An HIV-1 Mini Vaccine Induced Long-lived Cellular and Humoral Immune Responses.

Memory formation is the most important aspect of a vaccine which can guarantee long-lasting immunity and protection. The main aim of the present study was to evaluate the memory immune responses after immunization with a mini vaccine. Mice were immunized with human immunodeficiency virus-1 P24-Nef fusion peptide and then cellular and humoral immune responses were evaluated. In order to determine long-lived memory, immune responses were monitored for 20 weeks after final immunization. The results showed that the candidate vaccine induced proliferation and cytotoxic T lymphocyte responses and shifted cytokine patterns to T helper-1 profile. Evaluation of humoral immune responses also showed an increase in total peptide specific-IgG titer and a shift to IgG2a humoral response. Monitoring of immune responses at weeks 4, 12 and 20 after last immunization showed that immunologic parameters have been sustained for 20 weeks. Our findings support the notion that long-lived memory responses were achieved using a mini vaccine immunization.

Evaluation of a Novel Herbal Immunomodulator Drug (IMOD) in Treatment of Experimental Canine Visceral leishmaniasis.

Toxicity and drug resistance against pentavalent antimonials, medications of choice in treatment of leishmaniasis for more than 5 decades, have become important subjects globally. This study was a randomized, open labeled trial that was designed to determine efficacy and safety of IMOD as a novel herbal immunomodulator drug for treatment of canine visceral leishmaniasis (CVL). Twenty healthy mongrel dogs were infected with Iranian strain of L. Infantum amastigotes and randomly divided to 5 groups with four animals for each included on: I: negative control (non-infected) II: Glucantime® III: Glucantime® plus IMOD (immune-chemotherapy) IV: IMOD and V: positive control (non-treated). Physical examination, hematological, biochemical, serological, parasitological, pathological and imaging evaluations were performed pre-/post- interventions every month for 3 months. Comparing with control groups (I&V), immune-chemotherapy group (Glucantime® plus IMOD) showed significantly higher efficacy in resolving the clinical signs and hematobiochemistry factors. Based on our results, using IMOD in combination with meglumine antimoniate (Glucantime®) has significantly improved CVL than the latter drug alone. So, it seems this new herbal medicine is useful as adjuvant therapy for canine visceral leishmaniasis.

Assessment of the Effects of a Novel Herbal Immunomodulator Drug (IMOD) on Cytokine Profiles in Experimental Canine Visceral Leishmaniasis: a Preliminary Survey.

BACKGROUND: Cytokines play a fundamental role in the regulation of immune responses in remission and/or relapsing of leishmaniasis. Therefore, immunotherapy for the treatment of canine visceral leishmaniasis (CVL) has represented a principle approach in control of the infection. The present research aimed to evaluating the immunotherapeutic potential of a novel herbal immunomodulator drug (IMOD) on CVL. METHODS: Twelve mongrel dogs were intravenously infected with Iranian strain of L. infantum and randomly divided into three groups; 1: negative control (non-infected), 2: immunotherapy with IMOD and 3: positive control (non-treated). Cell proliferation and Th1-/Th2-type cytokines were measured in peripheral blood mononuclear cell (PBMC) by cell proliferation kit I (MTT) and enzyme-linked immunospot (ELISpot) assays, respectively. RESULTS: At the 60 days follow-up assessment, no adverse effects were observed in treated interventional group. Cellular proliferation assay indicated that PBMCs of IMOD group had higher stimulation index (SI) than positive control group (p < 0.05). Enhancement of CD4+T cells such as IL-2, IL-4 & IL-10 were detected in negative control group due to in vitro IMOD stimulation 30 days post-treatment. In accordance to decreasing trends of Th1 & Th2 cytokines in positive control group, the mean number of IFN-γ IL-2, IL-4 and IL-10 spot forming cells (SFCs) down regulated for IMOD group during the study. CONCLUSION: These data indicate that IMOD had immunomodulatory potential but is not sufficient for total parasitic cure due to balance of Th1/Th2 cytokines. This is a preliminary study and we propose to undertake a series of experiments to evaluate the CVL due to in vitro modulatory effects of IMOD.

Plasminogen activator inhibitor 1 and methylenetetrahydrofolate reductase gene mutations in iranian women with polycystic ovary syndrome.

PROBLEM: Mutations in genes related to thrombophilia and hypofibrinolysis have been associated with recurrent pregnancy loss (RPL) and polycystic ovary syndrome (PCOS). METHODS: Using PCR-RFLP, we investigated the frequencies of MTHFR (A1298C and C677T) as well as PAI-1 (-675 4G/5G) gene polymorphisms in 177 RPL and 100 control women. RPL women were stratified into 38 women with PCOS (RPL-PCOS), 33 with ovarian PCO (RPL-ovarian PCO), and 106 without PCOS (RPL). RESULTS: RPL, RPL-PCOS, and RPL-ovarian PCO groups showed significantly higher frequencies of MTHFR A1298C (P < 0.001) and PAI-1 4G/5G (P < 0.001) mutations than the controls. No significant differences were found between the RPL groups. The respective odds ratios (OR) for bearing MTHFR (A1298C, C677T) and PAI-1 (4G/5G) gene mutations were 33.9-, 2.2-, and 5.2-fold higher in RPL, 66.3-, 6.7-, and 2.8-fold higher in RPL-PCOS, and 27.3-, 1.9-, and 3.9-fold higher in RPL-ovarian PCO women than those in controls. CONCLUSION: Our results showed the significance of MTHFR A1298C and PAI-1 4G/5G mutations in Iranian women suffering from RPL with and without PCOS.

Immunogenicity of a new HIV-1 DNA construct in a BALB/c mouse model.

BACKGROUND: Cell mediated immunity, especially cytotoxic T cell responses against HIV-1 infection, plays a critical role in controlling viral replication and disease progression. DNA vaccine is a novel technology which is known to stimulate strong cellular immune responses. Many DNA vaccines have been tested for HIV infection but there is still no effective vaccine against this infection. Construction of a vaccine consisting of multiple conserved and immunogenic epitopes may increase vaccine efficacy. OBJECTIVE: In the present study a DNA vaccine candidate constructed from HIV-1 P24-Nef was evaluated and cellular immune responses were assessed in murine BALB/c model. METHODS: HIV-1 P24-Nef gene was cloned in PCDNA3.1 expression vector. Mice were immunized with DNA construct and IL-4 and IFN-gamma evaluation was performed using ELISPOT. Cytotoxicity response was evaluated with Granzyme B ELISPOT assay and lymphocyte proliferation was evaluated with LTT assay. RESULTS: Analysis of immune responses showed that, compared to control groups, the candidate vaccine induced production of higher levels of both IL-4 and IFN-gamma (p<0.05). Cytotoxicity and lymphocyte proliferation responses of mice vaccinated with the candidate vaccine were significantly increased compared to control groups (p<0.05). CONCLUSION: HIV-1 P24-Nef DNA construct displayed strong immunogenicity in a murine model.

A large family with spinocerebellar ataxia type 6 in Iran: a clinical and genetic study.

The authors describe a large Iranian family with autosomal dominant cerebellar ataxia, which included 14 patients in four generations. We examined seven patients who had expanded CAG repeats in the CACNA1A gene with repeat instability (24 and 25 repeats). Although all patients showed cerebellar ataxia, each patient exhibited peripheral neuropathy or spasticity indicating intrafamilial phenotypic variability.