Immunogenicity of a polyvalent HIV-1 candidate vaccine based on fourteen wild type gp120 proteins in golden hamsters
Immunogenicity of a polyvalent HIV-1 candidate vaccine based on fourteen wild type gp120 proteins in golden hamsters
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DOI：
10.1186/1471-2172-7-25
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发表时间：
2006-10-31
期刊：
影响因子：
3
通讯作者：
Diaz-Mitoma, Francisco
中科院分区：
文献类型：
--
作者：
Azizi, Ali;Anderson, David E.;Diaz-Mitoma, Francisco
背景资料：在设计针对HIV- 1的有效疫苗中的主要障碍之一是HIV- 1包膜糖蛋白的高度可变性。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，它们都没有引起广泛的体液免疫反应。在此，我们假设含有多个表位的HIV- 1 gp 120蛋白的混合物可以增加针对HIV- 1的免疫应答的广度。我们在免疫仓鼠中比较和评估了单独含有gp 120蛋白或含有来自不同HIV- 1原代分离株的4种或14种gp 120蛋白的组合的HIV- 1疫苗的免疫原性。我们扩增并表征了来自主要亚型B分离物的14种不同的gp 120，其具有合胞体和非合胞体诱导特性，并在中国卵巢癌（CHO）细胞系中表达。纯化的蛋白质单独使用或与四种或十四种不同的gp 120组合使用来接种金仓鼠。与接受一种或四种gp 120蛋白的组相比，多价疫苗显示出对HIV- 1亚型B分离株MN和SF 162的更高的抗体滴度。然而，多价疫苗不能显示针对HIV- 1原代分离株的更高中和抗体应答。有趣的是，多价疫苗组具有最高的增殖性免疫应答，并显示出相当大比例的交叉亚型CD 4对HIV- 1亚型B、C和A/ E的反应性。虽然多价方法仅实现了体液和细胞免疫广度的适度增加，疫苗的质的变化（14对1 gp 120）导致疫苗诱导的免疫力的定量改善。
Background: 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.Results: 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.