Randomized Controlled Clinical Trial of Pediatric Pneumococcus and Hepatitis A Vaccinations With or Without a High-Dose Oral Vitamin A Supplement.

Previous studies have shown that high-dose vitamin supplements can improve vaccine-induced immune responses and pathogen protection in the context of vitamin deficiencies. To further elucidate the influence of vitamin supplements on immune responses toward pediatric vaccines, we performed a randomized controlled clinical trial (PCVIT) of 20 healthy children 1-4 years of age in Memphis, Tennessee. Study participants received a booster vaccine for pneumococcus and a primary vaccine for hepatitis A virus with or without a high-dose, oral, liquid supplement of 10,000 IU retinyl palmitate. We found that the children enrolled in PCVIT had higher baseline vitamin levels than previously described older children and adults living in Memphis. Only one child in PCVIT had a serum retinol level of less than 0.3 µg/mL. The children frequently consumed milk and baby foods that were likely vitamin-fortified, providing an explanation for the relatively high vitamin levels. Most children in PCVIT responded well to pneumococcus and hepatitis A vaccines by pathogen-specific antibody upregulation. The one child with a serum retinol level below 0.3 µg/mL did not receive a vitamin supplement and exhibited the lowest fold-change in antibody responses toward pneumococcal serotypes. A correlation matrix encompassing demographics, vitamin levels, vaccine-induced immune responses, C-reactive protein, and total serum immunoglobulin isotypes, including IgG2 and IgA, identified variables associated with vaccination outcomes. Perhaps because children were predominantly retinol-sufficient at baseline, the high-dose vitamin A supplement exhibited no benefit to vaccine-induced immune responses. In fact, when vitamin supplemented and vitamin unsupplemented groups were compared among participants with the highest baseline retinol levels, there was a trend toward weaker vaccine-induced immune responses in the vitamin supplemented group. Results encourage the performance of larger clinical studies before high-dose vitamin supplements are recommended for populations that are otherwise vitamin-replete.