Peptide vaccines immune response

Dreesman, G.R., Sparrow, J.T., Frenchick, P.J., and Kennedy, R.C. (1985). Cyclic synthetic peptides and immune response to hepatitis B virus. In High-technology Route to Virus Vaccines. G.R.Dreesman, J.G.Bronson, and R.C.Kennedy, eds. (Washington, DC American Society of Microbiology), pp. 55 66. 

Fig. 3.9 Poly-L-arginine/CpG-ODN-based peptide vaccines induce strong peptide-specific immune responses. Mice were injected with the ovalbumin (OVA)-derived peptide OVA257-264 alone, or in combination with poly-L-arginine, CpG-ODN,...

Research on an hCG vaccine has been conducted over the past 15 years. WHO has conducted a phase I clinical study in AustraUa, using a vaccine based on a synthetic C-terminal peptide (109—141) of P-hCG conjugated to Diptheria Toxoid (CTP-DT), that showed potentially effective contraceptive levels of antibodies were produced in vaccinated women without any adverse side effects. Phase II clinical studies are under consideration to determine if the immune response, raised to its prototype anti-hCG vaccine, is capable of preventing pregnancy in fertile women volunteers (115). While research on the C-terminal peptide from the P-subunit of hCG has been carried out under the auspices of WHO, research supported by the Population Council and the National Institutes of Health has involved two alternative vaccine candidates (109,116,118). 

This chapter describes the design, preparation, and use of hapten-carrier conjugates used to elicit an immune response toward a coupled hapten. The chemical reactions discussed for these conjugations are useful for coupling peptides, proteins, carbohydrates, oligonucleotides, and other small organic molecules to various carrier macromolecules. The resultant conjugates are important in antibody production, immune response research, and in the creation of vaccines. 

Synthetic haptens mimicking some critical epitopic structures on larger macromolecules are often conjugated to carriers to create an immune response to the larger parent molecule. For instance, short peptide segments can be synthesized from the known sequence of a viral coat protein and coupled to a carrier to induce immunogenicity toward the native virus. This type of synthetic approach to immunogen production has become the basis of much of the current research into the creation of vaccines. 

Inactivated viral particles rgp 120 subunit vaccines rgp 160 subunit vaccines rp 24 subunit vaccines Live vaccines based on viral vectors Octameric V3 peptide Immune Response Genentech/Vaxgen, Biocine, Chiron/Ciba Geigy MicroGenes Sys. Inc., Immuno-Ag. MicroGenes Sys. Inc. Biocine, Merck, Sanofi Pasteur, Targeted Genetics UBI... 

Finally, besides conventional liposomes that are made from natural (e.g., egg yolk and soybean) or synthetic phospholipids, novel liposomes called archaeosomes that are prepared from the polar ether lipids extracted from various archaeobacteria proved also interesting for the design of vaccines as peptide antigen carriers (71) and as powerful self-adjuvanting vaccine delivery vesicles that promote both humoral and cell-mediated immunity (72). Related to this, one can mention that pseudopeptides, which are less prone to proteolysis when conjugated to liposomes, were also competent in triggering a humoral immune response (73). 

To review, in an experimental mouse model, LPDI/E7 vaccination both prevents the establishment of metastatic E7-expressing tumors in naive mice through an induced E7-specific T-cell immune response and, in mice with previously established E7-expressing tumors, causes tumor regression with one subcutaneous injection of LPDI/E7 [Han SJ, et al. Subcutaneous antigen loading of dendritic cells by liposome-protamine-DNA (LPD) nanoparticles results in their activation and induction of specific antitumor immune response (impublished)]. A robust immune response follows administration of LPDI/ peptide particles, which can be used as either a preventative or therapeutic cancer vaccination strategy due to the ability of the particles to prevent and eliminate tumors, respectively, in mouse models. 

As is documented in Table 2, the induction of anti-carbohydrate immune responses has been successfully demonstrated for many peptides. However, certain challenges remain. Often, the induced antibody titer (concentration) directed against the carbohydrate is rather weak, especially in comparison to the anti-peptide response the majority of antibodies recognize the peptide presumably in a nonmimetic conformation. Several recent studies have investigated these immime responses in more detail, with an extensive analysis of antibody isotypes and adjuvant effects [70,75], the effect of different protein carriers [194], the use of DNA vaccines [48,195], and the demonstration of protection by passive immunization [72,75,194]. In several cases, the anti-carbohydrate immune response has also been shown to be protective against infection in mice [30,72,75,78], and these cases are probably the most promising for the development of vaccines. 

Although there are a number of advantages associated with the use of subunit vaccines (e.g., highly purified peptides, proteins or DNA) as vaccines (e.g., specificity), one feature they all have in common is that they are generally poorly immunogenic. The more traditional vaccines contain many other components, some of which elicit additional T-cell assistance or function as adjuvants. An adjuvant is a substance that acts as an immunostimulator, one example being the bacterial DNA in a whole cell vaccine. The overall result is a more robust immune response than that provided by the antigen alone. 

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