University of New South Wales, Sydney, Australia.
School of Public Health and Community Medicine, University of New South Wales, Sydney, Australia.
Vaccine. 2019 Jul 18;37(31):4246-4255. doi: 10.1016/j.vaccine.2019.06.039. Epub 2019 Jun 26.
Although oil-in-water adjuvants improve pandemic influenza vaccine efficacy, AS03 versus MF59 adjuvant comparisons in A(H1N1)pdm09 pandemic vaccines are lacking.
We conducted an indirect-comparison meta-analysis extracting published data from randomised controlled trials in literature databases (01/01/2009-09/09/2018), evaluating immunogenicity and safety of AS03- or MF59-adjuvanted vaccines. We conducted comparisons of log-transformed haemagglutination inhibition geometric mean titre ratio (GMTR; primary outcome) of different regimens of each adjuvant versus unadjuvanted counterparts. Then via test of subgroup differences, we indirectly compared different AS03 versus MF59 regimens.
We identified 22 publications with 10,734 participants. In adults, AS03-adjuvanted vaccines (3.75 µg haemagglutinin) achieved superior GMTR versus unadjuvanted vaccines (all four comparisons); MD = 0.56 (95%CI 0.33 to 0.80, p < 0.001) to 1.18 (95%CI 0.72 to 1.65, p < 0.001). MF59 (full-dose)-adjuvanted vaccines (7.5 µg haemagglutinin) were superior to unadjuvanted vaccines (three of four comparisons); MD = 0.47 (95%CI 0.19 to 0.75, p = 0.001) to 0.80 (95%CI 0.44 to 1.16, p < 0.001). Adult indirect comparisons favoured AS03 over MF59 (six of eight comparisons; p < 0.001 to p = 0.088). Paediatric indirect comparisons favoured MF59-adjuvanted vaccines (two of seven comparisons; p = 0.011, 0.079). However, unadjuvanted control group seroconversion rate was lower in MF59 than AS03 studies (p < 0.001 to p = 0.097). There was substantial heterogeneity, and adult AS03 studies had lower risk of bias.
Despite limited studies, in adults, AS03-adjuvanted vaccines allow antigen sparing versus MF59-adjuvanted and unadjuvanted vaccines, with similar immunogenicity, but higher risk of pain and fatigue (secondary outcomes) than unadjuvanted vaccines. In children, adjuvanted vaccines are also superior, but the better adjuvant is uncertain.
虽然油包水佐剂可以提高大流行性流感疫苗的效果，但在 A(H1N1)pdm09 大流行疫苗中，AS03 与 MF59 佐剂的比较尚缺乏相关研究。
我们通过检索文献数据库（2009 年 1 月 1 日至 2018 年 9 月 9 日）中的随机对照试验，开展了一项间接比较荟萃分析，以提取发表的数据，评估 AS03 或 MF59 佐剂疫苗的免疫原性和安全性。我们对每种佐剂不同方案与未佐剂对照相比的血凝抑制几何平均滴度比（GMTR；主要结局）进行了对数变换。然后通过亚组差异检验，我们间接地比较了不同 AS03 与 MF59 方案。
我们共识别出 22 篇文献，涉及 10734 名参与者。在成年人中，与未佐剂疫苗相比，AS03 佐剂疫苗（3.75μg 血凝素）的 GMTR 更优（所有 4 项比较）；MD=0.56（95%CI 0.33 至 0.80，p<0.001）至 1.18（95%CI 0.72 至 1.65，p<0.001）。MF59（全剂量）佐剂疫苗（7.5μg 血凝素）优于未佐剂疫苗（4 项比较中的 3 项）；MD=0.47（95%CI 0.19 至 0.75，p=0.001）至 0.80（95%CI 0.44 至 1.16，p<0.001）。成人间接比较结果表明，AS03 优于 MF59（8 项比较中的 6 项；p<0.001 至 p=0.088）。儿科间接比较结果表明，MF59 佐剂疫苗更优（7 项比较中的 2 项；p=0.011，0.079）。然而，MF59 研究的未佐剂对照组的血清转化率较低（p<0.001 至 p=0.097）。存在较大的异质性，且成人 AS03 研究的偏倚风险较低。
尽管研究有限，但在成年人中，与 MF59 佐剂和未佐剂疫苗相比，AS03 佐剂疫苗可节省抗原，且具有相似的免疫原性，但与未佐剂疫苗相比，AS03 佐剂疫苗更易引发疼痛和疲劳（次要结局）。在儿童中，佐剂疫苗也更优，但哪种佐剂更好尚不确定。
