Expression of tak1 and tram induces synergistic pro-inflammatory signalling and adjuvants DNA vaccines

Larsen, Karen Colbjørn; Spencer, Alexandra J.; Goodman, Anna; Gilchrist, Ashley; Furze, Julie; Rollier, Christine S.; Kiss-Tóth, Endre; Gilbert, Sarah C.; Bregu, Migena; Soilleux, Elizabeth; Hill, Adrian V. S.; Wyllie, David

doi:10.1016/j.vaccine.2009.07.025

Cited by 20 publications

(27 citation statements)

References 57 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…For DNA plasmid vaccines, tandem human cytomegalovirus major immediate early promoters (phCMV) were utilised, each with its own polyadenylation signal (polyA) [37]. Yet when such dual-phCMV cassettes (which are stably propagable in E. coli ) were inserted into adenoviral vectors, genetic instability resulting from homologous recombination between the identical promoters was observed (Figure S1), as has also been subsequently reported by others [38].…”

Section: Resultsmentioning

confidence: 62%

“…We used a model antigen TIP comprising of a epitope string of CD4 + and CD8 + T cell epitopes [37] in DNA and modified vaccinia virus Ankara (MVA) vectors; and TIP-EGFP, the same antigen fused to enhanced green fluorescent protein (EGFP), in E1/E3-deleted human adenovirus 5 (HAdV5) vectors (Figure 1). …”

Section: Resultsmentioning

confidence: 99%

“…Bicistronic DNA plasmid vaccines utilizing tandem human cytomegalovirus immediate early promoters (phCMV) to express the model antigen TIP [37] and 4-1BBL were constructed as previously described [37].…”

Section: Methodsmentioning

confidence: 99%

“…The synthetic epitope string TIP [37], contains the H-2K d restricted P.berghei circumsporozoite protein CD8 + T cell epitope Pb9 SYIPSAEKI (aa 252–260) [42], H-2d Mycobacterium tuberculosis antigen 85A CD4 + T cell epitope P15 TFLTSELPGWLQANRHVKPT (aa 142–161) [56], [57], H-2K b CD8 + T cell epitope from SIV-gag AL11 AAVKNWMTQTL [58] (all purchased from Proimmune). To enable detection of antibodies from HAdV5 vectors, the TIP antigen was fused to EGFP, providing an additional H-2K d restricted CD8 + T cell epitope HYLSTQSAL [59] (Proimmune).…”

Section: Methodsmentioning

confidence: 99%

See 3 more Smart Citations

4-1BBL Enhances CD8+ T Cell Responses Induced by Vectored Vaccines in Mice but Fails to Improve Immunogenicity in Rhesus Macaques

et al. 2014

Self Cite

View full text Add to dashboard Cite

T cells play a central role in the immune response to many of the world’s major infectious diseases. In this study we investigated the tumour necrosis factor receptor superfamily costimulatory molecule, 4-1BBL (CD137L, TNFSF9), for its ability to increase T cell immunogenicity induced by a variety of recombinant vectored vaccines. To efficiently test this hypothesis, we assessed a number of promoters and developed a stable bi-cistronic vector expressing both the antigen and adjuvant. Co-expression of 4-1BBL, together with our model antigen TIP, was shown to increase the frequency of murine antigen-specific IFN-γ secreting CD8+ T cells in three vector platforms examined. Enhancement of the response was not limited by co-expression with the antigen, as an increase in CD8+ immunogenicity was also observed by co-administration of two vectors each expressing only the antigen or adjuvant. However, when this regimen was tested in non-human primates using a clinical malaria vaccine candidate, no adjuvant effect of 4-1BBL was observed limiting its potential use as a single adjuvant for translation into a clinical vaccine.

show abstract

Section: Resultsmentioning

confidence: 62%

Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

See 2 more Smart Citations

4-1BBL Enhances CD8+ T Cell Responses Induced by Vectored Vaccines in Mice but Fails to Improve Immunogenicity in Rhesus Macaques

et al. 2014

Self Cite

View full text Add to dashboard Cite

show abstract

“…Within the last few years, four plasmid DNA products TAK1, were shown to significantly enhance antigen-specific T cell responses in mice following DNA vaccination. 89 Adjuvants can act through a variety of mechanisms. For example, since DNA plasmids injected into the skin or muscle are taken up by cells inefficiently, adjuvants that enhance the uptake of the plasmid into the cell are being evaluated.…”

Section: Antigen Deliverymentioning

confidence: 99%

Molecular vaccines for malaria

Bruder¹,

Angov²,

Limbach³

et al. 2010

Human Vaccines

View full text Add to dashboard Cite

The impact of immuno-aging on SARS-CoV-2 vaccine development

et al. 2021

View full text Add to dashboard Cite

The SARS-CoV-2 pandemic has almost 56 million confirmed cases resulting in over 1.3 million deaths as of November 2020. This infection has proved more deadly to older adults (those >65 years of age) and those with immunocompromising conditions. The worldwide population aged 65 years and older is increasing, and the total number of aged individuals will outnumber those younger than 65 years by the year 2050. Aging is associated with a decline in immune function and chronic activation of inflammation that contributes to enhanced viral susceptibility and reduced responses to vaccination. Here we briefly review the pathogenicity of the virus, epidemiology and clinical response, and the underlying mechanisms of human aging in improving vaccination. We review current methods to improve vaccination in the older adults using novel vaccine platforms and adjuvant systems. We conclude by summarizing the existing clinical trials for a SARS-CoV-2 vaccine and discussing how to address the unique challenges for vaccine development presented with an aging immune system.

show abstract

Expression of tak1 and tram induces synergistic pro-inflammatory signalling and adjuvants DNA vaccines

Cited by 20 publications

References 57 publications

4-1BBL Enhances CD8+ T Cell Responses Induced by Vectored Vaccines in Mice but Fails to Improve Immunogenicity in Rhesus Macaques

4-1BBL Enhances CD8+ T Cell Responses Induced by Vectored Vaccines in Mice but Fails to Improve Immunogenicity in Rhesus Macaques

Molecular vaccines for malaria

The impact of immuno-aging on SARS-CoV-2 vaccine development

Contact Info

Product

Resources

About