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Infection and Immunity, July 2003, p. 3909-3913, Vol. 71, No. 7
0019-9567/03/$08.00+0     DOI: 10.1128/IAI.71.7.3909-3913.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

Intestinal and Systemic Immune Responses to an Oral Cholera Toxoid B Subunit Whole-Cell Vaccine Administered during Zinc Supplementation

Centre for International Health,¹ Department of Microbiology and Immunology,² Department of Clinical Biochemistry,⁵ University of Bergen, Bergen, Norway; Department of Epidemiology Research, Danish Epidemiology Science Centre, Statens Serum Institut,³ Department of Biostatistics, University of Copenhagen,⁴ Copenhagen, Denmark; and Department of Medical Microbiology and Immunology, University of Gothenburg, Gothenburg, Sweden⁶

Received 23 December 2002/ Returned for modification 14 February 2003/ Accepted 14 April 2003

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.

Editor: J. D. Clements

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