Fatemeh Namazi, Saba Davoodi and Azam Bolhassani* Pages 1 - 15 ( 15 )
Objectives: One of the promising strategies for effective HIV-1 vaccine design involves finding the polyepitope immunogens using T cell epitopes.
Methods: 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.
Results: 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.
Conclusion: The use of the Nef-Tat-Gp160-P24 polyepitope immunogen in heterologous prime-- boost 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.
HIV-1, Therapeutic vaccine, Polyepitope construct, Prime/boost strategy, Cell-penetrating peptides, Adjuvant.
Department of Biology, Science and Research Branch, Islamic Azad University, Tehran, Department of Biology, Science and Research Branch, Islamic Azad University, Tehran, Department of Hepatitis and AIDS, Pasteur Institute of Iran, Tehran