Peptide epitopes immunization with

If a monoclonal antibody was generated by immunization with a full-length native protein rather than a peptide, then the immunized mouse will generate antibodies that recognize both linear and conformationally dependent epitopes. Only a small subset of these monoclonal antibodies will likely be useful for clinical use on formalin-fixed, paraffin-embedded tissue (FFPE) samples. Those that are useful tend to have epitopes that are linear the epitopes are not dependent on the protein s three-dimensional conformation (see Chapter 16). Therefore, for antibodies generated in response to immunization with full-length proteins, the peptides that serve as positive controls will be linear stretches of amino acids derived from the native protein sequence, as listed in protein databases. 

Fig. 8.10 Titers of antibodies at day 50 induced by plant-derived CTB-2L21 recombinant protein. Balb/c mice were intraperitoneally immunized with leaf extract from CTB-2L21 transgenic plants. Animals were boosted at days 21 and 35. Each mouse received 20 pg of CTB-2L21 recombinant protein. Individual samples of mouse serum were titrated against 2L21 synthetic peptide,VP2 protein and a control peptide (amino acids 122-135 of hepatitis B virus surface antigen). Titers were expressed as the highest serum dilution to yield twice the absorbance mean of preimmune sera. M1-M6 mice 1 to 6 2L21 epitope from the VP2 protein of the canine parvovirus CTB cholera toxin B VP2 protein of the canine parvovirus that includes the 2L21 epitope.

Immunization with peptide epitopes in adjuvant can elicit both antibody-and cellular-mediated immune responses that are able to provide protective immunity against a repertoire of targeted pathogens that have included viruses (1-4), bacteria (4-7), parasites (4,8-10), tumors (11-14), and self-hormones (4,15-18). However, a major problem associated with the use of subunit... 

The requirement of multifunctional peptide complexes is perhaps most obvious for the development of subunit peptide vaccines. Successful immunizations with peptide antigens cannot be achieved without the inclusion of a bystander T-helper cell determinant in the chemical entity (4) or in the immunizing cocktail (5). For outbred animals and humans, multiple peptide epitopes, representing determinants of more than one major histocompatibility complex (MHC) proteins, are used to overcome subunit vaccine unresponsiveness, and this also improves antigen presentation in inbred animals (6). 

In this chimeric peptide construct the aim was to combine the carrier function and immunstimulatory activity of tuftsin derivatives with an epitope derived from HSV gD to achieve an increased antibody response. Tuftsin is a well-known natural tetrapeptide (TKPR) that has a pronounced effect on the immune system (28,29). Polymerized tuftsin (polytuftsin) is also considered as a carrier molecule that increased antibody levels against attached epitopes in mice (30,31). New, sequential oligopeptides based on repeated tuftsin derivatives (H-[Thr-Lys-Pro-Lys-Gly]n-NH2, where n = 2,4,6,8) were developed in our laboratory to eliminate the drawbacks of tuftsin derivatives produced by polymerization. These new, nontoxic, nonimmunogenic compounds have immunostimulatory activity and a minor chemoattractant effect on monocytes (32). An oligotuftsin derivative was used in this study for the synthesis of a peptide chimera containing an HSV peptide epitope. 

A second procedure to reduce 1-ASP immunogenicity has been described by Uren and Ragin [33]. They used poly-DL-alanyl peptides to block immunogenic epitopes within the 1-ASP molecule derived from both E. coli and Erwinia. Similar to the PEGylated enzyme, the half-life in mice was markedly prolonged compared to the native enzymes even if the animals had previously been immunized with the latter preparation. Hyperimmune animals, however, rapidly cleared both the native and modified enzymes. Clinical studies have not been performed to date. 

Another strategy aimed at inducing an immune response against TAAs is the application of peptides thereof with an immunogenic potential [92]. This soluble, rather than cell-based, material has been used to stimulate anti-tumor T cells and to destroy cells that present the peptide epitopes on their cell surface [93-95]. This therapy has several advantages, as peptide-based vac-... 

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