The realities of biodefense vaccines against Rickettsia

Walker, David H.

doi:10.1016/j.vaccine.2009.07.045

Cited by 55 publications

(55 citation statements)

References 46 publications

(24 reference statements)

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“…We thus hypothesize that anti-rickettsial monoclonal antibodies, such as rOmpB 5C7.31, could be used as an alternative therapy to antibiotic treatment of rickettsial disease, where the efficacy of antibodies would be unaffected by antibiotic-resistant strains of rickettsiae. In light of the historical and now potential use of rickettsial pathogens as bioweapons (12,26,48) and the engineering of antibiotic-resistant strains (51), investigation into new therapies for the treatment and prevention of SFG and TG rickettsial diseases is of the utmost importance.…”

Section: Vol 79 2011 Rompb-mediated Immunity In Sfg Rickettsial Dismentioning

confidence: 99%

Molecular Basis of Immunity to Rickettsial Infection Conferred through Outer Membrane Protein B

et al. 2011

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Pathogenic rickettsiae are the causative agents of Rocky Mountain spotted fever, typhus, and other human diseases with high mortality and an important impact on society. Although survivors of rickettsial infections are considered immune to disease, the molecular basis of this immunity or the identification of protective antigens that enable vaccine development was hitherto not known. By exploring the molecular pathogenesis of Rickettsia conorii, the agent of Mediterranean spotted fever, we report here that the autotransporter protein, rickettsial outer membrane protein B (rOmpB), constitutes a protective antigen for this group of pathogens. A recombinant, purified rOmpB passenger domain fragment comprised of amino acids 36 to 1334 is sufficient to elicit humoral immune responses that protect animals against lethal disease. Protective immunity requires folded antigen and production of antibodies that recognize conformational epitopes on the rickettsial surface. Monoclonal antibodies (MAbs) 5C7.27 and 5C7.31, which specifically recognize a conformation present in the folded, intact rOmpB passenger domain, are sufficient to confer immunity in vivo. Analyses in vitro indicate this protection involves a mechanism of complement-mediated killing in mammalian blood, a means of rickettsial clearance that has not been previously described. Considering the evolutionary conservation of rOmpB and its crucial contribution to bacterial invasion of host cells, we propose that rOmpB antibody-mediated killing confers immunity to rickettsial infection.

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Section: Vol 79 2011 Rompb-mediated Immunity In Sfg Rickettsial Dismentioning

confidence: 99%

Molecular Basis of Immunity to Rickettsial Infection Conferred through Outer Membrane Protein B

et al. 2011

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“…Devastating outbreaks occurred in concentration camps (Weiss, 1988). At present, R. prowazekii is considered a potential albeit unlikely category B bioterrorism agent (Walker, 2009). The majority of cases are reported from places with compromised conditions of hygiene, e.g.…”

Section: Epidemiologymentioning

confidence: 99%

Update on Rickettsioses in Slovakia

Sekeyová¹,

Socolovschi²,

Špitalská³

et al. 2013

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Summary. -The reported incidence of vector-borne diseases including various cases of Rickettsioses in humans is increasing due to a combination of climatic and social factors, escalating the opportunities for contact between people and ticks, fleas or lice. Many of the emerging infectious diseases currently challenging human health in Europe are transmitted by ticks which normally feed on domestic or wild animals. Each Rickettsia spp. has one or several tick vectors, and their geographical distribution varies according to geographical conditions; e.g.; altitude or temperature, which is gradually changing due to a global warming. Evidence of Rickettsia spp. particularly of a newly discovered species is a strong indication that a great number of diseases may be caused by so far undetected or unrecognized organisms. Their diagnosis relies mostly on rare "spot like" cooperation of clinicians with scientists, the members of the working groups that are devoted to the scientific studies of the corresponding research areas. The clinical picture of the disease caused by rickettsiae varies significantly from flu like symptoms to severe fatal outcomes, reflecting the various factors, e.g. a variability of virulence of rickettsial species due to cell invasion, dissemination of rickettsiae, genomics, immune response of an infected organism, or a tricky impact of a treatment. Several major reviews on rickettsioses have been previously published, e.g. in 1997(Parola et al., 2005, and in 2011 (Botelho-Nevers and Raoult, 2011). In this work we intend to present a short historical overview and to describe new trends in research studies of rickettsiology. The main focus will be on rickettsioses affecting Europe΄s population.

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“…Molecular biology techniques such as selection, cloning and expression of genes encoding R. prowazekii virulence-associated proteins, offer the opportunity to develop new rickettsial vaccines against typhus group rickettsiae. Further research is needed to develop effective vaccines without undesirable toxic reactions (Azad & Radulovic, 2003;Walker, 2009). …”

Section: Prophylaxismentioning

confidence: 99%