Experimental approaches of vaccination against rickettsiae. The figure shows all so far described approaches of vaccination against rickettsiae and names strains and antigens. WCA immunization was performed with either inactivated bacteria or avirulent strains. In addition, an attenuated knockout strain of R. prowazekii that lacks phospholipase D was generated and used for immunization in experimental infection of mice. The vast majority of vaccinations were performed with recombinant proteins, fusion proteins, or peptides. Other methods include recombinant protein coupled to nanoparticles, bacteria (M. vaccae), or transfected cells that express rickettsial antigens and DCs that were pulsed with recombinant protein. mRNA vaccination and vaccination with adenoviral vectors as they are used now for the immunization against SARS-Cov2 with great success have not been applied yet, but represent great new tools that should be taken under consideration.