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

BACKGROUND: Obesity 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. METHODS: Nonobese (BMI 22–25 kg/m(2)) and obese participants (BMI ≥30 kg/m(2)) 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. RESULTS: Forty-six participants were categorized as nonobese (n = 23; 56.5% women; mean BMI 23.3 kg/m(2)) or obese (n = 23; 65.2% women; mean BMI 36.3 kg/m(2)). 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). CONCLUSIONS: These observations demonstrate a positive association between obesity and PPSV23 efficacy specifically in participants with the WT STING1 genotype. TRIAL REGISTRATION: ClinicalTrials.gov NCT02471014. FUNDING: This research was supported by the NIH and the University of Florida MD-PhD Training Program.