Elias Fernanda, Flo Juan, Rodriguez Juan M, De Nichilo Analia, Lopez Ricardo A, Zorzopulos Jorge, Nagle Carlos, Lahoz Mónica, Montaner Alejandro
Immunotech S.A, Florida 1, Buenos Aires (1440), Argentina.
Vaccine. 2005 May 20;23(27):3597-603. doi: 10.1016/j.vaccine.2004.12.030.
PyNTTTTGT oligodeoxinucleotides (ODNs) cause activation, proliferation and immunoglobulin secretion on B cells, and the expression of co-stimulatory molecules on plasmacytoid dendritic cells of primates. It has now been discovered that these ODNs are also active on rat cells. This fact allowed us to investigate the adjuvant properties of PyNTTTTGT ODNs in a human Hepatitis B vaccine using this animal model. A very significant increment, as compared with the antigen alone, was observed in the antibody production induced by vaccination with the recombinant Hepatitis B surface antigen adjuvated with the PyNTTTTGT prototype IMT504 ODN. Analysis of the IgG subclass distribution in the sera of vaccinated animals indicated that, although an increase was observed in the titer of all the IgG subclasses, the increase on the Th1-associated IgG2b subclass was clearly more pronounced. Remarkably, this effect on the IgG2b titer was observed even if alum, a Th2 promoting adjuvant, was present together with IMT504 in the vaccine formulation. The increase in the Th1 response induced by IMT504 was also suggested by in vitro gamma interferon secretion assays. Monkeys of the species Cebus apella immunized with the recombinant Hepatitis B surface antigen plus alum and IMT504 also showed titers of antibodies against the antigen several times superior to the titers observed in control animals immunized with the antigen plus alum without ODN. Since rat and monkey cells are significantly less immunostimulated "in vitro" by PyNTTTTGT ODNs than human cells, the present results reasonably predict a very good performance of these ODNs as adjuvants in human vaccination.
PyNTTTTGT寡脱氧核苷酸（ODN）可引起B细胞活化、增殖及免疫球蛋白分泌，并使灵长类动物浆细胞样树突状细胞上共刺激分子表达。现已发现这些ODN对大鼠细胞也有活性。这一事实使我们能够利用该动物模型研究PyNTTTTGT ODN在人用乙型肝炎疫苗中的佐剂特性。与单独使用抗原相比，用重组乙型肝炎表面抗原与PyNTTTTGT原型IMT504 ODN佐剂联合接种诱导产生的抗体有非常显著的增加。对接种动物血清中IgG亚类分布的分析表明，虽然所有IgG亚类的滴度均有增加，但与Th1相关的IgG2b亚类的增加更为明显。值得注意的是，即使在疫苗配方中Th2促进佐剂明矾与IMT504同时存在时，也观察到了对IgG2b滴度的这种影响。体外γ干扰素分泌试验也提示IMT504诱导Th1反应增加。用重组乙型肝炎表面抗原加明矾和IMT504免疫的僧帽猴产生的抗该抗原抗体滴度也比用抗原加明矾但无ODN免疫的对照动物观察到的滴度高出数倍。由于大鼠和猴细胞在“体外”受到PyNTTTTGT ODN的免疫刺激明显低于人类细胞，目前的结果合理地预测了这些ODN作为佐剂在人类疫苗接种中的良好性能。
