Meseda Clement A, Elkins Karen L, Merchlinsky Michael J, Weir Jerry P
Laboratory of DNA Viruses, Division of Viral Products, Center for Biologics Evaluation and Research, Food and Drug Administration, 1401 Rockville Pike, Bethesda, MD 20852, USA.
J Infect Dis. 2002 Oct 15;186(8):1065-73. doi: 10.1086/344234. Epub 2002 Sep 25.
Several reports have indicated that prime-boost strategies of vaccination can enhance the level of specific immunity induced by nucleic acid vaccines. The present report describes such a strategy with herpes simplex virus (HSV)-2 glycoprotein D (gD), using combinations of plasmid vector that expresses gD (pgD2) and a recombinant modified vaccinia virus Ankara vector that expresses gD (MVA-gD2). The IgG antibody response to gD and the HSV-2 neutralizing antibody response were greatest when the MVA-gD2 vector was used as the priming immunization and then was boosted with either pgD2 or MVA-gD2. Determination of the isotype profile of MVA-gD2-primed mice revealed a much broader distribution of isotypes than that seen after DNA vaccination. In addition, antigen-stimulated spleen cells from mice primed with MVA-gD2 and boosted with either MVA-gD2 or pgD2 produced higher levels of interleukin-2 and interferon-gamma than did those from pgD2-primed mice, indicating that a prime-boost immunization strategy that uses the MVA and plasmid DNA vector dramatically enhances and diversifies the humoral and cellular immune response to HSV-2 gD.
多项报告表明，疫苗接种的初免-加强策略可提高核酸疫苗诱导的特异性免疫水平。本报告描述了一种针对单纯疱疹病毒2型（HSV-2）糖蛋白D（gD）的策略，使用表达gD的质粒载体（pgD2）和表达gD的重组改良安卡拉痘苗病毒载体（MVA-gD2）的组合。当使用MVA-gD2载体进行初次免疫，然后用pgD2或MVA-gD2进行加强免疫时，对gD的IgG抗体反应和HSV-2中和抗体反应最强。对用MVA-gD2进行初免的小鼠的同种型谱分析显示，与DNA疫苗接种后相比，同种型的分布更为广泛。此外，用MVA-gD2进行初免并用MVA-gD2或pgD2进行加强免疫的小鼠的抗原刺激脾细胞产生的白细胞介素-2和干扰素γ水平高于用pgD2进行初免的小鼠，这表明使用MVA和质粒DNA载体的初免-加强免疫策略显著增强了对HSV-2 gD的体液免疫和细胞免疫反应，并使其多样化。
