Baseline Serum Vitamin A and D Levels Determine Benefit of Oral Vitamin A&D Supplements to Humoral Immune Responses Following Pediatric Influenza Vaccination

Maximizing vaccine efficacy is critical, but previous research has failed to provide a one-size-fits-all solution. Although vitamin A and vitamin D supplementation studies have been designed to improve vaccine efficacy, experimental results have been inconclusive. Information is urgently needed to e...

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Main Authors: Nehali Patel, Rhiannon R. Penkert, Bart G. Jones, Robert E. Sealy, Sherri L. Surman, Yilun Sun, Li Tang, Jennifer DeBeauchamp, Ashley Webb, Julie Richardson, Ryan Heine, Ronald H. Dallas, A. Catharine Ross, Richard Webby, Julia L. Hurwitz
Format: Article
Language:English
Published: MDPI AG 2019-09-01
Series:Viruses
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Online Access:https://www.mdpi.com/1999-4915/11/10/907
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author Nehali Patel
Rhiannon R. Penkert
Bart G. Jones
Robert E. Sealy
Sherri L. Surman
Yilun Sun
Li Tang
Jennifer DeBeauchamp
Ashley Webb
Julie Richardson
Ryan Heine
Ronald H. Dallas
A. Catharine Ross
Richard Webby
Julia L. Hurwitz
author_facet Nehali Patel
Rhiannon R. Penkert
Bart G. Jones
Robert E. Sealy
Sherri L. Surman
Yilun Sun
Li Tang
Jennifer DeBeauchamp
Ashley Webb
Julie Richardson
Ryan Heine
Ronald H. Dallas
A. Catharine Ross
Richard Webby
Julia L. Hurwitz
author_sort Nehali Patel
collection DOAJ
description Maximizing vaccine efficacy is critical, but previous research has failed to provide a one-size-fits-all solution. Although vitamin A and vitamin D supplementation studies have been designed to improve vaccine efficacy, experimental results have been inconclusive. Information is urgently needed to explain study discrepancies and to provide guidance for the future use of vitamin supplements at the time of vaccination. We conducted a randomized, blinded, placebo-controlled study of influenza virus vaccination and vitamin supplementation among 2 to 8 (inclusive) year old children over three seasons, including 2015&#8722;2016 (<i>n</i> = 9), 2016&#8722;2017 (<i>n</i> = 44), and 2017&#8722;2018 (<i>n</i> = 26). Baseline measurements of vitamins A and D were obtained from all participants. Measurements were of serum retinol, retinol-binding protein (RBP, a surrogate for retinol), and 25-hydroxyvitamin D (25(OH)D). Participants were stratified into two groups based on high and low incoming levels of RBP. Children received two doses of the seasonal influenza virus vaccine on days 0 and 28, either with an oral vitamin supplement (termed A&amp;D; 20,000 IU retinyl palmitate and 2000 IU cholecalciferol) or a matched placebo. Hemagglutination inhibition (HAI) antibody responses were evaluated toward all four components of the influenza virus vaccines on days 0, 28, and 56. Our primary data were from season 2016&#8722;2017, as enrollment was highest in this season and all children exhibited homogeneous and negative HAI responses toward the Phuket vaccine at study entry. Responses among children who entered the study with insufficient or deficient levels of RBP and 25(OH)D benefited from the A&amp;D supplement (<i>p</i> &lt; 0.001 for the day 28 Phuket response), whereas responses among children with replete levels of RBP and 25(OH)D at baseline were unaffected or weakened (<i>p</i> = 0.02 for the day 28 Phuket response). High baseline RBP levels associated with high HAI titers, particularly for children in the placebo group (baseline RBP correlated positively with Phuket HAI titers on day 28, <i>r</i> = 0.6, <i>p</i> = 0.003). In contrast, high baseline 25(OH)D levels associated with weak HAI titers, particularly for children in the A&amp;D group (baseline 25(OH)D correlated negatively with Phuket HAI titers on day 28, <i>r</i> = &#8722;0.5, <i>p</i> = 0.02). Overall, our study demonstrates that vitamin A&amp;D supplementation can improve immune responses to vaccines when children are vitamin A and D-insufficient at baseline. Results provide guidance for the appropriate use of vitamins A and D in future clinical vaccine studies.
