An alternative approach to the production of subunit vaccines entails their direct chemical synthesis. Peptides identical in sequence to short stretches of pathogen-derived polypeptide antigens can be easily and economically synthesized. The feasibility of this approach was first verified in the 1960s, when a hexapeptide purified from the enzymatic digest of tobacco mosaic virus was found to confer limited immunological protection against subsequent administration of the intact virus. (The hexapeptide hapten was initially coupled to bovine serum albumin, used as a carrier to ensure an immunological response.)
Similar synthetic vaccines have also been constructed that confer immunological protection against bacterial toxins, including diphtheria and cholera toxins. Although coupling to a carrier is
generally required to elicit and immunological response, some carriers are inappropriate due to their ability to elicit a hypersensitive reaction, particularly when repeat injections are undertaken. Such difficulties can be avoided by judicious choice of carrier. Often, a carrier normally used for vaccination itself is used. For example, tetanus toxoid has been used as a carrier for peptides derived from influenza haemaglutanin and Plasmodium falciparum.
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