?(Figs.11C2). Open in a separate window Figure 8-Hydroxyguanine 1. StatVax CONSORT Diagram. Open in a separate window Figure 2. StatVax Trial Design Outcomes Fasting blood samples were taken on the following days: ?7, 0, 1, 7, 14, 21, and 24 in mid-morning. Background: The immunomodulatory effects of statins on vaccine response remain uncertain. Therefore, the objective of this study was to determine if atorvastatin enhances pneumococcal-specific antibody titer following 23-valent pneumococcal polysaccharide vaccination. Methods: Double-blind, placebo-controlled, single-center randomized clinical trial entitled StatVax. Subjects were enrolled between June and July 2014 and followed up through September 2014. 33 healthy volunteers signed informed consent after volunteer sampling. 11 participants were excluded; 22 healthy volunteers without prior pneumococcal vaccination were enrolled and completed the study. Participants were randomized to receive a 28-day course of 40mg atorvastatin (n=12) or matching lactose placebo (n=10). On day 7 of treatment, Pneumovax 23 was administered intramuscularly. The primary outcome was fold change in total pneumococcal-specific antibody titer determined by a ratio of post-vaccination titer over baseline titer. Secondary outcomes included serotype-specific pneumococcal antibody titer, seroconversion, complete blood counts (CBC), erythrocyte sedimentation rate (ESR) and serum cytokine analysis. Results: Of the 22 randomized patients (mean age, 23.86; SD, 4.121; 11 women [50%]), 22 completed the trial. Total anti-pneumococcal antibody titer in the atorvastatin group went 8-Hydroxyguanine from a baseline mean of 32.58 (SD, 15.96) to Igf2r 147.7 (SD, 71.52) g/mL at 21 days post-vaccination while titer in the placebo group went from a mean of 30.81 (SD, 13.04) to 104.4 (SD, 45) g/mL. When comparing fold change between treatment groups, there was a significant increase in fold change of total anti-pneumococcal antibody titer in the atorvastatin group compared to the placebo group (2-way ANOVA, p=.0177). Conclusions: Atorvastatin enhances antigen-specific primary humoral immune response to a T cell-independent pneumonia vaccination. Pending confirmation by larger cohort studies of target populations, peri-vaccination conventional doses of statins can become a novel adjuvant for poorly-immunogenic polysaccharide-based vaccines. Trial Registration: clinicaltrials.gov Identifier: NCT02097589 Keywords: pneumococcal pneumonia, atorvastatin, vaccination, healthy volunteers, humoral immunity Introduction Pneumococcal pneumonia is a major cause of morbidity and mortality in children and elderly patients [1C3]. Pneumonia vaccines which include Prevnar 13, a 13-valent conjugate vaccine, and Pneumovax 23, a T cell-independent, 23-valent polysaccharide vaccine, are scheduled for patients over the age of 65 to reduce the risk of infection [2, 4, 5]. However, vaccination responses are dampened in elderly patients by immune senescence rendering them vulnerable to infection [4, 6]. Vaccination in these patients is further complicated by concurrent treatment with other medications. Over 80% of patients over the age of 65 take at least one prescription medication, and 39% take five or more prescriptions [7]. The effects of these medications on immunologic response to vaccination are largely unknown. Statins are HMG-CoA reductase inhibitors used to block endogenous cholesterol generation in over 38.6 million Americans [8]. While statins are prescribed to reduce the risk of cardiovascular events, multiple recent reports have indicated a significant role for statins in modulating immunity. Statins have specifically been implicated in skewing Th1/Th2 cytokines [9C11], 8-Hydroxyguanine impairing T cell function [12], enhancing regulatory T cell function [13], impairing basophil activation and degranulation [14C16], and modulating acute phase reactants [17C23]. Retrospective cohort studies suggest that statins reduce the mortality associated with influenza infection and reduce the incidence and mortality of pneumonia by modulating humoral immune responses [24C31]. Although previous clinical evidence from a small cohort suggests that a short-term (10-day) conventional dose atorvastatin significantly enhanced production of antibody titers in a recall response to the T-cell dependent tetanus toxoid vaccine, no reports describe the effect of atorvastatin on primary humoral response to pneumonia vaccination [32]. What remains unclear is whether statin-mediated immune-modulation is only evident during T cell-dependent vaccines. Additionally, it remains unknown if prolonged conventional dose statin use during the immune response to vaccination differentially impacts immunity. Therefore, the primary aim of the StatVax study was to evaluate the effect of a 28-day course of conventional dose atorvastatin on humoral responses to the T-cell independent pneumonia vaccine Pneumovax 23. Methods Study Design and Oversight This single-center, randomized, double-blind, placebo-controlled study was approved by the University of Florida Internal Review Board, Research Advisory Committee, and Scientific Advisory Committee. All healthy volunteers provided written informed consent. Participants Posted flyers were used to recruit participants. After a telephone.
