Vaccine Design and Vaccination Strategies against Rickettsiae

Abstract

Rickettsioses are febrile, potentially lethal infectious diseases that are a serious health threat, especially in poor income countries. The causative agents are small obligate intracellular bacteria, rickettsiae. Rickettsial infections are emerging worldwide with increasing incidence and geographic distribution. Nonetheless, these infections are clearly underdiagnosed because methods of diagnosis are still limited and often not available. Another problem is that the bacteria respond to only a few antibiotics, so delayed or wrong antibiotic treatment often leads to a more severe outcome of the disease. In addition to that, the development of antibiotic resistance is a serious threat because alternative antibiotics are missing. For these reasons, prophylactic vaccines against rickettsiae are urgently needed. In the past years, knowledge about protective immunity against rickettsiae and immunogenic determinants has been increasing and provides a basis for vaccine development against these bacterial pathogens. This review provides an overview of experimental vaccination approaches against rickettsial infections and perspectives on vaccination strategies.

Keywords: immunity; orientia; rickettsiae; vaccination.

Figure 1

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.