Vibrio cholerae 666 Cholera is transmitted via the fecal–oral route through contaminated food or water. Soon after oral ingestion, V. cholerae colonizes in the small intestine and produces virulence factors, including cholera toxin (CT). Acute secretory diarrhea mediated primarily by CT causes massive dehydration and a mortality rate of 20–50% if left untreated (Xu et al., 2009). Cholera The adapted protective immunity against cholera is thought to be essentially humoral and predominantly based on intestinal mucosal antibodies, especially secretory IgA (sIgA), which is generally considered a correlation of protection for cholera (Xu et al., 2009). Cholera can be modeled in an infant mouse model (Kirn and Taylor, 2005). Cholera is an acute intestinal infection caused by ingestion of food or water contaminated with the bacterium Vibrio cholerae. It has a short incubation period and produces an enterotoxin that causes a copious, painless, watery diarrhoea that can quickly lead to severe dehydration and death if treatment is not promptly given. Vomiting also occurs in most patients. Most persons infected with V. cholerae do not become ill, although the bacterium is present in their faeces for 7-14 days. When illness does occur, about 80-90% of episodes are of mild or moderate severity and are difficult to distinguish clinically from other types of acute diarrhoea. Less than 20% of ill persons develop typical cholera with signs of moderate or severe dehydration. Cholera remains a global threat and is one of the key indicators of social development. While the disease no longer poses a threat to countries with minimum standards of hygiene, it remains a challenge to countries where access to safe drinking water and adequate sanitation cannot be guaranteed. Almost every developing country faces cholera outbreaks or the threat of a cholera epidemic (WHO: Cholera). 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 Dukoral Oral Inactivated Cholera vaccine Dukoral SBL Vaccine, Sanofi Pasteur Ltd VO_0010710 Subunit vaccine + Inactivated or "killed" vaccine Licensed Oral Canada Products: Proteins + killed bacteria. Other components: Saccharin. Store in a refrigerator (2°C – 8°C) Oral licensed Cholera human vaccine Generic Unknown VO_0000763 Inactivated or "killed" vaccine Licensed A generic representation of vaccines utilized to prevent cholera infection in humans, most commonly formulated as inactivated (killed) whole-cell preparations. These vaccines are administered orally and have been historically licensed for widespread use against cholera. Mutacol Mutacol Berna Biotech