Hegmann Theresa E, Walter Emmanuel B, Smith Michael J, Campbell James, El Sahly Hana M, Whitaker Jennifer A, Creech C Buddy, Ustyugova Irina V, Goncalvez Ana P, Pandey Aseem, Alefantis Timothy, Sridhar Saranya, Honda-Okubo Yoshikazu, Petrovsky Nikolai, Frey Sharon E, Abate Getahun, Paulsen Grant, Anderson Evan J, Rostad Christina A, Rouphael Nadine, Makhene Mamodikoe, Roberts Paul C, Tuyishimire Bonifride, Bryant Christopher, Winokur Patricia
Department of Internal Medicine, University of Iowa Roy J. and Lucille A. Carver College of Medicine, 200 Hawkins Dr, Iowa City, IA, USA.
Duke Human Vaccine Institute, Department of Pediatrics, Duke University School of Medicine, 40 Duke Medicine Circle, Durham, NC, USA.
Vaccine. 2025 Apr 30;54:126991. doi: 10.1016/j.vaccine.2025.126991. Epub 2025 Mar 18.
Seasonal influenza continues to cause significant morbidity and mortality, particularly for the elderly and immunocompromised. Current licensed influenza vaccines provide only partial protection even for immunocompetent hosts. Vaccine adjuvants can improve the magnitude and breadth of immune responses and there is considerable interest in identifying new adjuvants that can improve immune responses to seasonal influenza vaccines. This phase I, randomized, double-blind trial evaluated the safety and immunogenicity of one dose of 2018/2019 quadrivalent influenza vaccine (either Fluzone® or Flublok®) administered intramuscularly with or without one of two adjuvants (AF03 or Advax-CpG55.2). A total of 241 healthy adults aged 18-45 years were enrolled and randomized to 1 of 6 groups. Groups 1-3 received one dose of Fluzone® QIV 2018/2019 administered alone or with AF03 or Advax-CpG55.2 and Groups 4-6 received one dose of Flublok® QIV 2018/2019 alone or with one of these two adjuvants. All participants received Fluzone® or Flublok® QIV 2019/2020 ninety days later. Primary objectives were to evaluate safety and reactogenicity along with changes in hemagglutinin inhibition (HAI), neuraminidase inhibition (NAI) and neutralizing antibodies to 2018/2019 seasonal influenza antigens, comparing Day 1 and Day 29 titers. Secondary objectives evaluated the impact of adjuvants on immune responses after subsequent doses of unadjuvanted seasonal influenza vaccine and immunologic responses to heterologous influenza H1 and H3 antigens. Overall, the adjuvanted vaccines were safe and generated robust immune responses against both homologous and heterologous strains. Similar responses were seen across all six study arms. Both adjuvants were associated with qualitatively improved immune responses against some strains at varying timepoints, but results were inconsistent. There were no substantial differences in safety or reactogenicity identified between the study groups and all vaccine formulations were well tolerated. In this highly immunologically-experienced cohort, neither AF03 nor Advax-CpG55.2 demonstrated notable benefit when added to the seasonal influenza vaccine. (ClinicalTrials.gov ID# NCT03945825).
季节性流感继续导致显著的发病率和死亡率，尤其是对老年人和免疫功能低下者而言。目前获得许可的流感疫苗即使对免疫功能正常的宿主也只能提供部分保护。疫苗佐剂可以提高免疫反应的强度和广度，人们对鉴定能够改善季节性流感疫苗免疫反应的新型佐剂有着浓厚兴趣。这项I期随机双盲试验评估了单剂量2018/2019四价流感疫苗（Fluzone®或Flublok®）在联合或不联合两种佐剂之一（AF03或Advax-CpG55.2）情况下肌肉注射的安全性和免疫原性。总共招募了241名年龄在18至45岁的健康成年人，并将他们随机分为6组中的1组。第1至3组接受单剂量2018/2019 Fluzone®四价流感疫苗单独注射或联合AF03或Advax-CpG55.2注射，第4至6组接受单剂量2018/2019 Flublok®四价流感疫苗单独注射或联合这两种佐剂之一注射。所有参与者在90天后接受Fluzone®或Flublok® 2019/2020四价流感疫苗。主要目标是评估安全性和反应原性以及血凝素抑制（HAI）、神经氨酸酶抑制（NAI）和针对2018/2019季节性流感抗原的中和抗体的变化，比较第1天和第29天的滴度。次要目标评估了佐剂对后续剂量无佐剂季节性流感疫苗免疫反应的影响以及对异源流感H1和H3抗原的免疫反应。总体而言，佐剂疫苗是安全的，并且对同源和异源毒株均产生了强烈的免疫反应。在所有六个研究组中都观察到了类似的反应。两种佐剂在不同时间点对某些毒株的免疫反应在质量上均有所改善，但结果并不一致。研究组之间在安全性或反应原性方面未发现实质性差异，所有疫苗制剂的耐受性都良好。在这个具有高度免疫经验的队列中，当添加到季节性流感疫苗中时，AF03和Advax-CpG55.2均未显示出显著益处。（ClinicalTrials.gov标识符：NCT03945825）
