The thymus-dependent nature of the murine antibody response to a monoclonal anti-idiotypic antibody to the Neisseria meningitidis serogroup C capsular polysaccharide

Idiotype vaccines are proteins which may offer an alternative strategy for the conversion of a thymus-independent antigen into a thymus-dependent immunogen. To examine this question, we have studied the nature of the immune response to a monoclonal anti-idiotypic antibody, designated 6F9, which acts as a surrogate of Neisseria meningitidis serogroup C capsular polysaccharide, and compared this response to the nominal antigen, the meningococcal C-polysaccharide (MCP). BALB/c mice immunized with an optimal dose (100 μg) of 6F9 generate a specific anti-MCP IgG response which is maximal after 4 weeks. Secondary immunization with 6F9 results in a three- to five-fold increase in the specific IgG response. Mice given an optimal immunizing dose of MCP (5 μg) failed to generate an anti-MCP IgG response. No secondary response is detectable in mice immunized with MCP. Animals immunized with 6F9 and subsequently challenged with live meningococci group C show a significant anti-MCP IgG response. BALB/c nu/nu mice fail to generate an anti-MCP IgG antibody response to 6F9, while the nu/+ controls generate an anti-MCP IgG antibody titer 100 times that of the MCP-immunized mice. Neonatal mice that failed to respond to MCP developed early IgM and a subsequent IgG anti-MCP response after immunization with 6F9. These data demonstrate that the anti-idiotype 6F9, the combining site of which contains a surrogate image of the meningococcal group C capsular polysaccharide, evokes the responses expected of a T-dependent antigen.