VO_0010728 Live, attenuated vaccine Licensed oral Canada Products: Live bacteria. It uses the V. Cholera live attenuated strain CVD 103-HGR. Other components: Yeast extract, Lactose, Aspartame. oral V. cholerae CTB DNA Vaccine VO_0011360 DNA vaccine Research pJW4303 [Ref1328:Xu et al., 2009] Intramuscular injection (i.m.) Intramuscular injection (i.m.) cholera toxin B subunit (CTB) (Xu et al., 2009). DNA vaccine construction BALB/c mice Mice were immunized intramuscularly with 100 μg of the CTB DNA vaccine or vector control. The DNA immunizations for mice were given at Weeks 0 and 2 in DNA alone prime boost groups, or Week 0 only for those receiving DNA prime followed by KWC-B vaccine boost at Week 2 (Xu et al., 2009). The immune sera elicited by CTB DNA vaccine were functional and protective against V. cholerae O1 infection in mice (Xu et al., 2009). Naïve suckling BALB/C mice at 5- to 6-day-old were separated from their mothers for 4 h, then inoculated by oral gavage with 50 μl of the appropriate serial dilution of the inoculum. To prepare the inoculum, V. cholerae O1 El Tor biotype Ogawa strain V48-65 growing overnight on an LB plate, were re-suspended in PBS and adjusted to 5 LD50 in 25 μl, then incubated with 25 of properly diluted immune or normal rabbit serum samples for 1 h at 37 °C. The suckling mice were kept in a 25 °C environment and observed every 4 h for 48 h post-inoculation. The survival rates were documented at each time point (Xu et al., 2009). Vaxchora Vaxchora PaxVax, Inc. VO_0003082 Live, attenuated vaccine Licensed Oral USA VAXCHORA (Cholera Vaccine, Live, Oral) is a live, attenuated bacterial vaccine suspension for oral administration containing the V. cholerae strain CVD 103-HgR. CVD 103-HgR was constructed from the serogroup O1 classical Inaba strain 569B by deleting the catalytic domain sequence of both copies of the ctxA gene, which prevents the synthesis of active cholera toxin (CT). (FDA: Vaxchora) Store at −25°C to −15°C (−13°F to 5°F), and protect from light and moisture. Oral Vibrio cholerae hemA mutant vaccine VO_0002934 Live, attenuated vaccine Research Oral immunization Oral immunization Gene mutation This hemA mutant is from Vibrio cholerae (Ravichandran et al., 2006). A hemA mutant is highly attenuated in rabbits (Ravichandran et al., 2006). A hemA mutant induces protection in rabbits from challenge with wild type V. cholerae (Ravichandran et al., 2006). VCUSM2 elicited high titer of anti-LPS IgG/IgA antibodies on the fourth week post-vaccination. These titers were comparable to those elicited by the wild type strain and were