A Vaccine for Canine Rocky Mountain Spotted Fever: An Unmet One Health Need
Abstract
:1. Introduction
2. The Current Status of the One Health Canine-Brown Dog Tick-Rickettsia rickettsii Threat
3. Clinical and Epidemiological Significance of Rocky Mountain Spotted Fever
4. Brown Dog Ticks as Vectors of Rickettsia rickettsii
5. Potential Vaccine Strategies
6. Prospects for an Effective Subunit Vaccine
7. Prospects for a Live Attenuated Vaccine
8. Scope of Rickettsial Mutants for Vaccine Development
9. Summary
Funding
Acknowledgments
Conflicts of Interest
References
- Breitschwerdt, E.B.; Meuten, D.J.; Walker, D.H.; Levy, M.; Kennedy, K.; King, M.; Curtis, B. Canine Rocky Mountain spotted fever: A kennel epizootic. Am. J. Vet. Res. 1985, 46, 2124–2128. [Google Scholar] [PubMed]
- Gasser, A.M.; Birkenheuer, A.J.; Breitschwerdt, E.B. Canine Rocky Mountain Spotted fever: A retrospective study of 30 cases. J. Am. Anim. Hosp. Assoc. 2001, 37, 41–48. [Google Scholar] [CrossRef]
- Keenan, K.P.; Buhles, W.C., Jr.; Huxsoll, D.L.; Williams, R.G.; Hildebrandt, P.K.; Campbell, J.M.; Stephenson, E.H. Pathogenesis of infection with Rickettsia rickettsii in the dog: A disease model for Rocky Mountain spotted fever. J. Infect. Dis. 1977, 135, 911–917. [Google Scholar] [CrossRef] [PubMed]
- Keenan, K.P.; Buhles, W.C., Jr.; Huxsoll, D.L.; Williams, R.G.; Hildebrandt, P.K. Studies on the pathogenesis of Rickettsia rickettsii in the dog: Clinical and clinicopathologic changes of experimental infection. Am. J. Vet. Res. 1977, 38, 851–856. [Google Scholar]
- Breitschwerdt, E.B.; Walker, D.H.; Levy, M.G.; Burgdorfer, W.; Corbett, W.T.; Hurlbert, S.A.; Stebbins, M.E.; Curtis, B.C.; Allen, D.A. Clinical, hematologic, and humoral immune response in female dogs inoculated with Rickettsia rickettsii and Rickettsia montana. Am. J. Vet. Res. 1988, 49, 70–76. [Google Scholar] [PubMed]
- Piranda, E.M.; Faccini, J.L.; Pinter, A.; Saito, T.B.; Pacheco, R.C.; Hagiwara, M.K.; Labruna, M.B. Experimental infection of dogs with a Brazilian strain of Rickettsia rickettsii: Clinical and laboratory findings. Mem. Inst. Oswaldo Cruz 2008, 103, 696–701. [Google Scholar] [CrossRef]
- Álvarez-Hernández, G.; Roldán, J.F.G.; Milan, N.S.H.; Lash, R.R.; Behravesh, C.B.; Paddock, C.D. Rocky Mountain spotted fever in Mexico: Past, present, and future. Lancet Infect. Dis. 2017, 17, e189–e196. [Google Scholar] [CrossRef]
- Bustamante, M.E.; Varela, G. Una nueva rickettsiosis en México. Existencia de la fiebre manchada Americana en los estados de Sinaloa y Sonora. Rev. Inst. Salub. Enf. Trop. 1943, 4, 189–211. [Google Scholar]
- Bustamante, M.E.; Varela, G. Características de la fiebre manchada de las Montañas Rocosas en Sonora y Sinaloa, México (estudio de 12 casos y dos cepas). Rev. Inst. Salub. Enf. Trop. 1944, 5, 129–134. [Google Scholar]
- Bustamante, M.E.; Varela, G.; Ortiz-Mariotte, C., II. Estudios de fiebre manchada en México. Fiebre manchada en La Laguna. Rev. Inst. Salub. Enf. Trop. 1946, 7, 39–49. [Google Scholar]
- Bustamante, M.E.; Varela, G., IV. Estudios de fiebre manchada en Mexico. Papel del Rhipicephalus sanguineus en la transmisión de la fiebre manchada en la República Mexicana. Rev. Inst. Salub. Enf. Trop. 1947, 7, 139–144. [Google Scholar]
- Ortiz Mariotte, C.; Bustamante, M.E.; Varela, G. Hallazgo del Rhipicephalus sanguineus Latreille infectado naturalmente con fiebre manchada de las Montañas Rocosas, en Sonora (Mexico). Rev. Inst. Salub. Enf. Trop. 1944, 5, 297–300. [Google Scholar]
- Silva-Goytia, R.; Elizondo, A. Estudios sobre fiebre manchada en México. IV. Características epidemiológicas de casos de fiebre manchada ocurridos en La Laguna. Med. Rev. Mex. 1952, 2, 569–579. [Google Scholar]
- De Lara Huerta, J.; Barragán, R.C. Fiebre manchada de las Montañas Rocosas en pediatría. Revisión clínica de una serie de 115 casos. Rev. Enf. Infec. Ped. 2008, 22, 4–9. [Google Scholar]
- Eremeeva, M.E.; Zambrano, M.L.; Anaya, L.; Beati, L.; Karpathy, S.E.; Santos-Silva, M.M.; Salceda, B.; MacBeth, D.; Olguin, H.; Dasch, G.A.; et al. Rickettsia rickettsii in Rhipicephalus ticks, Mexicali, Mexico. J. Med. Entomol. 2011, 48, 418–421. [Google Scholar] [CrossRef] [PubMed]
