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Adeno-Associated Viral Vector Mediated Expression of Broadlyneutralizing Antibodies Against HIV - Hitting a Fast-Moving Target

Author(s):

Chringma Sherpa* and Stuart F.J. Le Grice   Pages 1 - 18 ( 18 )

Abstract:


The vast genetic variability of HIV has impeded efforts towards a cure for HIV. Lifelong administration of combined antiretroviral therapy (cART) is highly effective against HIV and has markedly increased the life expectancy of HIV infected individuals. However, the usage of long-term cART is associated with co-morbidities and the emergence of multidrug-resistant escape mutants necessitating the development of alternative approaches to combat HIV/AIDS. In the past decade, the development of single-cell antibody cloning methods has facilitated the characterization of a diverse array of highly potent neutralizing antibodies against a broad range of HIV strains. Although the passive transfer of these broadly neutralizing antibodies (bnAbs) in both animal models and humans has been shown to elicit significant antiviral effects, long term virologic suppression requires repeated administration of these antibodies. Adeno-associated virus (AAV) mediated antibody gene transfer provides a long-term expression of these antibodies from a single administration of the recombinant vector. Therefore, this vectored approach holds promises in the treatment and prevention of a chronic disease like HIV infection. Here, we provide an overview of HIV genetic diversity, AAV vectorology, and anti-HIV bnAbs and summarize the promises and challenges of the application of AAV in the delivery of bnAbs for HIV prevention and therapy.

Keywords:

Adenovirus-associated virus, broadly neutralizing antibodies, HIV, genetic diversity, viral vector, gene therapy.

Affiliation:

Basic Research Laboratory, Center for Cancer Research, National Cancer Institute, National Institute of Health, Frederick, Maryland, 21702, Basic Research Laboratory, Center for Cancer Research, National Cancer Institute, National Institute of Health, Frederick, Maryland, 21702



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