significantly higher than titers pre-vaccination (Ravichandran et al., 2006). VCUSM2 elicited high titer of anti-LPS IgG/IgA antibodies on the fourth week post-vaccination. These titers were comparable to those elicited by the wild type strain and were significantly higher than titers pre-vaccination (Ravichandran et al., 2006). ctxB VO_0011270 110264635 CDD:279687 127906 ? cholera toxin B 8.47 11386.27 165 Heat-labile enterotoxin beta chain; pfam01376 >ABG56901.1 cholera toxin B, partial [Vibrio cholerae O1] MIKLKFGVFFTVLLSSAYAHGTPQNITDLCAEYHNTQIHTLNDKIFSYTESLAGKREMAIITFKNGATFQ VEVPGSQHIDSQKKAIERMKDTLRIAYLTEAKVE Protective antigen The immune sera elicited by CTB DNA vaccine were functional and protective against V. cholerae O1 infection in mice [Ref1328:Xu et al., 2009]. hemA 12656010 CDD:178819 CDD:133452 CDD:144372 666 ? glutamyl-tRNA reductase 419 glutamyl-tRNA reductase; Reviewed; PRK00045 >gi|12656010|gb|AAK00701.1|AF227752_2 glutamyl-tRNA reductase [Vibrio cholerae] MSLLAIGINHNTASVELREKVAFGPEKLSLALNQLSTSSHVKGGVILSTCNRTEIYCDVRSASKNKVIEW LSQFHQVSLDELKPSLYVHEEQAAIRHLMRVACGLDSLVLGEPQILGQVKQAYAEARENHAVNPATEKLF QKAFSVAKRVRTETEIGGSAVSVAYAACTLAKHIFESLADATVLLVGAGETIELVAKHLAGHHCKRMIVA NRTRERALSLAQQFGADVIALNEIPDYLAQADIVISSTASPLPIIGKGMVESALKARRHQPMLLVDIAVP RDIEPQVGKLNDAYLYSVDDLQSIVDSNIEQRKVEAIQAEAIVSEESATFMSWMRSLQAVDSIRDYRKQA NEAREELLNKSLQALAAGGDPEKLLIELSNKLTNKLIHTPTRALQTAAEQGEPAKLAVIRQSLGLDDLN Virmugen A hemA mutant is highly attenuated in mice and rabbits and induces protection from challenge with wild type V. cholerae in rabbits [Ref1661:Ravichandran et al., 2006]. IgA Oryctolagus cuniculus 4063655 CDD:143182 CDD:197704 CDD:209398 9986 ? immunoglobulin heavy chain VDJC-alpha transrecombinant region 306 Immunoglobulin (Ig) heavy chain (H), variable (V) domain; cd04981 >gi|4063655|gb|AAC98362.1| immunoglobulin heavy chain VDJC-alpha transrecombinant region [Oryctolagus cuniculus] METGLRWLLLVAVLKGVQCQSVEESGGRLVTPGGSLTLTCTVSGFSLNTYPMQWVRQAPGKGLEWIGWMN NNGNIYYASWAKSRSTITRNTNENTVTLKMTSLTTEDTATYFCARYLSSHGYDIWGPGTLVTVSSDPVNT RPILIPLPCPILGPGEPVVIGCLIRGFFPLGPLSVTWNTSGENLTFPPVQSATSSLYTTCSLLRLPAEQC PEENSVACHVEHNYDKGQDVTVPSPPECQPPTPGPSDTTTCPCPCPSPSCGEPSLSLQRPDLRDLLLNSN ASLTCTLRGLKNPEGAVFTWEPTNGN Vaximmutor IgG Fc fragment Oryctolagus cuniculus 100343867 9986 Un 315920 352013 + Fc fragment of IgG binding protein >gi|283557656:315920-352013 Oryctolagus cuniculus breed Thorbecke inbred unplaced genomic scaffold, OryCun2.0 chrUn0214, whole genome shotgun sequence CATGGGTTCCCTGAGAAGCTGGTGGACGCTGTGGGCCGGAGCCACCCTCCTGTGGGGTAAGTCAGACCCA GTCCCCATCTGTGTCTTTCTCCCACTCTGCCTGGGTGGCCCATGCCCAACTTGTGCCCCTCCAGGCACTC