- Zazueta, O.E.; Armstrong, P.A.; Márquez-Elguea, A.; Hernández Milán, N.S.; Peterson, A.E.; Ovalle-Marroquín, D.F.; Fierro, M.; Arroyo-Machado, R.; Rodriguez-Lomeli, M.; Trejo-Dozal, G.; et al. Rocky Mountain Spotted Fever in a Large Metropolitan Center, Mexico-United States Border, 2009–2019. Emerg. Infect. Dis. 2021, 27, 1567–1576. [Google Scholar] [CrossRef]
- Tinoco-Gracia, L.; Lomelí, M.R.; Hori-Oshima, S.; Stephenson, N.; Foley, J. Molecular Confirmation of Rocky Mountain Spotted Fever Epidemic Agent in Mexicali, Mexico. Emerg. Infect. Dis. 2018, 24, 1723–1725. [Google Scholar] [CrossRef]
- López-Pérez, A.M.; Orozco, L.; Zazueta, O.E.; Fierro, M.; Gomez, P.; Foley, J. An exploratory analysis of demography and movement patterns of dogs: New insights in the ecology of endemic Rocky Mountain-Spotted Fever in Mexicali, Mexico. PLoS ONE 2020, 15, e0233567. [Google Scholar] [CrossRef]
- Demma, L.J.; Traeger, M.S.; Nicholson, W.L.; Paddock, C.D.; Blau, D.M.; Eremeeva, M.E.; Dasch, G.A.; Levin, M.L.; Singleton, J., Jr.; Zaki, S.R.; et al. Rocky Mountain spotted fever from an unexpected tick vector in Arizona. N. Engl. J. Med. 2005, 353, 587–594. [Google Scholar] [CrossRef]
- Nicholson, W.L.; Paddock, C.D.; Demma, L.; Traeger, M.; Johnson, B.; Dickson, J.; McQuiston, J.; Swerdlow, D. Rocky Mountain spotted fever in Arizona: Documentation of heavy environmental infestations of Rhipicephalus sanguineus at an endemic site. Ann. N. Y. Acad. Sc.i 2006, 1078, 338–341. [Google Scholar] [CrossRef]
- Traeger, M.S.; Regan, J.J.; Humpherys, D.; Mahoney, D.L.; Martinez, M.; Emerson, G.L.; Tack, D.M.; Geissler, A.; Yasmin, S.; Lawson, R.; et al. Rocky mountain spotted fever characterization and comparison to similar illnesses in a highly endemic area-Arizona, 2002–2011. Clin. Infect. Dis. 2015, 60, 1650–1658. [Google Scholar] [CrossRef] [PubMed]
- Alhassan, A.; Liu, H.; McGill, J.; Cerezo, A.; Jakkula, L.U.M.R.; Nair, A.D.S.; Winkley, E.; Olson, S.; Marlow, D.; Sahni, A.; et al. Rickettsia rickettsii Whole-Cell Antigens Offer Protection against Rocky Mountain Spotted Fever in the Canine Host. Infect. Immun. 2019, 87, e00628-18. [Google Scholar] [CrossRef]
- Spencer, R.R.; Parker, R.R. Rocky Mountain spotted fever: Vaccination of monkeys and man. Public Health Rep. 1925, 40, 2159–2167. [Google Scholar] [CrossRef]
- Parker, R.R. Rocky Mountain spotted fever: Results of fifteen years’ prophylactic vaccination. Am. J. Trop. Med. 1941, 21, 369–383. [Google Scholar] [CrossRef]
- Cox, H.R. Use of yolk sac of developing chick embryo as medium for growing Rickettsiae of Rocky Mountain spotted fever and typhus groups. Public Health Rep. 1938, 53, 2241–2247. [Google Scholar] [CrossRef]
- DuPont, H.L.; Hornick, R.B.; Dawkins, A.T.; Heiner, G.G.; Fabrikant, I.B.; Wisseman, C.L., Jr.; Woodward, T.E. Rocky Mountain spotted fever: A comparative study of the active immunity induced by inactivated and viable pathogenic Rickettsia rickettsii. J. Infect. Dis. 1973, 128, 340–344. [Google Scholar] [CrossRef] [PubMed]
- Kenyon, R.H.; Pedersen, C.E., Jr. Preparation of Rocky Mountain spotted fever vaccine suitable for human immunization. J. Clin. Microbiol. 1975, 1, 500–503. [Google Scholar] [CrossRef] [PubMed]
- Clements, M.L.; Wisseman, C.L., Jr.; Woodward, T.E.; Fiset, P.; Dumler, J.S.; McNamee, W.; Black, R.E.; Rooney, J.; Hughes, T.P.; Levine, M.M. Reactogenicity, immunogenicity, and efficacy of a chick embryo cell-derived vaccine for Rocky Mountain spotted fever. J. Infect. Dis. 1983, 148, 922–930. [Google Scholar] [CrossRef]
- Helmick, C.G.; Bernard, K.W.; D’Angelo, L.J. Rocky Mountain spotted fever: Clinical, laboratory, and epidemiological features of 262 cases. J. Infect. Dis. 1984, 150, 480–488. [Google Scholar] [CrossRef]
- Holman, R.C.; Paddock, C.D.; Curns, A.T.; Krebs, J.W.; McQuiston, J.H.; Childs, J.E. Analysis of risk factors for fatal Rocky Mountain Spotted Fever: Evidence for superiority of tetracyclines for therapy. J. Infect. Dis. 2001, 184, 1437–1444. [Google Scholar] [CrossRef]
- Biggs, H.M.; Behravesh, C.B.; Bradley, K.K.; Dahlgren, F.S.; Drexler, N.A.; Dumler, J.S.; Folk, S.M.; Kato, C.Y.; Lash, R.R.; Levin, M.L.; et al. Diagnosis and Management of Tickborne Rickettsial Diseases: Rocky Mountain Spotted Fever and Other Spotted Fever Group Rickettsioses, Ehrlichioses, and Anaplasmosis—United States. MMWR Recomm. Rep. 2016, 65, 1–44. [Google Scholar] [CrossRef] [PubMed]
