Azizi Ali, Anderson David E, Ghorbani Masoud, Gee Katrina, Diaz-Mitoma Francisco
Infectious Disease and Vaccine Research Centre, Research Institute Children's Hospital of Eastern Ontario, 401 Smyth Road, Ottawa, ON, K1H 8L1, Canada.
BMC Immunol. 2006 Oct 31;7:25. doi: 10.1186/1471-2172-7-25.
One of the major obstacles in the design of an effective vaccine against HIV-1 is the hypervariability of the HIV-1 envelope glycoprotein. Most HIV-1 vaccine candidates have utilized envelope glycoprotein from a single virus isolate, but to date, none of them elicited broadly reactive humoral immunity. Herein, we hypothesised that a cocktail of HIV-1 gp120 proteins containing multiple epitopes may increase the breadth of immune responses against HIV-1. We compared and evaluated the immunogenicity of HIV-1 vaccines containing either gp120 protein alone or in combinations of four or fourteen gp120s from different primary HIV-1 isolates in immunized hamsters.
We amplified and characterized 14 different gp120s from primary subtype B isolates with both syncytium and non-syncytium inducing properties, and expressed the proteins in Chinese Hamster Ovary (CHO) cell lines. Purified proteins were used either alone or in combinations of four or fourteen different gp120s to vaccinate golden hamsters. The polyvalent vaccine showed higher antibody titers to HIV-1 subtype B isolates MN and SF162 compared to the groups that received one or four gp120 proteins. However, the polyvalent vaccine was not able to show higher neutralizing antibody responses against HIV-1 primary isolates. Interestingly, the polyvalent vaccine group had the highest proliferative immune responses and showed a substantial proportion of cross-subtype CD4 reactivity to HIV-1 subtypes B, C, and A/E CONCLUSION: Although the polyvalent approach achieved only a modest increase in the breadth of humoral and cellular immunity, the qualitative change in the vaccine (14 vs. 1 gp120) resulted in a quantitative improvement in vaccine-induced immunity.
设计一种有效的抗HIV-1疫苗的主要障碍之一是HIV-1包膜糖蛋白的高度变异性。大多数HIV-1候选疫苗都利用了来自单一病毒分离株的包膜糖蛋白，但迄今为止，它们均未引发广泛的反应性体液免疫。在此，我们假设包含多个表位的HIV-1 gp120蛋白混合物可能会增加针对HIV-1的免疫反应广度。我们比较并评估了在免疫仓鼠中单独含有gp120蛋白或含有来自不同原发性HIV-1分离株的四种或十四种gp120组合的HIV-1疫苗的免疫原性。
我们从具有合胞体诱导和非合胞体诱导特性的原发性B亚型分离株中扩增并鉴定了14种不同的gp120，并在中国仓鼠卵巢（CHO）细胞系中表达了这些蛋白。纯化后的蛋白单独使用，或与四种或十四种不同的gp120组合使用，对金黄仓鼠进行免疫接种。与接受一种或四种gp120蛋白的组相比，多价疫苗对HIV-1 B亚型分离株MN和SF162显示出更高的抗体滴度。然而，多价疫苗未能显示出针对HIV-1原发性分离株的更高中和抗体反应。有趣的是，多价疫苗组具有最高的增殖性免疫反应，并显示出相当比例的针对HIV-1 B、C和A/E亚型的跨亚型CD4反应性。结论：尽管多价方法仅在体液和细胞免疫广度上实现了适度增加，但疫苗的质性变化（14种vs. 1种gp120）导致了疫苗诱导免疫的定量改善。
