Tag: <span>HIV</span>

Despite 20 years of intensive research, the development of an effective vaccine to combat the worldwide AIDS pandemic remains an elusive goal. Currently, more than 40 million individuals are infected with human immunodeficiency virus (HIV) and there have been more than 25 million related deaths. Globally, the rate of new infections is alarming, with ten new infections occurring every minute. Ninety-five percent of these infections occur in the developing world. Several significant challenges face the development of an effective HIV vaccine…

Manufacturing Viral Vectors

As human immunodeficiency virus type-1 (HIV-1) continues to spread around the world, scientists are actively pursuing effective vaccines against the infectious disease that results in AIDS. A number of vaccine designs have been developed, including plasmid DNA constructs encoding HIV proteins. One advantage of DNA vaccination is that after the uptake of the plasmid by the host cells, the encoded antigens are expressed in the native conformation and allow authentic immunological processing of the antigen. Another advantage of DNA vaccines is that they can be repeatedly administered without vector-directed immunity limiting the efficacy of the boost. DNA vaccines alone can induce both humoral and cellular immune responses and provide modest protection against disease progression in the preclinical, nonhuman primate model when challenged with simian immunodeficiency virus (SIV)…

Biologics Production

The first HIV-based lentiviral vector to be used in humans, VRX496, is currently being tested in Phase I clinical trials (initiated in January 2003). With each new therapeutic comes the need to establish quality control (QC) testing designed specifically for that product. The QC testing for VRX496 was developed in accordance with the Code of Federal Regulations (CFR) 21 for pharmaceutical and bulk chemical GMPs, Points to Consider in the Characterization of Cell Lines Used to Produce Biologicals (1993) from the Center for Biologics Evaluation and Research (CBER) at FDA, and the United States Pharmacopeia (USP) 1046 for Cell and Gene Therapy Products. This report describes the QC testing of lot VRX496V02-009 of our clinical grade vector, which is being used in an ongoing clinical trial evaluating the first lentiviral gene therapy vector in humans. All assays are performed according to established standard operating procedures (SOPs) and in accordance with the principles of cGMP regulations…

Cell & Gene Therapy Viral Vectors

Globally, an estimated 36 million people are living with HIV, and some 20 million people have already died of AIDS. Today, there is still no HIV vaccine available. HIV virus-like particles are an attractive vaccine candidate due to their ability to induce both antibody and cytotoxic T-lymphocyte responses. In this article, we describe the development of a production process for an HIV particle vaccine, HIV-1 p55 (gag). The gag precursor protein (p55) is sufficient for assembly and cellular release of retrovirus-like particles. We expressed the p55 gag protein using the BEVS technology in Spodoptera frugiperda expresSF+ cells…

Baculovirus Expression Technology Biologics Production

We have developed a procedure for large-scale enrichment, growth and harvesting of T cells suitable for adoptive immunotherapy. In two recently completed clinical trials, we investigated the feasibility of immune reconstitution in patients with HIV infection, or with relapsed/refractory Non-Hodgkin’s Lymphoma (NHL) following infusions of autologous activated CD4+ T cells or CD4+/CD8+ T cells. Autologous T cells were activated via CD3/CD28 stimulation, ex vivo, and were then reinfused…

Cell & Gene Therapy