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Infection and Immunity, April 2003, p. 2009-2013, Vol. 71, No. 4
0019-9567/03/$08.00+0     DOI: 10.1128/IAI.71.4.2009-2013.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

Effects of Zinc Deficiency and Pneumococcal Surface Protein A Immunization on Zinc Status and the Risk of Severe Infection in Mice

Centre for International Health and Department of Microbiology and Immunology, The Gade Institute, University of Bergen, Bergen N-5021,¹ Institute of Nutrition, Directorate of Fisheries, Bergen N-5804, Norway,³ Department of Microbiology, University of Alabama at Birmingham, Birmingham, Alabama 35294²

Received 9 October 2002/ Returned for modification 20 November 2002/ Accepted 15 January 2003

Streptococcus pneumoniae is a major cause of illness and death in children in developing countries. In these children, zinc deficiency is associated with an increased risk of acute respiratory tract infections, which can be reduced by daily zinc administration. Severe infections decrease zinc levels in plasma and may thereby move individuals with preexisting low zinc stores into a vicious cycle of infection and unavailable zinc. Pneumococcal surface protein A (PspA) has emerged as a promising vaccine candidate, and immunization with this antigen protects animals from pneumococcal infection. In an animal experiment, we measured the effect of zinc depletion on the immune response to parenterally administrated PspA and assessed the effect of this PspA vaccination and zinc depletion on the severity of pneumococcal infection and on zinc status. Mice were kept on different diets for 5 weeks, immunized twice 14 days apart, and challenged intranasally with S. pneumoniae. Mice on the zinc-deficient diet showed substantially reduced immune responses to PspA, more extensive pneumococcal colonization in the nasal mucosa, more severe infections, and an increased risk of death. PspA immunization reduced the risk of severe disease, and the reduction in severity was reflected in substantially reduced zinc depletion from bones.

Editor: V. J. DiRita

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