Molecular Approaches to Vaccines

Recombinant DNA (rDNA) and monoclonal antibody technologies are being used to develop new types of vaccines that are expected eventually to sup-plement or supplant conventional whole-agent vaccines for both animals and humans. Impetus for the new vaccines stems from findings that the surface proteins of most infectious agents possess immunogenic activity and that the corresponding genes can be manipulated to produce these products in quantity devoid of the infectious agents themselves. In addition, conventional vaccines that employ killed and attenuated viruses have certain limitations. For example, standard methods have failed to produce effective vaccines for many important diseases, including hepatitis A and B, and for most diseases caused by retroviruses, herpes viruses, and parasites, including those that cause malaria, trypanosomiasis, and anaplasmosis. Also, attenuated whole-agent vaccines can cause acute or slowly progressive diseases in immunodeficient individuals or in alternate animal hosts. Live poliovirus vaccine produces a few cases each year of paralytic polio in vaccinees or their contacts (91). Even so-called killed virus vaccines can contain infectious particles. This was the case with some of the early batches of commercially produced, inactivated poliovirus vaccine, and is still the case for foot-and-mouth disease (FMD) virus vaccines in wide use today. At least 44% of the outbreaks of FMD in Europe from 1968 to 1981 were caused by incomplete inactivation procedures or the escape of virus from vaccine manufacturing facilities (43). Whole-agent vaccines can also induce postvaccinal sequelae, including pyrogenic and allergic reactions, and Guillain-Barré and other neurological syndromes as well as immune enhancement of disease, e.g., dengue-2 virus infections of young children (62).