4-1BBL enhances CD8+ T cell responses induced by vectored vaccines in mice but fails to improve immunogenicity in rhesus macaques
| Autor: | Alexandra J Spencer, Julie Furze, Jared D Honeycutt, Alice Calvert, Saroj Saurya, Stefano Colloca, David H Wyllie, Sarah C Gilbert, Migena Bregu, Matthew G Cottingham, Adrian V S Hill |
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| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
Male
Immunology lcsh:Medicine CD8-Positive T-Lymphocytes Microbiology Mice Species Specificity Virology Animals Plasmodium Malariae lcsh:Science Protozoans Vaccines Mice Inbred BALB C Vaccines Synthetic Recombinant Vaccines lcsh:R Organisms Malarial Parasites Biology and Life Sciences Viral Vaccines Vaccination and Immunization Macaca mulatta Parasitic Protozoans Mice Inbred C57BL 4-1BB Ligand lcsh:Q Female Research Article |
| Zdroj: | PLoS ONE PLoS ONE, Vol 9, Iss 8, p e105520 (2014) |
| DOI: | 10.1371/journal.pone.0105520 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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