GCCTTCCGAGGCCTCCCCATGCCAGCTGGGATGGGAGAGAGGCCCCCAGTTCCTGCAGAGGGGCACGGCG GGCTCTGCCCAGGCTCACTCTTCTGGAGGGAAGCCACAGAGCCCTCGGCCCCCAAAGCCGAGGGCGCAAC AGAAACCACTGTCTTGGTTCTCTGCAACTCAGCTAAGCCATGGCTCTGAGTCTCCTTCTGCCAAGGTGAT GGGAACCGTCACCAAGGACATTCCTGGAGAGCTCTGGTGCCCAGTTCTCCTGGGGGAACCGCCAAGAGTC TTAGGTGAACCCGGAGGTCCCTTGACTCTTGACCCCCTGGGCCTGGGGCACACTGGGATGTCCTCCAAGT CTCCCTGAACTTGGCAAGTTGTCACTCCAGCGCCCCCAACTCTCTCTCTATCTCTCTCAGCACTGGGCAC TCTCTTCCTGGTAGGGGCTGTTGAGACATCCACCTTTCCCACAACCCCCTTCTTTCCTTTACCTTCTTCA CACAAACCCTCCGGGTCGTATCAAGACAAAAGTCACCCGCCGGCCGCGGAGTGCTGCCGGTTGGGACCCC CGAGGTGCCTCAAAACAATTTTGGGTTGAAGAGTTCACATACACATTCAGAGAGCCAGTTTCTCTTGAAC ATGGTAAGATCTAGCACTGAAGATAAAAATAAAAATAAAAAAAGGCCGCAATCCCTCCTGTCAGCCCCCT GCAACAGCAGGCAGCGAGCGCCCACTCTGCCTTCCACGTCGCCGCGGGACTGCGCGTCTGTGTGTCTCAC CGGCCCCCTCAGCACCTGAGAGCCCTGTCCAAAGAGTTTGGGCTTGTAGAAAAATGAAAGCCAGAATGGC TTGTAGGCAGGTGAGCGGTGCAGGAATAAGAACAAAGGCAAGAGAAGAGGAAAAAAAAAAAAGTTCCTGG CACAGGGCAAAGGGTTGGCCGACTGACCAGGCGGATTAGGTAAGTGGACCAACGACTGCATTTTCTCAAG GGTGGACCCAGGAGGCAGCTGTGGAGCCCAGGAATCCTGGGGGGCAGGAATTCCTCATGGCCTTCCTGCA GAATTACCAGCCCGAGTACAGCGCCGCCTCCCTCTACCTGCTCGTGTCCAGCCTATCGGAGAGCCCGGCC TTGGTCTCCGTGCTCAGCCAGGCCGACAAAGCCTCGCAGACGGTCACAGTGAAGCCAGGGGAGTCAGTCG TGGTCAATATCAGTGCTGCGGCTGAGATGACCGGCAGCAACATCTTCCAGCACGCGGTTGTGGTCCGCTC CGACCACCGCATCACTGTGCAGGCCCTCAGTGCCAAGCCCAGCACGGCGGAGCTGACCCTGTTGCGACCG GTCAGCGCTCTGGGCACCGAATACTTCGTGCTCACACCCCCGGGTACCTCAGCCAACAGCCTCAGGGAGT TTGCTGTGGTGGCCGGGGCGTCAGGTGCCTCGGTCAGTATCACCCTGAAGGGGGCAGTGACGTTCCAGGA CAAGATCTACCCAGCAGGCGATGTGCTGAGCGTGACCCTGCAGCCCTACGAGGTGGCTCAGGTACAGGGC GAAGTTGATCTCTCGGGATCGAAGGTCACAGCCAGTAACCCTGTGGCTGTCCTCTCGGGCCACAGCTGTG CCCAGAAACACACAAACTGCAACCACGTGGTAGAGCAGCTGCTGCCCACGTCTGCGTGGGGCACCCAGTA TGTGGTGCCCCCACTGGCCTCCCAGAGCCGCTATGATCTGGCCTACGTAGTGGCCAGCCAGGCCACGAAA CTGACCTACAACCACGGAGGTACCACAGGCTCCCGTTCACTCCAGATGGGAGGCGTGGTAGAGTTTGAGG TGCGGCCGTCCCGGCCACTCTACCTGTCCGCAGATGTGGGCATCCAGGTCCTGCTCTTCGGCACGGGGGC TATAAAGAATGACATGACCTATGACCCCTACCTGGTGCTGATCCCGGATGTGGCAGCCTACTGCCCCACC TATGTGGTCCAGAGCGCACCAGGCTCTATGGGTGTGGCTGTGCTGGTGGCACAGACAAAGGCTGTCAACG GGCTGACCATGGATGGAGACACGCTGAAGGCCACGCTCCCCTGGGTGGCTGTGCCAGGCAGTGAATTCTC ATATACTGAAGTGGACCTTGGCACAGCTAACAGGATTCACACAGTCAACGCCAACACCAACATCGGGCTG CTCACGTTCGGGCTGGGCCAGGCTATGGGCTACGGGACAGCAGCTTCCTGCGGCCAAAGTGAGTGATGGG AAATGGCCCCTGGCCCCCACCCACCTGCTCCTCCATGGCTTTCTGGTTCAATGGGGCTGTCCACCCTCAC CTCCATCCTCCCCGCCATCCTTTCTTGAGTCCAGGACATGGATGCCACTCAACTTCAAGGGATCACTTTG GGGCTTGGATAATCAAAGAGAGGAGGAATCGATGATCCATCTCCGTAGCTAACACTCACTGTGACACCTG GGTTCACTTCCAAATCTTACTTCTGTTTTAGCTTCTTCAGGGGCGGGCATTGTGGTGCAGTGTGCTGAGC