Editors' ChoiceAIDS

Vectored Immunoprophylaxis and HIV: The New VIP on the Block

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Science Translational Medicine  14 Dec 2011:
Vol. 3, Issue 113, pp. 113ec204
DOI: 10.1126/scitranslmed.3003555

World AIDS Day passed on 1 December, marking 30 years since the condition was first identified. At the end of 2010, 34 million people were living with HIV, with 1.8 million AIDS-related deaths occurring in 2009. Although enormous strides have been made in early diagnosis and treatment, a vaccine with more than modest efficacy has been elusive. One roadblock is the highly variable HIV genome, so that a single vaccine cannot elicit an immune response against many different HIV variants. To address this issue, researchers have turned to broadly neutralizing antibodies (BNAs) that are capable of binding diverse circulating HIV strains. Balazs and colleagues now demonstrate vectored immunoprophylaxis (VIP), a technique in which BNAs are expressed from an adeno-associated virus (AAV) vector in vivo.

Balazs et al. developed an AAV vector that could express high levels of a complete HIV-neutralizing human monoclonal antibody, named b12, in vivo. They then administered this vector to both immunodeficient and immunocompetent mice with an intramuscular injection; high serum concentrations of the encoded antibody were observed in all strains, and this expression was stable throughout the lifetime of the mouse. The investigators then used a humanized mouse model to assess whether the VIP protected mice from an HIV challenge. Mice injected with the AAV-b12 vector and later challenged with HIV showed no depletion of CD4+ T cells (the immune cells that are normally killed by HIV), whereas mice injected with a control vector exhibited dramatic loss of these cells. Other BNAs, expressed in a similar manner, were partially protective against HIV infection. Furthermore, mice expressing b12 did not have immunohistochemical evidence of HIV-expressed p24 antigen in spleen sections (a measure of the extent of the infection), whereas those mice expressing other BNAs did display p24 staining, although generally less than mice that received the control vector.

Balazs and colleagues have shown that their VIP approach protects mice from high-dose HIV exposure. The challenge doses of HIV were nearly 100-fold higher than needed for robust infection, suggesting that the AAV-b12 vector is both avid and effective. From a translational vantage point, the authors note that this level of protection might exceed what is required to prevent human to human transmission.

A. B. Balazs et al., Antibody-based protection against HIV infection by vectored immunoprophylaxis. Nature 30 November 2011 (10.1038/nature10660). [Abstract]

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