- Regan, J.J.; Traeger, M.S.; Humpherys, D.; Mahoney, D.L.; Martinez, M.; Emerson, G.L.; Tack, D.M.; Geissler, A.; Yasmin, S.; Lawson, R.; et al. Risk factors for fatal outcome from rocky mountain spotted Fever in a highly endemic area-Arizona, 2002–2011. Clin. Infect. Dis. 2015, 60, 1659–1666. [Google Scholar] [CrossRef] [PubMed]
- Kirkland, K.B.; Wilkinson, W.E.; Sexton, D.J. Therapeutic delay and mortality in cases of Rocky Mountain spotted fever. Clin. Infect. Dis. 1995, 20, 1118–1121. [Google Scholar] [CrossRef] [PubMed]
- Donohue, J.F. Lower respiratory tract involvement in Rocky Mountain spotted fever. Arch. Intern. Med. 1980, 140, 223–227. [Google Scholar] [CrossRef] [PubMed]
- Kirkland, K.B.; Marcom, P.K.; Sexton, D.J.; Dumler, J.S.; Walker, D.H. Rocky Mountain spotted fever complicated by gangrene: Report of six cases and review. Clin. Infect. Dis. 1993, 16, 629–634. [Google Scholar] [CrossRef] [PubMed]
- Archibald, L.K.; Sexton, D.J. Long-term sequelae of Rocky Mountain spotted fever. Clin. Infect. Dis. 1995, 20, 1122–1125. [Google Scholar] [CrossRef] [PubMed]
- Bradshaw, M.J.; Byrge, K.C.; Ivey, K.S.; Pruthi, S.; Bloch, K.C. Meningoencephalitis due to Spotted Fever Rickettsioses, Including Rocky Mountain Spotted Fever. Clin. Infect. Dis. 2020, 71, 188–195. [Google Scholar] [CrossRef]
- Smadel, J.E. Status of the rickettsioses in the United States. Ann. Intern. Med. 1959, 51, 421–435. [Google Scholar] [CrossRef]
- Drexler, N.A.; Dahlgren, F.S.; Heitman, K.N.; Massung, R.F.; Paddock, C.D.; Behravesh, C.B. National Surveillance of Spotted Fever Group Rickettsioses in the United States, 2008–2012. Am. J. Trop. Med. Hyg. 2016, 94, 26–34. [Google Scholar] [CrossRef]
- Walker, D.H.; Paddock, C.D.; Dumler, J.S. Emerging and re-emerging tick-transmitted rickettsial and ehrlichial infections. Med. Clin. N. Am. 2008, 92, 1345–1361. [Google Scholar] [CrossRef]
- Centers for Disease Control and Prevention (CDC). Fatal cases of Rocky Mountain spotted fever in family clusters--three states, 2003. MMWR Morb. Mortal. Weekly Rep. 2004, 53, 407–410. [Google Scholar]
- Dalton, M.J.; Clarke, M.J.; Holman, R.C.; Krebs, J.W.; Fishbein, D.B.; Olson, J.G.; Childs, J.E. National surveillance for Rocky Mountain spotted fever, 1981–1992: Epidemiologic summary and evaluation of risk factors for fatal outcome. Am. J. Trop. Med. Hyg. 1995, 52, 405–413. [Google Scholar] [CrossRef]
- Treadwell, T.A.; Holman, R.C.; Clarke, M.J.; Krebs, J.W.; Paddock, C.D.; Childs, J.E. Rocky Mountain spotted fever in the United States, 1993-1996. Am. J. Trop. Med. Hyg. 2000, 63, 21–26. [Google Scholar] [CrossRef] [PubMed]
- Folkema, A.M.; Holman, R.C.; McQuiston, J.H.; Cheek, J.E. Trends in clinical diagnoses of Rocky Mountain spotted fever among American Indians, 2001-2008. Am. J. Trop. Med. Hyg. 2012, 86, 152–158. [Google Scholar] [CrossRef]
- Newhouse, V.F.; D’Angelo, L.J.; Holman, R.C. DDT use and the incidence of Rocky Mountain spotted fever: A hypothesis. Environ. Entomol. 1979, 8, 777–781. [Google Scholar] [CrossRef]
- Álvarez-López, D.I.; Ochoa-Mora, E.; Nichols Heitman, K.; Binder, A.M.; Álvarez-Hernández, G.; Armstrong, P.A. Epidemiology and Clinical Features of Rocky Mountain Spotted Fever from Enhanced Surveillance, Sonora, Mexico: 2015–2018. Am. J. Trop. Med. Hyg. 2021, 104, 190–197. [Google Scholar] [CrossRef]
- Labruna, M.B. Ecology of rickettsia in South America. Ann. N. Y. Acad. Sci. 2009, 1166, 156–166. [Google Scholar] [CrossRef] [PubMed]
- Szabo, M.P.; Pinter, A.; Labruna, M.B. Ecology, biology and distribution of spotted-fever tick vectors in Brazil. Front. Cell Infect. Microbiol. 2013, 3, 27. [Google Scholar] [CrossRef]
- Angerami, R.N.; Resende, M.R.; Feltrin, A.F.; Katz, G.; Nascimento, E.M.; Stucchi, R.S.; Silva, L.J. Brazilian spotted fever: A case series from an endemic area in southeastern Brazil: Clinical aspects. Ann. N. Y. Acad. Sci. 2006, 1078, 252–254. [Google Scholar] [CrossRef]
- Alkmim, M.A.; Ferreira, L.L.; Bastianetto, E.; Bastos, C.V.E.; Silveira, J.A.G.D. Report of Amblyomma sculptum in a House in a Rickettsia rickettsii Circulation Area. Vector Borne Zoonotic Dis. 2021, 21, 388–390. [Google Scholar] [CrossRef]
