Induction of Cell Cycle and NK Cell Responses by Live-Attenuated Oral Vaccines against Typhoid Fever.
The mechanisms by which oral, live-attenuated vaccines protect against typhoid fever are poorly understood. Here, we analyze transcriptional responses after vaccination with Ty21a or vaccine candidate, M01ZH09. Alterations in response profiles were related to vaccine-induced immune responses and subsequent outcome after wild-type Salmonella Typhi challenge. Despite broad genetic similarity, we detected differences in transcriptional responses to each vaccine. Seven days after M01ZH09 vaccination, marked cell cycle activation was identified and associated with humoral immunogenicity. By contrast, vaccination with Ty21a was associated with NK cell activity and validated in peripheral blood mononuclear cell stimulation assays confirming superior induction of an NK cell response. Moreover, transcriptional signatures of amino acid metabolism in Ty21a recipients were associated with protection against infection, including increased incubation time and decreased severity. Our data provide detailed insight into molecular immune responses to typhoid vaccines, which could aid the rational design of improved oral, live-attenuated vaccines against enteric pathogens.
Authors
Christoph J Blohmke; Jennifer Hill; Thomas C Darton; Matheus Carvalho-Burger; Andrew Eustace; Claire Jones; Fernanda Schreiber; Martin R Goodier; Gordon Dougan; Helder I Nakaya; Andrew J Pollard
External link
Publication Year
2017
Publication Journal
Frontiers in immunology
Associeted Project
Systems Vaccinology
Lista de serviços
-
Chapter 15 - Systems Biology of Infectious Diseases and VaccinesChapter 15 - Systems Biology of Infectious Diseases and Vaccines
-
Synergy of Omeprazole and Praziquantel In Vitro Treatment against Schistosoma mansoni Adult Worms.Synergy of Omeprazole and Praziquantel In Vitro Treatment against Schistosoma mansoni Adult Worms.
-
Systems Immunology of Diabetes-Tuberculosis Comorbidity Reveals Signatures of Disease Complications.Systems Immunology of Diabetes-Tuberculosis Comorbidity Reveals Signatures of Disease Complications.
-
Systems ImmunologySystems Immunology
-
Gene profiling of Chikungunya virus arthritis in a mouse model reveals significant overlap with rheumatoid arthritis.Gene profiling of Chikungunya virus arthritis in a mouse model reveals significant overlap with rheumatoid arthritis.
-
Toward an Integrated View of Operational Tolerance in Human Renal Transplantation: A Systems Biology Perspective.Toward an Integrated View of Operational Tolerance in Human Renal Transplantation: A Systems Biology Perspective.
-
Total parasite biomass but not peripheral parasitaemia is associated with endothelial and haematological perturbations in Plasmodium vivax patientsTotal parasite biomass but not peripheral parasitaemia is associated with endothelial and haematological perturbations in Plasmodium vivax patients
-
Acid pH Increases SARS-CoV-2 Infection and the Risk of Death by COVID-19Acid pH Increases SARS-CoV-2 Infection and the Risk of Death by COVID-19
-
The relationship between cytokine and neutrophil gene network distinguishes SARS-CoV-2-infected patients by sex and age.The relationship between cytokine and neutrophil gene network distinguishes SARS-CoV-2-infected patients by sex and age.
-
Immature neutrophil signature associated with the sexual dimorphism of systemic juvenile idiopathic arthritis.Immature neutrophil signature associated with the sexual dimorphism of systemic juvenile idiopathic arthritis.
-
Platelet disturbances correlate with endothelial cell activation in uncomplicated Plasmodium vivax malaria.Platelet disturbances correlate with endothelial cell activation in uncomplicated Plasmodium vivax malaria.
-
miRNAs may play a major role in the control of gene expression in key pathobiological processes in Chagas disease cardiomyopathy.miRNAs may play a major role in the control of gene expression in key pathobiological processes in Chagas disease cardiomyopathy.
-
Zika virus infection and cytokines.Zika virus infection and cytokines.
-
Systems immunology of flavivirus infection.Systems immunology of flavivirus infection.
