1. Long-Term Anti-Bacterial Immunity against Systemic Infection by Salmonella enterica Serovar Typhimurium Elicited by a GMMA-Based Vaccine
- Author
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Oliver Koeberling, Gianni Pozzi, Elena Pettini, Donata Medaglini, Laura B. Martin, Fabio Fiorino, and Annalisa Ciabattini
- Subjects
0301 basic medicine ,Serotype ,Salmonella ,salmonellosis ,Immunology ,Spleen ,medicine.disease_cause ,Article ,Microbiology ,03 medical and health sciences ,0302 clinical medicine ,systemic infection ,Antigen ,Immunity ,Drug Discovery ,medicine ,Pharmacology (medical) ,030212 general & internal medicine ,GMMA vaccine ,cellular immune response ,Pharmacology ,Salmonella Typhimurium ,biology ,business.industry ,antibody response ,biology.organism_classification ,030104 developmental biology ,Infectious Diseases ,medicine.anatomical_structure ,Immunization ,Salmonella enterica ,Medicine ,Bone marrow ,business ,Antibody response ,Cellular immune response ,Salmonellosis ,Systemic infection - Abstract
Salmonella Typhimurium (STm) represents the most prevalent cause of invasive non-typhoidal Salmonella (iNTS) disease, and currently no licensed vaccine is available. In this work we characterized the long-term anti-bacterial immunity elicited by a STm vaccine based on Generalized Modules of Membrane Antigens (GMMA) delivering O:4,5 antigen, using a murine model of systemic infection. Subcutaneous immunization of mice with STmGMMA/Alhydrogel elicited rapid, high, and persistent antigen-specific serum IgG and IgM responses. The serum was bactericidal in vitro. O:4,5-specific IgG were also detected in fecal samples after immunization and positively correlated with IgG observed in intestinal washes. Long-lived plasma cells and O:4,5-specific memory B cells were detected in spleen and bone marrow. After systemic STm challenge, a significant reduction of bacterial load in blood, spleen, and liver, as well as a reduction of circulating neutrophils and G-CSF glycoprotein was observed in STmGMMA/Alhydrogel immunized mice compared to untreated animals. Taken together, these data support the development of a GMMA-based vaccine for prevention of iNTS disease.
- Published
- 2021