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Vaccination (continued) is, a substance that enhances the potency of the antigen. The induction of cellular immune responses may be poor, and the protection induced by killed-virus vaccines may be of short duration, so booster vaccinations are needed. Vaccines pro- duced by killing viruses have been known to contain surviv- ing, infectious particles that have caused outbreaks of disease (Cutter polio vaccine and foot-and-mouth-disease vaccine). Although incapable of producing direct cellular destruction, noninfectious vaccines may elicit abnormal hypersensitivity re- actions. The process involved in the production of an injectable killed vaccine is shown in Fig. 2; this example shows the steps involved in the flu gene reassortment that researchers carry out to create a proper flu vaccine. Polysaccharide vaccines Polysaccharide vaccines consist of the polysaccharide coats, or capsules, of encapsulated bacteria. Although polysaccha- rides are recognized mainly by T-cell-independent mecha- nisms, they do not effectively produce high-level, high-affinity antibodies, nor do they induce the T-cell memory required for booster responses. However, the immunogenicity of polysac- charides can be significantly increased by covalently linking them to carrier proteins. This approach is thought to work through the recruitment of T-cell help. For example, Haemophi- lus influenzae type b vaccines developed with this conjugate approach have been very successful in inducing high, boost- able, protective antibody levels in infants and have dramatically reduced Haemophilus influenzae type b–associated disease in countries where they are in general use. Subunit vaccines Subunit vaccines consist of immunogenic viral proteins stripped free from whole virus particles and then purified from other irrelevant components, thereby reducing the risk of ad- verse reactions and residual infectious virus. Subunit vaccines require the addition of adjuvants or their formation into other forms [for example, lipid vesicles (liposomes and virosomes) or micelles]. The inability to propagate hepatitis B virus in tissue culture provided an incentive for the production of one of the first subunit vaccines, Heptavax-B, which was obtained by pu- rifying and formalin-inactivating the surface antigen from the plasma of chronic carriers of hepatitis B. Experimental subunit vaccines have also been produced from purified glycoproteins derived from the virus membranes of enveloped virus particles, including parainfluenza-3, measles, rabies, influenza, respira- tory syncytial virus (RSV), feline leukemia virus, bovine herpes virus-1, and pseudorabies. Immune stimulating complexes (ISCOMs) are very immuno- genic and represent an interesting delivery system for glyco- protein subunit vaccines. These complexes are really advanced liposomes that look like small balls and are made from an adjuvant. Synthetic peptide vaccines Chemically synthesized peptides are perceived as one alternative to conventional vaccines to elicit virus-neutralizing antibodies, or to "prime" the host for neutralizing antibody responses. A conventional approach to preparing antipeptide antibodies is conjugation of a peptide to a known protein or synthetic polymer carrier. Methods designed to avoid the use of carrier by polymerizing or cyclizing the peptides have also been reported, as well as an approach known as the multiple- antigen peptide system, in which a small peptidyl core matrix is covalently bound to radially branching synthetic peptides. The peptide sequences chosen for synthesis in developing new vaccines correspond to antigenic determinants (epitopes) on the surface of virus particles that have been identified through chemical, electron-microscopic, and crystallographic analyses. Application of recombinant DNA technology has also allowed nucleotide sequences of viral genomes to be deter- mined, from which primary amino acid sequences, secondary structure, and potential B-cell antigenic and T-cell (amphipa- thic) sequences may be deduced. Carrier-free polypeptide vaccines are anticipated to be especially safe because they are chemically well defined, do not contain nucleic acids or extraneous proteins, and are unlikely to have any of the pathogens that might be present in serum or tissue extracts. Polypeptide vaccines are also extremely stable, withstanding thermal extremes and ambient conditions that might inactivate other types of vaccines under field conditions. This is important where target populations may lack access to refrigeration equipment. Synthetic peptide vaccines may be feasible for agents for which protection is based mainly on humoral (antibody-medi- ated) immunity and suitable conserved antigenic sites can be found. Synthetic peptide vaccines are more realistic for DNA than for ribonucleic acid (RNA) viruses because DNA viruses mutate much less frequently than RNA viruses. Thus, antibod- ies against a single antigenic site of an RNA virus may allow too many escape mutants and, in contrast to DNA viruses, may require antibodies against different antigenic sites. Successful synthetic peptide vaccines have been produced for the simple, DNA-containing canine parvovirus and mink enteritis virus, which readily induce full protection of all vaccinated animals after a severe challenge with virulent viruses. + ward ' s science