GSK, Wavre, Belgium.
University of Massachusetts Medical School, Worcester, MA, USA.
Influenza Other Respir Viruses. 2021 Jan;15(1):110-120. doi: 10.1111/irv.12780. Epub 2020 Sep 5.
Non-neutralizing antibodies inducing complement-dependent lysis (CDL) and antibody-dependent cell-mediated cytotoxicity (ADCC) activity may contribute to protection against influenza infection. We investigated CDL and ADCC responses in healthy adults randomized to receive either non-adjuvanted or AS03-adjuvanted monovalent A(H1N1)pdm09 vaccine (containing 15 µg/3.75 μg of hemagglutinin, respectively) on a 2-dose schedule 21 days apart.
We conducted an exploratory analysis of a subset of 106 subjects having no prior history of A(H1N1)pdm09 infection or seasonal influenza vaccination enrolled in a previously reported study (NCT00985673). Antibody responses against the homologous A/California/7/2009 (H1N1) vaccine strain and a related A/Brisbane/59/2007 (H1N1) seasonal influenza strain were analyzed up to Day 42.
Baseline seropositivity determined with hemagglutination inhibition (HI), CDL and ADCC antibody titers against viral strains was high; A/California/7/2009 (HI [40.4-48.1%]; CDL [34.6-36.0%]; ADCC [92.1-92.3%]); A/Brisbane/59/2007 (HI [73.1-88.9%]; CDL [38.0-42.0%]; ADCC [86.8-97.0%]). CDL seropositivity increased following vaccination with both adjuvanted and non-adjuvanted formulations (A/California/7/2009 [95.9-100%]; A/Brisbane/59/2007 [75.5-79.6%]). At Day 21, increases in CDL and ADCC antibody geometric mean titers against both strains were observed for both formulations. After 2 doses of AS03-adjuvanted vaccine, vaccine responses of 95.8% (≥9-fold increase from baseline in CDL titers) and 34.3% (≥16-fold increase from baseline in ADCC titers) were seen against A/California/7/2009; and 22.4% and 42.9%, respectively, against A/Brisbane/59/2007. Vaccine responses after 2 doses of the non-adjuvanted vaccine were broadly similar.
Broadly comparable non-neutralizing immune responses were observed following vaccination with non-adjuvanted and AS03-adjuvanted A(H1N1)pdm09 formulations; including activity against a related vaccine strain.
诱导补体依赖性细胞溶解（CDL）和抗体依赖性细胞介导的细胞毒性（ADCC）活性的非中和抗体可能有助于预防流感感染。我们研究了在 21 天的间隔内分别接受无佐剂或 AS03 佐剂单价 A（H1N1）pdm09 疫苗（分别含有 15 µg/3.75 µg 的血凝素）的健康成年人中的 CDL 和 ADCC 反应。
我们对先前报告的研究（NCT00985673）中没有 A（H1N1）pdm09 感染或季节性流感疫苗接种史的 106 名受试者的亚组进行了探索性分析。在第 42 天之前分析了针对同源 A/加利福尼亚/7/2009（H1N1）疫苗株和相关 A/Brisbane/59/2007（H1N1）季节性流感株的抗体反应。
使用血凝抑制（HI）、针对病毒株的 CDL 和 ADCC 抗体滴度确定的基线血清阳性率较高；A/加利福尼亚/7/2009（HI [40.4-48.1%]；CDL [34.6-36.0%]；ADCC [92.1-92.3%]）；A/Brisbane/59/2007（HI [73.1-88.9%]；CDL [38.0-42.0%]；ADCC [86.8-97.0%]）。用两种佐剂和非佐剂制剂接种疫苗后，CDL 血清阳性率均增加（A/加利福尼亚/7/2009 [95.9-100%]；A/Brisbane/59/2007 [75.5-79.6%]）。在第 21 天，两种制剂均观察到针对两种菌株的 CDL 和 ADCC 抗体几何平均滴度增加。在接受两剂 AS03 佐剂疫苗后，针对 A/加利福尼亚/7/2009 的疫苗反应分别为 95.8%（CDL 滴度比基线增加 9 倍）和 34.3%（ADCC 滴度比基线增加 16 倍）；针对 A/Brisbane/59/2007 的疫苗反应分别为 22.4%和 42.9%。两剂非佐剂疫苗接种后的疫苗反应大致相似。
接种无佐剂和 AS03 佐剂 A（H1N1）pdm09 制剂后观察到广泛可比的非中和免疫反应；包括对相关疫苗株的活性。
