Format

Send to

Choose Destination
Retrovirology. 2018 Oct 1;15(1):66. doi: 10.1186/s12977-018-0449-7.

Adeno-associated virus gene delivery of broadly neutralizing antibodies as prevention and therapy against HIV-1.

Author information

1
Ragon Institute of MGH, MIT and Harvard, Cambridge, MA, 02139, USA.
2
Department of Systems Biology, Harvard University, Boston, MA, 02115, USA.
3
Ragon Institute of MGH, MIT and Harvard, Cambridge, MA, 02139, USA. abalazs@mgh.harvard.edu.

Abstract

Vectored gene delivery of HIV-1 broadly neutralizing antibodies (bNAbs) using recombinant adeno-associated virus (rAAV) is a promising alternative to conventional vaccines for preventing new HIV-1 infections and for therapeutically suppressing established HIV-1 infections. Passive infusion of single bNAbs has already shown promise in initial clinical trials to temporarily decrease HIV-1 load in viremic patients, and to delay viral rebound from latent reservoirs in suppressed patients during analytical treatment interruptions of antiretroviral therapy. Long-term, continuous, systemic expression of such bNAbs could be achieved with a single injection of rAAV encoding antibody genes into muscle tissue, which would bypass the challenges of eliciting such bNAbs through traditional vaccination in naïve patients, and of life-long repeated passive transfers of such biologics for therapy. rAAV delivery of single bNAbs has already demonstrated protection from repeated HIV-1 vaginal challenge in humanized mouse models, and phase I clinical trials of this approach are underway. Selection of which individual, or combination of, bNAbs to deliver to counter pre-existing resistance and the rise of escape mutations in the virus remains a challenge, and such choices may differ depending on use of this technology for prevention versus therapy.

KEYWORDS:

AAV; Animal models; Antibody gene transfer; Clinical trials; HIV-1; Vectored delivery; bNAb

Supplemental Content

Full text links

Icon for BioMed Central Icon for PubMed Central
Loading ...
Support Center