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Immunogenicity of an oral rotavirus vaccine administered with prenatal nutritional support in Niger: A cluster randomized clinical trial.
Isanaka, S, Garba, S, Plikaytis, B, Malone McNeal, M, Guindo, O, Langendorf, C, Adehossi, E, Ciglenecki, I, Grais, RF
PLoS medicine. 2021;(8):e1003720
Abstract
BACKGROUND Nutritional status may play a role in infant immune development. To identify potential boosters of immunogenicity in low-income countries where oral vaccine efficacy is low, we tested the effect of prenatal nutritional supplementation on immune response to 3 doses of a live oral rotavirus vaccine. METHODS AND FINDINGS We nested a cluster randomized trial within a double-blind, placebo-controlled randomized efficacy trial to assess the effect of 3 prenatal nutritional supplements (lipid-based nutrient supplement [LNS], multiple micronutrient supplement [MMS], or iron-folic acid [IFA]) on infant immune response (n = 53 villages and 1,525 infants with valid serology results: 794 in the vaccine group and 731 in the placebo group). From September 2015 to February 2017, participating women received prenatal nutrient supplement during pregnancy. Eligible infants were then randomized to receive 3 doses of an oral rotavirus vaccine or placebo at 6-8 weeks of age (mean age: 6.3 weeks, 50% female). Infant sera (pre-Dose 1 and 28 days post-Dose 3) were analyzed for anti-rotavirus immunoglobulin A (IgA) using enzyme-linked immunosorbent assay (ELISA). The primary immunogenicity end point, seroconversion defined as ≥3-fold increase in IgA, was compared in vaccinated infants among the 3 supplement groups and between vaccine/placebo groups using mixed model analysis of variance procedures. Seroconversion did not differ by supplementation group (41.1% (94/229) with LNS vs. 39.1% (102/261) with multiple micronutrients (MMN) vs. 38.8% (118/304) with IFA, p = 0.91). Overall, 39.6% (n = 314/794) of infants who received vaccine seroconverted, compared to 29.0% (n = 212/731) of infants who received placebo (relative risk [RR]: 1.36; 95% confidence interval [CI]: 1.18, 1.57, p < 0.001). This study was conducted in a high rotavirus transmission setting. Study limitations include the absence of an immune correlate of protection for rotavirus vaccines, with the implications of using serum anti-rotavirus IgA for the assessment of immunogenicity and efficacy in low-income countries unclear. CONCLUSIONS This study showed no effect of the type of prenatal nutrient supplementation on immune response in this setting. Immune response varied depending on previous exposure to rotavirus, suggesting that alternative delivery modalities and schedules may be considered to improve vaccine performance in high transmission settings. TRIAL REGISTRATION ClinicalTrials.gov NCT02145000.
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B Vitamins and One-Carbon Metabolism: Implications in Human Health and Disease.
Lyon, P, Strippoli, V, Fang, B, Cimmino, L
Nutrients. 2020;(9)
Abstract
Vitamins B9 (folate) and B12 are essential water-soluble vitamins that play a crucial role in the maintenance of one-carbon metabolism: a set of interconnected biochemical pathways driven by folate and methionine to generate methyl groups for use in DNA synthesis, amino acid homeostasis, antioxidant generation, and epigenetic regulation. Dietary deficiencies in B9 and B12, or genetic polymorphisms that influence the activity of enzymes involved in the folate or methionine cycles, are known to cause developmental defects, impair cognitive function, or block normal blood production. Nutritional deficiencies have historically been treated with dietary supplementation or high-dose parenteral administration that can reverse symptoms in the majority of cases. Elevated levels of these vitamins have more recently been shown to correlate with immune dysfunction, cancer, and increased mortality. Therapies that specifically target one-carbon metabolism are therefore currently being explored for the treatment of immune disorders and cancer. In this review, we will highlight recent studies aimed at elucidating the role of folate, B12, and methionine in one-carbon metabolism during normal cellular processes and in the context of disease progression.
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Folate-targeted nanoparticles for rheumatoid arthritis therapy.
Nogueira, E, Gomes, AC, Preto, A, Cavaco-Paulo, A
Nanomedicine : nanotechnology, biology, and medicine. 2016;(4):1113-1126
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Abstract
UNLABELLED Rheumatoid arthritis (RA) is the most common inflammatory rheumatic disease, affecting almost 1% of the world population. Although the cause of RA remains unknown, the complex interaction between immune mediators (cytokines and effector cells) is responsible for the joint damage that begins at the synovial membrane. Activated macrophages are critical in the pathogenesis of RA and showed specifically express a receptor for the vitamin folic acid (FA), folate receptor β (FRβ). This particular receptor allows internalization of FA-coupled cargo. In this review we will address the potential of nanoparticles as an effective drug delivery system for therapies that will directly target activated macrophages. Special attention will be given to stealth degree of the nanoparticles as a strategy to avoid clearance by macrophages of the mononuclear phagocytic system (MPS). This review summarizes the application of FA-target nanoparticles as drug delivery systems for RA and proposes prospective future directions. FROM THE CLINICAL EDITOR Rheumatoid arthritis is a debilitating autoimmune disease of the joints which affects many people worldwide. Up till now, there is a lack of optimal therapy against this disease. In this review article, the authors outlined in depth the current mechanism of disease for rheumatoid arthritis and described the latest research in using folic acid-targeted nanoparticles to target synovial macrophages in the fight against rheumatoid arthritis.
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Adding zinc to supplemental iron and folic acid does not affect mortality and severe morbidity in young children.
Bhandari, N, Taneja, S, Mazumder, S, Bahl, R, Fontaine, O, Bhan, MK, ,
The Journal of nutrition. 2007;(1):112-7
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Abstract
Studies have found a substantial reduction in diarrhea and respiratory morbidity in young children receiving zinc supplementation. The impact of daily zinc supplementation administered with iron plus folic acid (IFA) in young children on all-cause hospitalizations and mortality in comparison with IFA alone was evaluated. In a double blind cluster-randomized controlled trial, 94,359 subjects aged 1-23 mo were administered a daily dose of zinc plus IFA or IFA alone for a duration of 12 mo after enrollment. The intervention group tablet contained 10 mg of elemental zinc, 12.5 mg of iron, and 50 microg of folic acid. The control group tablets were similar except that they contained a placebo for zinc. Infants aged <6 mo were administered half a tablet, and those older received 1 tablet dissolved in breast milk or water. Hospitalizations were captured by trained study physicians through the surveillance of 8 hospitals. Deaths and hospitalizations were ascertained through visits to households by study supervisors once every 2 mo. The overall death rates did not differ significantly between the 2 groups when adjusted for cluster randomization (hazard ratio = 1.02, 95% CI 0.87, 1.19). Zinc and IFA supplementation compared with IFA alone did not affect adjusted hospitalization rates (overall rate ratio = 1.08, 95% CI 0.98, 1.19; diarrhea-specific rate ratio = 1.15, 95% CI 0.99, 1.34; or pneumonia-specific rate ratio = 1.09, 95% CI 0.94, 1.25). The lack of impact of zinc on mortality and hospitalization rates in this study may have been due to the use of lower daily zinc dosing than used in some of the morbidity prevention trials or from an interaction between zinc and iron, where the addition of iron may have adversely affected potential effects of zinc on immune function and morbidity. Future research should address iron and zinc interaction effects on important functional outcomes.