Influences of Vitamin A on Vaccine Immunogenicity and Efficacy

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.

Strengthening the Immune System and Reducing Inflammation and Oxidative Stress through Diet and Nutrition: Considerations during the COVID-19 Crisis

“…In a recent review, it has been highlighted that vitamin A losses occur in infection via impaired vitamin A absorption and urinary losses [ 19 ]. In general, studies investigating the efficacy of vitamin A supplementation on improvement of immune responses to vaccines have produced conflicting results [ 225 ]. However, it is suspected that the influence of pre-existing vitamin A stores and extra-nuclear activities of their hormone receptors play crucial roles in resulting responses.…”

Sendai Virus-Vectored Vaccines That Express Envelope Glycoproteins of Respiratory Viruses

“…In animal models of vitamin A deficiencies and obesity, supplementation with vitamin A at the time of vaccination improved immune responses toward vaccines [134][135][136][137][138]. In a clinical study, vitamin supplementation of children who had low baseline levels of vitamins A and D also significantly improved responses toward an influenza vaccine [131].…”

Dietary Intervention Impacts Immune Cell Functions and Dynamics by Inducing Metabolic Rewiring

“…To deal with VA deficiency, the World Health Organization has recommended high-dose VA supplementation in children 6–59 months of age in locations where VA deficiency is endemic. Oral supplementation of VA or RA potentiated vaccine efficacy by facilitating the trafficking of vaccine-antigen-specific T lymphocytes to the gastrointestinal mucosa in mice ( 127 , 128 ). Moreover, the supplementation of VA or RA upregulated Stimulated by retinoic acid-6 (Stra6) in the spleen, enhancing anti-tetanus toxoid antibody production ( 129 ).…”