Recombinant alphaviruses as vectors for anti-tumour and anti-microbial immunotherapy

Riezebos‐Brilman, Annelies; Mare, Arjan de; Bungener, Laura; Huckriede, Anke; Wilschut, Jan; Daemen, Toos

doi:10.1016/j.jcv.2005.12.001

Cited by 32 publications

(29 citation statements)

References 63 publications

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“…We are developing immunotherapeutic strategies against cervical cancer or premalignant cervical disease using replication-defective recombinant viral vector systems [1][2][3][4][5] or protein-based immunization approaches. 6 Cervical cancer is the second most common type of cancer among women worldwide, and the first malignancy recognized by the World Health Organization to be 100% attributable to infection with a virus, specifically a high-risk type human papillomavirus (HPV).…”

Section: Introductionmentioning

confidence: 99%

A comparative study on the immunotherapeutic efficacy of recombinant Semliki Forest virus and adenovirus vector systems in a murine model for cervical cancer

et al. 2007

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Currently, various therapeutic strategies are being explored as a potential means to immunize against metastatic malignant cells or even primary tumours. Using recombinant viral vectors systems or protein-based immunization approaches, we are developing immunotherapeutic strategies against cervical cancer or premalignant cervical disease, as induced by high-risk type human papillomaviruses (HPVs). We previously demonstrated that immunization of mice with recombinant replication-defective Semliki Forest virus (rSFV) encoding a fusion protein of HPV16 E6 and -E7 (SFV-eE6,7) induces strong cytotoxic T-lymphocyte (CTL) activity and eradication of established HPV-transformed tumours. In this study, we compared the antitumour efficacy of SFV-eE6,7 with that of a recombinant adenovirus (rAd) type 5 vector, expressing the same antigen construct (AdeE6,7). Prime-boosting with SFV-eE6,7 resulted in higher precursor CTL frequencies and CTL activity compared to prime-boosting with Ad-eE6,7 and also in murine tumour treatment experiments SFV-eE6,7 was more effective than Ad-eE6,7. To elicit a therapeutic effect with Ad-eE6,7, 100/1000-fold higher doses were needed compared to SFV-eE6,7. In vivo T-cell depletion experiments demonstrated that these differences could not be explained by the induction of a different type of effector cells, since CD8 + T cells were the main effector cells involved in the protection against tumour growth in both rSFV-and rAd-immunized mice. Also comparable amounts of in vivo transgene expression were found upon immunization with rSFV and rAd encoding the reportor gene luciferase. However, antivector responses induced by a single injection with rAd resulted in a more than 3-log decrease in luciferase expression after a second injection of rAd. With rSFV, transgene expression was inhibited by only one to two orders of magnitude in preinjected mice. As an antigen-specific booster immunization strongly increases the level of the CTL response and is essential for efficient induction of immunological memory, it is likely that (part of) the difference in efficacy between rSFV and rAd type 5 can be ascribed to a diminished efficacy of the booster immunization in the case of rAd due to anti-vector antibody responses.

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Section: Introductionmentioning

confidence: 99%

A comparative study on the immunotherapeutic efficacy of recombinant Semliki Forest virus and adenovirus vector systems in a murine model for cervical cancer

et al. 2007

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“…This response is capable of alerting the entire infected animal to the presence of the invading pathogen and largely determines the outcome of infection. In addition, considering that several alphavirus family members are in development as vaccine vectors (9,16,43,50,52,54), insights gained from this model may influence the design of future preventative or therapeutic vaccines.…”

Section: Discussionmentioning

confidence: 99%

Acute Infection with Venezuelan Equine Encephalitis Virus Replicon Particles Catalyzes a Systemic Antiviral State and Protects from Lethal Virus Challenge

Konopka

Thompson

Whitmore

et al. 2009

J Virol

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The host innate immune response provides a critical first line of defense against invading pathogens, inducing an antiviral state to impede the spread of infection. While numerous studies have documented antiviral responses within actively infected tissues, few have described the earliest innate response induced systemically by infection. Here, utilizing Venezuelan equine encephalitis virus (VEE) replicon particles (VRP) to limit infection to the initially infected cells in vivo, a rapid activation of the antiviral response was demonstrated not only within the murine draining lymph node, where replication was confined, but also within distal tissues. In the liver and brain, expression of interferon-stimulated genes was detected by 1 to 3 h following VRP footpad inoculation, reaching peak expression of >100-fold over that in mock-infected animals. Moreover, mice receiving a VRP footpad inoculation 6, 12, or 24 h prior to an otherwise lethal VEE footpad challenge were completely protected from death, including a drastic reduction in challenge virus titers. VRP pretreatment also provided protection from intranasal VEE challenge and extended the average survival time following intracranial challenge. Signaling through the interferon receptor was necessary for antiviral gene induction and protection from VEE challenge. However, VRP pretreatment failed to protect mice from a heterologous, lethal challenge with vesicular stomatitis virus, yet conferred protection following challenge with influenza virus. Collectively, these results document a rapid modulation of the host innate response within hours of infection, capable of rapidly alerting the entire animal to pathogen invasion and leading to protection from viral disease.

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“…Immunogen delivery systems based upon the alphaviruses have proven to be efficient inducers of both neutralizing antibody responses and cell mediated immune responses to multiple antigens, including HIV antigens, expressed from the viral genome (reviewed in [5][6][7][8][9][10][11]). Alphavirus vectors derived from Sindbis virus, Semliki forest virus (SFV), and Venezuelan equine encephalitis virus (VEE) have generated the most promising results to date and all three of these systems are actively under investigation as candidate HIV vaccine vectors in several laboratories.…”

Section: Introductionmentioning

confidence: 99%

Alphavirus replicon particles acting as adjuvants promote CD8+ T cell responses to co-delivered antigen

Thompson

Whitmore²,

Staats

et al. 2008

Vaccine

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Alphavirus replicon particles induce strong antibody and CD8 + T cell responses to expressed antigens in numerous experimental systems. We have recently demonstrated that Venezuelan equine encephalitis virus replicon particles (VRP) possess adjuvant activity for systemic and mucosal antibody responses. In this report, we demonstrate that VRP induced an increased and balanced serum IgG subtype response to co-delivered antigen, with simultaneous induction of antigen-specific IgG1 and IgG2a antibodies, and increased both systemic and mucosal antigenspecific CD8 + T cell responses, as measured by an IFN-γ ELISPOT assay. Additionally, VRP further increased antigen-specific T cell immunity in an additive fashion following co-delivery with the TLR ligand, CpG DNA. VRP infection led to recruitment of CD8 + T cells into the mucosal compartment, possibly utilizing the mucosal homing receptor, as this integrin was upregulated on CD8 + T cells in the draining lymph node of VRP-infected animals, where VRPinfected dendritic cells reside. This newly recognized ability of VRP to mediate increased T cell response towards co-delivered antigen provides the potential to both define the molecular basis of alphavirus-induced immunity, and improve alphavirus-based vaccines.

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Recombinant alphaviruses as vectors for anti-tumour and anti-microbial immunotherapy

Cited by 32 publications

References 63 publications

A comparative study on the immunotherapeutic efficacy of recombinant Semliki Forest virus and adenovirus vector systems in a murine model for cervical cancer

A comparative study on the immunotherapeutic efficacy of recombinant Semliki Forest virus and adenovirus vector systems in a murine model for cervical cancer

Acute Infection with Venezuelan Equine Encephalitis Virus Replicon Particles Catalyzes a Systemic Antiviral State and Protects from Lethal Virus Challenge

Alphavirus replicon particles acting as adjuvants promote CD8+ T cell responses to co-delivered antigen

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