Graham B S, Gorse G J, Schwartz D H, Keefer M C, McElrath M J, Matthews T J, Wright P F, Belshe R B, Clements M L, Dolin R
Dept. of Medicine, Vanderbilt University School of Medicine, Nashville, TN 37232.
J Infect Dis. 1994 Oct;170(4):782-6. doi: 10.1093/infdis/170.4.782.
Priming with a live recombinant vector followed by subunit boosting is a promising strategy for human immunodeficiency virus (HIV) immunization. Twenty-nine vaccinia-naive volunteers were primed with gp160-recombinant vaccinia virus (HIVAC-1e) and boosted with recombinant (r) gp160 to define factors associated with the magnitude and specificity of antibody response after booster immunization. A longer interval between inoculation and boost, two inoculations of HIVAC-1e with lesion formation occurring after the first, and Western blot-detectable antibody to gp160 after inoculation were significantly associated with higher neutralizing antibody titers and fusion-inhibiting activity after boosting. HIVAC-1e-primed vaccinees were more likely to have antibody to V3- and CD4-binding regions of gp120 and less likely to have antibody to constant regions 2 and 3 than vaccinees immunized with rgp160 alone. Priming volunteers with HIVAC-1e was a key determinant of the epitope specificity and magnitude of functional antibody responses induced by rgp160 boosting.
先用活重组载体进行初免,随后用亚单位进行加强免疫,是一种很有前景的人类免疫缺陷病毒(HIV)免疫策略。29名未接种过痘苗的志愿者先用gp160重组痘苗病毒(HIVAC-1e)进行初免,然后用重组(r)gp160进行加强免疫,以确定与加强免疫后抗体反应的强度和特异性相关的因素。接种与加强免疫之间的间隔时间更长、首次接种后出现病变的两次HIVAC-1e接种以及接种后Western印迹法可检测到的针对gp160的抗体,与加强免疫后更高的中和抗体滴度和融合抑制活性显著相关。与仅用rgp160免疫的接种者相比,用HIVAC-1e进行初免的接种者更有可能产生针对gp120的V3和CD4结合区的抗体,而产生针对恒定区2和3的抗体的可能性较小。用HIVAC-1e对志愿者进行初免是rgp160加强免疫诱导的表位特异性和功能性抗体反应强度的关键决定因素。