A Salmonella typhimurium ghost vaccine induces cytokine expression in vitro and immune responses in vivo and protects rats against homologous and heterologous challenges.

Salmonella enteritidis and Salmonella typhimurium are important food-borne bacterial pathogens, which are responsible for diarrhea and gastroenteritis in humans and animals. In this study, S. typhimurium bacterial ghost (STG) was generated based on minimum inhibitory concentration (MIC) of sodium hy...

Full description

Bibliographic Details
Main Authors: Nagarajan Vinod, Han Byul Noh, Sung Oh, Seongmi Ji, Hyun Jung Park, Ki-Sung Lee, Sei Chang Kim, Han-Oh Park, Joo-Sung Yang, Chang Won Choi
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2017-01-01
Series:PLoS ONE
Online Access:http://europepmc.org/articles/PMC5621678?pdf=render
_version_ 1818954991362113536
author Nagarajan Vinod
Han Byul Noh
Sung Oh
Seongmi Ji
Hyun Jung Park
Ki-Sung Lee
Sei Chang Kim
Han-Oh Park
Joo-Sung Yang
Chang Won Choi
author_facet Nagarajan Vinod
Han Byul Noh
Sung Oh
Seongmi Ji
Hyun Jung Park
Ki-Sung Lee
Sei Chang Kim
Han-Oh Park
Joo-Sung Yang
Chang Won Choi
author_sort Nagarajan Vinod
collection DOAJ
description Salmonella enteritidis and Salmonella typhimurium are important food-borne bacterial pathogens, which are responsible for diarrhea and gastroenteritis in humans and animals. In this study, S. typhimurium bacterial ghost (STG) was generated based on minimum inhibitory concentration (MIC) of sodium hydroxide (NaOH). Experimental studies performed using in vitro and in vivo experimental model systems to characterize effects of STG as a vaccine candidate. When compared with murine macrophages (RAW 264.7) exposed to PBS buffer (98.1%), the macrophages exposed to formalin-killed inactivated cells (FKC), live wild-type bacterial cells and NaOH-induced STG at 1 × 108 CFU/mL showed 85.6%, 66.5% and 84.6% cell viability, respectively. It suggests that STG significantly reduces the cytotoxic effect of wild-type bacterial cells. Furthermore, STG is an excellent inducer for mRNAs of pro-inflammatory cytokine (TNF-α, IL-1β) and factor (iNOS), anti-inflammatory cytokine (IL-10) and dual activities (IL-6) in the stimulated macrophage cells. In vivo, STG vaccine induced humoral and cellular immune responses and protection against homologous and heterologous challenges in rats. Furthermore, the immunogenicity and protective efficacy of STG vaccine were compared with those of FKC and non-vaccinated PBS control groups. The vaccinated rats from STG group exhibited higher levels of serum IgG antibody responses, serum bactericidal antibodies, and CD4+ and CD8+ T-cell populations than those of the FKC and PBS control groups. Most importantly, after challenge with homologous and heterologous strains, the bacterial loads in the STG group were markedly lower than the FKC and PBS control groups. In conclusion, these findings suggest that the STG vaccine induces protective immunity against homologous and heterologous challenges.
first_indexed 2024-12-20T10:30:57Z
format Article
id doaj.art-00892e5561a44abd8aa87157ddee77bd
institution Directory Open Access Journal
issn 1932-6203
language English
last_indexed 2024-12-20T10:30:57Z
publishDate 2017-01-01
publisher Public Library of Science (PLoS)
record_format Article
series PLoS ONE
spelling doaj.art-00892e5561a44abd8aa87157ddee77bd2022-12-21T19:43:43ZengPublic Library of Science (PLoS)PLoS ONE1932-62032017-01-01129e018548810.1371/journal.pone.0185488A Salmonella typhimurium ghost vaccine induces cytokine expression in vitro and immune responses in vivo and protects rats against homologous and heterologous challenges.Nagarajan VinodHan Byul NohSung OhSeongmi JiHyun Jung ParkKi-Sung LeeSei Chang KimHan-Oh ParkJoo-Sung YangChang Won ChoiSalmonella enteritidis and Salmonella typhimurium are important food-borne bacterial pathogens, which are responsible for diarrhea and gastroenteritis in humans and animals. In this study, S. typhimurium bacterial ghost (STG) was generated based on minimum inhibitory concentration (MIC) of sodium hydroxide (NaOH). Experimental studies performed using in vitro and in vivo experimental model systems to characterize effects of STG as a vaccine candidate. When compared with murine macrophages (RAW 264.7) exposed to PBS buffer (98.1%), the macrophages exposed to formalin-killed inactivated cells (FKC), live wild-type bacterial cells and NaOH-induced STG at 1 × 108 CFU/mL showed 85.6%, 66.5% and 84.6% cell viability, respectively. It suggests that STG significantly reduces the cytotoxic effect of wild-type bacterial cells. Furthermore, STG is an excellent inducer for mRNAs of pro-inflammatory cytokine (TNF-α, IL-1β) and factor (iNOS), anti-inflammatory cytokine (IL-10) and dual activities (IL-6) in the stimulated macrophage cells. In vivo, STG vaccine induced humoral and cellular immune responses and protection against homologous and heterologous challenges in rats. Furthermore, the immunogenicity and protective efficacy of STG vaccine were compared with those of FKC and non-vaccinated PBS control groups. The vaccinated rats from STG group exhibited higher levels of serum IgG antibody responses, serum bactericidal antibodies, and CD4+ and CD8+ T-cell populations than those of the FKC and PBS control groups. Most importantly, after challenge with homologous and heterologous strains, the bacterial loads in the STG group were markedly lower than the FKC and PBS control groups. In conclusion, these findings suggest that the STG vaccine induces protective immunity against homologous and heterologous challenges.http://europepmc.org/articles/PMC5621678?pdf=render
