Journal
JOURNAL OF CONTROLLED RELEASE
Volume 330, Issue -, Pages 866-877Publisher
ELSEVIER
DOI: 10.1016/j.jconrel.2020.10.060
Keywords
-
Funding
- Georgia Tech Foundation
- Georgia Clinical and Translational Science Alliance
- NIH [U01-AI124270-02]
- Georgia Tech President's Undergraduate Research Award
- Georgia Tech Petit Scholars program
- Cell Manufacturing Technologies (CMaT) Research Experiences for Undergraduates program
- Robert A. Milton Chaired Professorship
Ask authors/readers for more resources
The study suggests that simultaneous engagement of small molecule adjuvant R848 and RNA adjuvant PUUC can induce robust cellular immune responses in both mice and human cells, enhancing the effectiveness of flu vaccines.
Although the existing flu vaccines elicit strong antigen-specific antibody responses, they fail to provide effective, long term protection - partly due to the absence of robust cellular memory immunity. We hypothesized that co-administration of combination adjuvants, mirroring the flu-virus related innate signaling pathways, could elicit strong cellular immunity. Here, we show that the small molecule adjuvant R848 and the RNA adjuvant PUUC, targeting endosomal TLR7s and cytoplasmic RLRs respectively, when delivered together in polymer nanoparticles (NP), elicits a broadened immune responses in mouse bone marrow-derived dendritic cells (mBMDCs) and a synergistic response in both mouse and human plasmacytoid dendritic cells (pDCs). In mBMDCs, NP-R848-PUUC induced both NF-kappa B and interferon signaling. Interferon responses to co-delivered R848 and PUUC were additive in human peripheral blood mononuclear cells (PBMCs) and synergistic in human FLT3-differentiated mBMDCs and CAL-1 pDCs. Vaccination with NPs loaded with H1N1 Flu antigen, R848, and PUUC increased percentage of CD8+ T-cells in the lungs, percentage of antigen-specific CD4-T-cells in the spleen, and enhanced overall cytokine-secreting T cell percentages upon antigen restimulation. Also, in the spleen, T lymphopenia, especially after in vitro restimulation with dual adjuvants, was observed, indicating highly antigen-reactive T cells. Our results demonstrate that simultaneous engagement of TLR7 and RIG-I pathways using particulate carriers is a potential approach to improve cellular immunity in flu vaccination.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available