Altmeyer R, Escriou N, Girard M, Palmenberg A, van der Werf S
Unité de Virologie Moléculaire, Institut Pasteur, Paris, France.
Proc Natl Acad Sci U S A. 1994 Oct 11;91(21):9775-9. doi: 10.1073/pnas.91.21.9775.
Introduction of a sequence encoding 147 amino acids from human immunodeficiency virus type I (HIV-1) strain MN glycoprotein gp120 into the RNA genome of the stably attenuated Mengo virus strain vM16 yielded an infectious recombinant virus, vMLN450, which expressed the heterologous HIV-1 sequence along with the normal Mengo virus proteins. The HIV-1 gp120 sequence, fused to the amino terminus of the short, nonstructural Mengo virus leader polypeptide was recognized by a gp120 V3 loop-specific monoclonal antibody. When inoculated into mice, recombinant virus vMLN450 elicited a high-titer anti-HIV-1 antibody response as well as an HIV-1MN-specific cytotoxic cellular immune response. An anti-HIV-1 antibody response could also be detected in cynomolgus monkeys after a single immunization. We propose that attenuated Mengo virus can serve as an effective expression vector in cell systems and various animal species and offers another approach to the development of new, live recombinant vaccines.
将来自人类免疫缺陷病毒I型(HIV-1)MN株糖蛋白gp120的一段编码147个氨基酸的序列引入稳定减毒的Mengo病毒株vM16的RNA基因组中,产生了一种感染性重组病毒vMLN450,它表达了异源HIV-1序列以及正常的Mengo病毒蛋白。与短的、非结构的Mengo病毒前导多肽的氨基末端融合的HIV-1 gp120序列被一种gp120 V3环特异性单克隆抗体识别。当接种到小鼠体内时,重组病毒vMLN450引发了高滴度的抗HIV-1抗体反应以及HIV-1MN特异性细胞毒性细胞免疫反应。单次免疫后,在食蟹猴中也能检测到抗HIV-1抗体反应。我们提出,减毒的Mengo病毒可以作为细胞系统和各种动物物种中的一种有效表达载体,并为开发新型活重组疫苗提供了另一种方法。