Cargando…

Regulated Delayed Shigella flexneri 2a O-antigen Synthesis in Live Recombinant Salmonella enterica Serovar Typhimurium Induces Comparable Levels of Protective Immune Responses with Constitutive Antigen Synthesis System

Shigella flexneri (S. flexneri), a leading cause of bacillary dysentery, is a major public health concern particularly affecting children in developing nations. We have constructed a novel attenuated Salmonella vaccine system based on the regulated delayed antigen synthesis (RDAS) and regulated dela...

Descripción completa

Detalles Bibliográficos
Autores principales: Su, Huali, Liu, Qing, Wang, Shifeng, Curtiss, Roy, Kong, Qingke
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Ivyspring International Publisher 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6587160/
https://www.ncbi.nlm.nih.gov/pubmed/31281498
http://dx.doi.org/10.7150/thno.33046
_version_ 1783429014732406784
author Su, Huali
Liu, Qing
Wang, Shifeng
Curtiss, Roy
Kong, Qingke
author_facet Su, Huali
Liu, Qing
Wang, Shifeng
Curtiss, Roy
Kong, Qingke
author_sort Su, Huali
collection PubMed
description Shigella flexneri (S. flexneri), a leading cause of bacillary dysentery, is a major public health concern particularly affecting children in developing nations. We have constructed a novel attenuated Salmonella vaccine system based on the regulated delayed antigen synthesis (RDAS) and regulated delayed expression of attenuating phenotype (RDEAP) systems for delivering the S. flexneri 2a (Sf2a) O-antigen. Methods: The new Salmonella vaccine platform was constructed through chromosomal integration of the araC P(BAD) lacI and araC P(BAD) wbaP cassettes, resulting in a gradual depletion of WbaP enzyme. An expression vector, encoding Sf2a O-antigen biosynthesis under the control of the LacI-repressible P(trc) promoter, was maintained in the Salmonella vaccine strain through antibiotic-independent selection. Mice immunized with the vaccine candidates were evaluated for cell-mediate and humoral immune responses. Results: In the presence of exogenous arabinose, the Salmonella vaccine strain synthesized native Salmonella LPS as a consequence of WbaP expression. Moreover, arabinose supported LacI expression, thereby repressing Sf2a O-antigen production. In the absence of arabinose in vivo, native Salmonella LPS synthesis is repressed whilst the synthesis of the Sf2a O-antigen is induced. Murine immunization with the Salmonella vaccine strain elicited robust Sf2a-specific protective immune responses together with long term immunity. Conclusion: These findings demonstrate the protective efficacy of recombinant Sf2a O-antigen delivered by a Salmonella vaccine platform.
format Online
Article
Text
id pubmed-6587160
institution National Center for Biotechnology Information
language English
publishDate 2019
publisher Ivyspring International Publisher
record_format MEDLINE/PubMed
spelling pubmed-65871602019-07-05 Regulated Delayed Shigella flexneri 2a O-antigen Synthesis in Live Recombinant Salmonella enterica Serovar Typhimurium Induces Comparable Levels of Protective Immune Responses with Constitutive Antigen Synthesis System Su, Huali Liu, Qing Wang, Shifeng Curtiss, Roy Kong, Qingke Theranostics Research Paper Shigella flexneri (S. flexneri), a leading cause of bacillary dysentery, is a major public health concern particularly affecting children in developing nations. We have constructed a novel attenuated Salmonella vaccine system based on the regulated delayed antigen synthesis (RDAS) and regulated delayed expression of attenuating phenotype (RDEAP) systems for delivering the S. flexneri 2a (Sf2a) O-antigen. Methods: The new Salmonella vaccine platform was constructed through chromosomal integration of the araC P(BAD) lacI and araC P(BAD) wbaP cassettes, resulting in a gradual depletion of WbaP enzyme. An expression vector, encoding Sf2a O-antigen biosynthesis under the control of the LacI-repressible P(trc) promoter, was maintained in the Salmonella vaccine strain through antibiotic-independent