Colloids Surf B Biointerfaces. 2018 Nov 15;174:536-543. doi: 10.1016/j.colsurfb.2018.11.031. [Epub ahead of print]
Novel imiquimod nanovesicles for topical vaccination.

Caimi AT1, Altube MJ1, de Farias MA2, Portugal RV2, Perez AP1, Romero EL1, Morilla MJ3.
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Development of needle and pain free noninvasive immunization procedures is a top priority for public health agencies. In this work the topical adjuvant activity of the immunomodulator imiquimod (IMQ) carried by ultradeformable archaeosomes (UDA2) (nanovesicles containing sn-2,3 ether linked phytanyl saturated archaeolipids) was surveyed and compared with that of ultradeformable liposomes lacking archaeolipids (UDL2) and free IMQ, using the model antigen ovalbumin and a seasonal influenza vaccine in Balb/c mice. UDA2 (250  94 nm, -26  4 mV Z potential) induced higher IMQ accumulation in human skin and higher production of TNF-α and IL-6 by macrophages and keratinocytes than free IMQ and UDL2. Mixed with ovalbumin, UDA2 was more efficient at generating cellular response, as measured by an increase in serum IgG2a and INF-γ production by splenocytes, compared with free IMQ and UDL2. Moreover, mixed with a seasonal influenza vaccine UDA2 produced same IgG titers and IgG2a/IgG1 isotypes ratio (≈1) than the subcutaneously administered influenza vaccine. Topical UDA2 however, induced highest stimulation index and INF-γ levels by splenocytes. UDA2 might be a promising adjuvant for topical immunization, since it produced cell-biased systemic response with ≈ 13-fold lower IMQ dose than the delivered as the commercial IMQ cream, Aldara.


Archaeolipids; Cellular response; Immunomodulator; Influenza vaccine

PMID: 30500742 DOI: 10.1016/j.colsurfb.2018.11.031