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First human trial of AAV as a delivery vehicle for HIV neutralising antibodies gets underway

Richard Jefferys, TAG

Over the past few years there has been growing interest in the use of adeno-associated virus (AAV) as a vehicle for generating anti-HIV neutralising antibodies in humans.

The approach is different from traditional vaccination, in that AAV is used essentially as a gene therapy: the AAV vector is designed to take up residence in cells and then act as a factory for churning out broadly neutralising antibodies against HIV (genes that encode these antibodies are inserted into the vector).

This novel idea may be able to circumvent the challenging problem of inducing the production of broadly neutralising antibodies with traditional vaccines, and could potentially offer significant protection against HIV acquisition.

As covered previously on the blog, there are two main research groups working on AAV-based HIV prevention. [1]

The laboratory of David Baltimore has named their approach vectored immunoprophylaxis (VIP) and published a study in Nature Medicine demonstrating protection against vaginal HIV transmission in a humanised mouse model. [2] The study was supported by the National Institute of Allergy and Infectious Diseases, who issued a press release drawing attention to the findings). [3]

Meanwhile Philip Johnson and colleagues at the Children’s Hospital of Philadelphia are collaborating with the International AIDS Vaccine Initiative (IAVI) on a phase-1 clinical trial of an AAV vector encoding the HIV neutralising antibody PG9, and, according to clinicaltrials.gov, the trial started recruiting participants last month. [4]

This is a major milestone for the research, as there were many challenges associated with obtaining regulatory approval for a human trial and Johnson and IAVI have been working toward this goal for many years. The estimated date for completion of the study is January 2016.

Source
TAG Basic Science Blog. First human trial of AAV as a delivery vehicle for HIV neutralising antibodies gets underway. (11 February 2014).

http://tagbasicscienceproject.typepad.com

References

  1. TAG Basic Science Blog. David Baltimore and vectored immunoprophylaxis. (18 January 2013).
  2. Balazs AB et al, Vectored immunoprophylaxis protects humanized mice from mucosal HIV transmission, Nature Medicine (2014) doi:10.1038/nm.3471. Published online 09 February 2014.
  3. US NIH press release. NIH-funded researchers use antibody treatment to protect humanized mice from HIV. (11 February 2014).
    http://www.niaid.nih.gov/news/newsreleases/2014/Pages/HIV-Humanized-Mice.aspx
  4. ClinicalTrials.gov. A phase 1, randomized, blinded, dose-escalation study of rAAV1-PG9DP recombinant AAV vector coding for PG9 antibody in healthy male adults.
    http://clinicaltrials.gov/ct2/show/NCT01937455

Links to other websites are current at date of posting but not maintained.