A Francisella tularensis live vaccine strain that improves stimulation of antigen-presenting cells does not enhance vaccine efficacy.

PloS One
Deanna M SchmittGerard J Nau

Abstract

Vaccination is a proven strategy to mitigate morbidity and mortality of infectious diseases. The methodology of identifying and testing new vaccine candidates could be improved with rational design and in vitro testing prior to animal experimentation. The tularemia vaccine, Francisella tularensis live vaccine strain (LVS), does not elicit complete protection against lethal challenge with a virulent type A Francisella strain. One factor that may contribute to this poor performance is limited stimulation of antigen-presenting cells. In this study, we examined whether the interaction of genetically modified LVS strains with human antigen-presenting cells correlated with effectiveness as tularemia vaccine candidates. Human dendritic cells infected with wild-type LVS secrete low levels of proinflammatory cytokines, fail to upregulate costimulatory molecules, and activate human T cells poorly in vitro. One LVS mutant, strain 13B47, stimulated higher levels of proinflammatory cytokines from dendritic cells and macrophages and increased costimulatory molecule expression on dendritic cells compared to wild type. Additionally, 13B47-infected dendritic cells activated T cells more efficiently than LVS-infected cells. A deletion allele of ...Continue Reading

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Citations

Oct 22, 2014·Journal of Immunology Research·Julia A TreeCaroline A Rowland
Jun 26, 2013·Cellular Microbiology·Ivo FabrikJiri Stulik
Nov 28, 2013·Journal of Fish Diseases·M Rozas, R Enríquez
Dec 6, 2012·Microbes and Infection·Deanna M SchmittGerard J Nau
Mar 27, 2013·Infection and Immunity·Lydia M BarriganJeffrey A Frelinger
Jun 6, 2018·Frontiers in Cellular and Infection Microbiology·Qingmei Jia, Marcus A Horwitz
Aug 28, 2021·Antibiotics·Kendall SouderDeanna M Schmitt

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Methods Mentioned

BETA
PCR
flow cytometry
FACS
ELISA
ELISAs
genetic modifications

Software Mentioned

Milliplex Analyst
FlowJo

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