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

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


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Antibodies, Neutralizing / genetics
  • Antibodies, Neutralizing / immunology
  • Antibodies, Neutralizing / therapeutic use*
  • Clinical Trials as Topic
  • Dependovirus / genetics*
  • Disease Models, Animal
  • Genetic Therapy
  • HIV Antibodies / genetics
  • HIV Antibodies / immunology
  • HIV Antibodies / therapeutic use*
  • HIV Infections / immunology
  • HIV Infections / prevention & control*
  • HIV Infections / therapy*
  • HIV-1 / immunology
  • Humans
  • Immunization, Passive


  • Antibodies, Neutralizing
  • HIV Antibodies