Rickettsia spp 780 All rickettsial infections begin with introduction of the organisms into the skin, either through a tick bite or cutaneous abrasions contaminated by flea or louse feces. Rickettsiae enter dermal cells including endothelium and proliferate locally intracellularly with endothelial cell-to-cell spread for most SFG rickettsioses resulting in an eschar or tache noire, a zone of dermal and epidermal necrosis approximately 1 cm in diameter with a surrounding zone of erythema. Eschars do not occur in epidemic and murine typhus and are rarely observed in Rocky Mountain spotted fever (Textbook of Bacteriology). Spotted Fever, Typhus Rickettsial infection stimulates an early innate immune response with activation of natural killer cells and production of gamma interferon (gamma IFN), which act in concert to dampen rickettsial growth. Acquired immunity develops with clonal expansion of CD4 and CD8 T lymphocytes as well as antibody-producing B cells. Clearance of intraendothelial rickettsiae is achieved by rickettsicidal effects due to cytokine activation of the infected endothelial cells themselves. Cell mediated immunity (CMI) plays an important role as expected in infection by an intracellular parasite, but antibodies (including those directed at epitopes of OmpA and OmpB) also play a role in protective immunity (Textbook of Bacteriology). Rickettsia are generally carried by ticks and fleas and can be transmitted to humans and other warm-blooded mammals (Wiki: Rickettsia). Rickettsia is a genus of non-motile, Gram-negative, non-sporeforming, highly pleomorphic bacteria that can present as cocci (0.1 μm in diameter), rods (1–4 μm long) or thread-like (10 μm long). Obligate intracellular parasites, the Rickettsia survival depends on entry, growth, and replication within the cytoplasm of eukaryotic host cells (typically endothelial cells). Because of this, Rickettsia cannot live in artificial nutrient environments and are grown either in tissue or embryo cultures (typically, chicken embryos are used). In the past they were positioned somewhere between viruses and true bacteria. The majority of Rickettsia bacteria are susceptible to antibiotics of the tetracycline group. Rickettsia species are carried by many ticks, fleas, and lice, and cause diseases in humans such as typhus, rickettsialpox, Boutonneuse fever, African tick bite fever, Rocky Mountain spotted fever, Australian Tick Typhus, Flinders Island Spotted Fever and Queensland tick typhus. They have also been associated with a range of plant diseases. Like viruses, they only grow inside living cells. The name rickettsia is often used for any member of the Rickettsiales. They are thought to be the closest living relatives to bacteria that were