Extracellular vesicle-inspired liposomes boost immune response against pathogen antigens

Area of Science:

• Vaccinology
• Immunology
• Nanotechnology

Background:

• Developing effective vaccines is a global health priority, requiring efficient adjuvant systems to enhance immunogenicity.
• Natural extracellular vesicles show promise as adjuvant platforms but face challenges in reproducibility and safety.

Purpose of the Study:

• To develop a synthetic extracellular vesicle mimetic (EVM) platform using the CD9 large extracellular loop (LEL) to enhance antigen immunogenicity.
• To evaluate the efficacy of CD9-LEL functionalized liposomes in boosting immune responses against pathogen antigens.

Main Methods:

• Liposomes were functionalized with recombinant CD9-LEL and pathogen antigens (KMP-11 from Leishmania, SARS-CoV-2 Spike protein).
• Mice were immunized with nanovesicles, and antigen-specific IgG responses were measured by ELISA.
• Vesicle uptake by immune cells was assessed via flow cytometry.

Main Results:

• Co-presentation of CD9-LEL with antigens significantly enhanced antigen-specific IgG titers compared to antigens alone.
• CD9-LEL functionalized nanovesicles induced strong IgG responses against KMP-11, which alone failed to elicit detectable antibodies.
• CD9-LEL promoted nanovesicle uptake by macrophages, suggesting improved antigen presentation.
• Classical adjuvants (alum, CpG ODNs) combined with EVMs modulated immune profiles towards Th2 or Th1 bias, respectively.

Conclusions:

• CD9-LEL-decorated EVMs represent a promising, scalable vaccine strategy.
• This platform effectively boosts antigen immunogenicity and can direct immune polarization.
• EVMs offer a versatile tool for developing vaccines against challenging or emergent infectious diseases.