Kim J J, Yang J S, VanCott T C, Lee D J, Manson K H, Wyand M S, Boyer J D, Ugen K E, Weiner D B
Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.
J Virol. 2000 Apr;74(7):3427-9. doi: 10.1128/jvi.74.7.3427-3429.2000.
An important limitation of DNA immunization in nonhuman primates is the difficulty in generating high levels of antigen-specific antibody responses; strategies to enhance the level of immune responses to DNA immunization may be important in the further development of this vaccine strategy for humans. We approached this issue by testing the ability of molecular adjuvants to enhance the levels of immune responses generated by multicomponent DNA vaccines in rhesus macaques. Rhesus macaques were coimmunized intramuscularly with expression plasmids bearing genes encoding Th1 (interleukin 2 [IL-2] and gamma interferon)- or Th2 (IL-4)-type cytokines and DNA vaccine constructs encoding human immunodeficiency virus Env and Rev and simian immunodeficiency virus Gag and Pol proteins. We observed that the cytokine gene adjuvants (especially IL-2 and IL-4) significantly enhanced antigen-specific humoral immune responses in the rhesus macaque model. These results support the assumption that antigen-specific responses can be engineered to a higher and presumably more desirable level in rhesus macaques by genetic adjuvants.
DNA免疫在非人类灵长类动物中的一个重要局限性是难以产生高水平的抗原特异性抗体反应；提高对DNA免疫的免疫反应水平的策略对于这种人类疫苗策略的进一步发展可能很重要。我们通过测试分子佐剂增强恒河猴多组分DNA疫苗产生的免疫反应水平的能力来解决这个问题。将恒河猴肌肉内共同免疫，分别注射携带编码Th1（白细胞介素2 [IL-2]和γ干扰素）或Th2（IL-4）型细胞因子的基因的表达质粒，以及编码人类免疫缺陷病毒Env和Rev以及猿猴免疫缺陷病毒Gag和Pol蛋白的DNA疫苗构建体。我们观察到细胞因子基因佐剂（尤其是IL-2和IL-4）在恒河猴模型中显著增强了抗原特异性体液免疫反应。这些结果支持这样一种假设，即通过基因佐剂可以将恒河猴中的抗原特异性反应设计到更高且可能更理想的水平。
