Trypanosoma brucei 5691 These obligate parasites have two hosts - an insect vector and mammalian host. Because of the large difference between these hosts the trypanosome undergoes complex changes during its life cycle to facilitate its survival in the insect gut and the mammalian bloodstream. It also features a unique and notable variable surface glycoprotein (VSG) coat in order to avoid the host's immune system (Wiki: T. brucei). African trypanosomiasis (African Sleeping Sickness) Trypanosomes are hemoflagellated protozoan parasites causing African sleeping sickness in humans and nagana in animals in Africa. African sleeping sickness is caused by the species Trypanosoma brucei. The incidence of disease in humans has increased 100-fold in the past 40 years, where about 55 million people and 25 million cattle have been estimated to be at risk of contracting African sleeping sickness or nagana. A total of 500,000 people estimated to be infected per year with 60,000 annual deaths. Treatment of African sleeping sickness has not advanced greatly in the last 50 years and is often highly toxic. Trypanosomiasis control programs aimed at eradication of the most common vector, the tsetse fly, though adequate if well managed, have not been fully effective (Rasooly and Balaban, 2004). 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 African trypanosomiasis human vaccine Generic Unknown VO_0012184 Subunit vaccine Licensed A generic representation of subunit vaccines developed to prevent African trypanosomiasis (African Sleeping Sickness) in humans. These vaccines typically utilize purified parasite antigens to elicit protective immune responses without introducing live or whole killed organisms. T. brucei DNA Vaccine encoding TSA protein VO_0011491 DNA vaccine Research pVAX1 [Ref1398:Silva et al., 2009] Intramuscular injection (i.m.) Intramuscular injection (i.m.) DNA vaccine construction BALB-c Mice were immunized by injecting 100 μg (200 μl) of plasmid DNA encoding nTSA gene by intramuscular route. As a control groups, five mice were injected with 100 μg of plasmid pVAX1LacZ (Invitrogen—USA) and with 200 μl of PBS by the same route (Silva et al., 2009). The DNA vaccination process was able to protect 60% of mice submitted to a challenge assay with the infective form of T. brucei brucei parasites (Silva et al., 2009). After 175 days of immunization, mice in vaccinated and control groups were submitted to the challenge assay, performed by intraperitoneal injection of 500 parasites (T. b. brucei GVR 35 1.5) per animal. The period of survival, defined as the number of days after infection that the infected animals remain alive, was evaluated (Silva et al., 2009). T. brucei Subunit p15 Protein Vaccine VO_0011492 Subunit vaccine Research Subcutaneous Freund’s adjuvant (Rasooly and Balaban, 2004) Subcutaneous Recombinant protein preparation Swiss Swiss male mice were injected three times subcutaneously on days 1, 7 and 21 with the antigen. Antigen contained 10 μg of native p15 isolated from T. brucei brucei KETRI 2693, recombinant p15 purified from Ad-p15 infected HEK293 cells, partially purified subpellicular microtubules as a positive control (subpellicular fraction >30 kDa), or with PIPES buffer used to purify p15 as a negative control. Vaccinations included complete Freund’s adjuvant on first injection and incomplete Freund’s adjuvant on second and third injections. To test the protective potential of the recombinant viral vaccine, mice were injected intramuscularly (on days 1, 7 and 21) with 2×10^9 Ad-p15 virus particles or with control Ad-lacZ (Rasooly and Balaban, 2004). Vaccination of mice with p15 (native or recombinant) generated up to 100% protection from an otherwise lethal challenge of a heterologous strain of Trypanosoma brucei (Rasooly and Balaban, 2004). Animals were challenged intraperitoneally on day 31 with 500 T. brucei brucei strain SB1 (Rasooly and Balaban, 2004). MAPP15 VO_0011334 777767 5691 ? microtubule-associated protein 12.57 7350.75 161 >AAA65193.1 microtubule-associated protein, partial [Trypanosoma brucei] ARATAVPKKAVAKKAAPKKTVAKKAAPKKAVAKKVAPKKAVAKKVVAKKAVAKKVVAKKVAPKKVVAKKV APKKVAGKKAAAKKA Protective antigen The microtubule-associate protein (MAP p15) was tested as a vaccine in mice, and tests showed that p15 (native or recombinant) generated up to 100% protection from an otherwise lethal challenge of a heterologous strain of Trypanosoma brucei [Ref1393:Rasooly and Balaban, 2004]. TSA VO_0011338 62175539 CDD:271234 CDD:290570 5691 ? trans-sialidase 6.57 77957.172 833 Non-viral sialidases; cd15482 >AAX69677.1 trans-sialidase [Trypanosoma brucei] MEELHQQMRMPISRLLLIFTAVCHCCALTSKAAGKGTTREAFLSGGAWALRKKLSEKDGEVWWWQDGPNW KDKYDKEWERWFKEEKGPWGGSEKRSEWFARMTGGYITLGKTKILSSAIEGSDKVERTVHSFRIPSFVEV DGVLMGIGDARYLTSTDYFFTDTVAKYSADGGKTWKTEVIIENGRVDPTYSRVVDPTVVAKADSVFVLVA RYNVTKGYWHNENNAAGIADWEPFMYKGVVTKGADGKTSDVRISWTKTPLKPLYDFTVAGSKGTQFIGGA GNGVVTLNGTILFPVQARNEDNAVVSMVMYSVDDGVSWHFARGETALLTSEASLTEWNGKLLMSARTDTS GVNVEGGFRKVFESNNLGATWEESLGTISRVIGNSPDRTKPSPTANYPGSSGALITVTLGDVPVMLITHP KNTKGAWSRDRLQLWMTDGNRMWLVGQISEGDDNSAYSSLLLARDGLLYCLHEQNIDEVYGLHLVHLVDE LEKVNATVRKWKAQDALLAGLCSSSRKKNDPTCSGVPTDGLVGLLAGPVGASVWADVYDCVNASISDGVK VSEGVQLGGKRNSRVLWPVSEQGQDQRYYFANTHFTLLATVRFAGEPKAEAPLMGFSNAEGKTSETLSLT VGGKKWVLTYGSVRKEGPTTSMDWNQTHQIALTLRDGKVDAHVNGELIIKEVSVGASESSAHLHLSHFFI GAPVNDSGEGGNNVIVRNVLLYNRKLDEDELQLLYSNREKIQPVVSAVGIPEGMSAPRLCCLLILMYVLA I Protective antigen BALB-c mice immunized intramuscularly with a single dose (100 microg) of a plasmid DNA encoding the 5'-terminal region of the trans-sialidase (nTSA) gene of T. brucei brucei are able to produce IgG antibodies that bind to the bloodstream form of T. brucei-protein extract and recognize the recombinant nTSA protein, expressed in Escherichia coli. Furthermore, this DNA vaccination process was able to protect 60% of mice submitted to a challenge assay with the infective form of T. brucei brucei parasites [Ref1398:Silva et al., 2009]. Rasooly and Balaban, 2004 journal Rasooly R, Balaban N 2004 22 8 1007-1015 Vaccine Silva et al., 2009 journal Silva MS, Prazeres DM, Lança A, Atouguia J, Monteiro GA 2009 105 5 1223-1229 Parasitology research Wiki: T. brucei website http://en.wikipedia.org/wiki/T._brucei