The Plasmodium yoelii sporozoite
surface protein 2 (PySSP2) is the target of protective cellular immunity. Cytotoxic T cells specific for the Plasmodium falciparum analog PfSSP2, also known as
thrombospondin-related anonymous
protein (TRAP), are induced in human volunteers immunized with irradiated sporozoites. PfSSP2 is an important candidate
antigen for a multicomponent
malaria vaccine. We generated and characterized three
monoclonal antibodies (MAbs) specific for PfSSP2/TRAP. The MAbs PfSSP2.1 (
immunoglobulin G1 [
IgG1]), PfSSP2.2 (
IgG2a), and PfSSP2.3 (
IgM) were species specific and identified three distinct
B-cell epitopes containing sequences DRYI, CHPSDGKC, and TRPHGR, respectively. PfSSP2.1 partially inhibited P. falciparum liver-stage parasite development in human hepatocyte cultures (42 and 86% in two experiments at 100 microg/ml). Mice immunized with vaccinia virus expressing full-length PfSSP2
protein produced
antibodies to (DRYIPYSP)3, and humans living in
malaria-endemic areas (Indonesia and Kenya), who have lifelong exposure and partial clinical immunity to
malaria, had
antibodies to both (DRYIPYSP)3 and (CHPSDGKCN)2. Mice immunized with multiple
antigen peptides MAP4 (DRYIPYSP)3P2P30 and
MAP4 (CHPSDGKCN)3P2P30 in
TiterMax developed
antibodies to sporozoites that partially inhibited sporozoite invasion of human
hepatoma cells (39 to 71% at a serum dilution of 1:50 in three different experiments). The modest inhibitory activities of the MAbs and the polyclonal
antibodies to PfSSP2/TRAP
epitopes do not suggest that a single-component
vaccine designed to induce
antibodies against PfSSP2/TRAP will be protective. Nonetheless, the MAbs directed against PfSSP2, and the
peptides recognized by these MAbs, will be essential
reagents in the development of PfSSP2/TRAP as a component of a multivalent P. falciparum human
malaria vaccine.