Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, United States of America.
The Emmes Corporation, Rockville, MD, United States of America.
PLoS One. 2019 Sep 18;14(9):e0222178. doi: 10.1371/journal.pone.0222178. eCollection 2019.
Seasonal influenza results in significant morbidity and mortality worldwide, but the currently licensed inactivated vaccines generally have low vaccine efficacies and could be improved. In this phase 1 clinical trial, we compared seasonal influenza vaccine regimens with different priming strategies, prime-boost intervals, and administration routes to determine the impact of these variables on the resulting antibody response.
Between August 17, 2012 and January 25, 2013, four sites enrolled healthy adults 18-70 years of age. Subjects were randomized to receive one of the following vaccination regimens: trivalent hemagglutinin (HA) DNA prime followed by trivalent inactivated influenza vaccine (IIV3) boost with a 3.5 month interval (DNA-IIV3), IIV3 prime followed by IIV3 boost with a 10 month interval (IIV3-IIV3), or concurrent DNA and IIV3 prime followed by IIV3 boost with a 10 month interval (DNA/IIV3-IIV3). Each regimen was additionally stratified by an IIV3 administration route of either intramuscular (IM) or intradermal (ID). DNA vaccines were administered by a needle-free jet injector (Biojector). Study objectives included evaluating the safety and tolerability of each regimen and measuring the antibody response by hemagglutination inhibition (HAI).
Three hundred and sixteen subjects enrolled. Local reactogenicity was mild to moderate in severity, with higher frequencies recorded following DNA vaccine administered by Biojector compared to IIV3 by either route (p <0.02 for pain, swelling, and redness) and following IIV3 by ID route compared to IM route (p <0.001 for swelling and redness). Systemic reactogenicity was similar between regimens. Though no overall differences were observed between regimens, the highest titers post boost were observed in the DNA-IIV3 group by ID route and in the IIV3-IIV3 group by IM route.
All vaccination regimens were found to be safe and tolerable. While there were no overall differences between regimens, the DNA-IIV3 group by ID route, and the IIV3-IIV3 group by IM route, showed higher responses compared to the other same-route regimens.
季节性流感在全球范围内导致了大量发病和死亡，但目前许可使用的灭活疫苗通常具有较低的疫苗效力，因此可以进行改进。在这项 1 期临床试验中，我们比较了具有不同起始策略、起始-加强间隔和给药途径的季节性流感疫苗方案，以确定这些变量对产生的抗体反应的影响。
在 2012 年 8 月 17 日至 2013 年 1 月 25 日期间，四个地点招募了 18-70 岁的健康成年人。受试者被随机分配接受以下一种疫苗接种方案：三价血凝素 (HA) DNA 起始，然后用三价灭活流感疫苗 (IIV3) 加强，间隔 3.5 个月（DNA-IIV3）；三价 IIV3 起始，然后用 IIV3 加强，间隔 10 个月（IIV3-IIV3）；或同时用 DNA 和 IIV3 起始，然后用 IIV3 加强，间隔 10 个月（DNA/IIV3-IIV3）。每个方案还根据 IIV3 的肌肉内（IM）或皮内（ID）给药途径进行分层。DNA 疫苗通过无针喷射注射器（Biojector）给药。研究目的包括评估每个方案的安全性和耐受性，并通过血凝抑制（HAI）测量抗体反应。
共招募了 316 名受试者。局部反应的严重程度为轻度至中度，与通过 Biojector 给予 DNA 疫苗相比，通过任何途径给予 IIV3 的频率更高（疼痛、肿胀和发红时为 p<0.02），与通过 IM 途径给予 IIV3 相比，通过 ID 途径给予 IIV3 的频率更高（肿胀和发红时为 p<0.001）。方案之间的全身反应相似。尽管方案之间没有观察到总体差异，但在 ID 途径的 DNA-IIV3 组和 IM 途径的 IIV3-IIV3 组中观察到了最高的加强后滴度。
所有疫苗接种方案均被发现是安全和耐受的。尽管方案之间没有总体差异，但 ID 途径的 DNA-IIV3 组和 IM 途径的 IIV3-IIV3 组与其他相同途径的方案相比，显示出更高的反应。
