Directing Immune Responses to the Gut

The underperformance of orally administered enteric vaccines in developing countries was the main topic of discussion today, the last day of the conference. In principle, this underperformance can be addressed by delivering vaccines through different routes. However, conventional intramuscular or subcutaneous immunizations often only induce weak immune responses in the gut where the infection occurs, and therefore protect only weakly against enteropathogens on the mucosal surface.   

But yesterday, Swantje Hammerschmidt of Medical School Hannover reported evidence that the problem can be addressed by adding the vitamin A derivative retinoic acid (RA). When combined with RA, subcutaneous immunization of mice with cholera toxin induced gut homing molecules on activated B and T cells, causing them to migrate to the gut (J. Clin. Invest. 121, 3051, 2011).   

The mice that had been immunized with the toxin together with RA had cholera toxin specific B cells and IgA antibodies in the gut, and after challenge with cholera toxin had no noticeable fluid influx into their intestine, suggesting they were protected from diarrhea.   

Hammerschmidt said the results were somewhat expected. “For me what I found was not really surprising because we are taking a molecule that is highly abundant in the intestinal immune system and bring it to the skin,” she said.   

Still, the findings seem to have caused considerable excitement among some researchers here because they suggest that it might be possible to develop versions of oral vaccines that are given intramuscularly together with RA, which should result in the induction of immune responses in the gut. Hammerschmidt said she doesn’t currently plan to translate her findings into human applications, but said the meeting was inspiring because it allowed her to interact with scientists who might be able to do so. “I think the best thing about this meeting is to bring together scientists who do basic research together with people who are translating this into applications,” she said.