Failure of a large dose of vitamin A to enhance the antibody response to tetanus toxoid in children

Abstract

Field studies to determine the effects of a large dose of water miscible vitamin A on selected parameters of children's immunological function were completed in rural Bangladesh. There was no difference between vitamin A treated or control groups in tetanus antitoxin responses after tetanus toxoid immunization or in skin test reactivity to common antigens. Subsequent studies with mice demonstrated vitamin A dose-related antitoxin responses, but the animals required amounts of vitamin that would be likely cause undesirable side effects if administered in similar doses to children.

Effects of Vitamin A Supplementation on Immune Responses and Correlation with Clinical Outcomes

“…There were no differences by treatment arm in the percentage of children with a DTH response to a protein derivative or Candida in a non-placebo-controlled trial of intramuscular vitamin A from Bangladesh (20); however, in a different trial among younger infants in the same country, (116). Children in this study had low mean retinol concentrations at baseline.…”

“…Low retinol concentrations have been widely used as an indicator of vitamin A deficiency; however, they may also be the result of the acute-phase response during generalized inflammatory states. The effect of vitamin A on the antibody response to tetanus or diphtheria has been examined in five clinical trials (16,20,79,108,131), four of which were randomized (20,79,108,131) (Table 3) and three of which (79,108,131) used a placebo group as control. In the first trial, conducted among Bangladeshi children 1 to 6 years of age, the intramuscular administration of 200,000 IU vitamin A at the time of the first tetanus immunization was not associated with the vaccine response after 4 or 12 weeks (a second dose of the toxoid had been administered 4 weeks after the first) (20).…”

Vitamin A Status: Relationship to Immunity and the Antibody Response

“…In vitamin Adeficient mice, the DTH response to dinitrofluorobenzene (33) or picryl chloride (42) was significantly reduced. However, in a study of Bangladeshi children, there was no difference in DTH response before and after vitamin A supplementation (43). Reports on DTH responses in humans have not been consistent, perhaps due to confounding of protein-energy malnutrition (14), which generally leads to impaired DTH.…”

Vitamin A Deficiency and Immunity.

“…However, the vitamin A stimulation of antibody production would be greater with T-dependent than with T-independent antigens [105]. One study on mice reported antibody titers proportional to vitamin A doses, but these were toxic levels when extrapolated to humans [106]. Subtoxic doses may sometimes be necessary in order to obtain immunostimulatory effects [107].…”

“…Indeed, in two surveys, vitamin A-deficient children had normal circulating B lymphocytes, immunoglobulin levels, and antibody production after vaccination against tetanus or diphtheria [110]. Intramuscular injection of 200,000 IU of retinyl palmitate into vitamin A-deficient children in Bangladesh did not increase the immune response to tetanus, nor the intradermal reaction to tuberculin or Molinia extract [106].…”