Figure 1.
Flow diagram of the study: study groups and timing of samples.
Table 1.
Baseline characteristics and adverse effects reported in 50 volunteers immunized with typhoid fever vaccines.
Table 2.
Descriptions of bacterial strains, magnitude of the plasmablast responses to various antigens and results of statistical comparisons in the Vi group.
Figure 2.
Plasmablasts on days 0 and 7 after immunization with Vi capsular polysaccharide or Salmonella Typhi Ty21a vaccines.
Numbers of circulating plasmablasts specific to Vi, O-9,12 and H-d antigens, and to Yersinia enterocolitica representing a negative control. The plasmablasts were identified as antibody-secreting cells (ASC) in (a) 25 volunteers vaccinated with the parenteral Vi capsular polysaccharide vaccine and in (b) 25 age- and gender-matched volunteers receiving the oral live whole-cell Salmonella Typhi Ty21a vaccine lacking the Vi antigen. The dots represent results of individual vaccinees, and the lines the medians of the numbers of Ig(A+G+M)-plasmablasts on day 0 and 7 after vaccination. LOD = lower limit of detection of the response.
Figure 3.
Comparison of the typhoid-specific plasmablast response in the two vaccination groups.
Comparison of the numbers of circulating antigen-specific plasmablasts (ASC) between 25 volunteers immunized with the parenteral Vi vaccine and 25 with the oral Ty21a vaccine. Plasmablasts were examined for specificity against the Vi, O-9,12, and H-d antigens, against Yersinia enterocolitica acting as a negative control and against whole-cell S. Typhi. The numbers of typhoid-specific plasmablasts are also indicated as a total of cells reactive with Vi, O-9,12 and H-d antigens. The dots represent results of individual vaccinees, and the lines the means of the numbers of Ig(A+G+M)-plasmablasts on day 7 after vaccination. The statistical comparisons (Bonferroni-corrected Wilcoxon signed rank test) between the strains in the two vaccination groups are indicated with asterisks (***p<0,001; **0.001<p<0.01, *p<0,05) above the bars. LOD = lower limit of detection of the response. No LOD values are given for Vi+O-9,12+ H-d, since this does not represent a result of the assay, but a calculated total value for three different antigens.
Figure 4.
Immunoglobulin isotype distribution.
Immunoglobulin isotype distribution of antibodies secreted by plasmablasts reactive with Vi and O-9,12 antigen (ASC/106 PBMC) in 25 volunteers immunized with the Vi capsular polysaccharide, and with O-9,12 antigen in 25 volunteers immunized with the Salmonella Typhi Ty21a vaccine. The dots represent results of individual vaccinees, and the lines the medians of the numbers of plasmablasts secreting specific antibodies of the IgA, IgG or IgM isotype on day 7 after vaccination.
Table 3.
Magnitude of the plasmablast responses to various antigens and results of statistical comparisons in the Ty21a group.
Figure 5.
Homing potentials of Salmonella Typhi-specific plasmablasts in the two vaccination groups.
The expression of α4β7, L-selectin and CLA on Salmonella Typhi-specific plasmablasts in the peripheral blood of volunteers seven days after vaccination with the Vi or the Ty21a vaccine. The bars indicate the arithmetic means +95%CI of percentages of HR-positive ASC among all pathogen-specific ASC (IgA+IgG+IgM). The HRs and the numbers of volunteers from whom the data were pooled are indicated under the data bars. The data on HR expressions on S. Typhi-specific plasmablasts in Ty21a-vaccinated volunteers has been reported earlier [32]. The statistical comparisons (Wilcoxon signed rank test) between the strains in the two vaccination groups are indicated with asterisks (***p<0,001; **0.001<p<0.01, *p<0,05).
Table 4.
Antibody responses in serum and ALS cultures.