Effects of zinc deficiency and pneumococcal surface protein a immunization on zinc status and the risk of severe infection in mice

Abstract

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.

Figures

FIG. 1.

Immune response to PspA in zinc-deficient and zinc-replete mice after one and two immunizations. ZD, mice on low-zinc diet, ZA, mice on zinc-adequate diet. Values are means and the upper 95% CI of log-transformed titers of anti-PspA immunoglobulin G. Day 14 is after the first immunization, while day 28 is after the second immunization with PspA. Significance levels of the differences: day 14, P = 0.052; day 28, P < 0.001. The preimmune anti-PspA titers were zero.