Department of Infectious Disease Immunology, Statens Serum Institut, Copenhagen, Denmark.
PLoS One. 2013 May 17;8(5):e63575. doi: 10.1371/journal.pone.0063575. Print 2013.
Induction of broad T-cell immune responses is regarded as critical for vaccines against the human immunodeficiency virus type 1 (HIV-1) which exhibit high diversity and, therefore, focus has been on inducing cytotoxic CD8 T-cell responses against the more conserved parts of the virus, such as the Gag protein. Herein, we have used the p24 protein which contains a range of conserved T-cell epitopes. We demonstrate that a vaccine of HIV-1 subtype B consensus group-specific antigen (Gag) p24 protein with the CD8-inducing liposomal cationic adjuvant formulation (CAF) 05, induces both CD4 and CD8 T-cell responses in CB6F1 mice. The adjuvanted vaccine also induced functional antigen-specific cytotoxicity in vivo. Furthermore, we found that when fragmenting the Gag p24 protein into overlapping Gag p24 peptides, a broader T-cell epitope specificity was induced in the humanized human leukocyte antigen (HLA)-A2/DR-transgenic mouse model. Thus, combining overlapping Gag p24 peptides with CAF05 appears to be a promising and simple strategy for inducing broader T-cell responses to multiple conserved epitopes which will be relevant for both prophylactic and therapeutic HIV-1 vaccines.
诱导广泛的 T 细胞免疫反应被认为是对抗人类免疫缺陷病毒 1（HIV-1）的疫苗的关键，因为 HIV-1 具有高度的多样性，因此，研究重点一直集中在诱导针对病毒更保守部分的细胞毒性 CD8 T 细胞反应上，例如 gag 蛋白。在此，我们使用了含有一系列保守 T 细胞表位的 p24 蛋白。我们证明，用含有 CD8 诱导性脂质体阳离子佐剂制剂（CAF）05 的 HIV-1 亚型 B 共识组特异性抗原（Gag）p24 蛋白疫苗，可以在 CB6F1 小鼠中诱导 CD4 和 CD8 T 细胞反应。佐剂疫苗还在体内诱导了功能性抗原特异性细胞毒性。此外，我们发现，当将 gag p24 蛋白分割成重叠的 gag p24 肽时，在人类白细胞抗原（HLA）-A2/DR 转基因小鼠模型中诱导了更广泛的 T 细胞表位特异性。因此，将重叠的 gag p24 肽与 CAF05 结合使用，似乎是一种很有前途和简单的策略，可以诱导针对多个保守表位的更广泛的 T 细胞反应，这对于预防性和治疗性 HIV-1 疫苗都具有重要意义。
