Retinoic Acid Promotes Mucosal and Systemic Immune Responses after Mucosal Priming and Systemic Boosting in MiceElisa Cirelli1,2, Antonella Riccomi1, Filippo Veglia2, Valentina Gesa1, Maria Teresa De Magistris1 and Silvia Vendetti1 *
- *Corresponding Author:
- Dr. Silvia Vendetti
Department of Infectious
Parasitic and Immune-Mediated Diseases
Istituto Superiore di Sanità
Viale regina Elena 29900161 Rome, Italy
E-mail: [email protected]
Received date: December 05, 2014; Accepted date: January 16, 2015; Published date: January 20, 2015
Citation: Cirelli E, Riccomi A, Veglia F, Gesa V, De Magistris MT, et al. (2015) Retinoic Acid Promotes Mucosal and Systemic Immune Responses after Mucosal Priming and Systemic Boosting in Mice. J Vaccines Vaccin 6:265. doi: 10.4172/2157-7560.1000265
Copyright: © 2015 Vendetti S, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Objective: Few mucosal vaccines are available for human use, none of which are recombinant proteins or subunits of pathogens, owing to the lack of potent and safe mucosal adjuvants. Given the crucial role of retinoic acid (RA) in favouring dendritic cell differentiation, imprinting a mucosal homing capacity on T and B cells, as well as its potential to promote the differentiation of IgA-producing plasma cells, we evaluated the capacity of RA to improve mucosal vaccinations.
Study design: BALB/c mice were treated for eight days with RA or its vehicle and then intranasally immunized with tetanus toxoid (TT) with or without CT and boosted three times. Alternatively, mice treated with RA or its vehicle, were exposed to intranasal delivery of TT alone and boosted systemically with TT and Alum. Serum and mucosal Ag-specific antibody responses were examined 2 weeks and 8 months after the priming.
Results: Treatment with RA synergises with the adjuvant capacity of CT to enhance both systemic and mucosal TT-specific antibody responses. The combination of mucosal priming with Ag alone, followed by a boost with systemic adjuvant was also evaluated. Mice treated with RA showed a higher titer of mucosal IgA compared to untreated mice, after intranasal priming with TT followed by a systemic boost with TT plus Alum. After eight months, higher IgG TT-specific antibodies in the serum and a higher frequency of TT-specific IgG and IgA secreting cells were detected in the bone marrow of mice treated with RA as compared to untreated mice. Higher percentages of proliferating CD4 and CD8 T cells upon TT stimulation were found in the spleens, in the mesenteric lymph nodes and in the colonic lamina propria of mice treated with RA.
Conclusion: This approach induces mucosal immunity in the absence of mucosal adjuvants and improves the effectiveness of mucosally-delivered vaccine.