Construction and functional activities of chimeric mouse-human immunoglobulin G and immunoglobulin M antibodies against the Neisseria meningitidis PorA P1.7 and P1.16 epitopes.
We studied the in vitro protective activities of human immunoglobulin G1 (IgG1), IgG3, and IgM antibodies against group B meningococci by constructing sets of chimeric mouse-human antibodies (chIgG1, chIgG3, and chIgM, respectively) with identical binding regions against the P1.7 and P1.16 epitopes on PorA. This was done by cloning the V genes of three mouse hybridoma antibodies and subsequently transfecting vectors containing the homologous heavy- and light-chain genes into NSO cells. Cell clones secreting intact human chIgG1, chIgG3, or chIgM antibodies originating from three parent mouse antibodies were isolated. The functional affinities appeared to be similar for all human isotypes and surprisingly also for the pentameric chIgM antibody. chIgG1 exhibited greater serum bactericidal activity (SBA) than chIgG3, while chIgG3 was more efficient in inducing a respiratory burst (RB) associated with opsonophagocytosis than chIgG1 was. On the other hand, chIgM exhibited SBA similar to that of chIgG1, but it exhibited much higher RB activity than chIgG3 and chIgG1 exhibited. The antibodies against the P1.16 epitope were more efficient in terms of SBA than the antibodies against the P1.7 epitope were; thus, 10- to 40-fold-lower concentrations of antibodies against P1.16 than of antibodies against P1.7 were needed to induce SBA. On the other hand, antibodies against these epitopes were equally effective in inducing RB. Our results revealed differences in the functional activities of human chIgG1, chIgG3, and chIgM antibodies against meningococci, which might influence their protective effects against meningococcal disease.
D000818:Animals; D000907:Antibodies, Bacterial / Q000235:genetics* / Q000494:pharmacology*; D000911:Antibodies, Monoclonal / Q000235:genetics / Q000494:pharmacology; D001770:Blood Bactericidal Activity; D000939:Epitopes; D005822:Genetic Vectors; D006801:Humans; D007074:Immunoglobulin G / Q000235:genetics* / Q000494:pharmacology; D007075:Immunoglobulin M / Q000235:genetics / Q000494:pharmacology; D066298:In Vitro Techniques; D051379:Mice; D008969:Molecular Sequence Data; D009345:Neisseria meningitidis / Q000276:immunology*; D018272:Porins / Q000276:immunology*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000276:immunology / Q000494:pharmacology
D000907:Antibodies, Bacterial; D000911:Antibodies, Monoclonal; D000939:Epitopes; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D018272:Porins; D011993:Recombinant Fusion Proteins; C057699:porin protein, Neisseria