期刊
JOURNAL OF CONTROLLED RELEASE
卷 330, 期 -, 页码 933-944出版社
ELSEVIER
DOI: 10.1016/j.jconrel.2020.10.066
关键词
Cationic delivery systems; Protein subunit; Vaccine adjuvant; Antigen processing; Pharmacokinetics; Antibody response
资金
- European Commission Project Leveraging Pharmaceutical Sciences and Structural Biology Training to Develop 21st 518 Century Vaccines (H2020-MSCA-ITN-2015 grant) [675370]
- Independent Research Fund Denmark [702600027B]
- Marie Curie Actions (MSCA) [675370] Funding Source: Marie Curie Actions (MSCA)
Through the study of four different cationic delivery systems, it was found that they have different characteristics and effects. In vitro, particulate systems were better at promoting cell uptake and antigen processing, while emulsions were less effective. However, emulsions induced the highest antibody responses in vivo compared to other systems tested.
A range of cationic delivery systems have been investigated as vaccine adjuvants, though few direct comparisons exist. To investigate the impact of the delivery platform, we prepared four cationic systems (emulsions, lipo-somes, polymeric nanoparticles and solid lipid nanoparticles) all containing equal concentrations of the cationic lipid dimethyldioctadecylammonium bromide in combination with the Neisseria adhesin A variant 3 subunit antigen. The formulations were physicochemically characterized and their ability to associate with cells and promote antigen processing (based on degradation of DQ-OVA, a substrate for proteases which upon hydrolysis is fluorescent) was compared in vitro and their vaccine efficacy (antigen-specific antibody responses and IFN-gamma production) and biodistribution (antigen and adjuvant) were evaluated in vivo. Due to their cationic nature, all delivery systems gave high antigen loading (> 85%) with liposomes, lipid nanoparticles and emulsions being <200 nm, whilst polymeric nanoparticles were larger (similar to 350 nm). In vitro, the particulate systems tended to promote cell uptake and antigen processing, whilst emulsions were less effective. Similarly, whilst the particulate delivery systems induced a depot (of both delivery system and antigen) at the injection site, the cationic emulsions did not. However, out of the systems tested the cationic emulsions induced the highest antibody responses. These results demonstrate that while cationic lipids can have strong adjuvant activity, their formulation platform influences their immunogenicity.
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