Background: the new vaccines constituted by antigenicsubunits are safe and less expensive, but are not very immunogenic, so theyrequire the incorporation of a vigorous adjuvant. Recently, CpG-ODNwas approved by FDA for a human vaccine. Our vaccine strategy is a nanoformulationwhere the ovalbumin antigen (OVA) and CpG-ODN are formulated with a liquidcrystal bilamellar nanostructure (Coa-ASC16) formed by self-assembly of6-O-ascorbyl palmitate. Previously, we demonstrated that this nanoformulation(OCC) elicited antibodies (IgG1 and IgG2a) and cellular (Th1/Th17 and CD8+ T-cells)responses superior to those induced by a solution of OVA and CpG-ODN (OC) undera three-dose immunization scheme. The CD8+ Tcellresponse induced by OCC was dependent of type I interferons (IFN-I) signaling.Here, we study if the IFN-I pathways have an impact on the antibodies response.Methods: wild-type C57BL/6 and Ifnar1-/- micewere subcutaneously immunized with a single-dose of OCC, OC and OVA and CpG-ODNin solution heated at 80ºC for 15 min and then cooled down to room temperaturein order to simulate the conditions of preparation of the nanostructured formulation(OCø). OVA-specific IgG, IgG2c, and IgG1 titers were evaluated by ELISA.Results: the magnitude and quality of OVA-specific humoral response weresimilar between wild-type and Ifnar1-/- mice. Theimmunization with OCC and OCø induced higher IgG, IgG2c and IgG1 titers than OC(p<0.05) in wild-type and Ifnar1-/- mice. Inconclusion, unlike the CD8+ T cell response,the positive effects on humoral responses induced by Coa-ASC16 were notaffected by the absence of IFN-I signaling.