We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
4-1BBL Enhances CD8<sup>+</sup> T Cell Responses Induced by Vectored Vaccines in Mice but Fails to Improve Immunogenicity in Rhesus Macaques.
- Authors
Spencer, Alexandra J.; Furze, Julie; Honeycutt, Jared D.; Calvert, Alice; Saurya, Saroj; Colloca, Stefano; Wyllie, David H.; Gilbert, Sarah C.; Bregu, Migena; Cottingham, Matthew G.; Hill, Adrian V. S.
- Abstract
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.
- Subjects
CD8 antigen; T cells; RHESUS monkeys; TUMOR necrosis factors; ANTIGENS; IMMUNOLOGY
- Publication
PLoS ONE, 2014, Vol 9, Issue 8, p1
- ISSN
1932-6203
- Publication type
Article
- DOI
10.1371/journal.pone.0105520