Evaluation of HIV-1 Regulatory and Structural Proteins as Antigen Candidate in Mice and Humans.

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, the development of therapeutic vaccines, along with antiretroviral therapy, is recommended. This study evaluates the values of four HIV proteins as antigen candidates in therapeutic vaccine design as well as a possible diagnostic marker for HIV infection in humans. 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 the healthy (control) group as a possible diagnostic marker for HIV infection. RESULTS: In humans, our results showed that among HIV-1 proteins, anti-Gp120 antibody was not detected in treated individuals compared to the healthy (control) group. The levels of anti-Gp120 antibody were significantly different between the treated group and Naïve as well as drug-resistant subjects. Moreover, the level of anti-p24 antibody was significantly lower in the treated group than the 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 the diagnosis of the HIV-infected individuals in different groups compared to the 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.

Antiviral therapy for the sexually transmitted viruses: recent updates on vaccine development.

INTRODUCTION: The sexually transmitted infections (STIs) caused by viruses including human T cell leukemia virus type-1 (HTLV-1), human immunodeficiency virus-1 (HIV-1), human simplex virus-2 (HSV-2), hepatitis C virus (HCV), hepatitis B virus (HBV), and human papillomavirus (HPV) are major public health issues. These infections can cause cancer or result in long-term health problems. Due to high prevalence of STIs, a safe and effective vaccine is required to overcome these fatal viruses. AREAS COVERED: This review includes a comprehensive overview of the literatures relevant to vaccine development against the sexually transmitted viruses (STVs) using PubMed and Sciencedirect electronic search engines. Herein, we discuss the efforts directed toward development of effective vaccines using different laboratory animal models including mice, guinea pig or non-human primates in preclinical trials, and human in clinical trials with different phases. EXPERT OPINION: There is no effective FDA approved vaccine against the sexually transmitted viruses (STVs) except for HBV and HPV as prophylactic vaccines. Many attempts are underway to develop vaccines against these viruses. There are several approaches for improving prophylactic or therapeutic vaccines such as heterologous prime/boost immunization, delivery system, administration route, adjuvants, etc. In this line, further studies can be helpful for understanding the immunobiology of STVs in human. Moreover, development of more relevant animal models is a worthy goal to induce effective immune responses in humans.