Safety and antigenicity of non-adjuvanted and MF59-adjuvanted influenza A/Duck/Singapore/97 (H5N3) vaccine: a randomised trial of two potential vaccines against H5N1 influenza
Safety and antigenicity of non-adjuvanted and MF59-adjuvanted influenza A/Duck/Singapore/97 (H5N3) vaccine: a randomised trial of two potential vaccines against H5N1 influenza
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DOI：
10.1016/s0140-6736(00)05066-2
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发表时间：
2001-06-16
期刊：
影响因子：
168.9
通讯作者：
Zambon, MC
中科院分区：
文献类型：
--
作者：
Nicholson, KG;Colegate, AE;Zambon, MC
背景1997年，致病性禽流感A/Hong Kong/97(H5N1)病毒对人类构成大流行威胁，非致病性变异株A/Duck/新加坡/97(H5N3)被确定为主要候选疫苗。我们在健康志愿者中进行了一项观察者盲法的I期随机试验，以评估MF59佐剂疫苗和非佐剂疫苗的安全性、耐受性和抗原性。两次接种间隔3周，分别接种7.5、15或30毫克的血凝素表面抗原H5N3疫苗。抗体反应通过血凝抑制、微量中和和单径向溶血(SRH)来测量。主要结果是接种21天后的几何平均抗体滴度。发现A/Duck/新加坡疫苗是安全的和良好的耐受性。对非佐剂疫苗的抗体反应较差，最佳反应发生在两个30杯剂量后：1、4、4和1人分别经血凝抑制、微量中和、H5N3 SRH和H5N1 SRH转换。MF59佐剂疫苗接种后，抗体几何平均滴度和血清阳转率均显著升高。两种7.5杯剂量的MF59佐剂疫苗的血清转换率最高：血凝抑制，10分中的6；微中和，10分中的8；H5N3 SRH，10中的10；H5N1 SRH，10中的9。致病病毒A/Hong Kong/489/97(H5N1)的抗体几何平均效价约为A/Duck/新加坡病毒的一半。解释的非佐剂A/Duck/新加坡/97(H5N3)疫苗的免疫原性较差，仅注射7.5-30杯血凝素不太可能对A/Hong Kong/97(H5N1)病毒产生保护作用。在A/Duck/新加坡/97疫苗中添加MF59可提高抗体对保护水平的反应。我们的发现对未来大流行疫苗的开发和评估具有重要意义。
Background In 1997, pathogenic avian influenza A/Hong Kong/97 (H5N1) viruses emerged as a pandemic threat tc human beings, A non-pathogenic variant, influenza A/Duck/Singapore/97 (H5N3), was identified as a leading vaccine candidate. We did an observer-blind, phase I, randomised trial in healthy volunteers to assess safety, tolerability, and antigenicity of MF59-adjuvanted and non-adjuvanted vaccines.Methods 32 participants were randomly assigned MF59, and 33 non-adjuvanted vaccine. Two doses were given 3 weeks apart, of 7.5, 15, or 30 mug haemagglutinin surface-antigen influenza A H5N3 vaccine. Antibody responses were measured by haemagglutination inhibition, microneutralisation, and single radial haemolysis (SRH). The primary outcome was geometric mean antibody titre 21 days after vaccination.Findings The A/Duck/Singapore vaccines were safe and well tolerated. Antibody response to non-adjuvanted vaccine was poor, the best response occurring after two 30 mug doses: one, four, four, and one person of eleven seroconverted by haemagglutination inhibition, microneutralisation, H5N3 SRH, and H5N1 SRH, respectively. The geometric mean titres of antibody, and seroconversion rates, were significantly higher after MF59 adjuvanted vaccine. Two 7.5 mug doses of MF59 adjuvanted vaccine gave the highest seroconversion rates: haemagglutination inhibition, six of ten; microneutralisation, eight of ten; H5N3 SRH, ten of ten; H5N1 SRH, nine of ten. Geometric mean titre of antibody to the pathogenic virus, A/Hong Kong/489/97 (H5N1), was about half that to A/Duck/Singapore virus.Interpretation Non-adjuvanted A/Duck/Singapore/97 (H5N3) vaccines are poorly immunogenic and doses of 7.5-30 mug haemagglutinin alone are unlikely to give protection from A/Hong Kong/97 (H5N1) virus. Addition of MF59 to A/Duck/Singapore/97 vaccines boost the antibody response to protection levels. Our findings have implications for development and assessment of vaccines for future pandemics.