<i>Rickettsia parkeri</i> with a Genetically Disrupted Phage Integrase Gene Exhibits Attenuated Virulence and Induces Protective Immunity against Fatal Rickettsioses in Mice

oleh: Esteban Arroyave, Ilirjana Hyseni, Nicole Burkhardt, Yong-Fang Kuo, Tian Wang, Ulrike Munderloh, Rong Fang

Format: Article
Diterbitkan: MDPI AG 2021-06-01

Deskripsi

Although rickettsiae can cause life-threatening infections in humans worldwide, no licensed vaccine is currently available. To evaluate the suitability of live-attenuated vaccine candidates against rickettsioses, we generated a <i>Rickettsia parkeri</i> mutant RPATATE_0245::pLoxHimar (named 3A2) by insertion of a modified pLoxHimar transposon into the gene encoding a phage integrase protein. For visualization and selection, <i>R. parkeri</i> 3A2 expressed mCherry fluorescence and resistance to spectinomycin. Compared to the parent wild type (WT) <i>R. parkeri</i>, the virulence of <i>R. parkeri</i> 3A2 was significantly attenuated as demonstrated by significantly smaller size of plaque, failure to grow in human macrophage-like cells, rapid elimination of <i>Rickettsia</i> and ameliorated histopathological changes in tissues in intravenously infected mice. A single dose intradermal (i.d.) immunization of <i>R. parkeri</i> 3A2 conferred complete protection against both fatal <i>R. parkeri</i> and <i>R. conorii</i> rickettsioses in mice, in association with a robust and durable rickettsiae-specific IgG antibody response. In summary, the disruption of RPATATE_0245 in <i>R. parkeri</i> resulted in a mutant with a significantly attenuated phenotype, potent immunogenicity and protective efficacy against two spotted fever group rickettsioses. Overall, this proof-of-concept study highlights the potential of <i>R. parkeri</i> mutants as a live-attenuated and multivalent vaccine platform in response to emergence of life-threatening spotted fever rickettsioses.