Obesity and Metabolic Dysregulation in Children Provide Protective Influenza Vaccine Responses

Abstract

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 elucidated 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. Differences 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.

SARS-CoV-2 and Influenza Vaccines in People with Excessive Body Mass—A Narrative Review

“…However, the total number of the cells seems to be similar between obese and non-obese people. Levels of the CD8+ cells expressing IFNγ ( p = 0.006) and granzyme B (GrB) ( p = 0.026), which are able to limit replication of the virus [ 43 ], were reduced for obese compared to normal-weight individuals. In another study, obesity was associated with a decreased number of activated CD8+ T cells expressing CD28, CD40 ligand (CD40L), IFNγ as well as both IFNγ and GrB, and both CD28 and interleukin 12 receptor (IL12R) [ 42 ].…”

“…Recent evidence indicates that obese adolescents (BMI ≥ 85th percentile) with unhealthy metabolic phenotype have a lower concentration of interleukin-13 (IL-13) ( p = 0.04) as well as interleukin-10 (IL-10) ( p = 0.07) compared to non-obese (BMI ≤ 85th percentile) and obese participants with healthy phenotype one month after vaccination [ 43 ]. Both IL-13 and IL-10 inhibit the production of pro-inflammatory cytokines.…”

“…Obese (mean BMI 37.8 ± 7.9 kg/m 2 ) and overweight (mean BMI 27.2 ± 1.5 kg/m 2 ) individuals showed no differences in proliferation, activation of dendritic cells, or expression of CD80, CD86, MHC II, IL-12, and IL-7 compared to healthy weight (mean BMI 22.3 ± 1.6 kg/m 2 ) vaccinated subjects. However, increased BMI level does impair the activation of CD4+ T cells resulting in lower expression of CD28, CD40L, IL12R, CD69, INF-γ, and GrB ( p < 0.05) [ 43 ].…”

Obesity as a risk factor for severe influenza infection in children and adolescents: a systematic review and meta-analysis

“…One study was performed postmortem and therefore didn't provide any valuable information [21]. Two studies provided information post-vaccination [22,23]. Another study provided no information regarding disease severity [24].…”

Special Issue “Pediatric Viral Infection Long-Term Consequences”

“…Vaccination is the most effective intervention for prevention, but it is unclear if children with obesity mount as robust and protective responses as compared to normal weight children. Kainth et al found that influenza vaccination provides similar cytokine and chemokine responses in normal weight and obese children, suggesting that a child's weight does not alter the efficacy of vaccination [6].…”