- Pacheco, R.C.; Moraes-Filho, J.; Guedes, E.; Silveira, I.; Richtzenhain, L.J.; Leite, R.C.; Labruna, M.B. Rickettsial infections of dogs, horses and ticks in Juiz de Fora, southeastern Brazil, and isolation of Rickettsia rickettsii from Rhipicephalus sanguineus ticks. Med. Vet. Entomol. 2011, 25, 148–155. [Google Scholar] [CrossRef] [PubMed]
- Pinter, A.; Horta, M.C.; Pacheco, R.C.; Moraes-Filho, J.; Labruna, M.B. Serosurvey of Rickettsia spp. in dogs and humans from an endemic area for Brazilian spotted fever in the State of São Paulo, Brazil. Cad. Saude Publica 2008, 24, 247–252. [Google Scholar] [CrossRef] [PubMed]
- Moraes-Filho, J.; Pinter, A.; Pacheco, R.C.; Gutmann, T.B.; Barbosa, S.O.; Gonzáles, M.A.; Muraro, M.A.; Cecílio, S.R.; Labruna, M.B. New epidemiological data on Brazilian spotted fever in an endemic area of the state of São Paulo, Brazil. Vector Borne Zoonotic Dis. 2009, 9, 73–78. [Google Scholar] [CrossRef]
- Savani, E.S.M.M.; Costa, F.B.; Silva, E.A.; Couto, A.C.F.; Gutjahr, M.; Alves, J.N.M.O.; Santos, F.C.P.; Labruna, M.B. Fatal Brazilian Spotted Fever Associated with Dogs and Amblyomma aureolatum Ticks, Brazil, 2013. Emerg. Infect. Dis. 2019, 25, 2322–2323. [Google Scholar] [CrossRef]
- Patino, L.; Afanador, A.; Paul, J.H. A spotted fever in Tobia, Colombia. 1937. Biomedica 2006, 26, 178–193. [Google Scholar] [CrossRef]
- Hidalgo, M.; Orejuela, L.; Fuya, P.; Carrillo, P.; Hernandez, J.; Parra, E.; Keng, C.; Small, M.; Olano, J.P.; Bouyer, D.; et al. Rocky Mountain spotted fever, Colombia. Emerg. Infect. Dis. 2007, 13, 1058–1060. [Google Scholar] [CrossRef]
- Hidalgo, M.; Miranda, J.; Heredia, D.; Zambrano, P.; Vesga, J.F.; Lizarazo, D.; Mattar, S.; Valbuena, G. Outbreak of Rocky Mountain spotted fever in Córdoba, Colombia. Mem. Inst. Oswaldo Cruz 2011, 106, 117–118. [Google Scholar] [CrossRef] [PubMed]
- Londoño, A.F.; Arango-Ferreira, C.; Acevedo-Gutiérrez, L.Y.; Paternina, L.E.; Montes, C.; Ruiz, I.; Labruna, M.B.; Díaz, F.J.; Walker, D.H.; Rodas, J.D. A Cluster of Cases of Rocky Mountain Spotted Fever in an Area of Colombia Not Known to be Endemic for This Disease. Am. J. Trop. Med. Hyg. 2019, 101, 336–342. [Google Scholar] [CrossRef]
- Nava, S.; Beati, L.; Venzal, J.M.; Labruna, M.B.; Szabó, M.P.J.; Petney, T.; Saracho-Bottero, M.N.; Tarragona, E.L.; Dantas-Torres, F.; Silva, M.M.S.; et al. Rhipicephalus sanguineus (Latreille, 1806): Neotype designation, morphological re-description of all parasitic stages and molecular characterization. Ticks Tick Borne Dis. 2018, 9, 1573–1585. [Google Scholar] [CrossRef]
- Piranda, E.M.; Faccini, J.L.; Pinter, A.; Pacheco, R.C.; Cançado, P.H.; Labruna, M.B. Experimental infection of Rhipicephalus sanguineus ticks with the bacterium Rickettsia rickettsii, using experimentally infected dogs. Vector Borne Zoonotic Dis. 2011, 11, 29–36. [Google Scholar] [CrossRef]
- Blanc, G.C.J. Epidemiological and experimental studies on Boutonneuse fever done at the Pasteur Institute in Athens. Arch. Inst. Pasteur Tunis 1932, 20, 343–394. [Google Scholar]
- Snellgrove, A.N.; Krapiunaya, I.; Ford, S.L.; Stanley, H.M.; Wickson, A.G.; Hartzer, K.L.; Levin, M.L. Vector competence of Rhipicephalus sanguineus sensu stricto for Anaplasma platys. Ticks Tick Borne Dis. 2020, 11, 101517. [Google Scholar] [CrossRef]
- Fourie, J.J.; Stanneck, D.; Luus, H.G.; Beugnet, F.; Wijnveld, M.; Jongejan, F. Transmission of Ehrlichia canis by Rhipicephalus sanguineus ticks feeding on dogs and on artificial membranes. Vet. Parasitol. 2013, 197, 595–603. [Google Scholar] [CrossRef]
- Peniche-Lara, G.; Jimenez-Delgadillo, B.; Dzul-Rosado, K. Rickettsia rickettsii and Rickettsia felis infection in Rhipicephalus sanguineus ticks and Ctenocephalides felis fleas co-existing in a small city in Yucatan, Mexico. J. Vector. Ecol. 2015, 40, 422–424. [Google Scholar] [CrossRef]
- Wikswo, M.E.; Hu, R.; Metzger, M.E.; Eremeeva, M.E. Detection of Rickettsia rickettsii and Bartonella henselae in Rhipicephalus sanguineus ticks from California. J. Med. Entomol. 2007, 44, 158–162. [Google Scholar] [CrossRef]
- Dantas-Torres, F. Biology and ecology of the brown dog tick, Rhipicephalus sanguineus. Parasit Vectors 2010, 3, 26. [Google Scholar] [CrossRef]
- Parola, P.; Socolovschi, C.; Jeanjean, L.; Bitam, I.; Fournier, P.E.; Sotto, A.; Labauge, P.; Raoult, D. Warmer weather linked to tick attack and emergence of severe rickettsioses. PLoS Negl. Trop. Dis. 2008, 2, e338. [Google Scholar] [CrossRef] [PubMed]