the origin of the mitochondria organelle that exists inside most eukaryotic cells (Wiki: Rickettsia). Rickettsial diseases vary in clinical severity according to the virulence of the Rickettsia and host factors, such as age, male gender, alcoholism, and other underlying diseases. The most virulent rickettsiae are R. rickettsii and R. prowazekii, which kill a significant portion of infected persons, unless the diseases are treated sufficiently early in the course of infection with an effective antimicrobial agent, usually doxycycline (Textbook of Bacteriology). Baboon Papio cynocephalus 9556 Bank vole Clethrionomys glareolus 447135 Bear Ursus americanus 9643 Birds Passeroidea 175121 Brown Trout Salmo trutta 8032 Buffalo Bison bison 9901 Carnivores Vulpes 9625 Cat Felis catus 9685 Catfishes Siluriformes 7995 Cattle Bos taurus 9913 Chicken Gallus gallus 9031 Chimpanzee Pan troglodytes 9598 chinchillas Chinchillidae 10150 Copper Pheasant Syrmaticus soemmerringii 9067 Deer Cervus elaphus 9860 Deer mouse Peromyscus maniculatus 10042 Dog Canis familiaris 9615 Ducks Anas 8835 Ferret Mustela putorius furo 9669 Fish Hyperotreti 117565 Gerbil Gerbillina 10045 Goat Capra hircus 9925 Gray wolf Canis lupus 9612 Guinea pig Cavia porcellus 10141 Hamster Mesocricetus auratus 10036 Horse Equus caballus 9796 Human Homo sapiens 9606 Macaque Macaca fascicularis 9541 Mongolian Gerbil Meriones unguiculatus 10047 Monkey Platyrrhini 9479 Mouse Mus musculus 10090 None None Parrot Psittacidae 9224 Pig Sus scrofa 9823 Rabbit Oryctolagus cuniculus 9986 Rainbow trout Oncorhynchus mykiss 8022 Rat Rattus 10114 Raven Corvus corax 56781 sei whale Balaenoptera borealis 9768 Sheep Ovis aries 9940 Squirrel Spermophilus richardsonii 37591 Tree shrew Tupaiidae 9393 Trouts, salmons & chars Salmoninae 504568 Turkey Meleagris gallopavo 9103 Vole Microtus ochrogaster 79684 Water buffalo Bubalus bubalis 391902 licensed Rickettsial diseases (Spotted fever and Typhus) human vaccine Generic Unknown VO_0000767 Inactivated or "killed" vaccine Licensed A generic representation of vaccines utilized to prevent Rickettsial diseases (Spotted fever and Typhus) in humans, most commonly based on inactivated or 'killed' whole-cell preparations of Rickettsia species. These vaccines aim to induce protective immunity without the risk of causing disease. Rickettsia DNA Vaccine encoding OmpB Protein boosted with Recombinant OmpB VO_0011389 DNA vaccine Research pcDNA3.1/V5-His-TOPO [Ref1240:Díaz-Montero et al., 2001] Intramuscular injection (i.m.) Intramuscular injection (i.m.) DNA vaccine construction C3H/ HeN Animals were immunized with only two doses of DNA (100 μg of recombinant plasmid and 100 μg of pIL-12) four weeks apart given intramuscularly in the tibialis