Muster T, Ferko B, Klima A, Purtscher M, Trkola A, Schulz P, Grassauer A, Engelhardt O G, García-Sástre A, Palese P
Institut für Angewandte Mikrobiologie, Universität für Bodenkultur, Vienna, Austria.
J Virol. 1995 Nov;69(11):6678-86. doi: 10.1128/JVI.69.11.6678-6686.1995.
Previously, we constructed a chimeric influenza virus that expresses the highly conserved amino acid sequence ELDKWA of gp41 of human immunodeficiency virus type 1 (HIV-1). Antisera elicited in mice by infection with this chimeric virus showed neutralizing activity against distantly related HIV-1 isolates (T. Muster, R. Guinea, A. Trkola, M. Purtscher, A. Klima, F. Steindl, P. Palese, and H. Katinger, J. Virol. 68:4031-4034, 1994). In the present study, we demonstrated that intranasal immunizations with this chimeric virus are also able to induce a humoral immune response at the mucosal level. The immunized mice had ELDKWA-specific immunoglobulins A in respiratory, intestinal, and vaginal secretions. Sustained levels of these secretory immunoglobulins A were detectable for more than 1 year after immunization. The results show that influenza virus can be used to efficiently induce secretory antibodies against antigens from foreign pathogens. Since long-lasting mucosal immunity in the genital and intestinal tracts might be essential for protective immunity against HIV-1, influenza virus appears to be a promising vector for HIV-1-derived immunogens.
此前，我们构建了一种嵌合流感病毒，其表达人类免疫缺陷病毒1型（HIV-1）gp41的高度保守氨基酸序列ELDKWA。用这种嵌合病毒感染小鼠所诱导产生的抗血清，对亲缘关系较远的HIV-1分离株表现出中和活性（T. 穆斯特、R. 几内亚、A. 特科拉、M. 普尔切尔、A. 克利马、F. 施泰因德尔、P. 帕莱斯和H. 卡廷格，《病毒学杂志》68:4031 - 4034，1994年）。在本研究中，我们证明用这种嵌合病毒进行鼻内免疫也能够在黏膜水平诱导体液免疫反应。免疫后的小鼠在呼吸道、肠道和阴道分泌物中具有ELDKWA特异性免疫球蛋白A。免疫后1年多的时间里都能检测到这些分泌型免疫球蛋白A的持续水平。结果表明，流感病毒可用于有效诱导针对外来病原体抗原的分泌性抗体。由于生殖道和肠道中的持久黏膜免疫对于针对HIV-1的保护性免疫可能至关重要，流感病毒似乎是一种用于HIV-1衍生免疫原的有前景的载体。
