Department of Biology, Science and Research Branch, Islamic Azad University, Tehran, Iran.
Department of Hepatitis and AIDS, Pasteur Institute of Iran, Tehran, Iran.
Curr Drug Deliv. 2022;19(1):142-156. doi: 10.2174/1567201818666210224101144.
One of the promising strategies for effective HIV-1 vaccine design involves finding the polyepitope immunogens using T cell epitopes.
Herein, an HIV-1 polyepitope construct (i.e., Nef-Tat-Gp160-P24) comprising of several epitopes from Nef, Tat, Gp160, and P24 proteins was designed. To improve its immunogenicity in BALB/c mice, cell-penetrating peptides (HR9 and MPG for DNA delivery, and LDP-NLS and Cy- LoP-1 for protein transfer), Montanide adjuvant, and heterologous DNA prime/polypeptide boost strategy were used. To compare the immunogenicity, Nef was utilized as a vaccine candidate. The levels of total IgG and its subclasses, cytokines, and Granzyme B were assessed using ELISA.
Immunological studies showed that heterologous prime-boost regimens for both antigens could considerably augment the levels of IgG2a, IgG2b, IFN-γ, and Granzyme B directed toward Th1 and CTL immune responses in comparison with homologous prime-boost strategies. The levels of IFN-γ, IL-10, total IgG, IgG1, and IgG2b were drastically higher in groups immunized with Nef-Tat-Gp160-P24 in heterologous prime-boost regimens than those in groups immunized with Nef.
The use of the Nef-Tat-Gp160-P24 polyepitope immunogen in heterologous primeboost strategy could generate the mixture of Th1 and Th2 responses directed further toward Th1 response as a hopeful method for improvement of HIV-1 vaccine.
寻找 T 细胞表位的多表位免疫原是设计有效 HIV-1 疫苗的有前途的策略之一。
本文设计了一种包含 Nef、Tat、Gp160 和 P24 蛋白多个表位的 HIV-1 多表位构建体（即 Nef-Tat-Gp160-P24）。为了提高其在 BALB/c 小鼠中的免疫原性，使用了细胞穿透肽（用于 DNA 传递的 HR9 和 MPG，以及用于蛋白传递的 LDP-NLS 和 Cy-LoP-1）、Montanide 佐剂和异源 DNA 初免/多肽加强策略。为了比较免疫原性，使用了 Nef 作为疫苗候选物。使用 ELISA 评估总 IgG 及其亚类、细胞因子和 Granzyme B 的水平。
免疫研究表明，与同源初免-加强策略相比，两种抗原的异源初免-加强方案都能显著提高 IgG2a、IgG2b、IFN-γ 和 Granzyme B 针对 Th1 和 CTL 免疫应答的水平。在异源初免-加强方案中，用 Nef-Tat-Gp160-P24 免疫的组的 IFN-γ、IL-10、总 IgG、IgG1 和 IgG2b 的水平明显高于用 Nef 免疫的组。
在异源初免-加强策略中使用 Nef-Tat-Gp160-P24 多表位免疫原可以产生针对 Th1 反应的 Th1 和 Th2 反应的混合物，这是改善 HIV-1 疫苗的有希望的方法。