TGCAGCTTGGAATGCCCACGTCCCAAATCGGAGTGCCAGTCTGAGTCCCCCCACCTCTGCTTCTACCCAG CTTCCTGCCAATGCATCCAGTGGGGGGAGGGGGAGGCAGCAGATGGTGGCTCAAGTACTTGGGTCCCTGA TGCCTATTTGGGAAACCCTGTTGAAGTTCTGGGCCCCTGGCTTAAGACTGGTCCTGTGCTGGCTGTTACA GGCACTTGGAGATTAAGCCAGCGGATGGAGTCTCTCTCTCTCTCTCTCTCTCTCTCTCTCTCTCTCTCTC TCTCTCTCTCTCTCCCTCTCCCTCTCCCTCTCCCTCTCTCCATCTCCCCCACTCACTCTCCTCTCTCCCT CTCTCCCTCCTCCTCTGCCTTTTAAGTAGATGAAAACAACTAAACATCTTTTAAAAATAAGCAAAACCAT CTCCACACCTCTGCCAGATTCCCCTATGGAGATGGGATTGCTATCCTATTCCCCTCATCCTACGAATGAG GCAACTGGGGCACTAAGAGTTTAAAAATAAGTTGCCCGGTGTCTCCGAGCTGCATGATGCAGCCCGGATT CCTAGCTAGACAACGTGACTCCACAGTCATTGCCACTGTGCTGAGCGGCCTCTGCCTTCTACTTTCTGCT CTTCAAAAGATCCCTCAGCCTTTAGAGCCTGGTGGGATGGCAGGGGTGAGGGGGAAAAGGGAGGGAATAC AATGAAGATGTCAATAACAGTTCCTGTCACTCCATCTGCACTGCCTTCCCTTCTGCTCAGCTGCTCTGTG TTAAACAGGGGGATCAGAAAGCCCAGGCCTGAGCAGCTCTGTCTCTGTGTGATGCCAGCCCTCAGTCTCC CCATCTCTAAAATGGGCAGCTATGAATGCACTCCTTGTGGTGAGAGAGACCCAGGACTCCTGCCCCTGTG GGCATTTCTTTTTATTTTTTCTGAGGCAGTGAGAGAGAGAGATTTCATCAGTTGGTTCATTCCCTTTGCA AAGGGCCAACACAGTGGGAGCCAGGAGGCAGACCTCAATGCAGGCCTCCCACATGGGTAGGGGAACCCAG CCCCACTGCCTGCCAGGGTCTCCAGCCAGCAGGAAGCTGTAGCCAGGAGCCAGAGGTGGGAACTGGCCCC AGGCACTCTGATGTGGCACGTAGGTTTCTGGACCATTGGGCTAATGGCCCCCGCTGGCCCTGGGTGTGGC TGACTCTGCTCCCACCCTCTTCCCCCCAGGCCTGGTGTCCTCGGAGGAGCCCTCCTGTGAAGGCGTGACG TGCGCGGCAGGGCAGCAATGCCAGGTGGTGGACGGGAAGGCCGTGTGCGTGGCAGAGTCCACGGCCGTGT GCCGCGCCCAGGGCGACCCCCACTACACCACCTTCGACGGCCGGCGCTATGACATGATGGGCACTTGCTC CTACACGATGGCCGAGCTGTGTGGCTTGGACGAAACCCTGCCTGCCTTCAGCGTGGAGGCCAAGAACGAG CACCGGGGCAGCCTCCTGGTCTCCTACGTGGGCTTGGTCACCGTGCGTGCCTACAACCACGACGTGACAC TGGCCCGCGGGGAGGTCGGCTTTGTTCGGGTGAGTGTCCGGGGGCTTGGGGGCTTGGCCCCCTGGGAGCC GTGAGTCTGAAGGCAGAGGCAAAGGCCTTTCTGTGGGCTGGGGAGTGGGAGACGGGGAGCGGGGGTTAGA AAACAATAGCTGAGCCTTAAAACCTTTCAATGCCACGTCTAGAAATTCCAAAGATGCTCAGAAAGACAAT TAGAAAAACAAATATGCCAACATGGTGTACAAATGAGGAATTTCTTTCTTTCTTTCTTTCTTTTTTTTTT GCTTTAAAGATTTATTTTATTAATTTTAAAGAGAGTTACAGAGAGAGGTAGACAGAGAGAAGAGAAAGGT CTTCCATCCGCTGGTTCACTCCCCAGGTGGCCACAACAGATCGGAGCTGTGTTGATCCAAAGCCAGGAGC CAGGAGTCTCCTCCAGGTCTCCCACATGGGCGCAGGGGCCCAAAGACTTGGGCCATCTTCTACTGCTATC CCAGGCCATAGCAGAGAGCTGGATCAGAAGAGGAGCAGCTGGTACTAGAACTGGCGCCCATATGGGATGC CAGCACTTCAGGCCAGGGTGTTAACCCACTGCGCCACAGCGCTGGCCCCATGAATGAGGAATTTCTTGGG ACCAAATCACTGACCTATTTAAGTGCCCCAGTTGGTTCTTAGCTCTTAATGCTCACAGCAACTCTGGGAG TAGGCCTTGTTATTACGGACATGCACAGAGGAGGGTACAGGGTGGGAAAGGTGAGTGATGCCCCAAGCAC TGGGAGCTGTAAGAGCTGGCGCTGGGAACGCAGGCAGACTGGCTCCCAAGTCCCCGTTCCTCGTCCCGAG TCTCTCTCTTCCACTGCTTGTCCGTGCTGTGCCGTTCCGCCAGTACCAGCAGCATCTGGAGCAATGACTT CCTTTTTTTTTTTTTTTTTTATTTTGACAGGCAGAGTGGACAGTGAGAGAGAGAGACAGAGAGAAAGGTC TTCCTTTGCCGTTGGTTCACCCTCCAATGGCCGCCGCGGCCGGCGCGCTGCGGCCGGCGCACCGCGCTGA