Influences of Vitamin A on Vaccine Immunogenicity and Efficacy.

Rhiannon R Penkert,Robert E Sealy,Jason Rosch,Julia L Hurwitz,Hannah M Rowe,Sherri L Surman

doi:10.3389/fimmu.2019.01576

Abstract

Vitamin A deficiencies and insufficiencies are widespread in developing countries, and may be gaining prevalence in industrialized nations. To combat vitamin A deficiency (VAD), the World Health Organization (WHO) recommends high-dose vitamin A supplementation (VAS) in children 6–59 months of age in locations where VAD is endemic. This practice has significantly reduced all-cause death and diarrhea-related mortalities in children, and may have in some cases improved immune responses toward pediatric vaccines. However, VAS studies have yielded conflicting results, perhaps due to influences of baseline vitamin A levels on VAS efficacy, and due to cross-regulation between vitamin A and related nuclear hormones. Here we provide a brief review of previous pre-clinical and clinical data, showing how VAD and VAS affect immune responses, vaccines, and infectious diseases. We additionally present new results from a VAD mouse model. We found that when VAS was administered to VAD mice at the time of vaccination with a pneumococcal vaccine (Prevnar-13), pneumococcus (T4)-specific antibodies were significantly improved. Preliminary data further showed that after challenge with Streptococcus pneumoniae, all mice that had received VAS at the time of vaccination survived. This was a significant improvement compared to vaccination without VAS. Data encourage renewed attention to vitamin A levels, both in developed and developing countries, to assist interpretation of data from vaccine research and to improve the success of vaccine programs.

Highlights

Vitamin A deficiency (VAD) adversely affects children and adults worldwide
When vitamin A deficiency (VAD)+VDD mice receive vitamin A supplementation (VAS), CD103 levels on virus-specific CD8+ T cells are reduced, and the percentages of CD4+ and CD8+ T cells in the lower respiratory tract (LRT) are improved [72]. As another example of the complex influences of vitamin A on immune responses, we find that serum antibody isotype distributions differ between VAD and control animals, but patterns are dependent on the animal’s background and sex [50]
We suggest that attention to, and correction of, low vitamin levels in Prevnar-13 vaccine recipients may improve vaccine success

Summary

INTRODUCTION

Vitamin A deficiency (VAD) adversely affects children and adults worldwide. Today, the World Health Organization (WHO) estimates that 250 million preschool children suffer from VAD, with the highest frequencies among low-income areas of Africa and South-East Asia [http://www.who.int (accessed March 01, 2019)]. When VAD+VDD mice receive VAS (with or without supplemental vitamin D), CD103 levels on virus-specific CD8+ T cells are reduced, and the percentages of CD4+ and CD8+ T cells in the LRT are improved [72] As another example of the complex influences of vitamin A on immune responses, we find that serum antibody isotype distributions differ between VAD and control animals, but patterns are dependent on the animal’s background and sex [50]. Outcomes are again dependent on cell targets, environment, and activation state [25] Both Th1 and Th2 cytokine responses are evident in VAD mice, and VAD animals express higher levels of Th1 and Th2 cytokines compared to controls at late stages following a respiratory virus infection, presumably as a consequence of poor virus clearance [32]. We extend findings to show that VAS improves the immunogenicity and protective capacity of Prevnar-13 in VAD and control animals

MATERIALS AND METHODS

RESULTS

DISCUSSION