Didion Elise M, Kass Joseph D, Wilk Dennis J, Buss Emily, Frischmann Sarah-Michelle, Rubeck Sabina, Banks Richard, Wilson Brigid M, Gravenstein Stefan, Canaday David H
Case Western Reserve University School of Medicine, Cleveland, OH.
Geriatric Research, Education and Clinical Center at Louis Stokes Cleveland VA Medical Center, Cleveland, OH.
medRxiv. 2024 Oct 15:2024.10.14.24315459. doi: 10.1101/2024.10.14.24315459.
The CDC recommends the more immunogenic adjuvanted and high-dose flu vaccines over standard-dose, non-adjuvanted vaccines for individuals above 65 years old. The current study compares adjuvanted trivalent inactivated flu vaccine (aTIV, FLUAD) versus high-dose flu vaccine (HD-IIV3, FLUZONE HD) to determine if they met non-inferiority standards for older long-term care facility (LTCF) residents.
We collected blood from long-term care facility residents participating in a randomized 1:1 active control trial comparing MF59C.1 adjuvanted trivalent inactivated flu vaccine, aTIV versus HD-IIV3 over the course of two flu seasons, 2018-2019 and 2019-2020 (Trial, NCT03694808). We assessed humoral immunity at set time points via hemagglutinin inhibition assays (HAI) and anti-neuraminidase (enzyme-linked lectin assays (ELLA)). The recombinant influenza vaccine (RIV, Flublok) was assessed similarly in year two for a small number of participants who were carried over from year 1 (n=32).
We enrolled 387 volunteers and administered either aTIV (n=194), HD-IIV3 (n=193) over the course of the 2018-2019 and 2019-2020 flu seasons. Among those enrolled and randomized in year one, a subset were administered RIV and studied in year two (n = 32). At 28 days post-vaccination, aTIV exhibited non-inferiority to HD-IIV3 for HAI for both H1N1 and H3N2 strains (GMT ratios (95% CI) for HD-IIV3/aTIV of 1.03(0.76, 1.4) and 1.04(0.73, 1.48), respectively; both 95% CI upper bounds < 1.5 to meet non-inferiority criteria) but not for Influenza B (GMT ratio (95% CI) = 1.21 (0.91, 1.61)). Non-inferiority criteria for HAI seroconversion were not met for any of the three strains. Applying the same non-inferiority criteria to neuraminidase inhibition (NI), both day 28 titer and seroconversion in aTIV were non-inferior to HD-IIV3 for H1N1 and H3N2 strains.
Both aTIV and HD-IIV3 elicited similar immune responses with robust antibody responses. For the primary outcome, aTIV is non-inferior to HD-IIV3 for HAI titer of H1N1 and H3N2 but failed to meet non-inferiority criteria for Influenza B and seroconversion for all assessed strains. For the secondary outcome, aTIV was non-inferior to HD-IIV3 for both titer and seroconversion of anti-neuraminidase for both H1N1 and H3N2.
美国疾病控制与预防中心（CDC）建议，65岁以上人群应接种免疫原性更强的佐剂流感疫苗和高剂量流感疫苗，而非标准剂量的无佐剂疫苗。本研究比较了佐剂三价灭活流感疫苗（aTIV，商品名FLUAD）和高剂量流感疫苗（HD-IIV3，商品名FLUZONE HD），以确定它们是否符合老年长期护理机构（LTCF）居民的非劣效性标准。
我们收集了参与一项随机1:1活性对照试验的长期护理机构居民的血液，该试验在2018 - 2019年和2019 - 2020年两个流感季节中比较了MF59C.1佐剂三价灭活流感疫苗aTIV与HD-IIV3（试验注册号：NCT03694808）。我们通过血凝抑制试验（HAI）和抗神经氨酸酶（酶联凝集素试验（ELLA））在设定时间点评估体液免疫。在第二年，对少数从第一年结转过来的参与者（n = 32），以类似方式评估了重组流感疫苗（RIV，商品名Flublok）。
我们招募了387名志愿者，并在2018 - 2019年和2019 - 2020年流感季节期间分别接种了aTIV（n = 194）或HD-IIV3（n = 193）。在第一年入组并随机分组的人群中，有一部分接种了RIV，并在第二年进行研究（n = 32）。接种疫苗后28天，对于H1N1和H3N2毒株，aTIV在HAI方面表现出非劣效于HD-IIV3（HD-IIV3/aTIV的几何平均滴度比值（95%置信区间）分别为1.03(0.76, 1.4)和1.04(0.73, 1.48)；两个95%置信区间上限均< 1.5，符合非劣效性标准），但对于乙型流感不成立（几何平均滴度比值（95%置信区间）= 1.21 (0.91, 1.61)）。对于三种毒株中的任何一种，HAI血清转化的非劣效性标准均未达到。将相同的非劣效性标准应用于神经氨酸酶抑制（NI），对于H1N1和H3N2毒株，aTIV在第28天的滴度和血清转化方面均非劣效于HD-IIV3。
aTIV和HD-IIV3均引发了相似的免疫反应，抗体反应强烈。对于主要结局，aTIV在H1N1和H3N2的HAI滴度方面非劣效于HD-IIV3，但在乙型流感和所有评估毒株的血清转化方面未达到非劣效性标准。对于次要结局，aTIV在H1N1和H3N2的抗神经氨酸酶滴度和血清转化方面均非劣效于HD-IIV3。
