1. Assessment of microbiological correlates and immunostimulatory potential of electron beam inactivated metabolically active yet non culturable (MAyNC) Salmonella Typhimurium
- Author
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Palmy R. Jesudhasan, Noah D. Cohen, Sohini S. Bhatia, Robert C. Alaniz, Chandni Praveen, Suresh D. Pillai, and Robert E. Droleskey
- Subjects
0301 basic medicine ,Bacterial Diseases ,CD4-Positive T-Lymphocytes ,Salmonella typhimurium ,Salmonella ,Physiology ,Cell Membranes ,medicine.disease_cause ,Pathology and Laboratory Medicine ,White Blood Cells ,Mice ,Medical Conditions ,Animal Cells ,Immune Physiology ,Medicine and Health Sciences ,Immune Response ,Cells, Cultured ,Innate Immune System ,Vaccines ,Multidisciplinary ,Attenuated vaccine ,Chemistry ,T Cells ,Immunogenicity ,Salmonella vaccine ,Bacterial Pathogens ,Infectious Diseases ,Medical Microbiology ,Medicine ,Cytokines ,Female ,Pathogens ,Cellular Types ,Cellular Structures and Organelles ,Research Article ,Attenuated Vaccines ,Infectious Disease Control ,Salmonella Vaccines ,Science ,Immune Cells ,030106 microbiology ,Immunology ,chemical and pharmacologic phenomena ,Cytotoxic T cells ,Electrons ,Vaccines, Attenuated ,Microbiology ,03 medical and health sciences ,Immune system ,Antigen ,Enterobacteriaceae ,medicine ,Animals ,Microbial Pathogens ,Salmonella Infections, Animal ,Blood Cells ,Bacteria ,Organisms ,Biology and Life Sciences ,Dendritic cell ,Cell Biology ,Dendritic Cells ,Molecular Development ,In vitro ,Mice, Inbred C57BL ,030104 developmental biology ,Vaccines, Inactivated ,Immune System ,Developmental Biology - Abstract
This study investigates the microbiological and immunological basis underlying the efficacy of electron beam-inactivated immune modulators. The underlying hypothesis is that exposure to eBeam-based ionization reactions inactivate microorganisms without modifying their antigenic properties and thereby creating immune modulators. The immunological correlates of protection induced by such eBeam based Salmonella Typhimurium (EBST) immune modulators in dendritic cell (DC) (in vitro) and mice (in vivo) models were assessed. The EBST stimulated innate pro inflammatory response (TNFα) and maturation (MHC-II, CD40, CD80 and CD86) of DC. Immuno-stimulatory potential of EBST was on par with both a commercial Salmonella vaccine, and live Salmonella cells. The EBST cells did not multiply under permissive in vitro and in vivo conditions. However, EBST cells remained metabolically active. EBST immunized mice developed Salmonella-specific CD4+ T-cells that produced the Th1 cytokine IFNγ at a level similar to that induced by the live attenuated vaccine (AroA- ST) formulation. The EBST retained stable immunogenic properties for several months at room temperature, 4°C, and -20°C as well as after lyophilization. Therefore, such eBeam-based immune modulators have potential as vaccine candidates since they offer the safety of a “killed” vaccine, while retaining the immunogenicity of an “attenuated” vaccine. The ability to store eBeam based immune modulators at room temperature without loss of potency is also noteworthy.
- Published
- 2021