anterior muscles. All mice that received DNA immunizations were also administered two booster immunizations of 100 μg each of the homologous purified recombinant protein. Control mice received either non-recombinant vector plus β-galactosidase-His recombinant protein (negative control) or a sublethal immunizing dose of R. conorii (positive control) (Díaz-Montero et al., 2001). R. rickettsii OmpB contain B and T lymphocyte epitopes. Immunizations with each of two fragments from OmpB (rompB1550-2738 and rompB2459-4123) conferred protection against challenge with a lethal dose of R. conorii. Protection appeared to be better achieved among the groups that received both DNA and recombinant protein immunizations, although recombinant protein immunizations alone provided some protection (Díaz-Montero et al., 2001). Mice were challenged with 3 median lethal doses (LD50) of R. conorii. In a previous experiment, this dose was shown to kill 100% of naive mice. After challenge, animals were observed daily for morbidity and mortality (Díaz-Montero et al., 2001). Rickettsia rickettsii vaccine using M. vaccae expressing R. rickettsii OmpA Protein VO_0011388 Recombinant vector vaccine Research Mycobacterium vaccae [Ref1239:Crocquet-Valdes et al., 2001]. Subcutaneous injection Subcutaneous injection Recombinant vector construction C3H/HeN mice 6–8-week-old male C3H/HeN mice were were inoculated subcutaneously with 1×10^8 to 5×10^8 of recombinant M. vaccae transformants containing rompA3006–3960. As a negative control mice were immunized with either PBS or inoculated subcutaneously with M. vaccae/pCR7, another negative control. Booster inoculations were performed 1 month later with the same dose and route. Mice immunized with M. vaccae transformants were given two additional doses of 100 μg per mouse of recombinant rickettsial GST fusion protein OmpA755–1301 suspended in incomplete Freund’s adjuvant with a 1 month interval between the immunizations (Crocquet-Valdes et al., 2001). Immunization with one of the constructs of Mycobacterium vaccae expressing Rickettsia rickettsii OmpA in combination with booster immunization with the homologous recombinant protein protected a significant portion of mice from lethal challenge with the closely related bacterium, R. conorii, in mice (Crocquet-Valdes et al., 2001). One month after the last inoculation, all groups of mice were challenged intravenously with three LD50 of R. conorii and observed daily for 2 weeks for morbidity and mortality (Crocquet-Valdes et al., 2001). Production of IFN-gamma by antigen-exposed T-lymphocytes of DNA vaccine recipients indicated that cellular immunity had been stimulated. IFN-γ levels in supernatant fluid of rickettsial antigen-stimulated splenocytes from