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Evaluation of HIV-1 Regulatory and Structural Proteins as Antigen Candidate in Mouse and Human

Author(s):

Narges Farahani Khojasteh, Mehrshad Fekri, Samaneh H. Shabani, Alireza Milani, Kazem Baesi and Azam Bolhassani*   Pages 1 - 14 ( 14 )

Abstract:


Background: The diagnosis of HIV infection is important among different groups. Moreover, combination antiretroviral therapy is used to treat HIV-1, but it cannot eradicate the infection. Thus, development of therapeutic vaccines along with antiretroviral therapy is recommended. This study evaluates the values of four HIV proteins as an antigen candidate in therapeutic vaccine design as well as a possible diagnostic marker for HIV infection in human.

Methods: In this study, the HIV-1 Tat and Rev regulatory proteins and structural Gp120 and p24 proteins were generated in E. coli expression system. Their immunogenicity was evaluated in BALB/c mice using homologous and heterologous prime/boost strategies. Moreover, the detection of anti-HIV IgG antibodies against these recombinant proteins was assessed in untreated (Naïve/ HIV-infected), treated and drug-resistant patients compared to healthy (control) group as a possible diagnostic marker for HIV infection.

Results: In human, our results showed that among HIV-1 proteins, anti-Gp120 antibody was not detected in treated individuals compared to healthy (control) group. The levels of anti-Gp120 antibody were significantly different between treated group and Naïve as well as drug-resistant subjects. Moreover, the level of anti-p24 antibody was significantly lower in treated group than Naive group. In mice, the results of immunization indicated that the Rev antigen could significantly induce IgG2a, IgG2b and IFN-γ secretion aimed at Th1 response as well as Granzyme B generation as CTL activity in comparison with other antigens. Furthermore, the heterologous DNA prime/ protein boost regimen was more potent than the homologous regimen for stimulation of cellular immunity.

Conclusion: Briefly, the levels of both anti-Gp120 and anti-p24 antibodies can be considered for diagnosis of the HIVinfected individuals in different groups compared to healthy group. Moreover, among four recombinant proteins, Rev elicited Th1 cellular immunity and CTL activity in mice as an antigen candidate in therapeutic vaccine development.

Keywords:

HIV-1, Regulatory protein, Structural protein, Drug resistance, Immune responses, Diagnosis

Affiliation:

Department of Hepatitis and AIDS, Pasteur Institute of Iran, Tehran,, Department of Hepatitis and AIDS, Pasteur Institute of Iran, Tehran,, Department of Hepatitis and AIDS, Pasteur Institute of Iran, Tehran,, Department of Hepatitis and AIDS, Pasteur Institute of Iran, Tehran,, Department of Hepatitis and AIDS, Pasteur Institute of Iran, Tehran,, Department of Hepatitis and AIDS, Pasteur Institute of Iran, Tehran



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