Transmission Blockirg Immunity in Plasmodium vivax Malaria: Antibodies Raised against a Peptide Block Parasite Development in the Mosquito Vector

Abstract

One approach towards the development of a vaccin-e against mala-ria is to immunize against the parasite^sexual stages that mediate transmission of the parasite_frol man to mosquito. Anti Lodies against theie stages, ingested with the blood meal, inhibit the parasite dwelopmen-t in the mos[uito vector, co-nstitutlng "transmission blocking imm-unity." Most epitopes involved in transmission-blocking immunity depend on the tertiary conformational structure of surface antigens. However, o.r. of th. transmission-blocking monoclonal antibodies we have raised against Plasrnodiun uiuax rcacts with a linear epitope on both asexual stages and gametes' This monoclonal antibo dy (A12) is capable of totally blocking development -of the parasite in themosquito host when t.ri.d i., membiane feeding assays with gametocytes from P uiuax-infected patients. Immune screening of a P. uiuax \gt11-genomic expression library with A12 led to the isolation of a clone ro whi;h was mapped the si*amino acid epitope recognized by A12. Antisera raised in mice against a 72-mer synihetic peptide containing this epitope coupled to bovine serum albumin nJt only had higlr titers of antipeptide antibodies as measured by enzyme-linked immunosorbent assay, but in addition recognized the same 24- and 57-kD parasite comPonents as A12 on'Western blots and reacted wiih the parasite by immunofuorescence. When tested in membrane feeding assays, these antibodies have significant suPpressive effects on parasite development in the mosquito.