an animal that received both DNA and protein vaccinations were 47% or more higher than the controls that were vaccinated with the vector and GST or were sham-immunized with saline. This observed difference was significant and was seen in spleen cells the day before the challenge (Crocquet-Valdes et al., 2001). Ifng (Interferon gamma) Mouse 15978 33468859 NM_008337 NP_032363.1 MGI:107656; UniProt:P01580 10090 ? >gi|145966741|ref|NM_008337.3| Mus musculus interferon gamma (Ifng), mRNA ATAGCTGCCATCGGCTGACCTAGAGAAGACACATCAGCTGATCCTTTGGACCCTCTGACTTGAGACAGAA GTTCTGGGCTTCTCCTCCTGCGGCCTAGCTCTGAGACAATGAACGCTACACACTGCATCTTGGCTTTGCA GCTCTTCCTCATGGCTGTTTCTGGCTGTTACTGCCACGGCACAGTCATTGAAAGCCTAGAAAGTCTGAAT AACTATTTTAACTCAAGTGGCATAGATGTGGAAGAAAAGAGTCTCTTCTTGGATATCTGGAGGAACTGGC AAAAGGATGGTGACATGAAAATCCTGCAGAGCCAGATTATCTCTTTCTACCTCAGACTCTTTGAAGTCTT GAAAGACAATCAGGCCATCAGCAACAACATAAGCGTCATTGAATCACACCTGATTACTACCTTCTTCAGC AACAGCAAGGCGAAAAAGGATGCATTCATGAGTATTGCCAAGTTTGAGGTCAACAACCCACAGGTCCAGC GCCAAGCATTCAATGAGCTCATCCGAGTGGTCCACCAGCTGTTGCCGGAATCCAGCCTCAGGAAGCGGAA AAGGAGTCGCTGCTGATTCGGGGTGGGGAAGAGATTGTCCCAATAAGAATAATTCTGCCAGCACTATTTG AATTTTTAAATCTAAACCTATTTATTAATATTTAAAACTATTTATATGGAGAATCTATTTTAGATGCATC AACCAAAGAAGTATTTATAGTAACAACTTATATGTGATAAGAGTGAATTCCTATTAATATATGTGTTATT TATAATTTCTGTCTCCTCAACTATTTCTCTTTGACCAATTAATTATTCTTTCTGACTAATTAGCCAAGAC TGTGATTGCGGGGTTGTATCTGGGGGTGGGGGACAGCCAAGCGGCTGACTGAACTCAGATTGTAGCTTGT ACCTTTACTTCACTGACCAATAAGAAACATTCAGAGCTGCAGTGACCCCGGGAGGTGCTGCTGATGGGAG GAGATGTCTACACTCCGGGCCAGCGCTTTAACAGCAGGCCAGACAGCACTCGAATGTGTCAGGTAGTAAC AGGCTGTCCCTGAAAGAAAGCAGTGTCTCAAGAGACTTGACACCTGGTGCTTCCCTATACAGCTGAAAAC TGTGACTACACCCGAATGACAAATAACTCGCTCATTTATAGTTTATCACTGTCTAATTGCATATGAATAA AGTATACCTTTGCAACC >gi|33468859|ref|NP_032363.1| interferon gamma [Mus musculus] MNATHCILALQLFLMAVSGCYCHGTVIESLESLNNYFNSSGIDVEEKSLFLDIWRNWQKDGDMKILQSQI ISFYLRLFEVLKDNQAISNNISVIESHLITTFFSNSKAKKDAFMSIAKFEVNNPQVQRQAFNELIRVVHQ LLPESSLRKRKRSRC IFN-gamma plays a critical role in Th1 type immune response. It is important for protection against infections by various viruses and intracellular bacteria. Vaximmutor The experimental data demonstrated that three time vaccinations with BCG in BALB/c mice induced strong TB Ag-specific IFN-gamma immune responses in splenocytes [Ref2101:Wang et al., 2009]. ompA Rickettsia rickettsii VO_0011234 112710 CDD:225751 CDD:299123 CDD:273608 CDD:281750 783 ? Outer membrane protein A 5.23 209097.42 2619 190 kDa antigen; Cell surface antigen; rOmp A; rOmpA >sp|P15921.1|OMPA_RICRI RecName: Full=Outer membrane protein A; AltName: Full=190 kDa antigen; AltName: Full=Cell surface antigen; AltName: Full=rOmp A; Short=rOmpA; Contains: RecName: Full=120 kDa surface-exposed protein; AltName: Full=120 kDa outer membrane protein