Rational design of adjuvants for subunit vaccines: the format of cationic adjuvants affects the induction of antigen-specific antibody responses

Giulia Anderluzzi, Signe Tandrup Schmidt, Robert Cunliffe, Stuart Woods, Craig W. Roberts, Daniele Veggi, Ilaria Ferlenghi, Derek T. O'Hagan, Barbara C. Baudner, Yvonne Perrie

Research output: Contribution to journalArticlepeer-review

2 Citations (Scopus)

Abstract

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, liposomes, 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-γ 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 (~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.

Original languageEnglish
Pages (from-to)933-944
Number of pages12
JournalJournal of Controlled Release
Volume330
Early online date2 Nov 2020
DOIs
Publication statusPublished - 10 Feb 2021

Keywords

  • antibody response
  • antigen processing
  • cationic delivery systems
  • pharmacokinetics
  • protein subunit
  • vaccine adjuvant

Cite this