Mucosal and systemic immune responses in humans after primary and booster immunizations with orally administered invasive and noninvasive live attenuated bacteria

The mucosal and systemic immune responses after primary and booster immuniz ations with two attenuated live oral vaccine strains derived from a noninva sive (Vibrio cholerae) and an invasive (Salmonella typhi) enteric pathogen were comparatively evaluated. Vaccination with S. typhi Ty21a elicited anti body secreting cell (ASC) responses specific for S. typhi O9, 12 lipopolysa ccharide (LPS), as well as significant increases in levels of immunoglobuli n G (IgG) and IgA antibodies to the same antigen in serum. A strong systemi c CD4+ T-helper type 1 cell-mediated immune (CMI) response was also induced . In contrast to results with Ty21a, no evidence of a CR II response was ob tained after primary immunization with V. cholerae CVD 103-HgR in spite of the good immunogenicity of the vaccine. Volunteers who received a single do se of CVD 103-HgR primarily developed an IgM ASC response against whole vac cine cells and purified V. cholerae Inaba LPS, and seroconversion of serum vibriocidal antibodies occurred in four of five subjects. Serum IgG anti-ch olera toxin antibody titers were of lower magnitude. For both live vaccines , the volunteers still presented significant local immunity 14 months after primary immunization, as revealed by the elevated baseline antibody titers at the time of the booster immunization and the lower ASC, serum IgG, and vibriocidal antibody responses after the booster immunization. These result s suggest that local immunity may interfere with colonization of the gut by both vaccine strains at least up to 14 months after basis immunization. In terestingly, despite a low secondary ASC response, Ty21a was able to boost both humoral (anti-LPS systemic IgG and IgA) and CMI responses. Evidence of a CMI response was also observed for one of three volunteers given a chole ra vaccine booster dose. The direct comparison of results with two attenuat ed live oral vaccine strains in human volunteers clearly showed that the ca pacity of the vaccine strain to colonize specific body compartments conditi ons the pattern of vaccine-induced immune responses.