- Backus, L.H.; López Pérez, A.M.; Foley, J.E. Effect of Temperature on Host Preference in Two Lineages of the Brown Dog Tick, Rhipicephalus sanguineus. Am. J. Trop. Med. Hyg. 2021, 104, 2305–2311. [Google Scholar] [CrossRef] [PubMed]
- da Silva Costa, L.F.; Nunes, P.H.; Soares, J.F.; Labruna, M.B.; Camargo-Mathias, M.I. Distribution of Rickettsia rickettsii in ovary cells of Rhipicephalus sanguineus (Latreille1806) (Acari: Ixodidae). Parasit. Vectors 2011, 4, 222. [Google Scholar] [CrossRef]
- Parola, P.; Paddock, C.D.; Socolovschi, C.; Labruna, M.B.; Mediannikov, O.; Kernif, T.; Abdad, M.Y.; Stenos, J.; Bitam, I.; Fournier, P.E.; et al. Update on tick-borne rickettsioses around the world: A geographic approach. Clin. Microbiol. Rev. 2013, 26, 657–702, Erratum in Clin. Microbiol. Rev. 2014, 27, 166. [Google Scholar] [CrossRef] [Green Version]
- Socolovschi, C.; Gaudart, J.; Bitam, I.; Huynh, T.P.; Raoult, D.; Parola, P. Why are there so few Rickettsia conorii conorii-infected Rhipicephalus sanguineus ticks in the wild? PLoS Negl. Trop. Dis. 2012, 6, e1697. [Google Scholar] [CrossRef]
- Ioffe-Uspensky, I.; Mumcuoglu, K.Y.; Uspensky, I.; Galun, R. Rhipicephalus sanguineus and R. turanicus (Acari:Ixodidae): Closely related species with different biological characteristics. J. Med. Entomol. 1997, 34, 74–81. [Google Scholar] [CrossRef] [PubMed]
- Coimbra-Dores, M.J.; Nunes, T.; Dias, D.; Rosa, F. Rhipicephalus sanguineus (Acari: Ixodidae) species complex: Morphometric and ultrastructural analyses. Exp. Appl. Acarol. 2016, 70, 455–468. [Google Scholar] [CrossRef]
- Beati, L.; Raoult, D. Rickettsia massiliae sp. nov., a new spotted fever group Rickettsia. Int. J. Syst. Bacteriol. 1993, 43, 839–840. [Google Scholar] [CrossRef]
- Matsumoto, K.; Ogawa, M.; Brouqui, P.; Raoult, D.; Parola, P. Transmission of Rickettsia massiliae in the tick, Rhipicephalus turanicus. Med. Vet. Entomol. 2005, 19, 263–270. [Google Scholar] [CrossRef] [PubMed]
- Kenyon, R.H.; Sammons, L.S.; Pedersen, C.E., Jr. Comparison of three rocky mountain spotted fever vaccines. J. Clin. Microbiol. 1975, 2, 300–304. [Google Scholar] [CrossRef]
- Díaz-Montero, C.M.; Feng, H.M.; Crocquet-Valdes, P.A.; Walker, D.H. Identification of protective components of two major outer membrane proteins of spotted fever group Rickettsiae. Am. J. Trop. Med. Hyg. 2001, 65, 371–378. [Google Scholar] [CrossRef] [PubMed]
- Crocquet-Valdes, P.A.; Díaz-Montero, C.M.; Feng, H.M.; Li, H.; Barrett, A.D.; Walker, D.H. Immunization with a portion of rickettsial outer membrane protein A stimulates protective immunity against spotted fever rickettsiosis. Vaccine 2001, 20, 979–988. [Google Scholar] [CrossRef]
- Chan, Y.G.; Riley, S.P.; Chen, E.; Martinez, J.J. Molecular basis of immunity to rickettsial infection conferred through outer membrane protein B. Infect. Immun. 2011, 79, 2303–2313. [Google Scholar] [CrossRef] [PubMed]
- Cardwell, M.M.; Martinez, J.J. The Sca2 autotransporter protein from Rickettsia conorii is sufficient to mediate adherence to and invasion of cultured mammalian cells. Infect. Immun. 2009, 77, 5272–5280. [Google Scholar] [CrossRef] [Green Version]
- Cardwell, M.M.; Martinez, J.J. Identification and characterization of the mammalian association and actin-nucleating domains in the Rickettsia conorii autotransporter protein, Sca2. Cell Microbiol. 2012, 14, 1485–1495. [Google Scholar] [CrossRef] [PubMed]
- Madasu, Y.; Suarez, C.; Kast, D.J.; Kovar, D.R.; Dominguez, R. Rickettsia Sca2 has evolved formin-like activity through a different molecular mechanism. Proc. Natl. Acad. Sci. USA 2013, 110, E2677–E2686. [Google Scholar] [CrossRef]
- McDonald, G.A.; Anacker, R.L.; Garjian, K. Cloned gene of Rickettsia rickettsii surface antigen: Candidate vaccine for Rocky Mountain spotted fever. Science 1987, 235, 83–85. [Google Scholar] [CrossRef] [PubMed]
- Feng, H.M.; Walker, D.H. Cross-protection between distantly related spotted fever group rickettsiae. Vaccine 2003, 21, 3901–3905. [Google Scholar] [CrossRef]
- McDonald, G.A.; Anacker, R.L.; Mann, R.E.; Milch, L.J. Protection of guinea pigs from experimental Rocky Mountain spotted fever with a cloned antigen of Rickettsia rickettsii. J. Infect. Dis. 1988, 158, 228–231. [Google Scholar] [CrossRef]
