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Toll-Like Receptor Activation by Generalized Modules for Membrane Antigens from Lipid A Mutants of Salmonella enterica Serovars Typhimurium and Enteritidis

Overview of attention for article published in mSphere, April 2016
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Title
Toll-Like Receptor Activation by Generalized Modules for Membrane Antigens from Lipid A Mutants of Salmonella enterica Serovars Typhimurium and Enteritidis
Published in
mSphere, April 2016
DOI 10.1128/cvi.00023-16
Pubmed ID
Authors

Omar Rossi, Mariaelena Caboni, Aurel Negrea, Francesca Necchi, Renzo Alfini, Francesca Micoli, Allan Saul, Calman A. MacLennan, Simona Rondini, Christiane Gerke

Abstract

Invasive nontyphoidal Salmonella (iNTS) disease is a neglected disease with high mortality in children and HIV-positive individuals in Sub-Saharan Africa primarily caused by African-specific strains of Salmonella enterica serovars Typhimurium and Enteritidis. A vaccine is under development using GMMA (Generalized Modules for Membrane Antigens) from S. Typhimurium and S. Enteritidis containing lipid A modifications to reduce potential in vivo reactogenicity. GMMA with penta-acylated lipid A showed the greatest reduction of cytokine release from human peripheral blood monocytes compared to GMMA with wild-type lipid A. Deletion of lipid A modification genes msbB and pagP was required to achieve pure penta-acylation. Interestingly, ΔmsbBΔpagP GMMA from S. Enteritidis had a slightly higher stimulatory potential than those from S. Typhimurium, consistent with a higher LPS content and TLR2 stimulatory potential. Also TLR5 ligand flagellin was found in Salmonella GMMA. No relevant contribution to the stimulatory potential of GMMA was detected even when flagellin protein FliC from S. Typhimurium was added at up to 10% of total protein, suggesting that flagellin impurities are not a major factor for GMMA-mediated immune stimulation. Overall, the stimulatory potential of S. Typhimurium and S. Enteritidis ΔmsbBΔpagP GMMA was close to that of Shigella GMMA that are currently in Phase I clinical trials.

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The data shown below were compiled from readership statistics for 43 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 43 100%

Demographic breakdown

Readers by professional status Count As %
Student > Master 8 19%
Researcher 6 14%
Student > Ph. D. Student 5 12%
Student > Bachelor 5 12%
Other 2 5%
Other 1 2%
Unknown 16 37%
Readers by discipline Count As %
Immunology and Microbiology 9 21%
Biochemistry, Genetics and Molecular Biology 5 12%
Agricultural and Biological Sciences 4 9%
Medicine and Dentistry 3 7%
Nursing and Health Professions 1 2%
Other 5 12%
Unknown 16 37%