The goal of this proposal is the delineation of the quality and protective efficiency of the primary, memory and neonatal antibody responses induced in mice by an idiotope vaccine against a lethal Streptococcus pneumoniae infection. We have previously known that a monoclonal antibody, 4C11, coupled to a carrier, Keyhole Limpet hemocyanin, can completely substitute for antigen in inducing protective immunity against a S. pneumoniae infection in BALB/c mice. Although these initial studies were important in showing the potential of idiotype vaccines, there are gaps in our knowledge concerning the immune response stimulated by an idiotype vaccine. Specifically, we need to know 1) how long the immunity induced by idiotope antigens lasts. In addition, 2) the memory response needs to be studied, as does 3) the response of neonatal mice to an idiotope vaccine. The objectives of this proposal include studies comparing the duration of immunity against a S. pneumoniae infection provided by the primary and memory antibody responses to idiotope vs. nominal antigen. The temporal kinetics of the serum titer, idiotope, isotype, and antigen specificity of the immune responses will be correlated with the protection induced. The idiotope, isotope, antigen specificity, precursor frequency, and clone size of the memory B cells populations will also be studied in vitro. The neonatal B cell response to idiotope and nominal antigen will also be compared. In addition, we will try to increase the resistance of adult mice S. pneumoniae by priming during the neonatal stage with idiotope antigens. The results of these experiments will help establish rules for idiotype vaccine development by increasing our knowledge concerning the ability of idiotope vaccines to stimulate different B cell subpopulations. In doing so, certain situations will be exposed where the use of an idiotope vaccine may be used in place of, or in addition to, conventional vaccines. These experiments need to be done before we start to extend our studies on idiotope vaccines to humans.
| Wu, P; Ward, R E (1994) The secondary B cell lineage for phosphorylcholine is conserved in CBA/CaHN-xid/J mice. Cell Immunol 155:345-57 |
| Wu, P; Ward, R E (1993) Ig repertoire expression of BALB/c primary and secondary B cell precursors specific for phosphorylcholine. J Immunol 150:3862-72 |
| Su, S; Ward, M M; Apicella, M A et al. (1992) A nontoxic, idiotope vaccine against gram-negative bacterial infections. J Immunol 148:234-8 |
| Su, S D; Ward, M M; Apicella, M A et al. (1991) The primary B cell response to the O/core region of bacterial lipopolysaccharide is restricted to the Ly-1 lineage. J Immunol 146:327-31 |
| Su, S D; Ward, M M; Apicella, M A et al. (1990) Analysis of the immune response to lipopolysaccharide. Existence of an interspecies cross-reactive idiotype associated with anti-lipid A antibodies. J Immunol 145:2994-3001 |
