Research project supported by the Swedish Research Council.
Tularemia is caused by a highly infectious bacterium, Francisella tularensis and the disease is a public health problem in endemic areas in Sweden. Therefore, there is a need of an efficacious vaccine and we have a promising vaccine candidate. We are using immunological methods to characterize the immune response in tularemia patients and in vaccinees to obtain data that can used to license the vaccine in the future.
Francisella tularensis (Ft) is a highly virulent facultative intracellular bacterium that causes the severe disease tularemia in humans and many mammalian species. It can be disseminated by the aerosol route, has an extremely low infectious dose, and causes severe morbidity. Natural outbreaks of tularemia are occurring over the Northern hemisphere and a significant health problem, in particular in parts of Sweden and Finland. Here, more than 10,000 cases have been reported during the last 30 years; with a prominent increase during the last 10 years, e.g., > 1,000 cases in Sweden during autumn 2019. We have demonstrated that local incidences during years with outbreaks are very high, 400 - 1,000/100,000; numbers as high as those during influenza epidemics.
Thus, tularemia is a significant public health problem and protecting the population through vaccination would lead to considerable health gains. There is a live vaccine strain (LVS) empirically derived in the 1950’s, but it confers incomplete protection. We hypothesize that a more efficacious vaccine will be possible to develop, and our ongoing work is aimed to develop models that can identify the efficacy of new vaccines. We have so far generated a promising candidate vaccine, ∆clpB, which is highly attenuated and demonstrates better protective efficacy than does LVS. The overall aim of the ongoing work is to identify correlates of protection to validate the utility of this new vaccine, which in turn requires a comprehensive understanding of protective host immune responses.
The ongoing work is based on state of the art in vitro methods and several co-culture models, including a human model, will be used to characterize the immune responses to F. tularensis. The work will be essential for the future licensing of an efficacious vaccine. The licensing of an efficacious vaccine will be important, since tularemia is a significant public health problem in areas in Sweden and Finland. Moreover, due to the low likelihood of re-exposure, tularemia offers a unique model for understanding the longevity of cellular immune response in general.
Helena Lindgren, Kjell Eneslätt, Igor Golovliov, Carl Gelhaus, Patrik Rydén, Terry Wu, Wayne Conlan and Anders Sjöstedt. (2020) Vaccine-mediated Mechanisms Controlling Francisella tularensis SCHU S4 in a Rat co-culture system. Pathogens. 10.3390/pathogens9050338.
Nasibeh Mohammadi, Helena Lindgren, Igor Golovliov, Kjell Eneslätt, Masahiro Yamamoto, Amandine Martin, Thomas Henry, and Anders Sjöstedt. (2020) A critical role of Guanylate-binding proteins for effective killing of Francisella tularensis strains in a mouse co-culture system. Frontiers in Cellular and Infection Microbiology. https://doi.org/10.3389/fcimb.2020.594063
Kjell Eneslätt, Igor Golovliov, Patrik Ryden, and Anders Sjöstedt. (2018) An assay for assessment of vaccine-mediated mechanisms controlling growth of Francisella tularensis in human peripheral blood mononuclear cells. Frontiers in Cellular and Infection Microbiology. 8:27.doi: 10.3389/fcimb.2018.00027.