As the 21st century approaches, infections caused by encapsulated bacteria, specifically group B streptococci, Escherichia coli and Neisseria meningitidis remain a major cause of morbidity and mortality in infants and young children [1,7,11,25,36]. Despite the availability of effective anti-microbial agents and capsular polysaccharide vaccines the mortality rate in this age group has not declined over the past 30 years. The rationale for capsular polysaccharide vaccines is based on the observation that antibodies against the capsular polysaccharide correlate with protection against disease [15]. These vaccines have proven to be immunogenic and protective in adults but the sero response in infants and children less then 2 years of age is minimal and of short duration.
The poor immunogenicity of the polysaccharide vaccines is related to the T-independent nature of the immune response elicited by these antigens. The ability to respond to T-independent antigens develops late in ontogeny and fails to stimulate a memory or so-called booster response [10,16,23]. Efforts to overcome the neonatal unresponsiveness have led to the development of the polysaccharide-protein conjugate vaccines [2,5,32].
An alternate strategy for converting a T-independent antigen into a T-dependent antigen is through the development of an anti-idiotypic antibody which carries on its antigen-binding site the surrogate image of the polysaccharide. This technology is based on the immune network theory of Jerne, which describes the immune system as a network of interacting antibodies and lymphocytes [13]. Antibodies carry idiotypes which are regions in or near the antigen-recognition sites. Idiotypes can act as antigens and stimulate antibody or so-called anti-idiotypic antibody production. The normal immune system features an interlocking network of antibodies directed at one another's idiotype. Inherent in the network theory is the idea that at least some of anti-idiotypic antibodies are internal images of external antigens. Anti-idiotypic antibodies are defined according to their physical relationship to the antigen-binding site [14]. Anti-idiotypic antibodies which are not capable of inhibiting binding of nominal antigen to the Abl or idiotype are designated Ab2~. Anti-idiotypic antibodies which serve as surrogates