Induction of Robust Immune Responses against Human Immunodeficiency Virus Is Supported by the Inherent Tropism of Adeno-Associated Virus Type 5 forDendritic Cells

Abstract

The ability of adeno-associated virus serotype 1 to 8 (AAV1 to AAV8) vectors expressing the human immunodeficiency virus type 1 (HIV-1) Env gp160 (AAV-HIV) to induce an immune response was evaluated in BALB/c mice. The AAV5 vector showed a higher tropism for both mouse and human dendritic cells (DCs) than did the AAV2 vector, whereas other AAV serotype vectors transduced DCs only poorly. AAV1, AAV5, AAV7, and AAV8 were more highly expressed in muscle cells than AAV2. An immunogenicity study of AAV serotypes indicates that AAV1, AAV5, AAV7, and AAV8 vectors expressing the Env gp160 gene induced higher HIV-specific humoral and cell-mediated immune responses than the AAV2 vector did, with the AAV5 vector producing the best responses. Furthermore, mice injected with DCs that had been transduced ex vivo with an AAV5 vector expressing the gp160 gene elicited higher HIV-specific cellmediated immune responses than did DCs transduced with AAV1 and AAV2 vectors. We also found that AAV vectors produced by HEK293 cells and insect cells elicit similar levels of antigen-specific immune responses. These results demonstrate that the immunogenicity of AAV vectors depends on their tropism for both antigen-presenting cells (such as DCs) and non-antigen-presenting cells (such as muscular cells) and that AAV5 is a better vector than other AAV serotypes. These results may aid in the development of AAV-based vaccine and gene therapy.

Immunity to adeno-associated virus vectors in animals and humans: a continued challenge

“…41,42,57,58 In one recent study, Xin et al 59 compared the ability of most of the common AAV serotypes (serotypes 1, 2, 3, 4, 5, 7 and 8) to function as vaccine in a HIV-1gp160 antigen trial in mice. Although all AAV serotypes were able to induce humoral and T-cell responses to HIV-gp160, AAV5 vector transduced mouse and human DCs more efficiently and elicited higher HIVspecific cell-mediated immune responses compared to the other serotypes.…”

Distinct immune responses to transgene products from rAAV1 and rAAV8 vectors

“…It has been reported that the rAAV2 vector is less immunogenic compared to the adenovirus vector (5). Recent studies show some rAAV vectors including serotypes 1, 2, and 5 can transduce dendritic cells (DCs) and generate immune responses to transgene products (6)(7)(8)(9). Some studies have shown that rAAV8 vector has a low immunogenicity while it transduces liver, muscle, and many other cell types with high efficiency (10)(11)(12)(13)(14)(15).…”

Adeno-Associated Virus Activates an Innate Immune Response in Normal Human Cells but Not in Osteosarcoma Cells

“…Initial studies on the immune responses elicited by AAV-based vectors have focused on transgene product-specific immune responses and have indicated that although AAV is considered a poor activator of both innate and adaptive immunity (49), this feature highly depends on the transgene itself, the target tissue, the choice of promoter, and most importantly the host species (29). Viral capsids were also shown to be a source of antigens that activate T cell priming (45,47).…”