Wang Shixia, Arthos James, Lawrence John M, Van Ryk Donald, Mboudjeka Innocent, Shen Siyuan, Chou Te-Hui W, Montefiori David C, Lu Shan
Department of Medicine, University of Massachusetts Medical School, 364 Plantation Street, Lazare Research Building, Worcester, MA 01605-2397, USA.
J Virol. 2005 Jun;79(12):7933-7. doi: 10.1128/JVI.79.12.7933-7937.2005.
Strategies are needed for human immunodeficiency virus type 1 vaccine development that improves the neutralizing antibody response against primary isolates of the virus. Here we examined recombinant DNA priming followed by subunit protein boosting as a strategy to generate neutralizing antibodies. Both plasmid-based and recombinant protein envelope (Env) glycoprotein immunogens were derived from a primary viral isolate, JR-FL. Serum from rabbits immunized with either gp120 or gp140 DNA vaccines delivered by gene gun inoculation followed by recombinant gp120 protein boosting was capable of neutralizing JR-FL. Neither the DNA vaccines alone nor the gp120 protein alone generated a detectable neutralizing antibody response against this virus. Neutralizing antibody responses using gp120 DNA and gp140 DNA for priming were similar. The results suggest that Env DNA priming followed by gp120 protein boosting provides an advantage over either approach alone for generating a detectable neutralizing antibody response against primary isolates that are not easily neutralized.
需要制定策略来开发1型人类免疫缺陷病毒疫苗,以增强针对该病毒原始分离株的中和抗体反应。在此,我们研究了先进行重组DNA初免,然后进行亚单位蛋白加强免疫,以此作为产生中和抗体的一种策略。基于质粒的免疫原和重组蛋白包膜(Env)糖蛋白免疫原均来源于一株原始病毒分离株JR-FL。用基因枪接种gp120或gp140 DNA疫苗进行初免,随后用重组gp120蛋白进行加强免疫的兔子血清能够中和JR-FL。单独的DNA疫苗或单独的gp120蛋白均未产生针对该病毒的可检测到的中和抗体反应。使用gp120 DNA和gp140 DNA进行初免所产生的中和抗体反应相似。结果表明,与单独使用任何一种方法相比,先进行Env DNA初免,然后进行gp120蛋白加强免疫,在针对不易被中和的原始分离株产生可检测到的中和抗体反应方面具有优势。