Radosević Katarina, Rodriguez Ariane, Mintardjo Ratna, Tax Dennis, Bengtsson Karin Lövgren, Thompson Catherine, Zambon Maria, Weverling Gerrit Jan, Uytdehaag Fons, Goudsmit Jaap
Crucell Holland BV, Leiden, The Netherlands.
Vaccine. 2008 Jul 4;26(29-30):3640-6. doi: 10.1016/j.vaccine.2008.04.071. Epub 2008 May 15.
A highly efficacious vaccine is required to counteract a threat of an avian influenza pandemic. Increasing the potency of vaccines by adjuvation is essential not only to overcome generally low immunogenicity of pandemic strains, but also to allow dose sparing and as such to make it feasible to satisfy huge global production demands. In this study we evaluated the ability of four distinct adjuvants to further increase immune responses to a virosomal adjuvanted avian H9N2 influenza vaccine in mice. Currently registered adjuvants aluminium phosphate, aluminium hydroxide and MF59, as well as a novel promising adjuvant MATRIX-M were included in the study. Our results demonstrate that all adjuvants significantly increased the H9N2 haemagglutinin (HA) inhibition and ELISA antibody titers induced with the virosomal adjuvanted vaccine. The adjuvants exhibited different effect on the isotype of virus specific antibodies, with MATRIX-M inducing the most pronounced skewing to IgG2a, i.e. towards Th1 type of response. While the virosomal adjuvanted pandemic influenza vaccine efficiently induced CD4(+) T-cell response, with no further increase upon adjuvation, the CD8(+) T-cell responses induced with virosomal adjuvanted vaccine could be significantly improved upon additional adjuvation with MATRIX-M or MF59. All adjuvants demonstrated a dose sparing effect, i.e. in combination with the virosomal adjuvanted pandemic influenza vaccine they increased immune responses to comparable level independent of the tested vaccine dose. In conclusion, our results demonstrate that immune responses to a virosomal adjuvanted pandemic influenza vaccine can be further enhanced by add-on adjuvants, with MATRIX-M being overall the most potent adjuvant in combination with virosomes, followed by MF59 and finally aluminium-based adjuvants.
需要一种高效的疫苗来应对禽流感大流行的威胁。通过添加佐剂提高疫苗效力不仅对于克服大流行毒株普遍较低的免疫原性至关重要，而且对于减少剂量从而满足全球巨大的生产需求也是可行的。在本研究中，我们评估了四种不同佐剂进一步增强小鼠对病毒体佐剂化H9N2禽流感疫苗免疫反应的能力。本研究纳入了目前已注册的佐剂磷酸铝、氢氧化铝和MF59，以及一种有前景的新型佐剂MATRIX-M。我们的结果表明，所有佐剂均显著提高了病毒体佐剂化疫苗诱导的H9N2血凝素（HA）抑制和ELISA抗体滴度。这些佐剂对病毒特异性抗体的亚型表现出不同的影响，其中MATRIX-M诱导最明显的向IgG2a的偏移，即偏向Th1型反应。虽然病毒体佐剂化大流行性流感疫苗有效地诱导了CD4(+) T细胞反应，添加佐剂后没有进一步增加，但病毒体佐剂化疫苗诱导的CD8(+) T细胞反应在额外添加MATRIX-M或MF59佐剂后可显著改善。所有佐剂均显示出剂量节省效应，即与病毒体佐剂化大流行性流感疫苗联合使用时，它们能将免疫反应提高到可比水平，而与测试的疫苗剂量无关。总之，我们的结果表明，添加佐剂可进一步增强对病毒体佐剂化大流行性流感疫苗的免疫反应，其中MATRIX-M总体上是与病毒体联合使用时最有效的佐剂，其次是MF59，最后是铝基佐剂。
