Antigen Uptake After Intradermal Microinjection Depends on Antigen Nature and Formulation, but Not on Injection Depth

Area of Science:

• Dermatology
• Immunology
• Vaccinology

Background:

• The skin is a promising site for allergy vaccination due to abundant dendritic cells (DCs) and accessibility.
• Different DC subsets reside at varying depths within the skin, potentially influencing immune responses.

Purpose of the Study:

• To investigate the impact of intradermal injection depth on antigen uptake by skin dendritic cells.
• To compare the uptake of different model allergens (ovalbumin and Bet v 1) by skin DCs.
• To evaluate the effect of liposome formulations on allergen uptake by skin DCs.

Main Methods:

• Utilized a hollow microneedle system for depth-controlled intradermal injections of antigen formulations into ex vivo human skin.
• Cultured skin biopsies for 72 hours, collected migrated cells, and analyzed them via flow cytometry.
• Formulated antigens (ovalbumin and Bet v 1) in cationic and anionic liposomes.

Main Results:

• Intradermal injection depth did not influence the migration, maturation, or uptake of ovalbumin (OVA) by DCs.
• Bet v 1, a birch pollen allergen, showed poor uptake by dermal DCs (dDCs) compared to OVA.
• Uptake efficiency varied among DC subsets, with CD14+ dDCs showing higher uptake than CD1a+ dDCs and Langerhans cells.
• Liposome encapsulation increased Bet v 1 uptake by dDCs while decreasing OVA uptake.

Conclusions:

• Antigen uptake in the skin following intradermal microinjection is independent of injection depth.
• Allergen uptake is antigen-specific and significantly influenced by formulation, particularly with liposomes.
• Liposomes show potential as adjuvants for enhancing intradermal allergy vaccine delivery by modulating allergen uptake.