Rasmussen Robert A, Ong Helena, Kittel Christian, Ruprecht Claudia R, Ferrantelli Flavia, Hu Shiu-Lok, Polacino Patricia, McKenna Jennifer, Moon Jane, Travis Bruce, Ruprecht Ruth M
Department of Cancer Immunology & AIDS, Dana-Farber Cancer Institute, Boston, MA 02115, USA.
Vaccine. 2006 Mar 20;24(13):2324-32. doi: 10.1016/j.vaccine.2005.11.063. Epub 2005 Dec 19.
The induction of both cellular and humoral immunity is an important goal for vaccine development against HIV. As a step towards the development of an efficacious vaccine against HIV clade C, the world's most prevalent strain, a combination DNA prime/protein boost immunization strategy was tested. A DNA expression vector was prepared encoding a codon-optimized env gene derived from a pediatric HIV clade C isolate, 1084i. Mice were immunized with HIV1084i env-encoding DNA, then boosted with homologous 1084i gp160. HIV1084i Env-specific T-cell responses were induced with DNA vaccination alone, but the strongest cellular immune responses were seen after boosting with gp160. Immunization with gp160 alone induced high-titer antibodies but required two inoculations. In contrast, high-titer antibodies were seen after a single 1084i gp160 boost in DNA-primed animals. All animals given gp160 inoculations, whether DNA primed or not, developed neutralizing antibodies reactive with HIV1084i and a macaque-passaged simian/human immunodeficiency construct, SHIV-1084ip. The results demonstrate the utility of this DNA prime/protein boost approach to generate cellular immunity, as well as neutralizing antibodies, against HIV clade C env antigens.
诱导细胞免疫和体液免疫是开发抗HIV疫苗的一个重要目标。作为朝着开发针对全球最流行毒株HIV C亚型的有效疫苗迈出的一步,测试了一种DNA初免/蛋白加强免疫策略。制备了一种DNA表达载体,其编码源自儿科HIV C亚型分离株1084i的密码子优化env基因。用编码HIV1084i env的DNA免疫小鼠,然后用同源的1084i gp160进行加强免疫。单独使用DNA疫苗接种可诱导产生HIV1084i Env特异性T细胞反应,但在用gp160加强免疫后可观察到最强的细胞免疫反应。单独用gp160免疫可诱导产生高滴度抗体,但需要接种两次。相比之下,在DNA初免的动物中,单次用1084i gp160加强免疫后即可观察到高滴度抗体。所有接种gp160的动物,无论是否经过DNA初免,均产生了与HIV1084i和一种经猕猴传代的猿猴/人类免疫缺陷嵌合体SHIV-1084ip发生反应的中和抗体。结果证明了这种DNA初免/蛋白加强方法在产生针对HIV C亚型env抗原的细胞免疫以及中和抗体方面的效用。