Pandemic preparedness:: lessons learnt from H2N2 and H9N2 candidate vaccines
Pandemic preparedness:: lessons learnt from H2N2 and H9N2 candidate vaccines
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DOI：
10.1007/s00430-002-0147-9
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发表时间：
2002-12-01
影响因子：
5.4
通讯作者：
Sänger, R
中科院分区：
文献类型：
--
作者：
Hehme, N;Engelmann, H;Sänger, R
预防流感的疫苗接种被认为是发生大流行时的主要干预措施之一。不幸的是，由于全世界疫苗需求的大幅增加和现有供应资源的有限，将出现疫苗供应短缺。推荐使用单价疫苗——而不是目前的三价疫苗——每剂含有15杯血凝素（HA），理论上可以使疫苗量增加两倍，但不太可能满足需求。此外，以往的经验表明，一次剂量的15杯HA不足以在未启动的个体中引起保护性抗体水平。对改进的配方方法进行了研究，这将适合在一定时间内提供大量的强效疫苗。低剂量的透明质酸与铝（Al）佐剂联合使用，并使用整个病毒而不是分裂或亚基抗原，可导致工艺产量的大幅增加。此外，全病毒疫苗的生产将降低生产的复杂性。在一项针对健康成人和老年人的剂量发现研究中，将使用al佐剂低剂量制剂后的免疫反应与标准分裂病毒疫苗（Fluarix, GlaxoSmithKline Biologicals, Rixensart，比利时）进行比较。所有疫苗都是安全且耐受性良好的。每剂含佐剂的实验性疫苗抗原浓度低至1.9 μ g HA/株，可在引物人群中诱导保护性抗体水平。在一项可行性试验中，研究了al佐剂低剂量疫苗的反应原性。使用al佐剂或全病毒对一般反应均无显著影响。在使用H2N2和H9N2候选疫苗的未引物人群中进行的研究显示出不同的结果，可能需要两剂接种计划。事实上，在单次接种疫苗后，血凝抑制滴度没有达到保护水平，但在接种第二剂后可以达到保护水平。al佐剂的全病毒制剂也是如此，抗原含量降低了8倍。由此可以得出结论，使用低透明质酸含量的al佐剂全病毒疫苗可以在两次疫苗剂量后提高保护性抗体水平，这反过来可能导致大流行时疫苗供应的显着增加。
Vaccination against influenza is considered to be one of the key interventions in case of a pandemic. Unfortunately, shortages in vaccine supplies will occur because of the substantial increase in vaccine demands worldwide and the limited available supply resources. The recommended use of monovalent - instead of current trivalent - vaccines containing 15 mug hemagglutinin (HA) per dose can theoretically triple vaccine volumes but is unlikely to meet the demand. Furthermore, previous experiences demonstrated that one dose of 15 mug HA will not be sufficient to elicit protective antibody levels in unprimed individuals. Modified formulation approaches were investigated, that would be suitable to provide significantly higher volumes of potent vaccine within a given period of time. Low doses of HA combined with aluminum (Al) adjuvants and the use of whole virus instead of split or subunit antigens can lead to substantial increases in process yield. In addition, production of whole virus vaccines will reduce manufacturing complexity. In a dose-finding study in healthy adults and elderly, immune responses after administration of Al-adjuvanted low-dose formulations were compared to a standard split virus vaccine (Fluarix, GlaxoSmithKline Biologicals, Rixensart, Belgium). All vaccines were safe and well tolerated. Antigen concentrations as low as 1.9 mug HA/strain per dose of adjuvant-containing experimental vaccines induced protective antibody levels in primed populations. Reactogenicity profiles of Al-adjuvanted low-dose vaccines were investigated in a feasibility trial. Neither the use of Al-adjuvant nor of whole virus had a significant effect on general reactions. Studies in unprimed populations with H2N2 and H9N2 candidate vaccines showed different results, with a potential need for a two-dose schedule. Indeed, hemagglutination inhibition titers did not reach protective levels after a single vaccine dose but could be met following administration of a second dose. The same is true for Al-adjuvanted whole virus formulations with an up to eightfold-reduced antigen content. It may be concluded that the use of Al-adjuvanted whole virus vaccines with low HA content can raise protective antibody levels after two vaccine doses, which may, in turn, result in significant increases of vaccine supplies in the case of a pandemic.