Obesity and STING1 genotype associate with 23-valent pneumococcal vaccination efficacy

Mathew Sebastian, Chu J Hsiao, Hunter S Futch, Robert S Eisinger, Leanne Dumeny, Seema Patel, Mesfin Gobena, Divya S Katikaneni, Joel Cohen, Anne-Marie Carpenter, Lisa Spiryda, Coy D Heldermon, Lei Jin, Mark L Brantly, Mathew Sebastian, Chu J Hsiao, Hunter S Futch, Robert S Eisinger, Leanne Dumeny, Seema Patel, Mesfin Gobena, Divya S Katikaneni, Joel Cohen, Anne-Marie Carpenter, Lisa Spiryda, Coy D Heldermon, Lei Jin, Mark L Brantly

Abstract

BACKGROUNDObesity has been associated with attenuated vaccine responses and an increased risk of contracting pneumococcal pneumonia, but no study to our knowledge has assessed the impact of obesity and genetics on 23-valent pneumococcal vaccine (PPSV23) efficacy. We assessed the relationship of obesity (primary analysis) and stimulator of interferon genes (STING1) genotype (secondary analysis) on PPSV23 efficacy.METHODSNonobese (BMI 22-25 kg/m2) and obese participants (BMI ≥30 kg/m2) were given a single dose of PPSV23. Blood was drawn immediately prior to and 4-6 weeks after vaccination. Serum samples were used to assess PPSV23-specific antibodies. STING1 genotypes were identified using PCR on DNA extracted from peripheral blood samples.RESULTSForty-six participants were categorized as nonobese (n = 23; 56.5% women; mean BMI 23.3 kg/m2) or obese (n = 23; 65.2% women; mean BMI 36.3 kg/m2). Obese participants had an elevated fold change in vaccine-specific responses compared with nonobese participants (P < 0.0001). The WT STING1 group (R232/R232) had a significantly higher PPSV23 response than individuals with a single copy of HAQ-STING1 regardless of BMI (P = 0.0025). When WT was assessed alone, obese participants had a higher fold serotype-specific response compared with nonobese participants (P < 0.0001), but no difference was observed between obese and nonobese individuals with 1 HAQ allele (P = 0.693).CONCLUSIONSThese observations demonstrate a positive association between obesity and PPSV23 efficacy specifically in participants with the WT STING1 genotype.TRIAL REGISTRATIONClinicalTrials.gov NCT02471014.FUNDINGThis research was supported by the NIH and the University of Florida MD-PhD Training Program.

Keywords: Bacterial vaccines; Genetic variation; Infectious disease; Obesity; Vaccines.

Conflict of interest statement

Conflict of interest: The authors have declared that no conflict of interest exists.

Figures

Figure 1. Flow diagram of participating subjects.
Figure 1. Flow diagram of participating subjects.
Figure 2. No difference in baseline PPSV23…
Figure 2. No difference in baseline PPSV23 titers or seroconversion.
(A) Mean prevaccination titers to all serotypes among nonobese (n = 23) versus obese (n = 23) participants. (2-way ANOVA, P = 0.172). (B) Percentage of the 23 tested antibody concentrations per participant that were greater than or equal to a 2-fold increase over prevaccination levels in nonobese (n = 23) and obese (n = 23) participants (t test, P = 0.064). (C) Percentage of the 23 tested antibody concentrations that were greater than the reference values before vaccination in nonobese (n = 23) and obese (n = 23) participants (t test, P = 0.214). (D) Percentage of the 23 tested antibody concentrations that were greater than the reference values after vaccination in nonobese (n = 23) and obese (n = 23) participants (t test, P = 0.619). Segment inside the box indicates median; bounds of box represent 25th and 75th percentiles; and whiskers, minimum and maximum values.
Figure 3. Obese participants have increased response…
Figure 3. Obese participants have increased response to PPSV23.
(A) Mean postvaccination antibody concentrations to all serotypes comparing nonobese (n = 23) and obese participants (n = 23) (2-way ANOVA). (B) Mean fold change to all serotypes comparing nonobese (n = 23) and obese participants (n = 23) (2-way ANCOVA). (C) Mean fold change to all serotypes among White participants only, comparing nonobese (n = 17) and obese participants (n = 12) (2-way ANOVA). Segment inside the box indicates median; bounds of box represent 25th and 75th percentiles; and whiskers the minimum and maximum values. ****P < 0.0001.
Figure 4. R232/R232 STING1 genotype is positively…
Figure 4. R232/R232 STING1 genotype is positively associated with PPSV23 response.
(A) STING1 genotype frequencies in nonobese (n = 23) and obese populations (n = 23). (B) Mean fold change to all serotypes comparing R232/R232 (n = 26) and any genotype with a copy of HAQ (n = 11) (2-way ANOVA, P = 0.0025). (C) Mean fold change to all serotypes among R232/R232 participants only, comparing nonobese (n = 13) and obese participants (n = 14) (2-way ANOVA, P < 0.0001). (D) Mean fold change to all serotypes among R232/HAQ participants only, comparing nonobese (n = 6; 67% White) and obese (n = 2; 100% White) participants (2-way ANOVA, P = 0.693). Segment inside the box indicates median; bounds of boxes represent 25th and 75th percentiles; and whiskers, minimum and maximum values. **P < 0.01, ****P < 0.0001.

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