Vaccines Based On Adhesins
The study of adhesins as a point of exploitation for vaccines comes from early studies which indicated that an important component of protective immunity against certain bacteria came from an ability to prevent adhesin binding. Additionally, Adhesins are attractive vaccine candidates because they are often essential to infection and are surface-located, making them readily accessible to antibodies.
The effectiveness of anti-adhesin antibodies is illustrated by studies with FimH, the adhesin of uropathogenic Escherichia coli (UPEC).Work with E. coli stems from observations of human acquired immunity. Children in third world countries may suffer from several episodes of E. coli associated diarrhea during the first three years of life. If the child survives this initial period of susceptibility, infection rates typically drop substantially. Field studies show that this acquired immunity is directed primarily against bacterial adhesins.
Recent studies from Worchester Polytechnic institute show that the consumption of cranberry juice cocktail may inhibit the action of UPEC adhesins. Using atomic force microscopy researchers have shown that adhesion forces decrease with time following cranberry juice cocktail consumption. This type of research has opened the door to further exploration of orally administered vaccines which exploit bacterial adhesins.
A number of problems create challenges for the researcher exploring the anti-adhesin immunity concept. First and foremost among these problems is the large number of different bacterial adhesins which target the same human tissues. Further problems arise when considering an individual bacterium’s ability to produce multiple different types of adhesins most of which are produced at different times, in different places, and in response to different environmental triggers. Finally, the most pressing problem becomes evident when considering that many adhesins present as different immunologically distinct antigentic varieties, even within the same clone (as is the case in Neisseria gonorrhoeae).
Despite these challenges, progress is being made in the creation of anti-adhesion vaccines. In animal models, passive immunization with anti FimH-antibodies and vaccination with the protein significantly reduced colonization by UPEC. Moreover, the Bordetella pertussis adhesins FHA and pertactin are components of 3 of the 4 acellular pertussis vaccines currently licensed for use in the U.S. Additionally, anti-adhesion vaccines are being explored as a solution to urinary-tract infections] (UTIs). The use of synthetic FimH adhesion peptides was shown to prevent urogenital mucosal infection by
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