- Poster presentation
- Open Access
Evaluation of Latent Membrane Protein 1 as a novel vaccine adjuvant
© Termini et al; licensee BioMed Central Ltd. 2012
- Published: 13 September 2012
- Dendritic Cell
- Latent Membrane Protein
- Latent Membrane
- Dendritic Cell Activation
- High Migration Rate
The EBV protein Latent Membrane Protein-1 (LMP1) is known to constitutively activate B cells. The LMP1 signaling pathway mimics that of CD40, a molecule involved in dendritic cell activation and maturation. Therefore we decided to evaluate the use of LMP1 as a vaccine adjuvant for both dendritic cell therapeutic vaccines and DNA-based vaccines for HIV.
To determine activity, LMP1 was analyzed using a luciferase report assay for NF-kB and IFN-β. To establish if LMP1 could activate human monocyte-derived dendritic cells (DC), LMP1 transfected DC were analyzed for activation/maturation markers and cytokines. DC migration was determined using a transwell-migration assay. LMP1 was also evaluated in a DNA vaccination/flu challenge mouse model. To determine the benefits of incorporating LMP1 into a DC therapeutic vaccine, LMP1 was tested in a tumor DC therapy mouse model.
LMP1 activated high levels of NF-kB and IFN-β when evaluated using a luciferase reported assay. On primary DC, LMP1 induced DC activation, maturation, and proinflammatory cytokines. LMP1 induced 2-fold higher migration rates compared to the mature-DC control. As a DNA vaccine for flu, the addition of LMP1 provided superior TNF-α and IFN-γ responses. LMP1 vaccinated animals cleared virus more quickly and in the high-dose lethal flu challenge, LMP1 afforded more protection. Finally, LMP1 enhanced a DC therapeutic vaccine in a tumor model. Tumor progression was slowed compared to antigen-loaded DC alone and positive control mimic-matured DC.
These data suggest that LMP1 is an effective vaccine adjuvant. LMP1 can enhance the activation, maturation, and functional activity of DC. LMP1 can inducing a strong CD8+ T cell response in several mouse models, most notably the flu viral challenge model. LMP1 increased antigen-specific CD8+ T cells, improved survival to lethal flu high-dose challenge, and slowed tumor progression. These results suggest that LMP1 is a promising adjuvant for prophylactic vaccines for HIV.
This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.