Dengue virus (DENV) comprises four serotypes in the family Flaviviridae and is a causative agent of dengue-related diseases, including dengue fever. Dengue fever is generally a self-limited febrile illness. However, secondary infection of patients with a suboptimal antibody (Ab) response provokes life-threatening severe dengue hemorrhagic fever or dengue shock syndrome. To develop a potent candidate subunit vaccine against DENV infection, we developed the EDII-cEDIII antigen, which contains partial envelope domain II (EDII) including the fusion loop and BC loop epitopes together with consensus envelope domain III (cEDIII) of all four serotypes of DENV. We purified Ab from mice after immunization with EDII-cEDIII or cEDIII and compared their virus neutralization and Ab-dependent enhancement of DENV infection. Anti-EDII-cEDIII Ab showed stronger neutralizing activity and lower Ab-dependent peak enhancement of DENV infection compared with anti-cEDIII Ab. Following injection of Ab-treated DENV into AG129 mice, anti-EDII-cEDIII Ab ameliorated DENV infection in tissues with primary and secondary infection more effectively than anti-cEDIII Ab. In addition, anti-EDII-cEDIII Ab protected against DENV1, 2, and 4 challenge. We conclude that EDII-cEDIII induces neutralizing and protective Abs, and thus, shows promise as a candidate subunit vaccine for DENV infection.
Objective: To evaluate the safety and the efficacy of internal carotid artery (ICA) infusion of autologous bone marrow-derived stem cells (BMSC) in subacute middle cerebral artery (MCA) infarct. Subject and method: A prospective, open-label, non-randomized was conducted in patients with MCA infarct, within 7-40 days from onset. Sixty-two patients satisfying the inclusion criteria were enrolled and allocated into either BMSC group (n = 31) or control group (n = 31). Follow-ups were performed at 6 months and 1 year after therapy. Adverse events were noted to conclude safety outcome. The primary efficacy outcomes were percentages of recovered patients with a score of 0 to 2 on the modified Rankin Scale (mRS). The secondary efficacy outcomes were evaluated by the National Institutes of Health Stroke Scale (NIHSS), Barthel Index (BI), Brunnstrom stages of hand (BRS-H), and infarct volume on head MRI. Result: There were no significant differences in the percentages of noted adverse events. The percentages of the mRS 0-2 in BMSC group were remarkably higher as compared to control group at both 6-month and 1-year follow-up, but not statistically significant (25.8% vs 6.9%, p=0.08 and 26.7 vs 9.7, p=0.1, respectively). BI at 6 months was significantly better in the BMSC group, however no significant differences on other secondary efficacy measures. Conclusion: ICA infusion of BMSC was safe and tolerated in patients with subacute MCA infarct. Although the difference in the primary efficacy outcomes was not statistically significant, a favorable trend was found in BMSC group representing by the BI at 6 months and the percentages of mRS 0-2 at both main follow-ups.
Objective: To assess the safety and the efficacy of intravenous infusion of autologous bone marrow-derived stem cells (BMSC) in subacute middle cerebral artery (MCA) infarct. Subject and method: A prospective, open-label, non-randomized was performed in patients with MCA infarct, within 7-40 days from onset. Sixty-three patients, satisfying the inclusion criteria, were enrolled, and allocated into the IV-BMSC group (n = 32) or into control group (n = 31). Main follow-ups were at 6 months and 1 year after therapy. Adverse events were noted to conclude safety outcome. The primary efficacy outcomes were proportions of patients achieving a score of 0 to 2 on the modified Rankin Scale (mRS). The secondary efficacy outcomes were evaluated by the National Institutes of Health Stroke Scale (NIHSS), Barthel index (BI), Brunnstrom stages of hand (BRS-H), and infarct volume on head MRI. Result: There were no statistically significant differences in the rates of noted adverse events. There were no significant differences between the two groups on the proportions of the mRS 0-2 at both 6-month and 1-year follow-up (3.2% vs 6.9% with p=0.6, and 6.9 vs 9.7 with p=1.0, respectively). The improvement of BI at 6 months was significantly better in the IV-BMSC group compared to control group, however no significant differences on other secondary efficacy measures. Conclusion: Intravenous infusion of BMSC was safe in patients with subacute MCA infarct. Although the difference in the primary efficacy outcomes was not statistically significant, a favorable secondary outcome was observed in IV-BMSC group, presenting by the statistically significant improvement of the Barthel index at 6-month follow-up.
Background: Systemic lupus erythematosus (SLE) is a chronic disease that causes systemic inflammation which affects multiple organs. There is no cure for SLE. Conventional treatment options include antimalarial drugs, corticosteroids, and immune suppressants, but a number of patients are resistant to treatment or suffer from severe side effects. Stem cell transplantation has been used to treat SLE for the past 2 decades. We describe the first Vietnamese patient with refractory SLE who received an autologous hematopoietic stem cell transplant. Case presentation: The patient is a woman who was diagnosed 12 years ago with systemic lupus erythematosus. She was administered corticosteroids and high-dose immunosuppressive medicines, but the condition was refractory, manifesting as severe headache, arthralgia, chronic anemia, severe Cushing's syndrome, and proteinuria. At admission, the SLEDAI score was 28 and proteinuria was 6.7g/l. She received cyclophosphamide and G-CSF for HSCT mobilization. Peripheral blood stem cells were collected and selected for CD34+ cells. Antithymocyte, cyclophosphamide, and rituximab were used in conditioning regimens. The patient was then administered a CD34+ autologous hematopoietic stem cell transfusion with a CD34+ dose of 7.93 x 106 cells/kg body weight, T and B lymphocyte purity of the graft exceeded 99.99%. Post-transplant course was favorable, the patient did not experience serious complications. Recovery of neutrophils on post-HSCT day +9 and platelet on day +12. Six months after stem cell transplantation, the patient's clinical symptoms significantly improved, the SLEDAI score dropped from 28 to 0, and the patient discontinued receiving immunosuppressive drugs. Conclusion: Autologous hematopoietic stem cell transplantation promises to be a new, effective therapeutic method that can be implemented more broadly in Vietnam for SLE patients.
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