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Objective: Novel vaccination approaches are required to control human immunodeficiency virus (HIV) infections. The membrane proximal external region (MPER) of Env gp41 subunit and the V3/glycans of Env gp120 subunit were known as potential antigenic targets for anti-HIV-1 vaccines. In this study, we prepared the modified dendritic cells (DCs) and mesenchymal stem cells (MSCs) with HIV-1 MPER-V3 gene using mechanical and chemical approaches. Methods: At first, MPER-V3 fusion DNA delivery was optimized in dendritic cells (DCs) and mesenchymal stem cells (MSCs) using three mechanical (i.e., uniaxial cyclic stretch, equiaxial cyclic stretch and shear stress bioreactors), and two chemical (i.e., TurboFect or Lipofectamine) methods. Next, the modified DCs and MSCs with MPER-V3 antigen were compared to induce immune responses in vivo. Results: Our data showed that the combination of equiaxial cyclic stretch loading and lipofectamine twice with 48 h intervals increased the efficiency of transfection about 60.21 ± 1.05 % and 65.06 ± 0.09 % for MSCs and DCs, respectively. Moreover, DCs and MSCs transfected with MPER-V3 DNA in heterologous DC or MSC prime/ peptide boost immunizations induced high levels of IgG2a, IgG2b, IFN-γ and IL-10 directed toward Th1 responses as well as an increased level of Granzyme B. Indeed, the modified MSCs and DCs with MPER-V3 DNA could significantly enhance the MPER/V3-specific T-cell responses compared to MPER/V3 peptide immunization. Conclusions: These findings showed that the modified MSC-based immunization could elicit effective immune responses against HIV antigen similar to the modified DC-based immunization.

Background: The protective effects of heat shock proteins (Hsps) were studied in some infectious and non-infectious diseases, but their specificity was slightly known in various disorders. Among Hsps, small Hsps (e.g. Hsp27 and Hsp20) have important roles in protein folding and translocation, and also in immunity. Methods: In this study, overexpression of Hsp20 and Hsp27 was performed by transfection of the plasmids encoding Hsp20 and Hsp27 (pEGFP-Hsp20 and pEGFP-Hsp27) into Huh7.5, Hela and Vero cells using Lipofectamine along with heat shock. Then, their anti-herpes simplex virus-1 (HSV-1), anti- human immunodeficiency virus-1 (HIV-1) and anti-hepatitis C virus (HCV) effects, as well as cytotoxicity, were evaluated in vitro, for the first time. Results: Our data showed that simultaneous treatment with Lipofectamine and heat shock augmented the rate of transfection and subsequently the expression of Hsps in these cells. Moreover, overexpression of Hsp20 in HCV-infected Huh7.5 cells, HIV-infected Hela cells and HSV-infected Vero cells reduced the replication of HCV, HIV and HSV, respectively. In contrast, overexpression of Hsp27 significantly decreased HSV replication similar to Hsp20, but it did not affect the replication of HIV and HCV. Conclusion: Generally, Hsp20 was identified as a novel anti-HCV, anti-HSV and anti-HIV agent, but Hsp27 was efficient in the suppression of HSV infection. These Hsps may act through suppression of virus entry and/ or through interaction with viral proteins. Thus, it is necessary to determine their exact mechanisms in the near future.

Background: The protective effects of heat shock proteins (Hsps) were studied in some infectious and non-infectious diseases, but their specificity was slightly known in various disorders. Among Hsps, small Hsps (e.g. Hsp27 and Hsp20) have important roles in protein folding and translocation, and also in immunity. Methods: In this study, overexpression of Hsp20 and Hsp27 was performed by transfection of the plasmids encoding Hsp20 and Hsp27 (pEGFP-Hsp20 and pEGFP-Hsp27) into Huh7.5, Hela and Vero cells using Lipofectamine along with heat shock. Then, their anti-herpes simplex virus-1 (HSV-1), anti- human immunodeficiency virus-1 (HIV-1) and anti-hepatitis C virus (HCV) effects, as well as cytotoxicity, were evaluated in vitro, for the first time. Results: Our data showed that simultaneous treatment with Lipofectamine and heat shock augmented the rate of transfection and subsequently the expression of Hsps in these cells. Moreover, overexpression of Hsp20 in HCV-infected Huh7.5 cells, HIV-infected Hela cells and HSV-infected Vero cells reduced the replication of HCV, HIV and HSV, respectively. In contrast, overexpression of Hsp27 significantly decreased HSV replication similar to Hsp20, but it did not affect the replication of HIV and HCV. Conclusion: Generally, Hsp20 was identified as a novel anti-HCV, anti-HSV and anti-HIV agent, but Hsp27 was efficient in the suppression of HSV infection. These Hsps may act through suppression of virus entry and/ or through interaction with viral proteins. Thus, it is necessary to determine their exact mechanisms in the near future.