spellingShingle Nagarajan Vinod
Han Byul Noh
Sung Oh
Seongmi Ji
Hyun Jung Park
Ki-Sung Lee
Sei Chang Kim
Han-Oh Park
Joo-Sung Yang
Chang Won Choi
A Salmonella typhimurium ghost vaccine induces cytokine expression in vitro and immune responses in vivo and protects rats against homologous and heterologous challenges.
PLoS ONE
title A Salmonella typhimurium ghost vaccine induces cytokine expression in vitro and immune responses in vivo and protects rats against homologous and heterologous challenges.
title_full A Salmonella typhimurium ghost vaccine induces cytokine expression in vitro and immune responses in vivo and protects rats against homologous and heterologous challenges.
title_fullStr A Salmonella typhimurium ghost vaccine induces cytokine expression in vitro and immune responses in vivo and protects rats against homologous and heterologous challenges.
title_full_unstemmed A Salmonella typhimurium ghost vaccine induces cytokine expression in vitro and immune responses in vivo and protects rats against homologous and heterologous challenges.
title_short A Salmonella typhimurium ghost vaccine induces cytokine expression in vitro and immune responses in vivo and protects rats against homologous and heterologous challenges.
title_sort salmonella typhimurium ghost vaccine induces cytokine expression in vitro and immune responses in vivo and protects rats against homologous and heterologous challenges
url http://europepmc.org/articles/PMC5621678?pdf=render
work_keys_str_mv AT nagarajanvinod asalmonellatyphimuriumghostvaccineinducescytokineexpressioninvitroandimmuneresponsesinvivoandprotectsratsagainsthomologousandheterologouschallenges
AT hanbyulnoh asalmonellatyphimuriumghostvaccineinducescytokineexpressioninvitroandimmuneresponsesinvivoandprotectsratsagainsthomologousandheterologouschallenges
AT sungoh asalmonellatyphimuriumghostvaccineinducescytokineexpressioninvitroandimmuneresponsesinvivoandprotectsratsagainsthomologousandheterologouschallenges
AT seongmiji asalmonellatyphimuriumghostvaccineinducescytokineexpressioninvitroandimmuneresponsesinvivoandprotectsratsagainsthomologousandheterologouschallenges
AT hyunjungpark asalmonellatyphimuriumghostvaccineinducescytokineexpressioninvitroandimmuneresponsesinvivoandprotectsratsagainsthomologousandheterologouschallenges
AT kisunglee asalmonellatyphimuriumghostvaccineinducescytokineexpressioninvitroandimmuneresponsesinvivoandprotectsratsagainsthomologousandheterologouschallenges
AT seichangkim asalmonellatyphimuriumghostvaccineinducescytokineexpressioninvitroandimmuneresponsesinvivoandprotectsratsagainsthomologousandheterologouschallenges
AT hanohpark asalmonellatyphimuriumghostvaccineinducescytokineexpressioninvitroandimmuneresponsesinvivoandprotectsratsagainsthomologousandheterologouschallenges
AT joosungyang asalmonellatyphimuriumghostvaccineinducescytokineexpressioninvitroandimmuneresponsesinvivoandprotectsratsagainsthomologousandheterologouschallenges
AT changwonchoi asalmonellatyphimuriumghostvaccineinducescytokineexpressioninvitroandimmuneresponsesinvivoandprotectsratsagainsthomologousandheterologouschallenges
AT nagarajanvinod salmonellatyphimuriumghostvaccineinducescytokineexpressioninvitroandimmuneresponsesinvivoandprotectsratsagainsthomologousandheterologouschallenges
AT hanbyulnoh salmonellatyphimuriumghostvaccineinducescytokineexpressioninvitroandimmuneresponsesinvivoandprotectsratsagainsthomologousandheterologouschallenges
AT sungoh salmonellatyphimuriumghostvaccineinducescytokineexpressioninvitroandimmuneresponsesinvivoandprotectsratsagainsthomologousandheterologouschallenges
AT seongmiji salmonellatyphimuriumghostvaccineinducescytokineexpressioninvitroandimmuneresponsesinvivoandprotectsratsagainsthomologousandheterologouschallenges
AT hyunjungpark salmonellatyphimuriumghostvaccineinducescytokineexpressioninvitroandimmuneresponsesinvivoandprotectsratsagainsthomologousandheterologouschallenges
AT kisunglee salmonellatyphimuriumghostvaccineinducescytokineexpressioninvitroandimmuneresponsesinvivoandprotectsratsagainsthomologousandheterologouschallenges
AT seichangkim salmonellatyphimuriumghostvaccineinducescytokineexpressioninvitroandimmuneresponsesinvivoandprotectsratsagainsthomologousandheterologouschallenges
AT hanohpark salmonellatyphimuriumghostvaccineinducescytokineexpressioninvitroandimmuneresponsesinvivoandprotectsratsagainsthomologousandheterologouschallenges
AT joosungyang salmonellatyphimuriumghostvaccineinducescytokineexpressioninvitroandimmuneresponsesinvivoandprotectsratsagainsthomologousandheterologouschallenges
AT changwonchoi salmonellatyphimuriumghostvaccineinducescytokineexpressioninvitroandimmuneresponsesinvivoandprotectsratsagainsthomologousandheterologouschallenges