OmpA; Contains: RecName: Full=32 kDa beta peptide; Flags: Precursor MANISPKLFKKAIQQGLKAALFTTSTAAIMLSSSGALGVATGVIATNNNAAFSNNVGNNNWNEITAAGVA NGTPAGGPQNNWAFTYGGDYTVTADAADRIIKAINVAGTTPVGLNITQNTVVGSIITKGNLLPVTLNAGK SLTLNGNNAVAANHGFDAPADNYTGLGNIALGGANAALIIQSAAPSKITLAGNIDGGGIITVKTDAAING TIGNTNALATVNVGAGTATLGGAVIKATTTKLTNAASVLTLTNANAVLTGAIDNTTGGDNVGVLNLNGAL SQVTGDIGNTNSLATISVGAGTATLGGAVIKATTTKLTDAASAVKFTNPVVVTGAIDNTGNANNGIVTFT GNSTVTGNVGNTNALATVNVGAGLLQVQGGVVKANTINLTDNASAVTFTNPVVVTGAIDNTGNANNGIVT FTGNSTVTGDIGNTNALATVNVGAGTATLGGAVIKATTTKLTNAASVLTLTNANAVLTGAIDNTTGGDNV GVLNLNGALSQVTGNIGNTNSLATISVGAGTATLGGAVIKATTTKLTDAASAVKFTNPVVVTGAIDNTGN ANNGIVTFTGNSTVTGDIGNTNSLATISVGAGTATLGGAVIKATTTKLTNAASVLTLTNANAVLTGAIDN TTGGDNVGVLNLNGALSQVTGDIGNTNSLATISVGAGTATLGGAVIKATTTKITNAVSAVKFTNPVVVTG AIDSTGNANNGIVTFTGNSTVTGDIGNTNALATVNVGAGTATLGGAVIKATTTKLTNAASVLTLTNANAV LTGAIDNTTGGDNVGVLNLNGALSQVTGDIGNTNSLATISVGAGTATLGGAVIKATTTKLTNAASVLTLT NANAVLTGAVDNTTGGDNVGVLNLNGALSQVTGDIGNTNSLATISVGAGTATLGGAVIKATTTKLTNAAS VLTLTNANAVLTGAIDNTTGGDNVGVLNLNGALSQVTGDIGNTNSLATISVGAGTATLGGAVIKATTTKL TDAASAVKFTNPVVVTGAIDNTGNANNGIVTFTGNSTVTGNVGNTNALATVNVGAGLLQVQGGVVKANTI NLTDNASAVTFTNPVVVTGAIDNTGNANNGIVTFTGNSTVTGNVGNTNALATVNVGAGLLQVQGGVVKAN TINLTDNASAVTFTNPVVVTGAIDNTGNANNGIVTFTGNSTVTGDIGNTNALATVNVGAGITLQAGGSLA ANNIDFGARSTLEFNGPLDGGGKAIPYYFKGAIANGNNAILNVNTKLLTASHLTIGTVAEINIGAGNLFT IDASVGDVTILNAQNINFRARDSVLVLSNLTGVGVNNILLAADLVAPGADEGTVVFNGGVNGLNVGSNVA GTARNIGDGGGNKFNTLLIYNAVTITDDVNLEGIQNVLINKNADFTSSTAFNAGAIQINDATYTIDANNG NLNIPAGNIQFAHADAQLVLQNSSGNDRTITLGANIDPDNDDEGIVILNSVTAGKKLTIAGGKTFGGAHK LQTILFKGAGDCSTAGTTFNTTNIVLDITGQLELGATTANVVLFNDAVQLTQTGNIGGFLDFNAKNGMVT LNNNVNVAGAVQNTGGTNNGTLIVLGASNLNRVNGIAMLKVGAGNVTIAKGGKVKIGEIQGTGTNTLTLP AHFNLTGSINKTGGQALKLNFMNGGSVSGVVGTAANSVGDITTAGATSFASSVNAKGTATLGGTTSFANT FTNTGAVTLAKGSITSFAKNVTATSFVANSATINFSNSLAFNSNITGGGTTLTLGANQVTYTGTGSFTDT LTLNTTFDGAAKSGGNILIKSGSTLDLSGVSTLALVVTATNFDMNNISPDTKYTVISAETAGGLKPTSKE NVKITINNDNRFVDFTFDASTLTLFAEDIAADVIDGDFAPGGPLANIPNAANIKKSLELMEDAPNGSDAR QAFNNFGLMTPLQEADATTHLIQDVVKPSDTIAAVNNQVVASNISSNITALNARMDKVQSGNKGPVSSGD EDMDAKFGAWISPFVGNATQKMCNSISGYKSDTTGGTIGFDGFVSDDLALGLAYTRADTDIKLKNNKTGD KNKVESNIYSLYGLYNVPYENLFVEAIASYSDNKIRSKSRRVIATTLETVGYQTANGKYKSESYTGQLMA GYTYMMPENINLTPLAGLRYSTIKDKGYKETGTTYQNLTVKGKNYNTFDGLLGAKVSSNINVNEIVLTPE LYAMVDYAFKNKVSAIDARLQGMTAPLPTNSFKQSKTSFDVGVGVTAKHKMMEYRINYDTNIGSKYFAQQ GSVKVRVNF Protective antigen Immunization with one of the constructs of M. vaccae expressing OmpA in combination with booster immunization with the homologous recombinant protein protected a significant portion of mice from lethal challenge [Ref1239:Crocquet-Valdes et al., 2001]. ompB Rickettsia rickettsii VO_0011235 6685726 CDD:289131 CDD:273608 CDD:214872 783 ? Outer membrane protein B 6.04 160418.03 2141 168 