4-1BBL enhances CD8+ T cell responses induced by vectored vaccines in mice but fails to improve immunogenicity in rhesus macaques

• Published in: PloS one Vol. 9; no. 8; p. e105520
• Main 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
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 20.08.2014; Public Library of Science (PLoS)
• Subjects: 4-1BB Ligand - immunology; Animals; Antigens; Biology and Life Sciences; CD8 antigen; CD8-Positive T-Lymphocytes - immunology; Dendritic cells; Deoxyribonucleic acid; DNA; Female; Immune response; Immune system; Immunogenicity; Infectious diseases; Ligands; Lymphocytes; Lymphocytes T; Macaca mulatta; Malaria; Male; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Mycobacterium tuberculosis; Pathogens; Plasmodium falciparum; Primates; Proteins; Species Specificity; T cell receptors; Tuberculosis; Tumor necrosis factor; Tumors; Vaccines; Vaccines, Synthetic - immunology; Vector-borne diseases; Vectors; γ-Interferon; United Kingdom > UK; Ankara Turkey; Turkey
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0105520

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.