The Poxvirus Vectors MVA and NYVAC as Gene Delivery Systems for Vaccination Against Infectious Diseases and Cancer

Gómez, Carmen Elena; Nájera, José Luis; Krupa, Magdalena; Esteban, Mariano

doi:10.2174/156652308784049363

Cited by 127 publications

(91 citation statements)

References 209 publications

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“…On the basis of promising preclinical results, clinical trials for cancer immunotherapy have been and currently are being conducted using recombinant MVA that is injected subcutaneously (s.c.; ref. 1).…”

Section: Introductionmentioning

confidence: 99%

Intravenous Injection of MVA Virus Targets CD8+ Lymphocytes to Tumors to Control Tumor Growth upon Combinatorial Treatment with a TLR9 Agonist

Fend

Gatard-Scheikl

Kintz

et al. 2014

Cancer Immunology Research

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Effector T-cell access to tumor tissue is a limiting step for clinical efficacy of antigen-specific T cell-based immunotherapies. Ectopic mouse tumor models, in which a subcutaneously (s.c.) implanted tumor is treated with s.c. or intramuscular therapeutic immunization, may not be optimal for targeting effector T cells to an organ-borne tumor. We used an orthotopic renal carcinoma model to evaluate the impact of injection routes on therapeutic efficacy of a Modified Vaccinia virus Ankara viral vector expressing the human mucin 1 tumor-associated xeno-antigen (MVA-MUC1). We show that intravenous (i.v.) administration of MVA-MUC1 displayed enhanced efficacy when compared with s.c. injection. Therapeutic efficacy of MVA-MUC1 was further enhanced by i.v. injection of a TLR9 agonist. In all cases, infiltration of tumor-bearing kidney by CD8

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Section: Introductionmentioning

confidence: 99%

Intravenous Injection of MVA Virus Targets CD8+ Lymphocytes to Tumors to Control Tumor Growth upon Combinatorial Treatment with a TLR9 Agonist

Fend

Gatard-Scheikl

Kintz

et al. 2014

Cancer Immunology Research

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“…VACV represents a useful tool for understanding how immunity to viruses is regulated, as well as what factors might determine how to create strong vaccines. Smallpox, long considered to be the most deadly and persistent human pathogenic disease, was eradicated by 1977 through vaccination with live VACV (1), and attenuated vaccinia virus vectors have since been developed as vaccine vehicles for multiple infectious diseases (2)(3)(4). In addition to this, VACV also has many attributes that make it an attractive vector for tumor-directed gene therapy and oncolytic virotherapy (5,6).…”

Section: Introductionmentioning

confidence: 99%

Preferential Replication of Vaccinia Virus in the Ovaries is Independent of Immune Regulation Through IL-10 and TGF-β

Zhao

Adams²,

Croft³

2011

Viral Immunology

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Vaccinia virus (VACV) exhibits a strong tropism for ovarian tissue and can cause ovary pathology and sterility. Why VACV preferentially accumulates in this organ is not known. Here we show that multiple immune cell populations infiltrated the ovaries following VACV infection, including virus-specific CD8 T cells making both IFN-c and TNF. This was also accompanied by the induction of interleukin (IL)-10 and TGF-b, suggesting that VACV may exploit the ovarian environment for immune evasion via induction of these suppressive cytokines. To test this we used several strategies, including neutralizing these cytokines, and exogenous targeting of the T-cell response, to determine if this inhibited virus replication in the ovaries. We found that the VACV-specific CD8 T-cell immunity and the clearance of virus were not enhanced in the ovaries of infected mice in which IL-10 receptor (IL-10R) was blocked with antagonist antibody. VACV replication was also only moderately affected in the ovaries of infected IL-10 knockout mice. Similarly, blockade of TGF-b with antagonist antibody demonstrated no effect on CD8 T-cell immunity or VACV replication. Lastly, an agonist antibody targeting the tumor necrosis factor receptor superfamily member OX40 (TNFRSF4) enhanced the number of VACV-specific CD8 T cells producing IFN-c in lymphoid tissue, but had no effect on CD8 T-cell infiltration of the ovaries or on the viral load. Collectively, the results indicate that preferential replication of VACV in the ovaries may not be dependent on immune suppressive mechanisms in this tissue.

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“…Considerable research has been conducted using DNA vaccines (individually or with proteins and/or cytokines), 25 Ad-based vaccines (replication competent or replication deficient), vaccinia virus-based vaccines (MVA, canarypox virus (ALVAC) and attenuated vaccinia (NYVAC)), [31][32][33][34][35][36] and other vectors 37,38 alone or in combination to induce antigen-specific anti-retroviral responses in animals. Administration of a recombinant viral vector can induce strong humoral and cellmediated immune responses against both transgene and viral vectors.…”

Section: Discussionmentioning

confidence: 99%

Partial protection against SIV challenge by vaccination of adenovirus and MVA vectors in rhesus monkeys

Kondo

Yoshida

et al. 2009

Gene Ther

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This study explores the effect of priming rhesus monkeys with an Ad5/35 vector expressing simian immunodeficiency virus (SIV) gag and gp120, and then boosting the animals with an modified vaccinia virus Ankara (MVA) vector encoding the same antigens after a 2-month interval. The animals were intravenously challenged with 100 TCID50 of highly pathogenic SIVmac239 virus 2 months after the booster vaccination. The priming vaccination induced robust SIV-specific cell-mediated and humoral immune responses, and boosting further enhanced the cellular immunity. Vaccination reduced peak and long-term viral loads by 1-2 logs for a period of 46 months, as reflected by a reduction in both the SIV RNA and DNA levels. Of considerable interest, the immunized monkeys did not suffer from loss of CD4 T cells, particularly central memory CD4 T cells. These results demonstrate that prophylactic vaccination with Ad5/35 followed by MVA reduces viral replication and prevents CD4 T-cell loss, and that these effects may decrease the likelihood of disease progression.

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The Poxvirus Vectors MVA and NYVAC as Gene Delivery Systems for Vaccination Against Infectious Diseases and Cancer

Cited by 127 publications

References 209 publications

Intravenous Injection of MVA Virus Targets CD8+ Lymphocytes to Tumors to Control Tumor Growth upon Combinatorial Treatment with a TLR9 Agonist

Intravenous Injection of MVA Virus Targets CD8+ Lymphocytes to Tumors to Control Tumor Growth upon Combinatorial Treatment with a TLR9 Agonist

Preferential Replication of Vaccinia Virus in the Ovaries is Independent of Immune Regulation Through IL-10 and TGF-β

Partial protection against SIV challenge by vaccination of adenovirus and MVA vectors in rhesus monkeys

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