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Novel imiquimod nanovesicles for topical vaccination.

Authors :: Caimi AT
Altube MJ
de Farias MA
Portugal RV
Perez AP
Romero EL
Morilla MJ
Source :: Colloids and surfaces. B, Biointerfaces [Colloids Surf B Biointerfaces] 2019 Feb 01; Vol. 174, pp. 536-543. Date of Electronic Publication: 2018 Nov 15.
Publication Year :: 2019
Abstract: 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 (UDA <subscript>2</subscript> ) (nanovesicles containing sn-2,3 ether linked phytanyl saturated archaeolipids) was surveyed and compared with that of ultradeformable liposomes lacking archaeolipids (UDL <subscript>2</subscript> ) and free IMQ, using the model antigen ovalbumin and a seasonal influenza vaccine in Balb/c mice. UDA <subscript>2</subscript> (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 UDL <subscript>2</subscript> . Mixed with ovalbumin, UDA <subscript>2</subscript> 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 UDL <subscript>2</subscript> . Moreover, mixed with a seasonal influenza vaccine UDA <subscript>2</subscript> produced same IgG titers and IgG2a/IgG1 isotypes ratio (≈1) than the subcutaneously administered influenza vaccine. Topical UDA <subscript>2</subscript> however, induced highest stimulation index and INF-γ levels by splenocytes. UDA <subscript>2</subscript> 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.<br /> (Copyright © 2018 Elsevier B.V. All rights reserved.)