- Sumner, J.W.; Sims, K.G.; Jones, D.C.; Anderson, B.E. Protection of guinea-pigs from experimental Rocky Mountain spotted fever by immunization with baculovirus-expressed Rickettsia rickettsii rOmpA protein. Vaccine 1995, 13, 29–35. [Google Scholar] [CrossRef]
- Vishwanath, S.; McDonald, G.A.; Watkins, N.G. A recombinant Rickettsia conorii vaccine protects guinea pigs from experimental boutonneuse fever and Rocky Mountain spotted fever. Infect. Immun. 1990, 58, 646–653. [Google Scholar] [CrossRef]
- Feng, H.M.; Whitworth, T.; Olano, J.P.; Popov, V.L.; Walker, D.H. Fc-dependent polyclonal antibodies and antibodies to outer membrane proteins A and B, but not to lipopolysaccharide, protect SCID mice against fatal Rickettsia conorii infection. Infect. Immun. 2004, 72, 2222–2228. [Google Scholar] [CrossRef]
- Li, H.; Lenz, B.; Walker, D.H. Protective monoclonal antibodies recognize heat-labile epitopes on surface proteins of spotted fever group rickettsiae. Infect. Immun. 1988, 56, 2587–2593. [Google Scholar] [CrossRef]
- Riley, S.P.; Cardwell, M.M.; Chan, Y.G.; Pruneau, L.; Del Piero, F.; Martinez, J.J. Failure of a heterologous recombinant Sca5/OmpB protein-based vaccine to elicit effective protective immunity against Rickettsia rickettsii infections in C3H/HeN mice. Pathog. Dis. 2015, 73, ftv101. [Google Scholar] [CrossRef] [Green Version]
- Li, Z.; Díaz-Montero, C.M.; Valbuena, G.; Yu, X.J.; Olano, J.P.; Feng, H.M.; Walker, D.H. Identification of CD8 T-lymphocyte epitopes in OmpB of Rickettsia conorii. Infect. Immun. 2003, 71, 3920–3926. [Google Scholar] [CrossRef]
- Feng, H.; Popov, V.L.; Yuoh, G.; Walker, D.H. Role of T lymphocyte subsets in immunity to spotted fever group Rickettsiae. J. Immunol. 1997, 158, 5314–5320. [Google Scholar] [PubMed]
- Gong, W.; Xiong, X.; Qi, Y.; Jiao, J.; Duan, C.; Wen, B. Surface protein Adr2 of Rickettsia rickettsii induced protective immunity against Rocky Mountain spotted fever in C3H/HeN mice. Vaccine 2014, 32, 2027–2033. [Google Scholar] [CrossRef] [PubMed]
- Gong, W.; Wang, P.; Xiong, X.; Jiao, J.; Yang, X.; Wen, B. Enhanced protection against Rickettsia rickettsii infection in C3H/HeN mice by immunization with a combination of a recombinant adhesin rAdr2 and a protein fragment rOmpB-4 derived from outer membrane protein B. Vaccine 2015, 33, 985–992. [Google Scholar] [CrossRef] [PubMed]
- Fox, J.P.; Jordan, M.E.; Gelfand, H.M. Immunization of man against epidemic typhus by infection with avirulent Rickettsia prowazeki strain E. IV. Persistence of immunity and a note as to differing complement-fixation antigen requirements in post-infection and post-vaccination sera. J. Immunol. 1957, 79, 348–354. [Google Scholar]
- Liu, Y.; Wu, B.; Weinstock, G.; Walker, D.H.; Yu, X.J. Inactivation of SAM-methyltransferase is the mechanism of attenuation of a historic louse borne typhus vaccine strain. PLoS ONE 2014, 9, e113285. [Google Scholar] [CrossRef]
- Balayeva, N.M.; Eremeeva, M.E.; Ignatovich, V.F.; Dmitriev, B.A.; Lapina, E.B.; Belousova, L.S. Protein antigens of genetically related Rickettsia prowazekii strains with different virulence. Acta Virol. 1992, 36, 52–56. [Google Scholar]
- Zhang, J.Z.; Hao, J.F.; Walker, D.H.; Yu, X.J. A mutation inactivating the methyltransferase gene in avirulent Madrid E strain of Rickettsia prowazekii reverted to wild type in the virulent revertant strain Evir. Vaccine 2006, 24, 2317–2323. [Google Scholar] [CrossRef]
- Arroyave, E.; Hyseni, I.; Burkhardt, N.; Kuo, Y.F.; Wang, T.; Munderloh, U.; Fang, R. Rickettsia parkeri with a Genetically Disrupted Phage Integrase Gene Exhibits Attenuated Virulence and Induces Protective Immunity against Fatal Rickettsioses in Mice. Pathogens 2021, 10, 819. [Google Scholar] [CrossRef]
- Jordan, J.M.; Woods, M.E.; Olano, J.; Walker, D.H. The absence of Toll-like receptor 4 signaling in C3H/HeJ mice predisposes them to overwhelming rickettsial infection and decreased protective Th1 responses. Infect. Immun. 2008, 76, 3717–3724. [Google Scholar] [CrossRef]
- Bechelli, J.; Smalley, C.; Zhao, X.; Judy, B.; Valdes, P.; Walker, D.H.; Fang, R. MyD88 Mediates Instructive Signaling in Dendritic Cells and Protective Inflammatory Response during Rickettsial Infection. Infect. Immun. 2016, 84, 883–893. [Google Scholar] [CrossRef]
