Intranasal Immunization of Mice with Multiepitope Chimeric Vaccine Candidate Based on Conserved Autotransporters SigA, Pic and Sap, Confers Protection against Shigella flexneri

Vaccines

Gaj Okanovič¹  JoséL. Reyes²  LeonardoA. Gómez²  Yrvin León²  RaúlE. Molina²  Manuel Flores-Concha²  Carla Daza-Castro²  AngelA. Oñate²  Lionel Zapata³ 

[1] Faculty of Medicine, University of Ljubljana, Ljubljana 1500, Slovenia;Laboratory of Molecular Immunology, Department of Microbiology, Faculty of Biological Sciences, Universidad de Concepción, Concepción 4030000, Chile;Laboratory of Recombinant Biopharmaceuticals, Department of Pharmacology, Universidad de Concepción, Concepción 4030000, Chile;

关键词: bacillary dysentery;    Shigella flexneri;    mucosal immunity;    autotransporters;    GroEL;    multiepitope chimeric vaccine;   

DOI  :  10.3390/vaccines8040563

来源: DOAJ

【 摘 要 】

Shigellosis is a diarrheal disease and the World Health Organization prompts the development of a vaccine against Shigella flexneri. The autotransporters SigA, Pic and Sap are conserved among Shigella spp. We previously designed an in silico vaccine with immunodominat epitopes from those autotransporters, and the GroEL protein of S. typhi as an adjuvant. Here, we evaluated the immunogenicity and protective efficacy of the chimeric multiepitope protein, named rMESF, in mice against lethal infection with S. flexneri. rMESF was administered to mice alone through the intranasal (i.n.) route or accompanied with Complete Freund’s adjuvant (CFA) intradermically (i.d.), subcutaneously (s.c.), and intramuscular (i.m.), as well as with Imject alum (i.m.). All immunized mice increased IgG, IgG1, IgG2a, IgA and fecal IgA titers compared to PBS+CFA and PBS+alum control groups. Furthermore, i.n. immunization of mice with rMESF alone presented the highest titers of serum and fecal IgA. Cytokine levels (IFN-γ, TNF-α, IL-4, and IL-17) and lymphocyte proliferation increased in all experimental groups, with the highest lymphoproliferative response in i.n. mice immunized with rMESF alone, which presented 100% protection against S. flexneri. In summary, this vaccine vests protective immunity and highlights the importance of mucosal immunity activation for the elimination of S. flexneri.

【 授权许可】

Unknown