Novel imiquimod nanovesicles for topical vaccination

CAIMI, AYELEN TATIANA; ALTUBE MARÍA JULIA; DE FARIAS, MARCELO ALEXANDRE; RODRIGO VILLARES PORTUGAL; ROMERO EDER LILIA; MORILLA MARÍA JOSE

COLLOIDS AND SURFACES B-BIOINTERFACES

ELSEVIER SCIENCE BV

Lugar: Amsterdam; Año: 2018

0927-7765

Development of needle and pain free noninvasive immunizationprocedures is a top priority for public health agencies. In this work thetopical adjuvant activity of the immunomodulator imiquimod (IMQ) carriedby ultradeformable archaeosomes (UDA2) (nanovesicles containing sn 2,3ether linked phytanyl saturated archaeolipids) was surveyed and comparedwith that of ultradeformable liposomes lacking archaeolipids (UDL2) andfree IMQ, using the model antigen ovalbumin and a seasonal influenzavaccine in Balb/C mice. UDA2 (250 ± 94 nm, -26 ± 4 mV Z potential)induced higher IMQ accumulation in human skin and higher production ofTNF-alpha and IL-6 by macrophages and keratinocytes than free IMQ andUDL2. Mixed with ovalbumin, UDA2 was more efficient at generatingcellular response, as measured by an increase in serum IgG2a and INFgamma production by splenocytes, compared with free IMQ and UDL2.Moreover, mixed with a seasonal influenza vaccine UDA2 produced same IgGtiters and IgG2a/IgG1 isotypes ratio (1) than the subcutaneouslyadministered influenza vaccine. Topical UDA2 however, induced higheststimulation index and INF- levels by splenocytes. UDA2 might be apromising adjuvant for topical immunization, since it produced cellbiased systemic response with 13-fold lower IMQ dose than the deliveredas the commercial IMQ cream, Aldara.