Rodr Guez D, Rodr Guez J R, Llorente M, V Zquez I, Lucas P, Esteban M, Mart Nez-A C, Del Real G
J Gen Virol. 1999 Jan;80 ( Pt 1):217-223. doi: 10.1099/0022-1317-80-1-217.
Vaccinia virus (VV) infection induces protective T- and B-cell responses, making recombinants based on VV good candidates for the development of effective vaccines to other viruses. VV recombinants expressing the human immunodeficiency virus (HIV) envelope protein (Env) have been generated in several laboratories and shown to induce anti-HIV cellular and humoral immune responses in vaccinated humans and in chimpanzees. To increase the immunogenicity of the Env antigen, a VV recombinant was generated that expresses a chimeric antigen consisting of the Env protein fused to an immunostimulatory cytokine, granulocyte-macrophage colony-stimulating factor (GM-CSF). The chimeric protein retained GM-CSF biological activity when expressed by this recombinant virus (VV-GM-gp120) in cells infected in vitro. Infection of BALB/c mice with VV-GM-gp120 triggered a higher HIV-specific cellular immune response, as measured by interferon-gamma production, than that induced by a VV recombinant expressing the native Env protein. Moreover, although anti-gp120 antibody titres were similar in sera from mice inoculated with either of the VV recombinants, immunization with the recombinant expressing the fusion protein elicited antibodies against a broader spectrum of Env epitopes. These results indicate that HIV Env antigen fusion to GM-CSF provides a means to improve the anti-HIV immune response.
痘苗病毒（VV）感染可诱导保护性T细胞和B细胞反应，这使得基于VV的重组体成为开发针对其他病毒的有效疫苗的良好候选者。几个实验室已构建出表达人类免疫缺陷病毒（HIV）包膜蛋白（Env）的VV重组体，并证明其能在接种疫苗的人类和黑猩猩体内诱导抗HIV细胞免疫和体液免疫反应。为提高Env抗原的免疫原性，构建了一种VV重组体，它表达一种嵌合抗原，该嵌合抗原由与免疫刺激细胞因子粒细胞-巨噬细胞集落刺激因子（GM-CSF）融合的Env蛋白组成。当这种重组病毒（VV-GM-gp120）在体外感染的细胞中表达时，嵌合蛋白保留了GM-CSF的生物学活性。用VV-GM-gp120感染BALB/c小鼠，通过干扰素-γ产生量测定，引发的HIV特异性细胞免疫反应比表达天然Env蛋白的VV重组体诱导的反应更强。此外，尽管接种任何一种VV重组体的小鼠血清中的抗gp120抗体滴度相似，但用表达融合蛋白的重组体免疫可引发针对更广泛Env表位的抗体。这些结果表明，HIV Env抗原与GM-CSF融合提供了一种改善抗HIV免疫反应的方法。
