ABSTRACT
Abstract Despite the success of Antiretroviral Therapy (ART) in preventing HIV-1-associated clinical progression to AIDS, it is unable to eliminate the viral reservoirs and eradicate the HIV-1 infection. Therapeutic vaccination is an alternative approach to alter the HIV-1 infection course. It can induce effective HIV-1-specific immunity to control viremia and eliminate the need for lifelong ART. Immunological data from spontaneous HIV-1 controllers have shown that cross-reactive T-cell responses are the key immune mechanism in HIV-1 control. Directing these responses toward preferred HIV-1 epitopes is a promising strategy in therapeutic vaccine settings. Designing novel immunogens based on the HIV-1 conserved regions containing a wide range of critical T- and B-cell epitopes of the main viral antigens (conserved multiepitope approaches) supplies broad coverage of global diversity in HIV-1 strains and Human Leukocyte Antigen (HLA) alleles. It can also prevent immune induction to undesirable decoy epitopes theoretically. The efficacy of different novel HIV-1 immunogens based on the conserved and/or functional protective site of HIV-1 proteome has been evaluated in multiple clinical trials. Most of these immunogens were generally safe and able to induce potent HIV-1-specific immunity. However, despite these findings, several candidates have demonstrated limited efficacy in viral replication control. In this study, we used the PubMed and ClinicalTrial.gov databases to review the rationale of designing curative HIV-1 vaccine immunogens based on the conserved favorable site of the virus. Most of these studies evaluate the efficacy of vaccine candidates in combination with other therapeutics and/or with new formulations and immunization protocols. This review briefly describes the design of conserved multiepitope constructs and outlines the results of these vaccine candidates in the recent clinical pipeline.
ABSTRACT
Background & objectives: Cervical cancer is the second most frequent cancer among females worldwide, especially human papilloma viruses (HPV) types 16 and 18. In viral systems the identification of serological markers would facilitate the diagnosis of HPV infections and virus-related disease. The aim of the present investigation was to determine and search for serologic markers in cervical cancer patients associated with HPV. Methods: A total of 58 Iranian women with invasive cervical carcinoma including adenocarcinoma and squamous cell carcinoma (SCC) were included. Serum antibody response to HPV infections in patients was detected by Western blot and ELISA techniques based on recombinant HPV16E7 and the N-terminal and C-terminal fragments of gp96 (NT-gp96 and CT-gp96) proteins. These recombinant proteins were expressed in Escherichia coli as a His-tag protein and purified using affinity chromatography. Results: The ELISA results indicated that patients with high antibody response to HPV16E7 had significant seroreactivity to CT-gp96 fragment. In Western blot analysis, a strong association between anti-E7, anti-NT-gp96 and anti-CT-gp96 reactivity and cervical cancer was obtained using purified recombinant proteins. In adenocarcinoma cases, no significant difference was observed in seroreactivities between normal and patients. Interpretation & conclusions: The evaluation of cervical cancer patients' seroreactivities against three recombinant proteins (rE7, rNT-gp96 and rCT-gp96) showed significantly higher levels of these markers in SCC only, but not in adenocarcinoma and control groups. Also, the usage of both techniques (ELISA and Western blotting) can provide more reliable tools for diagnosis of cervical cancer.