Platelet microparticles are the most frequent bloodstream microparticles (∼70–90%) which act as a vector for delivery of mRNA, miRNA and signaling proteins under physiological conditions. A variety of platelet microparticles were produced during the storage of platelet concentrates. In this study, platelet microparticles were isolated from platelet concentrates at day 3 of storage and used to deliver anti-HIV drugs including Lamivudine and Tenofovir. At first, encapsulation efficiency and release of anti-HIV drugs were evaluated by spectrophotometry at different wavelengths. Then, cellular uptake, cytotoxicity and HIV-1 inhibitory effects of drugs and drugs-platelet microparticles were assessed using flow cytometry, MTT and P24 assay kit in vitro. Our data showed that the platelet microparticles (300–1000 nm) have high ability for entrapment of Lamivudine and Tenofovir drugs up to 60% and 40%, respectively. Moreover, the release of drugs from the microparticles slowly occurred. HIV-1 inhibitory effects of Lamivudine- and Tenofovir-platelet microparticles were increased in comparison with drugs alone at different concentrations. Also, the toxicity of drugs loaded in the microparticles was decreased at various doses due to their slow release compared to drugs. Generally, platelet microparticles could be considered as a safe, inexpensive and natural vehicle for anti-HIV drug delivery compared to other synthetic nanoparticles.

Background: The lack of an effective vaccine against viral infections, toxicity of the synthetic anti-viral drugs and the generation of resistant viral strains led to discover novel inhibitors. Recently, saffron and its compounds were used to treat different pathological conditions. Method: In this study, we tested the anti-HSV-1 and anti-HIV-1 activities of Iranian saffron extract and its major ingredients including crocin and picrocrocin as well as cytotoxicity in vitro. The data showed that the aqueous saffron extract was not active against HIV-1 and HSV-1 virions at certain doses (i.e., a mild activity), but crocin and picrocrocin indicated significant anti-HSV-1 and also anti-HIV-1 activities. Crocin inhibited the HSV replication at before and after entry of virions into Vero cells. Indeed, crocin carotenoid suppressed HSV penetration in the target cells as well as disturbed virus replication after entry into the cells. Picrocrocin was also effective for inhibiting virus entry and also its replication. Results: This monoterpen aldehyde showed higher anti-HSV effects after virus penetrating in the cells. Generally, these sugar-containing compounds extracted from saffron showed to be effective antiherpetic drug candidates. Conclusion: The recent study is the first report suggesting antiviral activities for saffron extract and its major ingredients. Crocin and picrocrocin could be a promising anti-HSV and anti-HIV agent for herbal therapy against viral infections.

ABSTRACTIntroduction: The development of an effective therapeutic vaccine to induce cancer-specific immunity remains problematic. Recently, a species of intracellular pathogen known as Listeria monocytogenes(Lm) has been used to transfer DNA, RNA and proteins into tumour cells as well as elicit an immune response against tumour-specific antigens.Areas covered: Herein, the authors provide the mechanisms of different Listeria monocytogenesstrains, which are potential therapeutic cancer vaccine vectors, in addition to their preclinical and clinical development. They also speculate on the future of Lm-based tumour immunotherapies. The article is based on literature published on PubMed and data reported in clinical trials.Expert opinion: Attenuated strains of Listeria monocytogeneshave safely been applied as therapeutic bacterial vectors for the delivery of cancer vaccines. These vectors stimulate MHCI and MHCII pathways as well as the proliferation of antigen-specific T lymphocytes. Several preclinical studies have demonstrated the potency of Lmin intracellular gene and protein delivery in vitroand in vivo. They have also indicated safety and efficiacy in clinical trials. Readers should be aware that the ability of attenuated Lmstrains to induce potent immune responses depends on the type of deleted or inactivated Lmvirulent gene or genes.