Incorporation of LpxL1, a detoxified lipopolysaccharide adjuvant, in influenza H5N1 virosomes increases vaccine immunogenicity
Incorporation of LpxL1, a detoxified lipopolysaccharide adjuvant, in influenza H5N1 virosomes increases vaccine immunogenicity
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DOI：
10.1016/j.vaccine.2008.11.046
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发表时间：
2009-02-05
期刊：
影响因子：
5.5
通讯作者：
Huckriede, A.
中科院分区：
文献类型：
--
作者：
de Vries, J. J. C.;Bungener, L.;Huckriede, A.
人类感染H5 N1流感病毒的人数不断增加，这突出表明需要开发H5 N1候选疫苗，以预防潜在的流感大流行。在此类疫苗中使用佐剂可显著有助于抗原剂量节省。在这项研究中，我们评估了无毒的脑膜炎奈瑟菌脂多糖类似物LpxL 1作为H5 N1流感病毒体疫苗佐剂的能力。使用灭活的流感H5 N1病毒（NIBRG-14）构建病毒体（重构的病毒包膜），其中LpxL 1掺入病毒体膜中，从而将流感血凝素（HA）抗原和佐剂组合在同一颗粒中。用掺入或不掺入LpxL 1的H5 N1病毒体以单剂量或两剂量免疫方案免疫小鼠。单次免疫后，掺入LpxL 1的H5 N1病毒体与未加佐剂的病毒体相比诱导显著增强的H5 N1特异性总IgG滴度，但血凝抑制（HI）滴度仍然较低。在两剂免疫方案中，LpxL 1修饰的H5 N1病毒体诱导的HI滴度高于40，这显著高于用无佐剂病毒体获得的那些。LpxL 1的掺入对病毒体诱导的IgG 1水平几乎没有影响，但在一次和两次封闭免疫方案中显著增加了IgC 2a水平。与未加佐剂的病毒体相比，LpxL 1修饰的病毒体诱导了相似数量的产生IFN γ的T细胞，但减少了产生IL-4的T细胞的数量，而与免疫接种次数无关。我们的结论是，LpxL 1纳入H5 N1流感病毒体有能力作为一个有效的佐剂，特别是刺激Th 1型免疫反应。(C)2008爱思唯尔有限公司保留所有权利。
The increasing number of human influenza H5N1 infections accentuates the need for the development of H5N1 vaccine candidates to prevent a potential influenza pandemic. The use of adjuvants in such vaccines can contribute significantly to antigen dose-sparing. In this study, we evaluated the capacity of the non toxic Neisseria meningitidis lipopolysaccharide analog LpxL1 to function as an adjuvant for an influenza H5N1 virosomal vaccine. Inactivated influenza H5N1 virus (NIBRG-14) was used to construct virosomes (reconstituted virus envelopes) with LpxL1 incorporated in the virosomal membrane thus combining the influenza hemagglutinin (HA) antigen and the adjuvant in the same particle. Mice were immunized in a one- or two-dose immunization regimen with H5N1 virosomes with or without incorporated LpxL1 After a single immunization, H5N1 virosomes with incorporated LpxL1 induced significantly enhanced H5N1-specific total IgG titers as compared to non-adjuvanted virosomes but hemagglutination inhibition (HI) titers remained low. In the two-dose immunization regimen, LpxL1-modified H5N1 virosomes induced HI titers above 40 which were significantly higher than those obtained with non-adjuvanted virosomes. Incorporation of LpxL1 had little effect on virosome-induced IgG1 levels, but significantly increased IgC2a levels in both the one- and two-close immunization regimen. Compared to non-adjuvanted virosomes, LpxL1-modified virosomes induced similar numbers of IFN gamma-producing T cells but decreased numbers of IL-4-producing T cells irrespective of the number of immunizations. We conclude that LpxL1 incorporated in H5N1 influenza virosomes has the capacity to function as a potent adjuvant particularly Stimulating Th1-type immune reactions. (C) 2008 Elsevier Ltd. All rights reserved.