Monovalent fragments (Fab) of monoclonal antibodies to a sporozoite surface antigen (Pb44) protect mice against malarial infection

Abstract

Monoclonal antibodies (IgGl,κ) directed against a surface component of Plasmodium berghei sporozoites (Pb44) confer complete protection to mice against a lethal inoculum of parasites. The degree of protection is a function of the number of parasites used in the challenge and of the antibody concentration in serum. Passive transfer of 10 μg of antibody per mouse abolished or profoundly diminished the infectivity of 103 sporozoites, but much higher amounts of antibody were required for complete protection against challenge with 104 parasites. Fab fragments of the monoclonal antibodies were as effective as the intact antibodies in mediating protection as determined by the neutralizing assay. This observation suggests that the antibodies interfere with a parasite function necessary for its infectivity, such as, for example, the ability to penetrate into the target cell or to multiply in the hepatocytes. When sporozoites are incubated with the intact monoclonal antibodies at 37°C, a long filament appears at its posterior end (circumsporozoite precipitation [CSP] reaction). Fab fragments are ineffective at high concentrations. However, if after treatment with Fab, the sporozoites are incubated with rabbit antibodies to mouse κ-chains, a strong CSP reaction is observed. We conclude that the CSP reaction can result from the cross-linking of Pb44 and that it has the characteristics of a capping reaction followed by the shedding of the immune complexes.