-
Kdm6b Regulates the Generation of Effector CD8 + T Cells by Inducing Chromatin Accessibility in Effector-Associated GenesKdm6b Regulates the Generation of Effector CD8 + T Cells by Inducing Chromatin Accessibility in Effector-Associated Genes
-
Neonatal T Follicular Helper Cells Are Lodged in a Pre-T Follicular Helper Stage Favoring Innate Over Adaptive Germinal Center Responses.Neonatal T Follicular Helper Cells Are Lodged in a Pre-T Follicular Helper Stage Favoring Innate Over Adaptive Germinal Center Responses.
-
Exacerbation of Chikungunya Virus Rheumatic Immunopathology by a High Fiber Diet and Butyrate.Exacerbation of Chikungunya Virus Rheumatic Immunopathology by a High Fiber Diet and Butyrate.
-
Severe COVID-19 shares a common neutrophil activation signature with other acute inflammatory statesSevere COVID-19 shares a common neutrophil activation signature with other acute inflammatory states
-
Efferocytosis of SARS-CoV-2-infected dying cells impairs macrophage anti-inflammatory functions and clearance of apoptotic cellsEfferocytosis of SARS-CoV-2-infected dying cells impairs macrophage anti-inflammatory functions and clearance of apoptotic cells
-
Daily Rhythms of TNFα Expression and Food Intake Regulate Synchrony of Plasmodium Stages with the Host Circadian Cycle.Daily Rhythms of TNFα Expression and Food Intake Regulate Synchrony of Plasmodium Stages with the Host Circadian Cycle.
-
Discordant congenital Zika syndrome twins show differential in vitro viral susceptibility of neural progenitor cells.Discordant congenital Zika syndrome twins show differential in vitro viral susceptibility of neural progenitor cells.
-
Elevated Glucose Levels Favor SARS-CoV-2 Infection and Monocyte Response through a HIF-1α/Glycolysis-Dependent Axis.Elevated Glucose Levels Favor SARS-CoV-2 Infection and Monocyte Response through a HIF-1α/Glycolysis-Dependent Axis.
-
Systems analysis of subjects acutely infected with the Chikungunya virus.Systems analysis of subjects acutely infected with the Chikungunya virus.
-
Molecular alterations in the extracellular matrix in the brains of newborns with congenital Zika syndrome.Molecular alterations in the extracellular matrix in the brains of newborns with congenital Zika syndrome.
-
Inflammation induced by influenza virus impairs human innate immune control of pneumococcus.Inflammation induced by influenza virus impairs human innate immune control of pneumococcus.
-
Tissue-resident glial cells associate with tumoral vasculature and promote cancer progressionTissue-resident glial cells associate with tumoral vasculature and promote cancer progression
-
Increased mTOR Signaling and Impaired Autophagic Flux Are Hallmarks of SARS-CoV-2 Infection.Increased mTOR Signaling and Impaired Autophagic Flux Are Hallmarks of SARS-CoV-2 Infection.
-
Chikungunya patient transcriptional signatures faithfully recapitulated in a C57BL/6J mouse modelChikungunya patient transcriptional signatures faithfully recapitulated in a C57BL/6J mouse model
-
Imbalanced IL-1B and IL-18 Expression in Sézary SyndromeImbalanced IL-1B and IL-18 Expression in Sézary Syndrome
-
C5aR1 signaling triggers lung immunopathology in COVID-19 through neutrophil extracellular trapsC5aR1 signaling triggers lung immunopathology in COVID-19 through neutrophil extracellular traps
-
Cutting Edge: Polycomb Repressive Complex 1 Subunit Cbx4 Positively Regulates Effector Responses in CD8 T CellsCutting Edge: Polycomb Repressive Complex 1 Subunit Cbx4 Positively Regulates Effector Responses in CD8 T Cells
-
COVID-19-related hyperglycemia is associated with infection of hepatocytes and stimulation of gluconeogenesisCOVID-19-related hyperglycemia is associated with infection of hepatocytes and stimulation of gluconeogenesis
-
Characteristics and anatomic location of PD-1(+)TCF1(+) stem-like CD8 T cells in chronic viral infection and cancerCharacteristics and anatomic location of PD-1(+)TCF1(+) stem-like CD8 T cells in chronic viral infection and cancer
-
Morphological, cellular, and molecular basis of brain infection in COVID-19 patientsMorphological, cellular, and molecular basis of brain infection in COVID-19 patients