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.
Highlights
Pneumococcal infections are a leading cause of adult and childhood hospitalizations and mortality, with an estimated 1.6 million annual deaths [1, 2]
STING has been implicated in vaccine efficacy, as reduced antibody responses to T cell–independent type II antigens have been demonstrated in Sting-deficient mice [15]
Participants in the obese group showed significantly elevated BMI, waist/hip ratio, WBC counts, hemoglobin A1C, erythrocyte sedimentation rate, and blood pressure compared with the nonobese group, which aligns with other studies involving obese participants (Table 1) [18,19,20]
Summary
Pneumococcal infections are a leading cause of adult and childhood hospitalizations and mortality, with an estimated 1.6 million annual deaths [1, 2]. A high BMI is associated with an increased risk for contracting pneumococcal pneumonia, suggesting that it is desirable to provide effective vaccination to this susceptible, and growing, population [3]. STING has been implicated in vaccine efficacy, as reduced antibody responses to T cell–independent type II antigens have been demonstrated in Sting-deficient mice [15]. Sting–/– mice have impaired antibody responses to the 23-valent pneumococcal vaccine (PPSV23; Pneumovax 23), which elicits a T cell–independent type II response [16]. A knockin mouse with the mouse equivalent of the human HAQ-STING1 allele has an attenuated PPSV23 response [16, 17]. 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
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