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Vaccination (continued) Biosynthetic polypeptide vaccines The nucleic acid sequences encoding microbial antigens and chemically synthesized peptides can be cloned in bacterial and yeast plasmids or in viral vectors and expressed efficiently in prokaryotic and eukaryotic cells, either as genetically purified (cloned) proteins or as parts of fusion proteins. The immuno- gens made in this way may be secreted into the medium or may be expressed on the surface or in the cytoplasm of cul- tured cells. The antigens can then be purified from the culture medium or from cell lysates. The biosynthetic production of an- tigens is particularly useful when the microbial agent is difficult to grow in tissue culture (for example, human hepatitis B virus) or dangerous [for example, rabies or human immunodeficiency virus (HIV)]. Anti-idiotype antibody vaccines The binding site of an antibody possesses a highly distinctive three-dimensional structure (the idiotype) that can itself act as an antigenic determinant to stimulate the formation of anti- bodies. The anti-idiotype antibodies, therefore, mimic the form of the surface antigen initially employed to induce the forma- tion of a specific idiotypic antibody. To prepare such vaccines, a monoclonal antibody is first pro- duced specifically against a microbial antigen. This monoclonal antibody is injected into an animal to induce a second antibody specific to the monoclonal antibody. If the second antibody binds to the idiotype of the initial monoclonal antibody, then the antigen-recognition portion of the second antibody should be structurally analogous to the original microbial neutraliza- tion antigen. Injection of the second antibody as a vaccine will then induce antibodies against the original microbial agent. Experimental anti-idiotype antibody vaccines have been made against hepatitis B virus, rabies virus, HIV, herpesvirus, poliovi- rus, and several bacterial and parasitic pathogens. DNA vaccines DNA (gene) vaccines, or the direct injection of DNA plasmids that express antigens of interest, represent another approach to subunit vaccines. In animal models, DNA vaccines stimulate cell-mediated and antibody-based immune responses, unlike most conventional inactivated vaccines. The DNA vaccines persistently express genes encoded by the plasmid without in- tegrating into chromosomal DNA. Gene expression from the di- rect intramuscular injection of DNA has been detected in mice, rats, rabbits, chicks, dogs, fish, cattle, and nonhuman primates, illustrating the diversity of species in which direct DNA vaccina- tion without a delivery vehicle is possible. DNA vaccines have a number of advantageous properties. They can protect against viral infections in which the antibody response alone is not protective, or where there is pronounced antigenic diversity among the target strains. Protection against lethal challenges has been achieved through parenteral or mucosal immuniza- tions, or by the use of gene guns that deliver tiny amounts of DNA-coated gold beads. The same or similar DNA plasmids can be used as vectors for subsequent immunizations because no immune response is elicited to the vector. The development of new DNA vaccines may be pertinent to several diseases, includ- ing acquired immune deficiency syndrome (AIDS) and hepatitis B, and will undoubtedly receive increasing attention. Adjuvants Adjuvants are chemicals that significantly enhance speed, vigor, and persistence of strong antigens and the potency of weak antigens. Adjuvant formulations consist of adjuvants in suitable delivery vehicles, such as mineral or vegetable oil emulsions, squalene, liposomes, nonionic block polymer sur- factants, and biodegradable polymer microspheres. Biodegrad- able microspheres can be especially useful as vehicles because of the ease of vaccine delivery by the oral route and the safety of the delivery vehicle (tissue compatibility and no secondary reactions). The most common microspheres range from a few micrometers (μm) to 200 μm in diameter. The most common adjuvants used in immunological research are Freund's incomplete adjuvant, which consists of an aqueous antigen solution emulsified with an equal volume of paraffin oil/mannide monooleate, and Freund's complete adjuvant (muramyl dipeptide delivered in oil emulsions), which also contains killed mycobacteria. The complete adjuvant con- sistently stimulates high and long-lasting antibody responses, which can be attributed to the slow release of antigen from the site of injection. Neither form of adjuvant is acceptable for human use because both induce pain, abscess formation, granulomas, synovial joint lesions, and other adverse reactions. The only adjuvants authorized in the United States for hu- man use are alum salts, which are both ineffective with some antigens and capable of producing adverse reactions, such as granulomas at the injection site. The emergence of subunit vac- cines created by recombinant DNA technology and of synthetic peptide vaccines has intensified the need for safer and more effective adjuvants. Cytokines and immunomodulation The induction of an immune response in the presence of an appropriate antigen initiates reciprocal interactions between antigen-presenting cells, such as dendritic and Langerhans cells (and possibly macrophages), and T lymphocytes (T cells) + ward ' s science