Black Steven, Nicolay Uwe, Del Giudice Giuseppe, Rappuoli Rino
Center for Global Health, Cincinnati Children's Hospital, Ohio.
Novartis Vaccines, Marburg, Germany.
J Infect Dis. 2016 Apr 15;213(8):1224-8. doi: 10.1093/infdis/jiv456. Epub 2015 Oct 28.
Influenza vaccination strategies have targeted elderly individuals because they are at high risk of disease complications and mortality. Statins are a class of drugs used to treat hypercholesterolemia and are frequently used in the elderly population to reduce the risk of cardiovascular disease. However, statins are also known to have immunomodulatory effects that could impact influenza vaccine response. In a post hoc analysis, we performed a cross-sectional observational study nested within a comparative immunogenicity clinical trial of adjuvanted versus unadjuvanted influenza vaccine in elderly persons to evaluate the influence of statin therapy on the immune response to vaccination. Overall, data on >5000 trial participants were available for analysis. Comparison of hemagglutination-inhibiting geometric mean titers to influenza A(H1N1), A(H3N2), and B strains revealed that titers were 38% (95% confidence interval [CI], 27%-50%), 67% (95% CI, 54%-80%), and 38% (95% CI, 28%-29%) lower, respectively, in subjects receiving chronic statin therapy, compared with those not receiving chronic statin therapy. This apparent immunosuppressive effect of statins on the vaccine immune response was most dramatic in individuals receiving synthetic statins. These effects were seen in both the adjuvanted and unadjuvanted vaccine groups in the clinical trial. These results, if confirmed, could have implications both for future clinical trials design, as well as for vaccine use recommendations for elderly individuals.
流感疫苗接种策略一直以老年人为目标人群，因为他们发生疾病并发症和死亡的风险很高。他汀类药物是一类用于治疗高胆固醇血症的药物，常用于老年人群以降低心血管疾病风险。然而，他汀类药物也具有免疫调节作用，可能会影响流感疫苗的反应。在一项事后分析中，我们进行了一项横断面观察性研究，该研究嵌套在一项针对老年人的佐剂流感疫苗与非佐剂流感疫苗的比较免疫原性临床试验中，以评估他汀类药物治疗对疫苗接种免疫反应的影响。总体而言，有超过5000名试验参与者的数据可供分析。对甲型流感（H1N1）、甲型流感（H3N2）和乙型流感病毒株的血凝抑制几何平均滴度进行比较发现，与未接受慢性他汀类药物治疗的受试者相比，接受慢性他汀类药物治疗的受试者的滴度分别低38%（95%置信区间[CI]，27%-50%）、67%（95%CI，54%-80%）和38%（95%CI，28%-29%）。他汀类药物对疫苗免疫反应的这种明显免疫抑制作用在接受合成他汀类药物的个体中最为显著。在临床试验的佐剂疫苗组和非佐剂疫苗组中均观察到了这些效应。这些结果如果得到证实，可能会对未来的临床试验设计以及老年人的疫苗使用建议产生影响。
