title: Failure of a heterologous recombinant Sca5/OmpB protein-based vaccine to elicit effective protective immunity against Rickettsia rickettsii infections in C3H/HeN mice.
abstract: Spotted fever group (SFG) rickettsial species are obligate intracellular tick-borne pathogens that are responsible for important human diseases. Previous reports have demonstrated the feasibility of using recombinant surface cell antigen Sca5/OmpB to elicit protective immunity against homologous challenges using murine models of Mediterranean spotted fever and Rocky Mountain spotted fever. In addition, the feasibility of generating cross-protective immunity against related rickettsial species has also been established, but the molecular basis for these phenomena was not explored. Here, we demonstrate that vaccination of C3H/HeN mice with a recombinant OmpB domain derived from Rickettsia conorii induced high titer humoral immune responses that are capable of recognizing the native OmpB protein at the R. rickettsii outer membrane, but this immunization was not sufficient to induce effective protective immunity. In contrast, animals vaccinated with a corresponding OmpB domain derived from R. rickettsii protected animals from fatal outcomes. These results demonstrate that vaccination with nearly identical antigens may not be an effective strategy to induce wide-ranging protective immunity against related SFG Rickettsia species.
authors.affiliation: University of Chicago, Department of Microbiology, Chicago, IL 60637, USA Howard T. Ricketts Laboratory, Argonne, IL 60439, USA Vector-Borne Disease Laboratories, Department of Pathobiological Sciences, Louisiana State University School of Veterinary Medicine, Baton Rouge, LA 70803, USA.
authors.forename: Sean P
authors.initials: SP
authors.lastname: Riley
authors.affiliation: University of Chicago, Department of Microbiology, Chicago, IL 60637, USA Howard T. Ricketts Laboratory, Argonne, IL 60439, USA.
authors.forename: Marissa M
authors.initials: MM
authors.lastname: Cardwell
authors.affiliation: University of Chicago, Department of Microbiology, Chicago, IL 60637, USA Howard T. Ricketts Laboratory, Argonne, IL 60439, USA.
authors.forename: Yvonne G Y
authors.initials: YG
authors.lastname: Chan
authors.affiliation: Vector-Borne Disease Laboratories, Department of Pathobiological Sciences, Louisiana State University School of Veterinary Medicine, Baton Rouge, LA 70803, USA.
authors.forename: Ludovic
authors.initials: L
authors.lastname: Pruneau
authors.affiliation: Vector-Borne Disease Laboratories, Department of Pathobiological Sciences, Louisiana State University School of Veterinary Medicine, Baton Rouge, LA 70803, USA.
authors.forename: Fabio
authors.initials: F
authors.lastname: Del Piero
authors.affiliation: University of Chicago, Department of Microbiology, Chicago, IL 60637, USA Howard T. Ricketts Laboratory, Argonne, IL 60439, USA Vector-Borne Disease Laboratories, Department of Pathobiological Sciences, Louisiana State University School of Veterinary Medicine, Baton Rouge, LA 70803, USA jmartinez@lsu.edu.
authors.forename: Juan J
authors.initials: JJ
authors.lastname: Martinez
mesh_terms: D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood; D000942:Antigens, Bacterial / Q000235:genetics / Q000276:immunology*; D001425:Bacterial Outer Membrane Proteins / Q000235:genetics / Q000276:immunology*; D001428:Bacterial Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D056738:Cross Protection; D003429:Cross Reactions; D004195:Disease Models, Animal; D008297:Male; D008809:Mice, Inbred C3H; D020114:Rickettsia conorii / Q000235:genetics / Q000276:immunology*; D012284:Rickettsia rickettsii / Q000235:genetics / Q000276:immunology*; D012373:Rocky Mountain Spotted Fever / Q000276:immunology / Q000517:prevention & control*; D016019:Survival Analysis; D022223:Vaccines, Subunit / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology
chemical_list: D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; D001425:Bacterial Outer Membrane Proteins; D001428:Bacterial Vaccines; D022223:Vaccines, Subunit; D014614:Vaccines, Synthetic
keywords: C3H/HeN mice; OmpB; Rickettsia conorii; Rickettsia rickettsii; protective immunity; spotted fever group