Oral retinyl palmitate or retinoic acid corrects mucosal IgA responses toward an intranasal influenza virus vaccine in vitamin A deficient mice

Abstract

Vitamin A deficiency (VAD) is a leading cause of pediatric morbidity and mortality due to infectious diseases. Recent pre-clinical studies have revealed that VAD impairs mucosal IgAproducing antibody forming cell (AFC) responses toward a paramyxovirus vaccine in the upper respiratory tract (URT), thus impeding a first line of defense at the pathogen's point-of-entry. The studies described here tested the hypothesis that VAD may also impair immune responses after FluMist vaccinations. Results show that (i) IgA-producing antibody forming cells (AFCs) are significantly reduced following FluMist vaccination in VAD mice, and (ii) oral doses of either retinyl palmitate or retinoic acid administered on days 0, 3, and 7 relative to vaccination rescue the response. Data encourage the conduct of clinical studies to identify FluMist vaccine weaknesses in human VAD populations and to test corrective supplementation strategies. Improvements in vaccine efficacy may ultimately reduce the morbidity and mortality caused by influenza virus worldwide.

Prevnar-13 vaccine failure in a mouse model for vitamin A deficiency

“…We further found that vaccinated VAD mice were incompletely protected from invasive bacterial challenge, whereas the PCV-13 vaccine protected control mice. The poor response to PCV-13 vaccination observed in VAD mice complements previous studies of respiratory virus vaccines in the context of VAD whereby mucosal antibody responses were poor toward a parainfluenza virus (Sendai virus), a human influenza virus vaccine (FluMist), and a cold-adapted, PR8-derived influenza virus vaccine [10, 13]. Molrine et.…”

“…Vitamin A deficiencies (VAD) and insufficiencies are present in both developed and developing countries [6–9] and have been associated with poor immune responses toward respiratory tract pathogens [10, 11], as well as an increased incidence of and morbidity from respiratory disease in school age children. Knowing that prevention of infection is critical in these highly susceptible populations, we employed a murine model of VAD to determine if PCV-13 was efficacious in the context of VAD.…”

Low Retinol-Binding Protein and Vitamin D Levels Are Associated with Severe Outcomes in Children Hospitalized with Lower Respiratory Tract Infection and Respiratory Syncytial Virus or Human Metapneumovirus Detection

“…Small animal studies previously showed that VAD is associated with poor IgA responses to respiratory viruses and that vitamin supplementation restores IgA responses (31, 35, 36). Apart from immunological deficiencies, VAD animals are characterized by a partial loss of cilia as well as squamous metaplasia within the epithelial lining of the respiratory tract (6–8).…”

Vitamin Supplementation at the Time of Immunization with a Cold-Adapted Influenza Virus Vaccine Corrects Poor Mucosal Antibody Responses in Mice Deficient for Vitamins A and D

“…Receptor proteins can bind promiscuously to ligands and to noncanonical DNA motifs. In some instances, vitamin receptors (and related members of the nuclear receptor superfamily) behave synergistically, but in other instances, they antagonize one another (e.g., vitamin D exerts a negative effect on the vitamin A-dependent commitment of bone marrow cells to the granulocytic lineage [13,[17][18][19][20] (23,24). These results have important clinical implications, as mucosal IgA may provide a first line of defense against infectious respiratory virus diseases in humans (25)(26)(27).…”