Emerging adjuvants for intradermal vaccination.

The majority of vaccines have been delivered into the muscular tissue. Skin contains large amounts of antigen-presenting cells and has been recognized as a more immunogenic site for vaccine delivery. Intradermal delivery has been approved to improve influenza vaccine efficacy and spare influenza vaccine doses. In response to the recent monkeypox outbreak, intradermal delivery has been also approved to stretch the limited monkeypox vaccine doses to immunize more people at risk. Incorporation of vaccine adjuvants is promising to further increase intradermal vaccine efficacy and spare more vaccine doses. Yet, intradermal vaccination is associated with more significant local reactions than intramuscular vaccination. Thus, adjuvants suitable to boost intradermal vaccination need to have a good local safety without inducing overt local reactions. This review introduces currently approved adjuvants in licensed human vaccines and their relative reactogenicity for intradermal delivery and then introduces emerging chemical and physical adjuvants with a good local safety to boost intradermal vaccination. The rational to develop physical adjuvants, the types of physical adjuvants, and the unique advantages of physical adjuvants to boost intradermal vaccination are also introduced in this review.