- Smalley, C.; Bechelli, J.; Rockx-Brouwer, D.; Saito, T.; Azar, S.R.; Ismail, N.; Walker, D.H.; Fang, R. Rickettsia australis Activates Inflammasome in Human and Murine Macrophages. PLoS ONE 2016, 11, e0157231. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Rumfield, C.; Hyseni, I.; McBride, J.W.; Walker, D.H.; Fang, R. Activation of ASC Inflammasome Driven by Toll-Like Receptor 4 Contributes to Host Immunity against Rickettsial Infection. Infect. Immun. 2020, 88, e00886-19. [Google Scholar] [CrossRef]
- Fang, R.; Ismail, N.; Soong, L.; Popov, V.L.; Whitworth, T.; Bouyer, D.H.; Walker, D.H. Differential interaction of dendritic cells with Rickettsia conorii: Impact on host susceptibility to murine spotted fever rickettsiosis. Infect. Immun. 2007, 75, 3112–3123. [Google Scholar] [CrossRef] [PubMed]
- Fang, R.; Ismail, N.; Walker, D.H. Contribution of NK cells to the innate phase of host protection against an intracellular bacterium targeting systemic endothelium. Am. J. Pathol. 2012, 181, 185–195. [Google Scholar] [CrossRef]
- Feng, H.M.; Walker, D.H.; Wang, J.G. Analysis of T-cell-dependent and -independent antigens of Rickettsia conorii with monoclonal antibodies. Infect. Immun. 1987, 5, 7–15. [Google Scholar] [CrossRef] [PubMed]
- Fang, R.; Ismail, N.; Shelite, T.; Walker, D.H. CD4+ CD25+ Foxp3− T-regulatory cells produce both gamma interferon and interleukin-10 during acute severe murine spotted fever rickettsiosis. Infect. Immun. 2009, 77, 3838–3849. [Google Scholar] [CrossRef]
- Feng, H.M.; Popov, V.L.; Walker, D.H. Depletion of gamma interferon and tumor necrosis factor alpha in mice with Rickettsia conorii-infected endothelium: Impairment of rickettsicidal nitric oxide production resulting in fatal, overwhelming rickettsial disease. Infect. Immun. 1994, 62, 1952–1960. [Google Scholar] [CrossRef]
- Walker, D.H.; Popov, V.L.; Crocquet-Valdes, P.A.; Welsh, C.J.; Feng, H.M. Cytokine-induced, nitric oxide-dependent, intracellular antirickettsial activity of mouse endothelial cells. Lab. Investig. 1997, 76, 129–138. [Google Scholar]
- Walker, D.H.; Olano, J.P.; Feng, H.M. Critical role of cytotoxic T lymphocytes in immune clearance of rickettsial infection. Infect. Immun. 2001, 69, 1841–1846. [Google Scholar] [CrossRef] [PubMed]
- Milano, S.; D’Agostino, P.; Di Bella, G.; La Rosa, M.; Barbera, C.; Ferlazzo, V.; Mansueto, P.; Rini, G.B.; Barera, A.; Vitale, G.; et al. Interleukin-12 in human boutonneuse fever caused by Rickettsia conorii. Scand. J. Immunol. 2000, 52, 91–95. [Google Scholar] [CrossRef] [PubMed]
- Whitworth, T.; Popov, V.L.; Yu, X.J.; Walker, D.H.; Bouyer, D.H. Expression of the Rickettsia prowazekii pld or tlyC gene in Salmonella enterica serovar Typhimurium mediates phagosomal escape. Infect. Immun. 2005, 73, 6668–6673. [Google Scholar] [CrossRef] [PubMed]
- Driskell, L.O.; Yu, X.J.; Zhang, L.; Liu, Y.; Popov, V.L.; Walker, D.H.; Tucker, A.M.; Wood, D.O. Directed mutagenesis of the Rickettsia prowazekii pld gene encoding phospholipase D. Infect. Immun. 2009, 77, 3244–3248. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Borgo, G.M.; Burke, T.P.; Tran, C.J.; Lo, N.T.N.; Engström, P.; Welch, M.D. A patatin-like phospholipase mediates Rickettsia parkeri escape from host membranes. Nat. Commun. 2022, 13, 3656. [Google Scholar] [CrossRef] [PubMed]
- Li, H.; Walker, D.H. rOmpA is a critical protein for the adhesion of Rickettsia rickettsii to host cells. Microb. Pathog. 1998, 24, 289–298. [Google Scholar] [CrossRef] [PubMed]
- Noriea, N.F.; Clark, T.R.; Hackstadt, T. Targeted knockout of the Rickettsia rickettsii OmpA surface antigen does not diminish virulence in a mammalian model system. mBio 2015, 6, e00323-15. [Google Scholar] [CrossRef] [PubMed]
- Engström, P.; Burke, T.P.; Mitchell, G.; Ingabire, N.; Mark, K.G.; Golovkine, G.; Iavarone, A.T.; Rape, M.; Cox, J.S.; Welch, M.D. Evasion of autophagy mediated by Rickettsia surface protein OmpB is critical for virulence. Nat. Microbiol. 2019, 4, 2538–2551. [Google Scholar] [CrossRef]
- Pelc, R.S.; McClure, J.C.; Kaur, S.J.; Sears, K.T.; Rahman, M.S.; Ceraul, S.M. Disrupting protein expression with Peptide Nucleic Acids reduces infection by obligate intracellular Rickettsia. PLoS ONE 2015, 10, e0119283. [Google Scholar] [CrossRef]
