Monoclonal Antibodies to Toxoplasma Cell Membrane Surface Antigens Protect Mice from Toxoplasmosis^1,2

Abstract

Groups of mice were given an intraperitoneal injection of one of six monoclonal antibodies to Toxoplasma gondii, a mixture of equal amounts of five monoclonal antibodies to T. gondii, or the murine myeloma protein MOPC 21, and challenged with either a highly virulent or moderately virulent parasite strain. Two monoclonal antibodies (FMC 19 and FMC 22) conferred total protection against the moderately virulent challenge, with all mice surviving, whereas 90% of control mice died. FMC 19 and FMC 22 also conferred significant protection against the highly virulent challenge as indicated by a prolonged mean time to death (MTD) of immunized compared with control groups of mice. One monoclonal antibody (FMC 23) and the mixture of five antibodies gave significant protection against the moderately virulent challenge only. Passive immunization with dilutions of FMC 22 antibody indicated that the lowest serum titer needed to confer significant protection to mice against a moderately virulent Toxoplasma challenge was 1/640. Mice challenged with highly virulent tachyzoites that had been preincubated with FMC 22 had a significantly longer MTD than mice challenged with highly virulent tachyzoites that had been preincubated with MOPC 21 or phosphate buffered saline, pH 7.2 (PBS). Immunoprecipitation and autoradiography of radiolabeled tachyzoites confirmed that FMC 19 was directed against a 35,000 molecular weight (mol. wt.) antigen and FMC 22 was directed against a 14,000 mol. wt. fraction. The potential for use of single antigens as protective immunogens in preventing toxoplasmosis is raised.

Toxoplasma gondii: Ultrastructural localization of specific antigens and inhibition of intracellular multiplication by monoclonal antibodies

“…The secreted dense granular proteins into the parasitophorous vacuole (PV) and parasitophorous vacuolar membrane (PVM) after the invasion changes the molecules of PVM and plays an important role for the multiplication of the parasite within the host cell and evasion of the host immune response (Dubremetz and Schwartman, 1993;Bonhomme, 1998). Many studies on the surface, cytoplasm, excretory and secretory antigens of Toxoplasma have been carried out (Johnson et al, 1983;Charif et al, 1990;Metsis et al, 1995).…”

B Cells Are Essential for Vaccination-Induced Resistance to VirulentToxoplasma gondii

“…Other studies in which mice were challenged with parasites after being given immune sera have produced mixed results regarding the protective potential of Toxoplasma-specific antibodies (6,15,17,25). Additional studies have shown that monoclonal antibodies against various Toxoplasma antigens have the potential to protect unimmunized mice against a challenge with moderately virulent parasites and, to a lesser extent, with highly virulent parasites (12,31). Such passive immunization experiments may reveal whether an anti-Toxoplasma antibody is capable of providing protection in the absence of an already developed cell-mediated immunity but do not address whether antibodies generated in the normal course of infection are required for protection of chronically infected mice or vaccinated and subsequently challenged mice.…”

Deficient Humoral Responses Underlie Susceptibility toToxoplasma gondiiin CD4-Deficient Mice

“…A role for antibodies in resistance to T. gondii has been examined in several older studies (7,16,20,22). For the most part, these studies have shown that immune serum, by itself, is not very protective.…”