B- and T- cell responses in colectomized and healthy individuals after mucosal vaccination
The overall aims were to study the induction of intestinal and systemic B- and T-cell immune responses in patients colectomized due to ulcerative colitis and in healthy volunteers after mucosal administration of enteric vaccines. An inactivated B-subunit whole-cell (B-WC) cholera vaccine and a live attenuated Salmonella enterica serovar Typhi Ty21a vaccine were used as model immunogens.Ileostomy fluid was shown to be a suitable specimen for determination of IgA antibodies in the intestine after mucosal vaccination. Two oral doses of B-WC vaccine induced significant IgA antibody responses in ileostomy fluids against cholera toxin in 14 of 15 colectomized patients and against whole bacteria in 9 cases. Increased IgA antitoxin levels were found in ileostomy fluids as late as 2 years after vaccination. The antibody responses in serum after oral B-WC vaccination were somewhat lower in colectomized patients than in healthy volunteers. When the B-WC vaccine was administered into the ileal pouch of colectomized patients, strong cholera toxin B subunit-specific IgA antibody-secreting cell (ASC) responses were found in the duodenum of 5 of 5 patients, whereas weaker and less frequent responses were seen in the ileal pouch and in peripheral blood. These findings clearly show that it is possible to induce B-cell responses within the "entire" small intestine without the presence of antigen at the effector site.No enhancement of the B-cell immune responses was noted when the B-WC vaccine was administered on intestinal mucosa with a mild lymphocytic infiltration, i.e. into the ileal pouch of colectomized patients, or when the vaccine was given together with a mucolytic substance, acetylcysteine, orally to healthy volunteers.Three oral doses of Ty21a vaccine induced significant anti-Salmonella IgA antibody titer increases in ileostomy fluids from 6 of 9 colectomized patients. Both the frequencies and magnitudes of the IgA as well as IgG antibody responses in serum were lower in the colectomized patients than in healthy volunteers. The vaccination failed to induce proliferative T-cell responses in peripheral blood in all the 6 colectomized patients, and increases in gamma interferon (IFN-g) production were only found among CD8+ cells from 3 patients. In contrast, a proliferative response and/or increased IFN-g production were observed for CD4+ cells in 5 of 10 healthy volunteers and for CD8+ cells in 8 individuals.In conclusion, both the B-WC and Ty21a vaccines induced strong intestinal B-cell responses in colectomized patients, whereas the B- and T-cell responses in the circulation were weaker than in healthy volunteers. The impaired responsiveness, in particular among the T cells, may be of relevance for the future use of live vaccine strains which predominantly colonize the colon, e.g. attenuated Salmonella or Salmonella vector vaccines. Our observations should be considered when planning immunizations for colectomized patients traveling to areas endemic for cholera or typhoid fever.
Göteborgs universitet/University of Gothenburg
Institute of Medical Microbiology /Immunology and Department of Infectious Diseases
Institutionen för medicinsk mikrobiologi och immunologi och avdelningen för infektionssjukdomar
föreläsningssalen, Avd för Infektionssjukdomar, Sahlgrenska Universitetssjukhuset/Östra, Göteborg, kl. 09.00
Date of defence