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Current Drug Delivery

Author(s): Fatemeh Namazi, Saba Davoodi and Azam Bolhassani*

DOI: 10.2174/1567201818666210224101144

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Comparison of the Efficacy of HIV-1 Nef-Tat-Gp160-p24 Polyepitope Vaccine Candidate with Nef Protein in Different Immunization Strategies

Page: [142 - 156] Pages: 15

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Abstract

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 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.

Keywords: HIV-1, Therapeutic vaccine, Polyepitope construct, Prime/boost strategy, Cell-penetrating peptides, Adjuvant.

Graphical Abstract

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