Results of the first clinical trial of AAV gene therapy for AIDS announced

HIV is a virus that attacks the human immune system, targeting the most important CD4+ T cells in the human immune system and destroying them in large numbers. The body loses its immune function, and due to the extreme decrease of resistance, many kinds of infections will occur, and in the later stage, malignant tumors will often occur, and the body will die of systemic failure. According to UNAIDS, the number of people living with Hiv and AIDS is currently 38 million worldwide, and is growing rapidly.

On April 11, 2022, a team of researchers from the National Institutes of Health (NIH) published a research paper in Nature Medicine titled: Safety and tolerability of AAV8 delivery of a broadly neutralizing antibody in adults living with HIV: a phase 1, dose-escalation trial.

Induced production of broadly neutralizing antibodies (bnAbs) is a powerful tool for HIV prevention and treatment. In this study, AAV virus-mediated gene therapy was administered to eight HIV-infected patients, and the delivery of DNA encoding potent broadly neutralizing antibodies (bnAbs) via the AAV virus resulted in long-lasting production of broadly neutralizing antibodies in vivo, bringing a powerful new tool for the treatment of diseases such as AIDS. This is the first time that monoclonal antibodies have been produced in the human body through AAV delivery.

The study recruited eight HIV-infected patients who received antiretroviral therapy for at least 3 months. They were then treated with intramuscularly delivered AAV8-delivered broadly neutralizing antibody (AAV8-VRC07) in three doses of administration: 5 x 10E10vg/kg, 5 x 10E11vg/kg, and 2.5 x 10E12vg/kg.

The major goal of this Phase 1 clinical trial is to investigate the safety and tolerability of AAV8-VRC07 treatment, as well as the pharmacokinetics and immunogenicity in vivo and the patient's immune response to the AAV8-VRC07 vector and its products. The effect of AAV8-VRC07 on CD4 T-cell counts and HIV viral load, as well as the persistence of broadly neutralizing antibodies produced by participants in vivo, were secondary objectives.

The results showed that intramuscular AAV8-VRC07 was safe and well-tolerated. No clinically significant changes in CD4 T-cell counts or viral load occurred during the 1-3 year follow-up period. Eight patients had increased broadly neutralizing antibodies at weeks 6 and 52 post-injection, and all eight produced measurable serum broadly neutralizing antibodies, with three of them having maximum antibody concentrations above 1 µg/ml. Serum broadly neutralizing antibody concentrations in four individuals approached maximum concentrations and remained stable over a 3-year follow-up period. The neutralizing activity of the broadly neutralizing antibodies produced in vivo was similar to that produced in vitro.

This study demonstrates that AAV vectors can persistently produce biologically active and difficult-to-induce broadly neutralizing antibodies in vivo, adding a powerful new tool in the fight against infectious diseases such as AIDS.

More importantly, this AAV delivery platform is capable of producing antibodies in a single injection over a long period of time, allowing the use of AAV to deliver the coding DNA of any required antibodies for the treatment of various infectious diseases such as malaria, and SARS-CoV-2, and for the delivery of other biological drugs for the treatment of various diseases such as autoimmune diseases and cancer.

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