Intranasal Immunization of Mice with Multiepitope Chimeric Vaccine Candidate Based on Conserved Autotransporters SigA, Pic and Sap, Confers Protection against Shigella flexneri
| Autor: | Leonardo A Gómez, José L Reyes, Gaj Okanovič, Angel Oñate, Raúl E Molina, Lionel Zapata, Carla Daza-Castro, Yrvin León, Manuel Flores-Concha |
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| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Shigellosis medicine.medical_treatment 030106 microbiology Immunology lcsh:Medicine chemical and pharmacologic phenomena Lymphocyte proliferation medicine.disease_cause GroEL Microbiology 03 medical and health sciences Shigella flexneri Drug Discovery medicine Pharmacology (medical) Shigella autotransporters Pharmacology multiepitope chimeric vaccine biology Immunogenicity lcsh:R biochemical phenomena metabolism and nutrition biology.organism_classification medicine.disease 030104 developmental biology Infectious Diseases bacteria mucosal immunity bacillary dysentery Adjuvant Lymphoproliferative response Autotransporters |
| Zdroj: | Vaccines Volume 8 Issue 4 Vaccines, Vol 8, Iss 563, p 563 (2020) |
| ISSN: | 2076-393X |
| DOI: | 10.3390/vaccines8040563 |
| Popis: | 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&rsquo 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-&gamma TNF-&alpha 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. |
| Databáze: | OpenAIRE |
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