The power of the mucosal approach is illustrated by the effectiveness of live-attenuated polio vaccines. The Sabin oral polio vaccine consists of three attenuated polio virus strains and is highly immunogenic. Moreover, just as polio itself can be transmitted by fecal contamination of public swimming pools and other failures of hygiene, the vaccine can be transmitted from one individual to another by the fecal–oral route. Infection with Salmonella likewise stimulates a powerful mucosal and systemic immune response.
Presentation of soluble protein antigens by the oral route often results in tolerance, which is important given the enormous load of food-borne and airborne antigens presented to the gut and respiratory tract (see Chapter 12). Nonetheless, the mucosal immune system responds to and eliminates mucosal infections that enter by the oral route, such as pertussis, cholera, and polio. The proteins from these microorganisms that stimulate immune responses are therefore of special interest. One group of powerfully immunogenic proteins at mucosal surfaces is a group of bacterial toxins that have the property of binding to eukaryotic cells and being resistant to proteases. A recent finding of potential practical importance is that certain of these proteins, such as the
E. coli heat-labile toxin and pertussis toxin, have adjuvant properties that are retained even when the parent molecule has been engineered to eliminate its toxic properties. These molecules can be used as adjuvants for oral or nasal vaccines. In mice, nasal insufflation of either of these mutant toxins together with tetanus toxoid resulted in the development of protection against lethal challenge with tetanus toxin.
16-26 Bordetella pertussis vaccination illustrates the importance of the perceived safety of a vaccine.
The history of vaccination against the bacterium that causes whooping cough, Bordetella pertussis, illustrates the challenges of developing and disseminating an effective vaccine, as well as the public appeal of acellular conjugate vaccines over attenuated live organisms. At the beginning of the 20th century, whooping cough killed about 0.5% of American children under the age of 5 years. In the early 1930s, a trial of a killed, whole bacterial cell vaccine on the Faroe Islands provided evidence of a protective effect. In the United States, systematic use of a whole-cell vaccine in combination with diphtheria and tetanus toxoids (the DTP vaccine) during the 1940s resulted in a decline in the annual infection rate from 200 to fewer than 2 cases per 100,000 of the population. First vaccination with DTP was typically given at the age of 3 months.