Title |
Toll-Like Receptor Activation by Generalized Modules for Membrane Antigens from Lipid A Mutants of Salmonella enterica Serovars Typhimurium and Enteritidis
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Published in |
mSphere, April 2016
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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. |
X Demographics
Geographical breakdown
Country | Count | As % |
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United States | 2 | 67% |
Unknown | 1 | 33% |
Demographic breakdown
Type | Count | As % |
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Scientists | 3 | 100% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
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Unknown | 43 | 100% |
Demographic breakdown
Readers by professional status | Count | As % |
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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 % |
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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% |