Journal Article

Intracellular signaling pathway in dendritic cells and antigen transport pathway in vivo mediated by an OVA@DDAB/PLGA nano-vaccine

Cai, Weibo, Wang, Yanping, Xu, Xiaojie, Kang, Lei, Wang, Lianyan, Lu, Yu, Zhang, Jing, Chen, Zhao, Ma, Wenyan, Sutherlin, Logan, Huo, Nan, Han, Shulan, Jiang, Dawei, Engle, Jonathan W.

2021

Overview

Background Poly(D, L-lactic-co-glycolic acid) (PLGA) nanoparticles have potential applications as a vaccine adjuvant and delivery system due to its unique advantages as biodegradability and biocompatibility. Experimental We fabricated cationic solid lipid nanoparticles using PLGA and dimethyl-dioctadecyl-ammonium bromide (DDAB), followed by loading of model antigen OVA (antigen ovalbumin, OVA 257-264 ) to form an OVA@DDAB/PLGA nano-vaccine. And we investigated the intracellular signaling pathway in dendritic cells in vitro and antigen transport pathway and immune response in vivo mediated by an OVA@DDAB/PLGA nano-vaccine. Results In vitro experiments revealed that the antigen uptake of BMDCs after nanovaccine incubation was two times higher than pure OVA or OVA@Al at 12 h. The BMDCs were well activated by p38 MAPK signaling pathway. Furthermore, the nano-vaccine induced antigen escape from lysosome into cytoplasm with 10 times increased cross-presentation activity than those of OVA or OVA@Al. Regarding the transport of antigen into draining lymph nodes (LNs), the nano-vaccine could rapidly transfer antigen to LNs by passive lymphatic drainage and active DC transport. The antigen + cells in inguinal/popliteal LNs for the nano-vaccine were increased over two folds comparing to OVA@Al and OVA at 12 h. Moreover, the antigen of nano-vaccine stayed in LNs for over 7 days, germinal center formation over two folds higher than those of OVA@Al and OVA. After immunization, the nano-vaccine induced a much higher ratio of IgG2c/IgG1 than OVA@Al. It also effectively activated CD4 + T, CD8 + T and B cells for immune memory with a strong cellular response. Conclusion These results indicated that DDAB/PLGA NP was a potent platform to improve vaccine immunogenicity by p38 signaling pathway in BMDCs, enhancing transport of antigens to LNs, and higher immunity response. Graphical Abstract

• Publisher: BioMed Central,BioMed Central Ltd,Springer Nature B.V,BMC
• Subject: Adjuvants, Vaccine - chemistry / Ammonium / Ammonium bromides / Animals / Antigen presentation / Antigen Presentation - drug effects / Antigen Presentation - immunology / Antigen transport / Antigens / Biocompatibility / Biodegradability / Biodegradable materials / Biodegradation / Biological transport / Biotechnology / Bone marrow / CD4 antigen / CD8 antigen / Cellular signal transduction / Chemistry / Chemistry and Materials Science / Cytoplasm / DCs activation / DDAB/PLGA / Dendritic cells / Dendritic Cells - drug effects / Dendritic Cells - immunology / Dendritic Cells - metabolism / Design and construction / Female / Flow cytometry / Glycolic acid / Health aspects / Immune response / Immune system / Immunization / Immunogenicity / Immunoglobulin G / Immunological memory / Incubation / Intracellular / Intracellular signalling / Laboratories / Lipids / Localization / Lymph nodes / Lymphatic drainage / Lymphatic system / Lymphocytes B / MAP kinase / Memory cells / Mice / Mice, Inbred BALB C / Microscopy / Molecular Medicine / Nano-vaccine / Nanoparticles / Nanostructures - chemistry / Nanotechnology / Ovalbumin / Ovalbumin - chemistry / p38 signaling pathway / Pharmaceutical research / Polylactic Acid-Polyglycolic Acid Copolymer - chemistry / Polylactide-co-glycolide / Quaternary Ammonium Compounds - chemistry / Signal transduction / Signal Transduction - drug effects / Signal Transduction - immunology / Signaling / Vaccines / Vaccines - chemistry / Vaccines - immunology / Vaccines - pharmacokinetics / Vaccines - pharmacology