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spelling doaj.art-8cd1bc12c45f49d5a6624b993e36b5272022-12-21T18:57:58ZengMDPI AGViruses1999-49152019-09-01111090710.3390/v11100907v11100907Baseline Serum Vitamin A and D Levels Determine Benefit of Oral Vitamin A&amp;D Supplements to Humoral Immune Responses Following Pediatric Influenza VaccinationNehali Patel0Rhiannon R. Penkert1Bart G. Jones2Robert E. Sealy3Sherri L. Surman4Yilun Sun5Li Tang6Jennifer DeBeauchamp7Ashley Webb8Julie Richardson9Ryan Heine10Ronald H. Dallas11A. Catharine Ross12Richard Webby13Julia L. Hurwitz14Department of Infectious Diseases, St. Jude Children’s Research Hospital, Memphis, TN 38105, USADepartment of Infectious Diseases, St. Jude Children’s Research Hospital, Memphis, TN 38105, USADepartment of Infectious Diseases, St. Jude Children’s Research Hospital, Memphis, TN 38105, USADepartment of Infectious Diseases, St. Jude Children’s Research Hospital, Memphis, TN 38105, USADepartment of Infectious Diseases, St. Jude Children’s Research Hospital, Memphis, TN 38105, USADepartment of Biostatistics, St. Jude Children’s Research Hospital, Memphis, TN 38105, USADepartment of Biostatistics, St. Jude Children’s Research Hospital, Memphis, TN 38105, USADepartment of Infectious Diseases, St. Jude Children’s Research Hospital, Memphis, TN 38105, USADepartment of Infectious Diseases, St. Jude Children’s Research Hospital, Memphis, TN 38105, USADepartment of Pharmaceuticals, St. Jude Children’s Research Hospital, Memphis, TN 38105, USADepartment of Infectious Diseases, St. Jude Children’s Research Hospital, Memphis, TN 38105, USADepartment of Infectious Diseases, St. Jude Children’s Research Hospital, Memphis, TN 38105, USADepartment of Nutritional Sciences, Pennsylvania State University, University Park, PA 16802, USADepartment of Infectious Diseases, St. Jude Children’s Research Hospital, Memphis, TN 38105, USADepartment of Infectious Diseases, St. Jude Children’s Research Hospital, Memphis, TN 38105, USAMaximizing vaccine efficacy is critical, but previous research has failed to provide a one-size-fits-all solution. Although vitamin A and vitamin D supplementation studies have been designed to improve vaccine efficacy, experimental results have been inconclusive. Information is urgently needed to explain study discrepancies and to provide guidance for the future use of vitamin supplements at the time of vaccination. We conducted a randomized, blinded, placebo-controlled study of influenza virus vaccination and vitamin supplementation among 2 to 8 (inclusive) year old children over three seasons, including 2015&#8722;2016 (<i>n</i> = 9), 2016&#8722;2017 (<i>n</i> = 44), and 2017&#8722;2018 (<i>n</i> = 26). Baseline measurements of vitamins A and D were obtained from all participants. Measurements were of serum retinol, retinol-binding protein (RBP, a surrogate for retinol), and 25-hydroxyvitamin D (25(OH)D). Participants were stratified into two groups based on high and low incoming levels of RBP. Children received two doses of the seasonal influenza virus vaccine on days 0 and 28, either with an oral vitamin supplement (termed A&amp;D; 20,000 IU retinyl palmitate and 2000 IU cholecalciferol) or a matched placebo. Hemagglutination inhibition (HAI) antibody responses were evaluated toward all four components of the influenza virus vaccines on days 0, 28, and 56. Our primary data were from season 2016&#8722;2017, as enrollment was highest in this season and all children exhibited homogeneous and negative HAI responses toward the Phuket vaccine at study entry. Responses among children who entered the study with insufficient or deficient levels of RBP and 25(OH)D benefited from the A&amp;D supplement (<i>p</i> &lt; 0.001 for the day 28 Phuket response), whereas responses among children with replete levels of RBP and 25(OH)D at baseline were unaffected or weakened (<i>p</i> = 0.02 for the day 28 Phuket response). High baseline RBP levels associated with high HAI titers, particularly for children in the placebo group (baseline RBP correlated positively with Phuket HAI titers on day 28, <i>r</i> = 0.6, <i>p</i> = 0.003). In contrast, high baseline 25(OH)D levels associated with weak HAI titers, particularly for children in the A&amp;D group (baseline 25(OH)D correlated negatively with Phuket HAI titers on day 28, <i>r</i> = &#8722;0.5, <i>p</i> = 0.02). Overall, our study demonstrates that vitamin A&amp;D supplementation can improve immune responses to vaccines when children are vitamin A and D-insufficient at baseline. Results provide guidance for the appropriate use of vitamins A and D in future clinical vaccine studies.https://www.mdpi.com/1999-4915/11/10/907influenza virus vaccinepediatricvitamins a and dbaselineantibody responsesupplement
spellingShingle Nehali Patel
Rhiannon R. Penkert
Bart G. Jones
Robert E. Sealy
Sherri L. Surman
Yilun Sun
Li Tang
Jennifer DeBeauchamp
Ashley Webb
Julie Richardson
Ryan Heine
Ronald H. Dallas
A. Catharine Ross
Richard Webby
Julia L. Hurwitz
Baseline Serum Vitamin A and D Levels Determine Benefit of Oral Vitamin A&amp;D Supplements to Humoral Immune Responses Following Pediatric Influenza Vaccination
Viruses
influenza virus vaccine
pediatric
vitamins a and d
baseline
antibody response
supplement
title Baseline Serum Vitamin A and D Levels Determine Benefit of Oral Vitamin A&amp;D Supplements to Humoral Immune Responses Following Pediatric Influenza Vaccination
title_full Baseline Serum Vitamin A and D Levels Determine Benefit of Oral Vitamin A&amp;D Supplements to Humoral Immune Responses Following Pediatric Influenza Vaccination
title_fullStr Baseline Serum Vitamin A and D Levels Determine Benefit of Oral Vitamin A&amp;D Supplements to Humoral Immune Responses Following Pediatric Influenza Vaccination
title_full_unstemmed Baseline Serum Vitamin A and D Levels Determine Benefit of Oral Vitamin A&amp;D Supplements to Humoral Immune Responses Following Pediatric Influenza Vaccination
title_short Baseline Serum Vitamin A and D Levels Determine Benefit of Oral Vitamin A&amp;D Supplements to Humoral Immune Responses Following Pediatric Influenza Vaccination
title_sort baseline serum vitamin a and d levels determine benefit of oral vitamin a amp d supplements to humoral immune responses following pediatric influenza vaccination
topic influenza virus vaccine
pediatric
vitamins a and d
baseline
antibody response
supplement
url https://www.mdpi.com/1999-4915/11/10/907
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