Novel imiquimod nanovesicles for topical vaccination

CAIMI, AYELEN TATIANA; ALTUBE, MARIA JULIA; DE FARIAS, MARCELO ALEXANDRE; PORTUGAL, RODRIGO VILLARES; PEREZ, ANA PAULA; ROMERO, EDER LILIA; MORILLA, MARIA JOSE

COLLOIDS AND SURFACES B-BIOINTERFACES

ELSEVIER SCIENCE BV

Lugar: Amsterdam; Año: 2018

0927-7765

Development of needle and pain free noninvasive immunization procedures is atop 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- 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-g 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-g 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.