selection. Mice immunized with the vaccine candidates were evaluated for cell-mediate and humoral immune responses. Results: In the presence of exogenous arabinose, the Salmonella vaccine strain synthesized native Salmonella LPS as a consequence of WbaP expression. Moreover, arabinose supported LacI expression, thereby repressing Sf2a O-antigen production. In the absence of arabinose in vivo, native Salmonella LPS synthesis is repressed whilst the synthesis of the Sf2a O-antigen is induced. Murine immunization with the Salmonella vaccine strain elicited robust Sf2a-specific protective immune responses together with long term immunity. Conclusion: These findings demonstrate the protective efficacy of recombinant Sf2a O-antigen delivered by a Salmonella vaccine platform. Ivyspring International Publisher 2019-05-26 /pmc/articles/PMC6587160/ /pubmed/31281498 http://dx.doi.org/10.7150/thno.33046 Text en © Ivyspring International Publisher This is an open access article distributed under the terms of the Creative Commons Attribution (CC BY-NC) license (https://creativecommons.org/licenses/by-nc/4.0/). See http://ivyspring.com/terms for full terms and conditions.
spellingShingle Research Paper
Su, Huali
Liu, Qing
Wang, Shifeng
Curtiss, Roy
Kong, Qingke
Regulated Delayed Shigella flexneri 2a O-antigen Synthesis in Live Recombinant Salmonella enterica Serovar Typhimurium Induces Comparable Levels of Protective Immune Responses with Constitutive Antigen Synthesis System
title Regulated Delayed Shigella flexneri 2a O-antigen Synthesis in Live Recombinant Salmonella enterica Serovar Typhimurium Induces Comparable Levels of Protective Immune Responses with Constitutive Antigen Synthesis System
title_full Regulated Delayed Shigella flexneri 2a O-antigen Synthesis in Live Recombinant Salmonella enterica Serovar Typhimurium Induces Comparable Levels of Protective Immune Responses with Constitutive Antigen Synthesis System
title_fullStr Regulated Delayed Shigella flexneri 2a O-antigen Synthesis in Live Recombinant Salmonella enterica Serovar Typhimurium Induces Comparable Levels of Protective Immune Responses with Constitutive Antigen Synthesis System
title_full_unstemmed Regulated Delayed Shigella flexneri 2a O-antigen Synthesis in Live Recombinant Salmonella enterica Serovar Typhimurium Induces Comparable Levels of Protective Immune Responses with Constitutive Antigen Synthesis System
title_short Regulated Delayed Shigella flexneri 2a O-antigen Synthesis in Live Recombinant Salmonella enterica Serovar Typhimurium Induces Comparable Levels of Protective Immune Responses with Constitutive Antigen Synthesis System
title_sort regulated delayed shigella flexneri 2a o-antigen synthesis in live recombinant salmonella enterica serovar typhimurium induces comparable levels of protective immune responses with constitutive antigen synthesis system
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6587160/
https://www.ncbi.nlm.nih.gov/pubmed/31281498
http://dx.doi.org/10.7150/thno.33046
work_keys_str_mv AT suhuali regulateddelayedshigellaflexneri2aoantigensynthesisinliverecombinantsalmonellaentericaserovartyphimuriuminducescomparablelevelsofprotectiveimmuneresponseswithconstitutiveantigensynthesissystem
AT liuqing regulateddelayedshigellaflexneri2aoantigensynthesisinliverecombinantsalmonellaentericaserovartyphimuriuminducescomparablelevelsofprotectiveimmuneresponseswithconstitutiveantigensynthesissystem
AT wangshifeng regulateddelayedshigellaflexneri2aoantigensynthesisinliverecombinantsalmonellaentericaserovartyphimuriuminducescomparablelevelsofprotectiveimmuneresponseswithconstitutiveantigensynthesissystem
AT curtissroy regulateddelayedshigellaflexneri2aoantigensynthesisinliverecombinantsalmonellaentericaserovartyphimuriuminducescomparablelevelsofprotectiveimmuneresponseswithconstitutiveantigensynthesissystem
AT kongqingke regulateddelayedshigellaflexneri2aoantigensynthesisinliverecombinantsalmonellaentericaserovartyphimuriuminducescomparablelevelsofprotectiveimmuneresponseswithconstitutiveantigensynthesissystem