- Kim, H.K.; Premaratna, R.; Missiakas, D.M.; Schneewind, O. Rickettsia conorii O antigen is the target of bactericidal Weil-Felix antibodies. Proc. Natl. Acad. Sci. USA 2019, 116, 19659–19664. [Google Scholar] [CrossRef]
- Kleba, B.; Clark, T.R.; Lutter, E.I.; Ellison, D.W.; Hackstadt, T. Disruption of the Rickettsia rickettsii Sca2 autotransporter inhibits actin-based motility. Infect. Immun. 2010, 78, 2240–2247. [Google Scholar] [CrossRef]
- Harris, E.K.; Jirakanwisal, K.; Verhoeve, V.I.; Fongsaran, C.; Suwanbongkot, C.; Welch, M.D.; Macaluso, K.R. Role of Sca2 and RickA in the Dissemination of Rickettsia parkeri in Amblyomma maculatum. Infect. Immun. 2018, 86, e00123-18. [Google Scholar] [CrossRef] [PubMed]
- Nock, A.M.; Clark, T.R.; Hackstadt, T. Regulator of Actin-Based Motility (RoaM) Downregulates Actin Tail Formation by Rickettsia rickettsii and Is Negatively Selected in Mammalian Cell Culture. mBio 2022, 13, e0035322. [Google Scholar] [CrossRef] [PubMed]
- Lehman, S.S.; Noriea, N.F.; Aistleitner, K.; Clark, T.R.; Dooley, C.A.; Nair, V.; Kaur, S.J.; Rahman, M.S.; Gillespie, J.J.; Azad, A.F.; et al. The Rickettsial Ankyrin Repeat Protein 2 Is a Type IV Secreted Effector That Associates with the Endoplasmic Reticulum. mBio 2018, 9, e00975-18. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Aistleitner, K.; Clark, T.; Dooley, C.; Hackstadt, T. Selective fragmentation of the trans-Golgi apparatus by Rickettsia rickettsii. PLoS Pathog. 2020, 16, e1008582. [Google Scholar] [CrossRef]
- Lamason, R.L.; Bastounis, E.; Kafai, N.M.; Serrano, R.; Del Álamo, J.C.; Theriot, J.A.; Welch, M.D. Rickettsia Sca4 Reduces Vinculin-Mediated Intercellular Tension to Promote Spread. Cell 2016, 167, 670–683.e10. [Google Scholar] [CrossRef] [Green Version]
Rickettsia Species | Gene | Outcome | Immunization & Protection | Reference |
---|---|---|---|---|
R. prowazekii | pld | Virulence of the mutant was attenuated in vivo | Yes | [113] |
R. rickettsii | sca2 | Mutant strain did not elicit fever in a guinea pig model of infection | No | [120] |
R. montanensis | rickAa | Knock down of RickA was shown to reduce the infectivity of host cells, in vitro | No | [118] |
R. typhi | sca5a | Knock down of Sca5 was shown to reduce the infectivity of host cells, in vitro | No | [118] |
R. rickettsii | sca0 | No change in virulence | No | [116] |
R. parkeri | sca4a | Sca4 was shown to bind to vinculin and promote protrusion engulfment, in vitro | No | [125] |
R. parkeri | rickA and sca2b | Both the genes were involved in actin polymerization but not involved in dissemination in ticks. | No | [121] |
R. rickettsii | Rickettsia ankyrin repeat protein 2 (rarp-2) c | The expression of RARP2 from Sheila Smith in Iowa did not restore virulence. | No | [123] |
R. conorii | RC0459 | No change in virulence | No | [119] |
R. conorii | RC0457 | Virulence of the mutant was attenuated in vivo | No | [119] |
R. parkeri | sca5 | Virulence of the mutant was attenuated in vivo | No | [117] |
R. parkeri | Phage integrase family protein | Virulence of the mutant was attenuated in vivo | Yes | [99] |
R. parkeri | Patatin-like phospholipase (pat1) | The pat1 mutant exhibited reduced virulence in Ifnar1−/− and Ifngr1−/− double knock out mice. | No | [114] |
R. rickettsii | A1G_06520 (RoaM [regulator of actin-based motility]) | Disruption of the gene increased the number of actin tails. There was no increase in virulence by the mutant in guinea pig model. | No | [122] |
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. |
© 2022 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
Share and Cite
Walker, D.H.; Blanton, L.S.; Laroche, M.; Fang, R.; Narra, H.P. A Vaccine for Canine Rocky Mountain Spotted Fever: An Unmet One Health Need. Vaccines 2022, 10, 1626. https://doi.org/10.3390/vaccines10101626
Walker DH, Blanton LS, Laroche M, Fang R, Narra HP. A Vaccine for Canine Rocky Mountain Spotted Fever: An Unmet One Health Need. Vaccines. 2022; 10(10):1626. https://doi.org/10.3390/vaccines10101626
Chicago/Turabian StyleWalker, David H., Lucas S. Blanton, Maureen Laroche, Rong Fang, and Hema P. Narra. 2022. "A Vaccine for Canine Rocky Mountain Spotted Fever: An Unmet One Health Need" Vaccines 10, no. 10: 1626. https://doi.org/10.3390/vaccines10101626