The four mouse IgG isotypes differ extensively in bactericidal and opsonophagocytic activity when reacting with the P1.16 epitope on the outer membrane PorA protein of Neisseria meningitidis.
Mouse monoclonal antibodies (MoAbs) of the four IgG isotypes, all specific for the P1.16 epitope on the meningcoccal PorA protein, were tested for functional activities. The avidities of the antibodies, measured by NH4SCN elution in enzyme-linked immunosorbent assay, showed similar values for all the MoAbs. The serum bactericidal activity (SBA) defined as the lowest concentration of antibodies giving 50% reduction in the number of meningococcal colony-forming units using human serum as complement, showed a hierarchy of IgG3 >> IgG2b > IgG2a >> IgG1. For the opsonophagocytosis (OP), the hierarchy was IgG3 > IgG2b = IgG2a >> IgG1. OP was measured in flow cytometry using log-phase live meningococci as target cells, normal human peripheral blood polymorphonuclear cells (PMNs) as effector cells and human serum as a complement source. The mouse MoAbs were negative in OP when using human PMNs in the absence of complement. The results demonstrate the importance of choosing the right isotype of mouse MoAbs when using them to judge the potential vaccine importance of their corresponding antigen. If such MoAbs should be used for passive vaccination against infectious diseases, the isotype would presumably play an important role for their anticipated clinical effects.
Michaelsen
T E
TE
Division of Infectious Disease Control, Norwegian Institute of Public Health, Nydalen, Norway. terje.e.michaelsen@fhi.no
Kolberg
J
J
Aase
A
A
Herstad
T K
TK
Høiby
E A
EA
D000818:Animals; D000907:Antibodies, Bacterial / Q000737:chemistry / Q000276:immunology; D000911:Antibodies, Monoclonal / Q000276:immunology; D000915:Antibody Affinity / Q000276:immunology; D003165:Complement System Proteins / Q000276:immunology / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D000939:Epitopes / Q000276:immunology; D005434:Flow Cytometry; D007074:Immunoglobulin G / Q000737:chemistry / Q000276:immunology*; D007132:Immunoglobulin Isotypes / Q000276:immunology*; D051379:Mice; D009345:Neisseria meningitidis / Q000276:immunology*; D009895:Opsonin Proteins / Q000276:immunology; D010587:Phagocytosis / Q000276:immunology; D018272:Porins / Q000276:immunology*
D000907:Antibodies, Bacterial; D000911:Antibodies, Monoclonal; D000939:Epitopes; D007074:Immunoglobulin G; D007132:Immunoglobulin Isotypes; D009895:Opsonin Proteins; D018272:Porins; C057699:porin protein, Neisseria; D003165:Complement System Proteins