The metabolic hormone adiponectin affects the correlation between nutritional status and pneumococcal vaccine response in vulnerable indigenous children

Abstract

Background: Almost 200 million children worldwide are either undernourished or overweight. Only a few studies have addressed the effect of variation in nutritional status on vaccine response. We previously demonstrated an association between stunting and an increased post-vaccination 13-valent pneumococcal conjugate vaccine (PCV13) response. In this prospective study, we assessed to what extent metabolic hormones may be a modifier in the association between nutritional status and PCV13 response.

Methods: Venezuelan children aged 6 weeks to 59 months were vaccinated with a primary series of PCV13. Nutritional status and serum levels of leptin, adiponectin and ghrelin were measured upon vaccination and their combined effect on serum post-vaccination antibody concentrations was assessed by generalized estimating equations multivariable regression analysis.

Results: A total of 210 children were included, of whom 80 were stunted, 81 had a normal weight and 49 were overweight. Overweight children had lower post-vaccination antibody concentrations than normal weight children (regression coefficient -1.15, 95% CI -2.22 --0.072). Additionally, there was a significant adiponectin-nutritional status interaction. In stunted children, higher adiponectin serum concentrations were associated with lower post-PCV13 antibody concentrations (regression coefficient -0.19, 95% CI -0.24 --0.14) while the opposite was seen in overweight children (regression coefficient 0.14, 95% CI 0.049-0.22).

Conclusion: Metabolic hormones, in particular adiponectin, may modify the effect of nutritional status on pneumococcal vaccine response. These findings emphasize the importance of further research to better understand the immunometabolic pathways underlying vaccine response and enable a future of optimal personalized vaccination schedules.

Fig 1. PCV13 vaccination schedule and sampling strategy.

A. PCV13 vaccination schedule based on age. B. Overview of sampling strategy. Blood samples were taken during both the 1^st and the 2^nd sampling moment. In the pre-vaccination serum samples (1^st sampling) PCV13 IgG levels and metabolic hormones were determined. In the post-vaccination serum samples (2^nd sampling) only PCV13 IgG levels were determined. * Median 6.7 weeks (IQR 6.4–6.9 weeks).

Fig 2

A: Correlation between adiponectin and post vaccination pneumococcal IgG antibody concentrations. Correlation, shown by a linear regression line, between pre-vaccination adiponectin levels and post-vaccination log-transformed pneumococcal IgG antibody concentrations for stunted, normal weight and overweight children. r = Pearson correlation coefficient. *p = <0.05. ^$ P-value value of interaction term in multivariable regression model (Table 3). B: Correlation between ghrelin and post vaccination pneumococcal IgG antibody concentrations. Correlation, shown by a linear regression line, between pre-vaccination ghrelin levels and post-vaccination log-transformed pneumococcal IgG antibody concentrations for stunted, normal weight and overweight children. r = Pearson correlation coefficient. ^$ P-value of interaction term in multivariable regression model (Table 3). C: Correlation between leptin and post vaccination pneumococcal IgG antibody concentrations. Correlation, shown by a linear regression line, between pre-vaccination leptin levels and post-vaccination log-transformed pneumococcal IgG antibody concentrations for stunted, normal weight and overweight children. r = Pearson correlation coefficient. *p = <0.05. ^$ P-value of interaction term in multivariable regression model (Table 3).