Genetic Adjuvantation of Recombinant MVA with CD40L Potentiates CD8 T Cell Mediated Immunity

Lauterbach, Henning; Pätzold, Juliane; Kassub, Ronny; Bathke, Barbara; Brinkmann, Kay; Chaplin, Paul; Suter, Mark; Hochrein, Hubertus

doi:10.3389/fimmu.2013.00251

Cited by 12 publications

(32 citation statements)

References 82 publications

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“…Please note that for a better comparison data for rMVA are derived from the same experiment as shown in Fig. 6 from our previous study with rMVA ‐ CD 40L 35. Data were confirmed in two independent experiments.…”

Section: Resultssupporting

confidence: 63%

“…The CD8 T‐cell‐enhancing effect of rMVA‐CD40L was also dependent on the i.v. route 35. Although CD70 expression on splenic DCs after MVA immunization was lower than after pIC + anti‐CD40 injection, our data clearly indicate that MVA‐based vaccines can exploit this co‐stimulatory pathway when delivered i.v.…”

Section: Discussionmentioning

confidence: 64%

“…4 and ref. 35). Hence, the superior immunogenicity of rMVA‐CD40L cannot solely be explained by intensified CD27/CD70 co‐stimulation.…”

Section: Discussionmentioning

confidence: 99%

“…MVA‐BN ® was developed by Bavarian Nordic and is deposited at the European Collection of Cell Cultures (ECACC) (V00083008). The generation of the MVA recombinants MVA‐ovalbumin (OVA) and MVA‐OVA‐CD70 was carried out as described recently 34, 35. The pS promoter was cloned upstream of the open reading frame for chicken OVA.…”

Section: Methodsmentioning

confidence: 99%

“…The generation of the MVA recombinants MVA-ovalbumin (OVA) and MVA-OVA-CD70 was carried out as described recently. 34,35 The pS promoter was cloned upstream of the open reading frame for chicken OVA. The pHyb promoter was developed and described by Baur et al 34 and cloned upstream of the open reading for murine CD70.…”

Section: Generation Of Mva-bn Recombinantsmentioning

confidence: 99%

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CD70 encoded by modified vaccinia virus Ankara enhances CD8 T‐cell‐dependent protective immunity in MHC class II‐deficient mice

et al. 2018

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SummaryThe immunological outcome of infections and vaccinations is largely determined during the initial first days in which antigen‐presenting cells instruct T cells to expand and differentiate into effector and memory cells. Besides the essential stimulation of the T‐cell receptor complex a plethora of co‐stimulatory signals not only ensures a proper T‐cell activation but also instils phenotypic and functional characteristics in the T cells appropriate to fight off the invading pathogen. The tumour necrosis factor receptor/ligand pair CD27/CD70 gained a lot of attention because of its key role in regulating T‐cell activation, survival, differentiation and maintenance, especially in the course of viral infections and cancer. We sought to investigate the role of CD70 co‐stimulation for immune responses induced by the vaccine vector modified vaccinia virus Ankara–Bavarian Nordic® (MVA‐BN ®). Short‐term blockade of CD70 diminished systemic CD8 T‐cell effector and memory responses in mice. The dependence on CD70 became even more apparent in the lungs of MHC class II‐deficient mice. Importantly, genetically encoded CD70 in MVA‐BN ® not only increased CD8 T‐cell responses in wild‐type mice but also substituted for CD4 T‐cell help. MHC class II‐deficient mice that were immunized with recombinant MVA‐CD70 were fully protected against a lethal virus infection, whereas MVA‐BN ®‐immunized mice failed to control the virus. These data are in line with CD70 playing an important role for vaccine‐induced CD8 T‐cell responses and prove the potency of integrating co‐stimulatory molecules into the MVA‐BN ® backbone.

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Section: Resultssupporting

confidence: 63%

Section: Discussionmentioning

confidence: 64%

“…4 and ref. 35). Hence, the superior immunogenicity of rMVA‐CD40L cannot solely be explained by intensified CD27/CD70 co‐stimulation.…”

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Generation Of Mva-bn Recombinantsmentioning

confidence: 99%

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CD70 encoded by modified vaccinia virus Ankara enhances CD8 T‐cell‐dependent protective immunity in MHC class II‐deficient mice

et al. 2018

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Vaccine adjuvants for infectious disease in the clinic

