University of Pittsburgh, Schools of the Health Sciences and UPMC, Pittsburgh, PA, USA.
Division of Infectious Diseases, Department of Internal Medicine, Korea University College of Medicine, Korea University, Ansan Hospital, Seoul, Republic of Korea.
Vaccine. 2020 Sep 29;38(42):6562-6569. doi: 10.1016/j.vaccine.2020.08.011. Epub 2020 Aug 13.
New influenza vaccine formulations are designed to improve vaccine effectiveness and protect those most vulnerable to infection. High dose trivalent inactivated influenza vaccine (HD-IIV3), licensed for ages ≥65 years, produces greater antibody responses and efficacy in clinical trials, but post-licensure vaccine effectiveness (VE) compared to standard dose (SD-IIV3/4) vaccine remains an open question.
Using a test-negative, case control design and propensity analyses to adjust for confounding, US Influenza VE Network data from the 2015-2016 through 2018-2019 seasons were analyzed to determine relative VE (rVE) between HD-IIV3 and SD-IIV3/4 among outpatients ≥65 years old presenting with acute respiratory illness. Influenza vaccination status was derived from electronic medical records and immunization registries.
Among 3861 enrollees, 2993 (78%) were vaccinated; 1573 (53%) received HD-IIV3 and 1420 (47%) received SD-IIV3/4. HD-IIV3 recipients differed from SD-IIV3/4 recipients by race, previous vaccination, number of outpatient visits in the previous year and timing of vaccination, and were balanced in the propensity model except the timing of vaccination. Compared with no vaccination, significant protection against any influenza A was observed from both HD-IIV3 (VE = 29%; 95%CI = 10%, 44%) and SD-IIV3/4 (VE = 24%; 95%CI = 5%, 39%); rVE = 18% (95%CI = 0%, 33%, SD as referent). When stratified by virus type, against A/H1N1, HD-IIV3 VE was 30% (95%CI = -7%, 54%), SD-IIV3/4 VE was 40% (95%CI = 10%, 61%), and rVE = -32%; (95%CI = -94%, 11%); Against A/H3N2, HD-IIV3 VE was 31% (95%CI = 9%, 47%), SD-IIV3/4 VE was 19% (95%CI = -5%, 37%), and rVE = 27%; (95% CI = 9%, 42%).
Among adults ≥65 years of age, recipients of standard and high dose influenza vaccines differed significantly in their characteristics. After adjusting for these differences, high dose vaccine offered more protection against A/H3N2 and borderline significant protection against all influenza A requiring outpatient care during the 2015-2018 influenza seasons.
新的流感疫苗制剂旨在提高疫苗的有效性，并保护那些最容易感染的人群。高剂量三价灭活流感疫苗（HD-IIV3）已获得许可用于年龄≥65 岁的人群，在临床试验中产生了更大的抗体反应和疗效，但与标准剂量（SD-IIV3/4）疫苗相比，上市后疫苗的有效性（VE）仍然是一个悬而未决的问题。
使用病例对照设计和倾向分析来调整混杂因素，分析了 2015-2016 年至 2018-2019 年美国流感 VE 网络的数据，以确定≥65 岁因急性呼吸道疾病就诊的门诊患者中 HD-IIV3 与 SD-IIV3/4 之间的相对 VE（rVE）。流感疫苗接种情况来源于电子病历和免疫登记处。
在 3861 名入组者中，2993 名（78%）接种了疫苗；1573 名（53%）接种了 HD-IIV3，1420 名（47%）接种了 SD-IIV3/4。与 SD-IIV3/4 相比，HD-IIV3 接种者在种族、既往接种情况、前一年的门诊就诊次数和接种时间等方面存在差异，但在倾向模型中是平衡的，除了接种时间。与未接种疫苗相比，两种疫苗均对任何流感 A 型均有显著的保护作用：HD-IIV3（VE=29%；95%CI=10%，44%）和 SD-IIV3/4（VE=24%；95%CI=5%，39%）；rVE=18%（95%CI=0%，33%，SD 作为参照）。当按病毒类型分层时，对 A/H1N1，HD-IIV3 的 VE 为 30%（95%CI=-7%，54%），SD-IIV3/4 的 VE 为 40%（95%CI=10%，61%），rVE=-32%（95%CI=-94%，11%）；对 A/H3N2，HD-IIV3 的 VE 为 31%（95%CI=9%，47%），SD-IIV3/4 的 VE 为 19%（95%CI=-5%，37%），rVE=27%（95%CI=9%，42%）。
在≥65 岁的成年人中，标准剂量和高剂量流感疫苗的接种者在其特征上存在显著差异。在调整这些差异后，高剂量疫苗对 A/H3N2 提供了更多的保护，对需要门诊治疗的所有流感 A 型也有边缘显著的保护作用，这在 2015-2018 年的流感季节中得到了证实。
