Extraction of Protective Components of Rickettsia rickettsii with n-Octyl- -D-Glucopyranoside

McDonald, Gregory A.; Anacker, R. L.; Mann, R E

doi:10.1093/cid/10.supplement_2.s382

Cited by 2 publications

(1 citation statement)

References 21 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Historically, multiple strategies have been employed to develop a protective vaccine against rickettsioses, including the use of killed whole bacteria, subunits, recombinant antigens, and live attenuated strains [ 8 , 9 , 10 , 11 ]. The first live vaccine against R. prowazekii was generated after World War II by serial passage in hens’ eggs, yielding an attenuated strain, Madrid E, which prevented or reduced disease from louse-borne typhus, although it caused mild typhus in about 14% of vaccinated persons [ 10 , 12 , 13 ].…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2021

View full text Add to dashboard Cite

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 Rickettsia parkeri 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, R. parkeri 3A2 expressed mCherry fluorescence and resistance to spectinomycin. Compared to the parent wild type (WT) R. parkeri, the virulence of R. parkeri 3A2 was significantly attenuated as demonstrated by significantly smaller size of plaque, failure to grow in human macrophage-like cells, rapid elimination of Rickettsia and ameliorated histopathological changes in tissues in intravenously infected mice. A single dose intradermal (i.d.) immunization of R. parkeri 3A2 conferred complete protection against both fatal R. parkeri and R. conorii rickettsioses in mice, in association with a robust and durable rickettsiae-specific IgG antibody response. In summary, the disruption of RPATATE_0245 in R. parkeri 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 R. parkeri mutants as a live-attenuated and multivalent vaccine platform in response to emergence of life-threatening spotted fever rickettsioses.

show abstract

Section: Introductionmentioning

confidence: 99%

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

et al. 2021

View full text Add to dashboard Cite

show abstract

Differential activity of Rickettsia rickettsii ompA and ompB promoter regions in a heterologous reporter gene system

Policastro¹,

Hackstadt²

1994

Microbiology

View full text Add to dashboard Cite

The outer membrane of the Gram-negative obligate intracellular parasite Rickettsia rickettsii contains t w o large surface protein antigens with approximate molecular masses of 200 and 135 kDa termed rOmpA and rOmpB, respectively. rOmpB is the most abundant protein in the outer membrane, while rOmpA i s a relatively minor constituent. Densitometry of intrinsically radiolabelled protein profiles from R. rickettsii-infected Vero cells indicated a molar ratio of approximately 1 :9 between rOmpA and rOmpB. The putative promoter-5' untranslated regions (5' UTR) from their recently characterized genes (rompA and rompB) were placed in the promoter assay vector pKK232-8 t o test whether these elements conserve aspects of differential expression in a heterologous host-reporter system. Primer extension analysis of RNA from Escherichia coli clones containing the constructs indicated that E. coli RNA polymerase faithfully utilizes mmpA and mmpB transcription start sites identified previously in R. rickettsii. The rompB insert directs 28-fold higher levels of chloramphenicol acetyl transferase activity than the rompA insert.

show abstract

Extraction of Protective Components of Rickettsia rickettsii with n-Octyl- -D-Glucopyranoside

Cited by 2 publications

References 21 publications

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

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

Differential activity of Rickettsia rickettsii ompA and ompB promoter regions in a heterologous reporter gene system

Contact Info

Product

Resources

About