TY - JOUR
T1 - Obesity and Metabolic Dysregulation in Children Provide Protective Influenza Vaccine Responses
AU - Kainth, Mundeep K.
AU - Fishbein, Joanna S.
AU - Aydillo, Teresa
AU - Escalera, Alba
AU - Odusanya, Rachael
AU - Grammatikopoulos, Kalliopi
AU - Scotto, Tiffany
AU - Sethna, Christine B.
AU - García-Sastre, Adolfo
AU - Deutschman, Clifford S.
N1 - Funding Information:
Conflicts of Interest: The A.G.-S. laboratory has received research support from Pfizer, Senhwa Biosciences, Kenall Manufacturing, Avimex, Johnson & Johnson, Dynavax, 7Hills Pharma, Phar-mamar, ImmunityBio, Accurius, Nanocomposix, Hexamer, N-fold LLC, Model Medicines, Atea Pharma and Merck outside of the reported work. A.G.-S. has consulting agreements for the following companies involving cash and/or stock: Vivaldi Biosciences, Contrafect, 7Hills Pharma, Avimex, Vaxalto, Pagoda, Accurius, Esperovax, Farmak, Applied Biological Laboratories, Pharmamar and Pfizer outside of the reported work. A.G.-S. is an inventor on patents and patent applications on the use of antivirals and vaccines for the treatment and prevention of virus infections and cancer, owned by the Icahn School of Medicine at Mount Sinai, New York, outside of the reported work. CSD is supported in part by the National Institute of General Medical Science and BARDA, receives a stipend from the Society of Critical Care Medicine as Scientific Editor of the journal Critical Care Medicine, has received support in kind (free study drug) from La Jolla Pharmaceuticals, has consulted for ICON Data Management and Pfizer and holds stock options in Enlivex Inc. The remaining authors have no conflict of interest to disclose.
Funding Information:
Funding: This work is partially supported by CRIPT (Center for Research on Influenza Pathogenesis and Transmission), a NIAID-funded Center of Excellence for Influenza Research and Response (CEIRR, contract 75N93021C00014), by the NIAID Collaborative Influenza Vaccine Innovation Centers (CIVIC, contract 75N93019C00051) to A.G.-S. MKK was awarded the Department of Pediatrics Early Career Investigator Chairman’s Award to support this project.
Publisher Copyright:
© 2022 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2022/1
Y1 - 2022/1
N2 - The most effective intervention for influenza prevention is vaccination. However, there are conflicting data on influenza vaccine antibody responses in obese children. Cardio-metabolic parameters such as waist circumference, cholesterol, insulin sensitivity, and blood pressure are used to subdivide individuals with overweight or obese BMI into ‘healthy’ (MHOO) or ‘unhealthy’ (MUOO) metabolic phenotypes. The ever-evolving metabolic phenotypes in children may be eluci-dated by using vaccine stimulation to characterize cytokine responses. We conducted a prospective cohort study evaluating influenza vaccine responses in children. Participants were identified as either normal-weight children (NWC) or overweight/obese using BMI. Children with obesity were then characterized using metabolic health metrics. These metrics consisted of changes in serum cytokine and chemokine concentrations measured via multiplex assay at baseline and repeated at one month following vaccination. Changes in NWC, MHOO and MUOO were compared using Chi-square/Fisher’s exact test for antibody responses and Kruskal–Wallis test for cytokines. Dif-ferences in influenza antibody responses in normal, MHOO and MUOO children were statistically indistinguishable. IL-13 was decreased in MUOO children compared to NWC and MHOO children (p = 0.04). IL-10 approached a statistically significant decrease in MUOO compared to MHOO and NWC (p = 0.07). Influenza vaccination does not provoke different responses in NCW, MHOO, or MUOO children, suggesting that obesity, whether metabolically healthy or unhealthy, does not alter the efficacy of vaccination. IL-13 levels in MUO children were significantly different from levels in normal and MHOO children, indicating that the metabolically unhealthy phenotypes may be associated with an altered inflammatory response. A larger sample size with greater numbers of metabolically unhealthy children may lend more insight into the relationship of chronic inflammation secondary to obesity with vaccine immunity.
AB - The most effective intervention for influenza prevention is vaccination. However, there are conflicting data on influenza vaccine antibody responses in obese children. Cardio-metabolic parameters such as waist circumference, cholesterol, insulin sensitivity, and blood pressure are used to subdivide individuals with overweight or obese BMI into ‘healthy’ (MHOO) or ‘unhealthy’ (MUOO) metabolic phenotypes. The ever-evolving metabolic phenotypes in children may be eluci-dated by using vaccine stimulation to characterize cytokine responses. We conducted a prospective cohort study evaluating influenza vaccine responses in children. Participants were identified as either normal-weight children (NWC) or overweight/obese using BMI. Children with obesity were then characterized using metabolic health metrics. These metrics consisted of changes in serum cytokine and chemokine concentrations measured via multiplex assay at baseline and repeated at one month following vaccination. Changes in NWC, MHOO and MUOO were compared using Chi-square/Fisher’s exact test for antibody responses and Kruskal–Wallis test for cytokines. Dif-ferences in influenza antibody responses in normal, MHOO and MUOO children were statistically indistinguishable. IL-13 was decreased in MUOO children compared to NWC and MHOO children (p = 0.04). IL-10 approached a statistically significant decrease in MUOO compared to MHOO and NWC (p = 0.07). Influenza vaccination does not provoke different responses in NCW, MHOO, or MUOO children, suggesting that obesity, whether metabolically healthy or unhealthy, does not alter the efficacy of vaccination. IL-13 levels in MUO children were significantly different from levels in normal and MHOO children, indicating that the metabolically unhealthy phenotypes may be associated with an altered inflammatory response. A larger sample size with greater numbers of metabolically unhealthy children may lend more insight into the relationship of chronic inflammation secondary to obesity with vaccine immunity.
KW - Influenza vaccine
KW - Metabolic health
KW - Pediatric obesity
UR - http://www.scopus.com/inward/record.url?scp=85122830407&partnerID=8YFLogxK
U2 - 10.3390/v14010124
DO - 10.3390/v14010124
M3 - Article
C2 - 35062328
AN - SCOPUS:85122830407
SN - 1999-4915
VL - 14
JO - Viruses
JF - Viruses
IS - 1
M1 - 124
ER -