HIV Universal Vaccine.

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.

Prospecting for an HIV vaccine.

Human immunodeficiency virus (HIV) sets several challenges for the development of a preventative HIV vaccine. Predictable, protective natural immunity against HIV does not occur and so unlike most other diseases for which vaccines exist, there are few guideposts from natural infection. Nonetheless, six vaccine efficacy trials have occurred. One in particular, the Thai trial called RV144, showed partial protective efficacy and potential ways ahead to a better vaccine approach. This coupled with other lessons from studies of acute infections as well as an increasingly complex knowledge of HIV-related vaccine immunology bring hope that a vaccine solution might be reached for this pervasive and deadly pandemic.

A Phase 1 Human Immunodeficiency Virus Vaccine Trial for Cross-Profiling the Kinetics of Serum and Mucosal Antibody Responses to CN54gp140 Modulated by Two Homologous Prime-Boost Vaccine Regimens.

A key aspect to finding an efficacious human immunodeficiency virus (HIV) vaccine is the optimization of vaccine schedules that can mediate the efficient maturation of protective immune responses. In the present study, we investigated the effect of alternate booster regimens on the immune responses to a candidate HIV-1 clade C CN54gp140 envelope protein, which was coadministered with the TLR4-agonist glucopyranosyl lipid A-aqueous formulation. Twelve study participants received a common three-dose intramuscular priming series followed by a final booster at either 6 or 12 months. The two homologous prime-boost regimens were well tolerated and induced CN54gp140-specific responses that were observed in both the systemic and mucosal compartments. Levels of vaccine-induced IgG-subclass antibodies correlated significantly with FcγR engagement, and both vaccine regimens were associated with strikingly similar patterns in antibody titer and FcγR-binding profiles. In both groups, identical changes in the antigen (Ag)-specific IgG-subclass fingerprint, leading to a decrease in IgG1 and an increase in IgG4 levels, were modulated by booster injections. Here, the dissection of immune profiles further supports the notion that prime-boost strategies are essential for the induction of diverse Ag-specific HIV-1 responses. The results reported here clearly demonstrate that identical responses were effectively and safely induced by both vaccine regimens, indicating that an accelerated 6-month regimen could be employed for the rapid induction of immune responses against CN54gp140 with no apparent impact on the overall quality of the induced immune response. (This study has been registered at http://ClinicalTrials.gov under registration no. NCT01966900.).

Autoimmunity and dysmetabolism of human acquired immunodeficiency syndrome.

Acquired immunodeficiency syndrome (AIDS) remains ill-defined by lists of symptoms, infections, tumors, and disorders in metabolism and immunity. Low CD4 cell count, severe loss of body weight, pneumocystis pneumonia, and Kaposi's sarcoma are the major disease indicators. Lines of evidence indicate that patients living with AIDS have both immunodeficiency and autoimmunity. Immunodeficiency is attributed to deficits in the skin- and mucosa-defined innate immunity, CD4 T cells and regulatory T cells, presumably relating human immunodeficiency virus (HIV) infection. The autoimmunity in AIDS is evident by: (1) overproduction of autoantibodies, (2) impaired response of CD4 cells and CD8 cells, (3) failure of clinical trials of HIV vaccines, and (4) therapeutic benefits of immunosuppression following solid organ transplantation and bone marrow transplantation in patients at risk of AIDS. Autoantibodies are generated in response to antigens such as debris and molecules de novo released from dead cells, infectious agents, and catabolic events. Disturbances in metabolic homeostasis occur at the interface of immunodeficiency and autoimmunity in the development of AIDS. Optimal treatments favor therapeutics targeting on the regulation of metabolism to restore immune homeostasis.

Human immunodeficiency virus vaccine an update.

Since the discovery of acquired immuno deficiency syndrome (AIDS) in late1980s, the spread of human immunodeficiency virus (HIV) has reached pandemic proportions, representing a global developmental and public health threat. Finding of a safe, globally effective and affordable HIV vaccine offers the best hope for the future control of the disease pandemic. Significant progress has been made over the past years in the areas of basic virology, immunology, and pathogenesis of HIV/AIDS and the development of anti-retroviral drugs. However, the search for an HIV vaccine faces formidable scientific challenges related to the high genetic variability of the virus, the lack of immune correlates of protection, limitations with the existing animal models and logistical problems associated with the conduct of multiple clinical trials. Most of the vaccine approaches developed so far aim at inducing cell-mediated immune responses. Multiple vaccine concepts and vaccination strategies have been tested, including DNA vaccines, subunit vaccines, live vectored recombinant vaccines, various prime-boost vaccine combinations and vaccine based on broadly neutralizing human anti-HIV Antibody 2G12. This article reviews the state of the art in HIV vaccine research, summarizes the results obtained so far and discusses the challenges to be met in the development of a successful HIV vaccine.