administered.Some vaccines are directed against toxic pro-teins (like the diphtheria toxin produced bysome organisms), preparing the body to neutral-ize them. Molecular cloning might make it pos-sible to produce inactivated toxins, or betternonvirulent fragments of toxins, by means ofmicro-organisms that are incapable of servingas disease-causing organisms.Immunity conferred by live vaccines invari-ably exceeds that conferred by nonliving anti-genic material–possibly because a living micro-organism creates more antigen over a longerperiod of time, providing continuous “boostershots.” Engineered micro-organisms might be-come productive sources of high-potency anti-gen, offering far larger, more sustained, dosesof vaccine without the side-effects from the con-taminants found in those vaccines that consistof killed micro-organisms.However, it is clear that formidable Federalregulatory requirements would have to be metbefore permission is granted for a novel livingorganism to be injected into human subjects.Because of problems encountered with live vac-cines, the most likely application will lie in thearea of killed vaccines (often using only parts ofmicro-organisms).It is impossible in the scope of this report todiscuss the pros, cons, and consequences of de-veloping a vaccine for each viral disease. How-ever, the most commercially important are theinfluenza vaccines, with an average of 20.8 mil-lion doses given per year from 1973 to 1975–asmaller number than the 25.0 million doses peryear of polio vaccine, but more profitable.Influenza is caused by a virus that has re-mained uncontrolled largely because of the fre-quency with which it can mutate and change itsantigenic structures. It has been suggested thatantigenic protein genes for influenza could bekept in a “gene bank” and used when needed. Inaddition, the genetic code for several antigenscould be introduced into an organism such as E.
Ch. 4—The Pharmaceutical Industry ●69coli, so that a vaccine with several antigensmight be produced in one fermentation. 1Two more viral diseases deserve at least briefcomment. Approximately 800 million doses offoot-and-mouth disease virus (FMDV) vaccineare annually used worldwide, making it thelargest volume vaccine produced. This vaccinemust be given frequently to livestock in areaswhere the disease is endemic, which includesmost of the world outside of North America.The present methods of producing the vaccinerequire that enormous quantities of hazardousvirus be contained. Many outbreaks are attrib-uted to incompletely inactivated vaccine or tothe escape of the virus from factories. (Seefigure 23.)Molecular cloning of the antigen could pro-duce a stable vaccine at considerably less ex-pense, without the risk of the virus escaping. Onthe basis of that potential, RAC has approved ajoint program between the U.S. Department ofAgriculture (USDA) and Genentech to clonepieces of the FMDV genome to produce pure an-tigen. The RAC decision marked the first excep-