Peptide epitopes vaccine

The two examples from our work we are going to describe below are the design and study of liposomal diepitope constructs combining either (i) B and T-helper (Th) peptide epitopes, which induced particularly powerful humoral responses (21) (Fig. 3) or (ii) CTL and Th epitopes, which provided a powerful antitumor vaccine (74) (Fig. 4). For the production of these constructs we have conjugated peptides that contain a cysteine residue either at the N- or C-terminus, to the surface of preformed liposomes by reaction with thiol reactive functionalized phospholipids and/or PamaCys lipopeptide anchors (Fig. 2). To that end, we have developed strategies that give, in aqueous media, high... 

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). 

As described above, peptide epitopes bound to MHC class I or II molecules are able to stimulate CD8+ and CD4+ T cells, respectively. Both CD4+ T-helper cells and CD8+ CTLs are critical to protective immunity and to vaccine efficacy. CD4+ T-helper cells play an important role in the development of memory B-cell (antibody) and memory CTL (cytotoxic T-cell) responses. CD4+ T-helper cells are also active against pathogens on their own. Therefore, CD4+ T-helper cells have been called the conductors of the immune system orchestra (14). CD8+ CTLs are able to directly kill infected target cells and thus are critical in the containment of... 

Dudek NL, Perlmutter P, Aguilar MI et al (2010) Epitope discovery and their use in peptide based vaccines. Curr Pharm Des 16 3149-3157... 

Peptides that present allergen-specific T-cell epitopes retain the ability to immuno-modulate T-cells, but less an ability to cross-link IgE and activate effectors cells. For example, synthetic peptides-based vaccine derived from major peanut allergen, Ara h 2 composed of thirty 20-mers that overlapped by 15 amino acids (Sicherer and Sampson 2007). Subcutaneous or intranasal administration of the vaccine reduced Ara h 2-specific IgE and plasma histamine release levels as well as anaphylactic symptoms scores in a murine model of peanut anaphylaxis. 

It is our belief that the ideal vaccines of the future will be constituted by synthetic peptide antigens, carbohydrates, and lipids. Because of the complexity of human T cells, it is also likely that several T-cell peptide epitopes would be required to create a vaccine that is able to induce a universal protective immune response. As vaccination of infants in developing countries is not a simple task, multivalent vaccines or cocktails of vaccines are highly recommended. 

Active immunizations using DNA which codes for the protein against which the immune response will be directed (genetic immunizations) provide additional safety as the immune response in DNA immunizations differs from the response elicited by peptide immunizations [366]. Ap DNA epitope vaccines have been proposed with optimism possibly combined with a prime boost regime in either very early AD, or preferably in preclinical stage individuals identified by validated AD biomarkers [367],... 

The peptide vaccines discussed earlier in the chapter promise an improvement, but more effective constructs for defense against epidemics in the future are peptide cartridge vaccines. These are peptide vaccines built in such a way that epitopes can be replaced and upgraded to counter new strains of pathogen, without starting the whole vaccine from scratch. Adjuvant analogues can be included, and sections can be added or removed to avoid complications such as autoimmunization. 

A 2C model antigen system [61] was used to evaluate the ability of microspheres to induce T-cell activation. The model antigen is a heat shock fusion protein containing a peptide epitope pi [62] (Fig. 6.9). A plasmid encoding the construct was used for encapsulation and vaccination. 

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