Novel Adeno-Associated Virus Vector Vaccine Restricts Replication of Simian Immunodeficiency Virus in Macaques

Johnson, Philip R.; Schnepp, Bruce C.; Connell, Mary J.; Rohne, Daniela; Robinson, Suzanne; Krivulka, Georgia R.; Lord, Carol I.; Zinn, Rebekah L.; Montefiori, David C.; Letvin, Norman L.; Clark, K. Reed

doi:10.1128/jvi.79.2.955-965.2005

Cited by 87 publications

(75 citation statements)

References 115 publications

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“…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.…”

Section: Aav As Vaccine Carrier: a Paradox?mentioning

confidence: 99%

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

2008

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Section: Aav As Vaccine Carrier: a Paradox?mentioning

confidence: 99%

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

2008

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“…[4][5][6] However, recent reports have indicated the potential of rAAV for nongenetic disorders including infectious diseases and cancer. [7][8][9][10] Potential advantages of AAV as vector for genetic immunotherapy are sustained transgene expression and absence of vector genes encoding viral structural proteins thereby minimizing antigenic competition. Most of the current understanding of the potential for rAAV in gene therapy is based upon studies with AAV serotype 2-based vectors.…”

Section: Introductionmentioning

confidence: 99%

Enhanced transduction of mouse bone marrow-derived dendritic cells by repetitive infection with self-complementary adeno-associated virus 6 combined with immunostimulatory ligands

Ren

et al. 2005

Gene Ther

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The potential of adeno-associated virus (AAV)-based vectors in human gene therapy is being explored for several diseases. Although sustained transgene expression and low vector-associated cellular immunity are attractive features of recombinant (r) AAV, the wider application of rAAV vectors encapsidated in serotype 2 capsid is hampered by poor transduction efficiency in many target tissues. These include ex vivo-generated dendritic cells (DC), which have demonstrated promising immunotherapeutic activity. We report here that efficient transduction of mouse bone marrow-derived DC can be achieved with self-complementary (sc) rAAV encapsidated in serotype 6 capsid. Sequential exposure of DC precursor cultures to IL-4 and GM-CSF with sc rAAV6 encoding the human tumor antigen, carcinoembryonic antigen (CEA), for 7 days followed by activation with CpG oligodeoxynucleotides (ODN) and anti-mouse CD40 antibody resulted in highly efficient transduction of DC. DC surface markers as determined by flow cytometry analysis of sc rAAV6-transduced DC were comparable to nontransduced DC. Efficiency of vector transduction and transgene expression were confirmed by immunostaining and real-time PCR. Microarray analysis of RNA from CpG ODN and CD40 antibody stimulated sc AAV6-transduced DC revealed upregulation of transcription factors and cytokines involved in immune activation and downregulation of inhibitory factors, suggesting a possible role of transcriptional activation in the observed effect. The adoptive transfer into syngeneic mice of the ex vivo-transduced and activated DC resulted in the development of CEA-specific antibody and T-helper 1-associated immune responses. Immunized mice also developed antibody to AAV6 capsid protein, which did not crossreact with AAV2 capsid protein. These studies demonstrate the potential utility of sc rAAV serotype 6-based vectors in transduction of DC for genetic vaccination approaches.

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“…Efforts have therefore been focused on developing novel vaccine vectors that can provide a more persistent source of Ag. These vectors either integrate into the host genome, such as adeno-associated virus (7), or replicate persistently in vivo, such as mycobacteria (8). Yet little is known about the relative contributions of host factors in restricting long-term expression of plasmid DNA vaccine Ags in vivo.…”

mentioning

confidence: 99%

Plasmid DNA Vaccine-Elicited Cellular Immune Responses Limit In Vivo Vaccine Antigen Expression through Fas-Mediated Apoptosis

Greenland

Geiben

Ghosh

et al. 2007

The Journal of Immunology

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Particularly potent cellular or humoral immune responses are needed to confer protection in animal models against such pathogens as HIV/SIV, Mycobacterium tuberculosis, and malarial parasites. Persistent, high-level vaccine Ag expression may be required for eliciting such potent and durable immune responses. Although plasmid DNA immunogens are being explored as potential vaccines for protection against these pathogens, little is known about host factors that restrict long-term plasmid DNA vaccine Ag expression in vivo. We observed rapid damping of transgene expression from a plasmid DNA immunogen in wild-type, but not in T cell-deficient mice. This damping of Ag expression was temporally associated with the emergence of Ag-specific cellular immune responses. A requirement for Fas and the appearance of apoptotic nuclei at the site of vaccine inoculation suggest that T cells induce Fas-mediated apoptosis of plasmid DNA vaccine Ag-expressing cells. These studies demonstrate that high levels of in vivo Ag expression are associated with high-frequency cellular immune responses that in turn rapidly down-regulate vaccine Ag expression in vivo. These findings argue that it may not be possible to maintain persistent, high-level production of vaccine Ag in vivo to drive persistent immune responses as long as vaccine Ag production can be limited by host immune responses.

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Novel Adeno-Associated Virus Vector Vaccine Restricts Replication of Simian Immunodeficiency Virus in Macaques

Cited by 87 publications

References 115 publications

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

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

Enhanced transduction of mouse bone marrow-derived dendritic cells by repetitive infection with self-complementary adeno-associated virus 6 combined with immunostimulatory ligands

Plasmid DNA Vaccine-Elicited Cellular Immune Responses Limit In Vivo Vaccine Antigen Expression through Fas-Mediated Apoptosis

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