Novak Miroslav J, Moldoveanu Zina, Huang Wen Qiang, Jackson Cheryl A, Palmer Matthew T, McPherson Sylvia A, Morrow Casey D
The Department of Microbiology, Research University of Alabama at Birmingham, Birmingham, Alabama 35294-0024, USA.
Viral Immunol. 2003;16(2):169-82. doi: 10.1089/088282403322017901.
Vaccines that stimulate both cellular and humoral immunity will probably be needed to control many infectious diseases. Previously, our laboratory generated a vaccine vector that uses poliovirus genomes (replicons) in which the capsid genes have been replaced by foreign proteins. In the current study, we have evaluated the immune responses induced by immunization using poliovirus replicons encoding green fluorescent protein (GFP). Although intramuscular administration of replicons resulted in GFP expression in the muscle, the levels of anti-GFP antibodies in serum were low compared to those of mice immunized with soluble, recombinant GFP (rGFP). Intramuscular booster immunization with rGFP in animals primed with replicons encoding GFP resulted in production of both serum IgG1 and IgG2a GFP-specific antibodies. The cells isolated from spleens of animals primed with replicons and boosted with rGFP secreted IFN-gamma after in vitro stimulation with rGFP. Intramuscular immunization of animals with a single dose of replicons encoding GFP followed by two intranasal applications of rGFP resulted in serum GFP-specific IgG1 and IgG2a isotypes, consistent with induction of both humoral and cellular responses. The results of this study establish that immunization with replicons followed by boost with soluble antigen, even at a different site, can generate a more diverse immune response compared with immunization regimen using soluble antigen alone. This strategy could be exploited for the development of new vaccine approaches against infectious diseases.
可能需要能够刺激细胞免疫和体液免疫的疫苗来控制多种传染病。此前，我们实验室构建了一种疫苗载体，它使用脊髓灰质炎病毒基因组（复制子），其中衣壳基因已被外源蛋白取代。在当前研究中，我们评估了使用编码绿色荧光蛋白（GFP）的脊髓灰质炎病毒复制子免疫诱导的免疫反应。尽管肌肉注射复制子导致肌肉中GFP表达，但与用可溶性重组GFP（rGFP）免疫的小鼠相比，血清中抗GFP抗体水平较低。在用编码GFP的复制子进行初免的动物中，用rGFP进行肌肉加强免疫导致产生血清IgG1和IgG2a GFP特异性抗体。从用复制子初免并用rGFP加强免疫的动物脾脏中分离的细胞，在体外经rGFP刺激后分泌干扰素-γ。用单剂量编码GFP的复制子对动物进行肌肉免疫，随后两次经鼻应用rGFP，产生了血清GFP特异性IgG1和IgG2a同种型，这与体液免疫和细胞免疫反应的诱导一致。本研究结果表明，与单独使用可溶性抗原的免疫方案相比先用复制子免疫然后在不同部位用可溶性抗原加强免疫可产生更多样化的免疫反应。该策略可用于开发针对传染病的新疫苗方法。
