Manzoli Lamberto, Salanti Georgia, De Vito Corrado, Boccia Antonio, Ioannidis John P A, Villari Paolo
Section of Epidemiology and Public Health, Department of Medicine and Aging Sciences, University G d'Annunzio of Chieti, Chieti, Italy.
Lancet Infect Dis. 2009 Aug;9(8):482-92. doi: 10.1016/S1473-3099(09)70153-7.
Influenza H5N1 is thought to be a likely causative agent for a future human influenza pandemic. Several types of H5N1 vaccine have been tested, including different doses and adjuvants, and a meta-analysis is needed to identify the best formulation. We searched Medline, Embase, the Cochrane Library, and other online databases to February, 2009, in any language for randomised trials comparing different H5N1 vaccines with or without placebo in healthy adults. Primary outcomes were seroconversion, seroresponse, or both according to haemagglutination-inhibition and microneutralisation. Secondary outcomes were adverse events. Because of the large number of compared formulations, multiple-treatments meta-analysis was used for primary outcomes. Direct-comparison meta-analyses were also done. We included 13 trials, which assessed 58 groups. With non-aluminium adjuvant, sufficiently high immunogenicity (greater than 70%) was achieved even at 12 microg or less (given as two doses of 6 microg or less), and higher doses did not provide major improvements. Immunogenicity for non-adjuvanted and aluminium-adjuvanted formulations increased with increasing dose, but was not sufficiently high. No serious vaccine-related adverse events were reported across 9600 participants. Currently, H5N1 influenza vaccines with non-aluminium adjuvants might represent the best available option in a pandemic. Large-scale studies are needed to verify the high immunogenicity of non-aluminium-adjuvanted vaccines that use very low doses of antigen.
H5N1流感被认为是未来可能引发人类流感大流行的病原体。几种类型的H5N1疫苗已进行了测试，包括不同剂量和佐剂，因此需要进行一项荟萃分析以确定最佳配方。我们检索了截至2009年2月的Medline、Embase、Cochrane图书馆及其他在线数据库，不限语言，查找在健康成年人中比较不同H5N1疫苗（有或无安慰剂）的随机试验。主要结局是根据血凝抑制和微量中和试验得出的血清转化、血清反应或两者兼有。次要结局是不良事件。由于比较的配方数量众多，主要结局采用多治疗荟萃分析。还进行了直接比较荟萃分析。我们纳入了13项试验，评估了58组。使用非铝佐剂时，即使剂量为12微克或更低（分两剂，每剂6微克或更低）也能达到足够高的免疫原性（大于70%），更高剂量并无显著改善。无佐剂和铝佐剂配方的免疫原性随剂量增加而提高，但不够高。在9600名参与者中未报告与疫苗相关的严重不良事件。目前，含非铝佐剂的H5N1流感疫苗可能是大流行情况下的最佳可用选择。需要开展大规模研究以验证使用极低剂量抗原的非铝佐剂疫苗的高免疫原性。
