Other factors reported to potentially, but not universally, influence outcome of immune responses have included antibody specificity (30,82,87), isotype (20,32,37,82), affinity (53), and route of administration (18,118)

Other factors reported to potentially, but not universally, influence outcome of immune responses have included antibody specificity (30,82,87), isotype (20,32,37,82), affinity (53), and route of administration (18,118). While the effect of immunomodulation by antibody around the kinetics, amount, and isotype of an elicited humoral response may be very easily measured and readily apparent, the effect on resultant antibody specificity may be less obvious and more likely overlooked. combination with antigen to achieve a desirable immune response is far less appreciated and is the focus of this minireview. There is increasing acknowledgement that exogenously administered antibody may exert a therapeutic effect by redirecting the host response rather than by playing a purely passive role (16,18,26,45,53,55,56,84,90,93,100,114,129). Both polyclonal and monoclonal reagents, administered either alone or in combination with antigen, have been used to up-regulate beneficial CAY10505 or protective immune responses against infectious brokers and malignant tumors as well as to down-regulate deleterious responses associated with inflammation, autoimmunity, and hypersensitivity (8,55,57,58,84,102,110). In light of a growing body of literature, the practicality of employing preformed antibody to manipulate an immune response toward a desired end is becoming more apparent and will broaden the strategies for active and passive immunization methods against infectious disease. == IMMUNIZATION WITH IMMUNE COMPLEXES == == Examples with individual antigens. == Immunization with immune complexes (IC) has been used to enhance immunogenicity of soluble molecules, to increase the number of monoclonal antibody (MAb) generating hybridomas against an antigen, and to elicit antibodies specific for poorly immunogenic epitopes. MAbs against human alpha-2-macroglobulin (36) as well as complement components (35) have been generated against IC composed of proteins immunoprecipitated with conventionally produced polyclonal antisera. Murine humoral (75) and T-cell (76,77) responses against human serum albumin were stronger when the antigen was administered as an IC with syngeneic antibodies. To facilitate production of MAbs against weakly immunogenic regions of human thyrotropin (9) and follitropin (10), mice were immunized with IC made up of MAbs against immunodominant epitopes in a successful effort to block the response against those sites. Antihapten immunoglobulin G2a (IgG2a) and IgG2b, but not IgG1, IgM, or IgA, complexed with trinitrophenol- or fluorescein-conjugated keyhole limpet hemocyanin (KLH) increased the primary antibody response in mice against the carrier protein by 20- to 1 1,000-fold, depending on the antigen-antibody combination, after a single injection of antibody-complexed haptenated KLH (32). Secondary responses were enhanced approximately threefold following improving with IgG2-complexed antigen rather than free antigen. In a series of studies, Bouige et al. exhibited that immunization with IC made up of MAbs and several different types of antigens, including human secretory IgA (sIgA), bacterial polysaccharide fromEscherichia coli, and a structural protein from hepatitis B computer virus, could result in the acknowledgement of new epitopes that differed in location from those recognized by the modulating MAbs (15-17). For example, the pre-S2 region Rabbit Polyclonal to CG028 of hepatitis B surface antigen (HbsAg) was rendered more immunogenic when a MAb was bound to the S region of the HbsAg. Not all anti-HbsAg MAbs resulted in enhancement of the response, and indifference or unfavorable modulations could also be demonstrated depending on the selection of the MAb (16). In some cases immunogenicity has been analyzed using IC made up of immunoglobulin-binding proteins in addition to antigen and antibody. For example, the presentation of a snake toxin in IC made up of MAbs and antigen was reported to be increased by the incorporation of bacterial Fc-binding proteins such as protein A and protein G in the complexes (69), and MAbs realizing novel epitopes have been generated against the feline homolog of CD4 with solid matrix antigen-MAb complexes made up of formalin-fixedStaphylococus aureus(128). While most published studies have evaluated changes in immunogenicity of protein antigens CAY10505 contained within IC, there is documentation that an antibody response against a nonprotein antigen CAY10505 can also be altered by using this approach. Unresponsiveness to pneumococcal cell wall polysaccharide (PnC) was reversed by immunization of transgenic mice, 90% of whose B cells express Ig specific for any phosphorylcholine (PC) determinant, with IC of PnC and anti-PC myeloma antibodies TEPC-15 and MOPC-603 (30). The effect was eliminated by treatment with anti-CD4, suggesting a mechanism engaging helper T cells. Interestingly, enhancement of the anti-PnC response varied depending on the fine specificity and variable light chain (VL) gene usage of the three IgA myeloma proteins tested. Anti-PC MOPC-167 expressing the same heavy chain variable (VH) and VLgenes used to encode the transgene antibody was not effective. Enhancement was also dependent on the ratio of antigen to antibody in the immune complexes. Whereas TEPC-15 markedly enhanced the anti-PnC response when it was incorporated into IC in 10-fold antigen excess, it had previously.