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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.

Author information

1
Nanomedicine Research & Development Center, Departamento de Ciencia y Tecnología, Universidad Nacional de Quilmes, Roque Saenz Peña 352, Bernal, B1876BXD, Argentina.
2
Brazilian Nanotechnology National Laboratory, CNPEM, Caixa Postal 6192, CEP 13.083-970, Campinas, São Paulo, Brazil.
3
Nanomedicine Research & Development Center, Departamento de Ciencia y Tecnología, Universidad Nacional de Quilmes, Roque Saenz Peña 352, Bernal, B1876BXD, Argentina. Electronic address: jmorilla@unq.edu.ar.

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 (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.

KEYWORDS:

Archaeolipids; Cellular response; Immunomodulator; Influenza vaccine

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