Effect of atorvastatin on humoral immune response to 23-valent pneumococcal polysaccharide vaccination in healthy volunteers: The StatVax randomized clinical trial

• Published in: Vaccine Vol. 37; no. 10; pp. 1313 - 1324
• Main Authors: Wildes, Tyler J., Grippin, Adam, Fasanya, Henrietta, Dyson, Kyle A., Brantly, Mark
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Ltd 28.02.2019; Elsevier Limited
• Subjects: adjuvants; analysis of variance; antibodies; Atorvastatin; blood serum; Body mass index; Clinical trials; cohort studies; Consent; Control methods; Cytokines; Erythrocyte sedimentation rate; Erythrocytes; Healthy volunteers; Humoral immunity; Immune response; Immune response (humoral); Immune system; Immunogenicity; Immunomodulation; immunomodulators; Infections; Informed consent; Lactose; Lymphocytes; Lymphocytes T; Medical screening; Mortality; patients; Pneumococcal pneumonia; Pneumonia; Polysaccharides; Population studies; randomized clinical trials; Seroconversion; Statins; Tetanus; Vaccination; Vaccines; Variance analysis; volunteers; women; Atorvastatin; Healthy volunteers; Pneumococcal pneumonia; Vaccination; Humoral immunity
• ISSN: 0264-410X; 1873-2518; 1873-2518
• DOI: 10.1016/j.vaccine.2019.01.023

•First trial on the impact of statins on pneumococcal polysaccharide vaccination.•Atorvastatin enhanced total pneumococcal-specific antibody response by 41.5%.•Atorvastatin enhanced primary humoral immunity to T cell-independent vaccination.•Statins may be a novel vaccine adjuvant. 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. 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 40 mg 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. 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 from a baseline mean of 32.58 (SD, 15.96) to 147.7 (SD, 71.52) μg/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) μg/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). 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