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

Yrvin León,Lionel Zapata,Leonardo A Gómez,Gaj Okanovič,Raúl E Molina,Carla Daza-Castro,Angel A Oñate,Manuel Flores-Concha,José L Reyes

doi:10.3390/vaccines8040563

Yrvin León, Lionel Zapata + Show 7 more

Open Access

https://doi.org/10.3390/vaccines8040563

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Journal: Vaccines	Publication Date: Oct 1, 2020
Citations: 11	License type: CC BY 4.0

Affiliation: University of Concepción, University of Ljubljana

Abstract

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.

Highlights

Shigella spp. are Gram-negative, non-motile, non-spore-forming, facultative anaerobic bacilli bacteria that invade the human colonic epithelium and cause bacillary dysentery or shigellosis [1].This pathogen has a very low infectious dose of about 10–100 bacteria cells [1], mainly affecting children under five years of age [2], and all age groups during outbreaks [3,4]
We demonstrate that the immunization of mice with chimeric antigens displaying selected epitopes fused to GroEL induce an immune response and high protective efficacy against S. flexneri
Shigella flexneri 2a strain was kindly facilitated by Dr Cecilia Toro of the Instituto de Ciencias

Summary

Introduction

Shigella spp. are Gram-negative, non-motile, non-spore-forming, facultative anaerobic bacilli bacteria that invade the human colonic epithelium and cause bacillary dysentery or shigellosis [1]. This pathogen has a very low infectious dose of about 10–100 bacteria cells [1], mainly affecting children under five years of age [2], and all age groups during outbreaks [3,4]. There are four serogroups of Shigella: S. dysenteriae (12 serotypes), S. flexneri (six serotypes), S. boydii (18 serotypes), and S. sonnei (one serotype), respectively [5]. Vaccines 2020, 8, 563 correlated with shigellosis in developing countries is S. flexneri [5].

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