kDa surface-layer protein; Cell surface antigen 5; Surface protein antigen; rOmp B; Sca5; rOmpB >sp|Q53047.1|OMPB_RICRI RecName: Full=Outer membrane protein B; AltName: Full=168 kDa surface-layer protein; AltName: Full=Cell surface antigen 5; Short=Sca5; AltName: Full=Surface protein antigen; AltName: Full=rOmp B; Short=rOmpB; Contains: RecName: Full=120 kDa surface-exposed protein; AltName: Full=120 kDa outer membrane protein OmpB; AltName: Full=Surface protein antigen; AltName: Full=p120; Contains: RecName: Full=32 kDa beta peptide; Flags: Precursor MAQKPNFLKKLISAGLVTASTATIVASFAGSAMGAAIQQNRTTNGAATTVDGAGFDQTAAPANVGVALNA VITANANNGINFNTPAGSFNGLLLNTANNLAVTVSEDTTLGFITNVVHNAHSFNLTLNAGKTLTITGQGV TNAQAAATKNAQNVVVQFNNGAAIDNNDLKGVGRIDFGAPASTLVFNLANPTTQKAPLILGDNAVIANGV NGTLNVTNGFIQVSNKSFATVKAINIADGQGIIFNTDANNANTLNLQAGGTTINFTGTDGTGRLVLLSKH AAATNFNITGSLGGNLKGVIEFNTVAVDGQLTANAGAANAVIGTNNGAGRAAGFVVSVDNGKVATIDGQV YAKDMVIQSANATGQVNFRHIVDVGADGTTAFKTAASKVTITQDSNFGNTDFGNLAAQIKVPNAITLTGN FTGDASNPGNTAGVITFDANGTLESASADANVAVTNNITAIEASGAGVVQLSGTHAAELRLGNAGSIFKL ADGTVINGKVNQTALVGGALAAGTITLDGSATITGDIGNAGGAAALQRITLANDAKKTLTLGGANIIGAG GGTIDLQANGGTIKLTSTQNNIVVDFDLAIATDQTGVVDASSLTNAQTLTINGKIGTIGANNKTLGQFNI GSSKTVLSNGNVAINELVIGNDGAVQFAHDTYLITRTTNAAGQGKIIFNPVVNNGTTLAAGTNLGSATNP LAEINFGSKGVNVDTVLNVGEGVNLYATNITTTDANVGSFVFNAGGTNIVSGTVGGQQGNKFNTVALENG TTVKFLGNATFNGNTTIAANSTLQIGGNYTADCVASADGTGIVEFVNTGPITVTLNKQAAPVNALKQITV SGPGNVVINEIGNAGNHHGAVTDTIAFENSSLGAVVFLPRGIPFNDAGNTMPLTIKSTVGNKTAKGFDVP SVVVLGVDSVIADGQVIGDQNNIVGLGLGSDNGIIVNATTLYAGISTLNNNQGTVTLSGGVPNTPGTVYG LGTGIGASKFKQVTFTTDYNNLGNIIATNATINDGVTVTTGGIAGIGFDGKITLGSVNGNGNVRFADGIL SNSTSMIGTTKANNGTVTYLGNAFVGNIGDSDTPVASVRFTGSDSGAGLQGNIYSQVIDFGTYNLGIVNS NIILGGGTTAINGKIDLVTNTLTFASGTSTWGNNTSIETTLTLANGNIGHIVILEGAQVNTTTTGTTTIK VQDNANANFSGTQTYTLIQGGARFNGTLGSPNFAVTGSNRFVNYSLIRAANQDYVITRTNNAENVVTNDI ANSPFGGAPGVDQNVTTFVNATNTAAYNNLLLAKNSANSANFVGAIVTDTSAAITNVQLDLAKDIQAQLG NRLGALRYLGTPETAEMAGPEAGAISAAVAAGDEAIDNVAYGIWAKPFYTDAHQSKKGGLAGYKAKTTGV VIGLDTLANDNLMIGAAIGITKTDIKHQDYKKGDKTDVNGFSFSLYGAQQLVKNFFAQGSAIFSLNQVKN KSQRYFFDANGNMSKQIAAGHYDNMTFGGNLTVGYDYNAMQGVLVTPMAGLSYLKSSDENYKETGTTVAN KQVNSKFSDRTDLIVGAKVAGSTMNITDLAVYPEVHAFVVHKVTGRLSKTQSVLDGQVTPCINQPDRTTK TSYNLGLSASIRSDAKMEYGIGYDAQISSKYTAHQGTLKVRVNF Protective antigen R. rickettsii OmpB contain B and T lymphocyte epitopes. Immunizations with each of two fragments from OmpB (rompB1550-2738 and rompB2459-4123) conferred protection against challenge with a lethal dose of R. conorii. Protection appeared to be better achieved among the groups that received both DNA and recombinant protein immunizations, although recombinant protein immunizations alone provided some protection [Ref1240:Díaz-Montero et al., 2001]. 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