Goetz,

Thotathil,

Zhao

et al. 2024

Bioengineering & Transla Med

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Adjuvants, materials added to vaccines to enhance the resulting immune response, are important components of vaccination that are many times overlooked. While vaccines always include an antigen to tell the body what to vaccinate to, of equal importance the adjuvant provides the how, a significant factor in producing a complete response. The adjuvant space has been slow to develop with the first use of an adjuvant in a licensed vaccine occurring in the 1930s, and remaining the only adjuvant in licensed vaccines for the next 80 years. However, with vaccination at the forefront of protection against new and complex pathogens, it is important to consider all components when designing an effective vaccine. Here we summarize the adjuvant space in licensed vaccines as well as the novel adjuvant space in clinical trials with a specific focus on the materials utilized and their resulting impact on the immune response. We discuss five major categories of adjuvant materials: aluminum salts, nanoparticles, viral vectors, TLR agonists, and emulsions. For each category, we delve into the current clinical trials space, the impact of these materials on vaccination, as well as some of the ways in which they could be improved. Adjuvants present an exciting opportunity to improve vaccine responses and stability, this review will help inform about the current progress of this space.Translational impact statementIn the aftermath of the COVID‐19 pandemic, vaccines for infectious diseases have come into the spotlight. While antigens have always been an important focus of vaccine design, the adjuvant is a significant tool for enhancing the immune response to the vaccine that has been largely underdeveloped. This article provides a broad review of the history of adjuvants and, the current vaccine adjuvant space, and the progress seen in adjuvants in clinical trials. There is specific emphasis on the material landscape for adjuvants and their resulting mechanism of action. Looking ahead, while the novel vaccine adjuvant space features exciting new technologies and materials, there is still a need for more to meet the protective needs of new and complex pathogens.

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Poxvirus-based active immunotherapy synergizes with CTLA-4 blockade to increase survival in a murine tumor model by improving the magnitude and quality of cytotoxic T cells

Foy

Mandl

Cruz

et al. 2016

Cancer Immunol Immunother

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The dramatic clinical benefit of immune checkpoint blockade for a fraction of cancer patients suggests the potential for further clinical benefit in a broader cancer patient population by combining immune checkpoint inhibitors with active immunotherapies. The anti-tumor efficacy of MVA-BN-HER2 poxvirus-based active immunotherapy alone or in combination with CTLA-4 checkpoint blockade was investigated in a therapeutic CT26-HER-2 lung metastasis mouse model. MVA-BN-HER2 immunotherapy significantly improved the median overall survival compared to untreated controls or CTLA-4 blockade alone (p < 0.001). Robust synergistic efficacy was achieved with the combination therapy (p < 0.01). Improved survival following MVA-BN-HER2 administration was accompanied by increased tumor infiltration by HER-2-specific cytotoxic T lymphocytes (CTL). These tumor-specific CTL had characteristics similar to antiviral CTL, including strong expression of activation markers and co-expression of IFNγ and TNFα. Combination with CTLA-4 blockade significantly increased the magnitude of HER-2-specific T cell responses, with a higher proportion co-expressing TNFα and/or IL-2 with IFNγ. Furthermore, in mice treated with MVA-BN-HER2 (alone or in combination with CTLA-4 blockade), the inducible T cell co-stimulator (ICOS) protein was expressed predominantly on CD4 and CD8 effector T cells but not on regulatory T cells (Treg). In contrast, mice left untreated or treated solely with CTLA-4 blockade harbored elevated ICOS+ Treg, a phenotype associated with highly suppressive activity. In conclusion, poxvirus-based active immunotherapy induced robust tumor infiltration by highly efficient effector T cells. Combination with CTLA-4 immune checkpoint blockade amplified this response resulting in synergistically improved efficacy. These hypothesis-generating data may help elucidate evidence of enhanced clinical benefit from combining CTLA-4 blockade with poxvirus-based active immunotherapy.Electronic supplementary materialThe online version of this article (doi:10.1007/s00262-016-1816-7) contains supplementary material, which is available to authorized users.

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Genetic Adjuvantation of Recombinant MVA with CD40L Potentiates CD8 T Cell Mediated Immunity

Cited by 12 publications

References 82 publications

CD70 encoded by modified vaccinia virus Ankara enhances CD8 T‐cell‐dependent protective immunity in MHC class II‐deficient mice

CD70 encoded by modified vaccinia virus Ankara enhances CD8 T‐cell‐dependent protective immunity in MHC class II‐deficient mice

Vaccine adjuvants for infectious disease in the clinic

Poxvirus-based active immunotherapy synergizes with CTLA-4 blockade to increase survival in a murine tumor model by improving the magnitude and quality of cytotoxic T cells

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