IMMUNOGENS CONTAINING SEQUENCES FROM ANTIGEN PF332 INDUCE PLASMODIUM FALCIPARUM-REACTIVE ANTIBODIES WHICH INHIBIT PARASITE GROWTH BUT NOT CYTOADHERENCE

Immunogens based upon sequences from the P. falciparum asexual blood s tage antigen Pf332 were assessed for their capacity to induce antibodi es inhibiting parasite growth ol cytoadherence of infected erythrocyte s in vitro. Selection of the Pf332 sequences was based on their reacti vity with the human monoclonal antibody (MoAb) 33G2 which inhibits par asite growth as well as cytoadherence in vitro. Octameric multiple ant igen peptides (MAP) were assembled based upon either a trimer of the m inimal epitope recognized by the MoAb, VTEEI, or a Pf332 sequence incl uding that motif, SVTEEIAEEDK. A dimer of SVTEEIAEEDK was also express ed in Escherichia coli, genetically fused to ZZ, two IgG-binding domai ns of staphylococcal protein A. Rabbit antibodies elicited by the immu nogens reacted with Pf332 in immunofluorescence and in ELISA with Pf33 2 peptides which were also recognized by MoAb 33G2. The MAP with branc hed (VTEEI)(3) peptide induced the highest titres of P. falciparum-rea ctive antibodies. In contrast to MoAb 33G2, none of the polyclonal Pf3 32 reactive sera cross-reacted with repeat sequences of the malaria an tigen Pfl55/RESA. The polyclonal Pf332-reactive antibodies inhibited p arasite growth efficiently but had no oi very low inhibitory effect in a cytoadherence assay. Thus, while Pf332 may be an important target f or parasite neutralizing antibodies its involvement in cytoadherence i s unclear.