats of the Pyy CSP, In th
is study, we report protection in BALB/c mice, against a challenge wit
h Pyy sporozoites after immunization with linear and multiple antigen
peptides containing Py1T as T epitope and three repeats QGPGAP (Py3) a
s B epitope, Multiple antigen peptide (MAP4-Py1T-Py3)-induced immunity
was shown to be more effective than immunity induced by the linear fo
rm of the conjugate (Py1T-Py3), protecting against challenges with hig
her numbers of sporozoites, In both cases, levels of anti-repeat antib
odies were strongly correlated with anti-parasite antibodies and prote
ction, When tested in vitro, sera from mice immunized with the protect
ive 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-immun
ized mice were not protected against a challenge with P. yoelii nigeri
ensis sporozoites, a parasite which has the same Py1T sequence but dif
fers 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.