Development of effective vaccines for old mice in a tumor model.

Development of effective vaccines for old mice in a tumor model.
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DOI:
10.1016/j.vaccine.2008.11.112
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发表时间:
2009-02-11
期刊:
影响因子:
5.5
通讯作者:
Houghton AN
Houghton AN
中科院分区:
医学3区
文献类型:
--
作者:
Posnett DN;Engelhorn ME;Lin Y;Merghoub T;Duan F;Wolchok JD;Houghton AN

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疫苗对老年人和老年小鼠往往无效。很少有研究集中在老年人身上测试疫苗。在这里,我们使用DNA肿瘤抗原疫苗来对抗黑色素瘤,并表明老年小鼠没有受到保护。将肿瘤抗原与微生物佐剂蛋白OmpA(大肠杆菌)或Vp22(单纯疱疹病毒-1)融合的疫苗显著提高了对老年小鼠的保护作用。这些辅助蛋白的作用机制是不同的。OmpA和Vp22都不需要TLR2。抗原加工和呈递没有被这些融合结构所促进。然而,与Vp22的融合构建体对B16黑色素瘤产生了强烈的CD4反应,并且OmpA反应依赖于MHC-II。在老年小鼠中,两种佐剂融合结构均能刺激CD4和CD8反应,否则会减弱。
Vaccines are often inefficient in old people and old mice. Few studies have focused on testing vaccines in old populations. Here we used DNA tumor antigen vaccines against melanoma and showed that old mice were not protected. Vaccines incorporating fusions of the tumor antigen with microbial adjuvant proteins OmpA (E. Coli) or Vp22 (Herpes simplex virus-1) dramatically improved protection of old mice. The mechanisms by which these adjuvant proteins act are distinct. TLR2 was not required for either OmpA or Vp22. Antigen processing and presentation were not boosted by these fusion constructs. However, fusion constructs with Vp22 gave a strong CD4 response to B16 melanoma and the OmpA response is MHC-II dependent. Both adjuvant fusion constructs stimulated CD4 and CD8 responses otherwise diminished in old mice.
DOI: 10.1097/00002371-199807000-00008
发表时间: 1998-07-01
影响因子: 3.9
作者:
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