Molecular and cellular therapies最新文献

Background: For many deadly viruses, there are no preventive and / or therapeutic vaccines approved by health authorities World-wide (e.g., HIV, Ebola, Dengue, and many others). Although, for some viruses, prophylactic vaccines are very effective (e.g., HBV, and many others).In this realm, we design, manufacture, test, and streamline into the clinics novel viral universal vaccines (VUV). VUV have such unique features, that medical vaccination or natural infection induced immunity against some viruses (e.g., HBV) upon the VUV's administration to the infected with other, different viruses patients, is redirected against these other, newly infecting viruses (e.g., HIV).

Specific aim: The specific aim of this work was biomolecular engineering of the HIV universal vaccine comprising the two main functional domains: CD4 or anti-gp120 - as the HIV tagging domain and HBsAg - as the immune response eliciting domain, so that upon its administration the HBV medical immunization or natural infection induced immunity would be redirected, accelerated, and amplified to fight the HIV infection.

Healthy donors and patients: Per the Institutional Review Board approval and in compliance with the Declaration of Helsinki, all healthy donors and patients were presented with the Patients' Bill of Rights and provided Patient Informed Consent. All the procedures were pursued by the licensed medical doctors.

Methods & results: We have biomolecularly engineered HIV universal vaccine (HIVUV) comprising human CD4 or anti-gp120 and HBsAg of HBV. By immunoblotting and magnetic activated molecular sorting, we have demonstrated high specificity of this vaccine in binding HIV. By flow cytometry and nuclear magnetic resonance, we have demonstrated high efficacy of these vaccines to engage HBV immunized patients' immune system against HIV. Administration of HIVUV to blood or lymph of the HIV+ patients resulted in rapid reduction of the HIV viremia down to undetectable. It also resulted in protection of populations of CD4+ cells against HIV caused decline.

Conclusions: We have demonstrated the proof of concept for high efficacy of VUV, specifically HIVUV, in annihilating HIV. Nevertheless, the same compositions, processes, and methods, for persons skilled in biotechnology, pharmacogenomics, and molecular medicine, are adaptable for other deadly viral infections, which we vigorously pursue.

Introduction: HIV viremia is the essential element for progression of an initial HIV infection into AIDS and death. The currently approved management relies primarily on chemotherapy repressing the HIV replication in the infected CD4+ cells, although with severe systemic adverse effects. The problem is that it does not physically eliminate viruses, which then not only keep infecting healthy cells of these patients, but also promote infections of other people.

Specific aim: An overall objective of our work is biomolecular engineering of virus apheresis tags (VAT) that eliminate viremias without adverse effects. The specific aim of this project was biomolecular engineering of Human Immunodeficiency Virus Apheresis Tags (HIVAT): CD4-Au-Fe₃O₄, CD4-SiO₂-Fe₃O₄, anti-gp120-Au-Fe₃O₄, and anti-gp120-SiO₂-Fe₃O₄.

Healthy donors and patients: Per the Institutional Review Board's approval and in compliance with Declaration of Helsinki, healthy donors and patients were presented with Patient Bill of Rights and provided Patient Informed Consent, while all the procedures were pursued by the licensed physicians.

Materials and methods: CD4, gp120, gp41, gp160, anti-gp120, p24 were transgenomically expressed. Superparamagnetic core-shell particles (SPM-CSP) were synthesized. SPM-CSP were used as the nucleation centers for assembling the expressed molecules upon them to create virus apheresis tags (VAT). VAT were injected into the blood or lymph acquired from the HIV+ and HBV+ patients followed by apheresis at 0.47 - 9.4 T. VAT efficacy in eliminating viremia was determined through immunoblots, NMR and q-RT-PCR.

Results: Treatment of blood or lymph of the HIV+ patients' with VAT followed by virus apheresis resulted in rapid elimination of the HIV viremia. Efficacy of apheresis was contingent upon the gravity of viremia versus doses and regimens of VAT. Importantly, administration of VAT also effectively improved levels of non-infected CD4+ lymphocytes.

Discussion / conclusions: Herein, we present the proof of concept for a new, effective treatment with virus apheresis tags (VAT), specifically Human Immunodeficiency Virus Apheresis Tags (HIVAT), of the HIV+ patients' blood and lymph, which is eliminating the HIV viremia.It can be easily adapted as treatments of viremias perpetrated by other deadly viruses, which we vigorously pursue.