N. Ahlborg et al., IMMUNE-RESPONSES IN CONGENIC MICE TO MULTIPLE ANTIGEN PEPTIDES BASED ON DEFINED EPITOPES FROM THE MALARIA ANTIGEN PF332, Immunology, 88(4), 1996, pp. 630-635
Repeat sequences from the Plasmodium falciparum blood stage antigen Pf
332 frequently comprise the pentapeptide VTEEI, an epitope recognized
by certain parasite neutralizing antibodies. This B-cell epitope was a
ssembled in an octavalent multiple antigen peptide (MAP) system either
as trimers (VTEEI)(3) (MAP1) or as an integral part of a naturally oc
curring Pf332 undecamer repeat sequence SVTEEIAEEDK (MAP2). Characteri
stics of the immunogenicity of these subunit constructs were evaluated
in H-2 congenic mice. MAP1 generated antibody responses in mice of th
e H-2(d), H-2(k) and H-2(q) haplotypes, but not in H-2(b) or H-2(s) mi
ce, whereas MAP2 only induced antibodies in mice of H-2(k) haplotype.
When analysing T-cell responses induced by the MAP, lymph node cells f
rom responder strains primed in vivo with MAP1 proliferated in respons
e to restimulation with both MAP1 and the peptide (VTEEI)(3). MAP2, ho
wever, did not induce a detectable T-cell proliferation. Additionally,
the lack of antibody response to MAP1 in H-2(b) mice could be circumv
ented by combining the MAP1 peptide and a H-2(b)-restricted T-cell epi
tope in a diepitope MAP construct. Despite the fact that the motif VTE
EI has not been identified in Pf332 sequences in the form of a trimer,
MAP1 did induce Pf332 protein-reactive antibodies. Assembly of multim
ers of short defined epitopes in MAP constitutes an interesting approa
ch for the design of polyvalent subunit immunogens.