Intestinal and systemic immune responses to an oral cholera toxoid B subunit whole-cell vaccine administered during zinc supplementation

Abstract

Zinc plays a critical role in the normal functioning of the immune system. We investigated whether zinc sulfate administered orally to adult zinc-replete volunteers modulates systemic and intestinal immune responses to an oral killed cholera toxoid B subunit (CTB) whole-cell cholera vaccine. The 30 participants were immunized twice, with a 17-day interval. The vaccinees in the intervention group ingested 45 mg of elemental zinc thrice daily for 9 days starting 2 days before each vaccine dose. The median serum anti-CTB immunoglobulin A (IgA) and IgG responses from day 0 to day 30, i.e. after two vaccine doses, were 13-fold lower (P value for identical distribution, <0.005) in the zinc-supplemented compared to the nonsupplemented vaccinees. The median serum vibriocidal responses from baseline to after one (day 0 to day 17) and two (day 0 to day 30) vaccine doses were at least sixfold (P = 0.033) and fourfold (P = 0.091) higher, while the median fecal anti-CTB IgA response after two doses was estimated to be fourfold higher (P = 0.084) in the zinc-supplemented vaccinees. These observations show that zinc reduces the antitoxin and may enhance the antibacterial responses in serum. Zinc may also improve the intestinal antitoxin immune response. Oral zinc administration has the potential to modify critical immune responses to antigens applied to mucosal surfaces.

FIG. 1.

Serum anti-CTB IgA (a) and IgG (b) titer rises 7 (day 10) and 14 (day 17) days after the first dose and 10 (day 30) days after the second dose of an oral killed CTB whole-cell cholera vaccine in nonsupplemented (•) and zinc-supplemented (▴) vaccinees. The box provides the interquartile range, the horizontal line within the box gives the median, and the whisker caps enclose values between the 10th and 90th percentiles. The arrow indicates the geometric mean.

FIG. 2.

Serum vibriocidal antibody titer rise 14 (day 17) days after the first and 10 (day 30) days after the second dose of an oral killed CTB whole-cell cholera vaccine in nonsupplemented (•) and zinc-supplemented (▴) vaccinees. The box provides the interquartile range, the horizontal line within the box gives the median, and the whisker caps enclose values between the 10th and 90th percentiles. The arrow indicates the geometric mean.

FIG. 3.

Fecal anti-CTB IgA index rise in nonsupplemented (•) and zinc- supplemented (▴) volunteers immunized with an oral killed CTB whole-cell cholera vaccine. The box provides the interquartile range, the horizontal line within the box gives the median, and the whisker caps enclose values between the 10th and 90th percentiles. The arrow indicates the geometric mean.