TCCGATGGCAGGAGCCAGGAGCCAGGTGCTTTTCCTGGTCTCCCATGGGGTGCAGGGCCCAAGCACCTGG GCCATCCTCCACTGCACTCCCTGGCCACAGCAGAGAGCTGGCCTGGAAGAGGGGCAACCGGGACAGAATC CGGCGCCCCGACCGGGACTAGAACCCGGTGTGCCGGCGCCGCTAGGCGGAGGATTAGCCTAGTGAGCCGC GGCGCTGGCCTGATTTCCTTTTTTGTCACGTTATTATGAAAATGTTAGAGCATCCAAAGCAGGTGAAATC ACCAGACAGTGAACCTCGTGGGCCCAGCGCCTCAGTTCCAAGCTTTTTGCTATTCTTGGCTGATTAGACC TCTGTCCACACAGTCTGCCCTCCCTCCAACAGCCGCTCTTGTCTATGTGCCTGGAAGTAAGCTCTGCACA CCAGCTCCACTTTCTGTAAGGTCTCCTCATGCAGATCACCCAGAAGGGTGCACTATTGTAAAACTCCCCC GTTTTGTTAATTTTAAGATTTTTAAGAAAACATTTAGTTTGTAACAGATTCAATATAGCTTTTAGATATG ATTCTAAGGATATAATGACATTCCCTTCCTCCTTTTTCCATGTTTTCAAGATTAAACTTACATATCACAA AATTCACAAATTGCAAATGAGCAGTTTGCTGTTTTGGCAAATGTGTAACCCAGAGTCCCATTAAGATACA GAATATTCCCATCAACTCAGAAAGTTCCCTCCCGAACAACCCCCAGCCCACTGCACAAGGCACAGTTCTA ATTTTTTTTCCCCACCATGATCTACCGTGGATCAGTTTTGCTTGCTTAAGAATGTCCAATAAAAGCAGGC ACACAGCTTAGCAGGCAAAGAATTCACATAGCACAAAATAAAAGGGGTAAGATACAAAAGATCTTGTTTC TATTCCAGTCTTCATCTACTCCCCTCCTCCGCCCTCCCCCCCACCCTCCCCCCACTCCTTACAGATAACT TCTCCTATTGGTTTCTGGAGAATTCATCTAGAGTTTCTTCCTGCCAATAGAAGCAAATACAAGCGGATGA CTTACCTTTCCCCTTTCTTAACAAAATGTACCCTACATGCTCCATTCTGCACTTGACCGTACCTTCTGGG CCCCTTTCCCTATCAGCACGTAGGGAGCCTCCTCTCTTCTTTTGGGTGCGGGGATGGGGGAGCTGCACAG TTCTGCATGGGATGAATGTCCCAGAGTTCACTGAAGCAGCGTGGGAGGGATGGATACTGTTCCATCTTGC AAACAGTGCTACAATGTATATTCTTACACCTGCTCAGCCTGTGAGTGTGCAGGTGGATCTGGGAGACCAA CAACCGGGTGTGTTACAGCAGGTGTTCTAGCGGGATAGGGCACAAGCTCAGGGGACTCCCGAGCCGCTGC AGTTGTGTGCAGCTTCTCATGGATCTTCTGTCAGCTCCTCACAGAGGTCACTGACTTTCTCAAGAGTTGG CGCTCCTGGTAGAATCGTGGTAGGATGTGCACAAAACATCGTGAGAAGGAGAGAGAGATCATGAAACTGT GACTTCTGCATGGTGGCATTATCTTTTTTCATTAAAGTATAAAAGCATTGAAAAGTAGTTGGAATAACAA NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN NNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNNN NNNNNNNNNNNNNNNNCCCCTGGACTGAGAAGCTGTGAGCAGGGGTCCCTAGCACTGGCTGGCGTGTTAC ATGGATGCATAGTAGGACTCCTGGTGGCTTTGCTGCAGGCCTGGGTGCGTGCATTCTGTCTTCTCCTCCT GCCATTGCTGAGGCTGTCCCCTCTGCCTGCTGCTCCTGTTTTTGGAGCTCTGGCACTTGGCTAAGACGTT CTCATCCCTCAAGTCTCAGCTCTAACATAGCCCCGGACATGTGTGAGGAGTGAGAAAGAAGTGTCTGCGG ACACACCGAGATGCTCCTGGCTCCTGGTATCTCAGGCAGCCCTGGCTGCCACAGCAGGGGTGGCTTCTCA ACAGCACAAGCTTCTAGCTCTGCTCTACAAGCTGGGAGCCTGAGGTCAGGGTGCCGGCATGGTTGGGTTC TGGTGAGGGCCTGCCTGCAGCCTGCAGACTGCAGGGTTCTCACTGTGTCCTGACCAGAGAGCGCTCTGCG GTGACATCATTCACCCATTGTGCACCTGCTGTTTTTACCAGACACAGTTTCTGCCTCTGTGGATAAAGCA GCAAAGTGCCTGGGTAGCGCAGATGTCTGGTGGACTCAGACTGACAATAAACAGGATGAATTTGCAAGTT ACTTTTTAGAAGGCAAGAAGCTATTCTTAACAAATGAAACATGTCAGGGGAAAGACATAGGGAATGGAGA GGGCTCGCCATGTGAAACAGGGCTGGGATGGGCATTTAGCCTGGCAGTCAGGATGCTGGTTCAGACGCTT GCAGCCCACACTGGAGTGCCTGGGTTCAAGTCCCAGCTTGGGATCCTGCTCACAGCTTTCTGTTCATGAA GACCCTGGGAGGCAACGTGGGTCCCTGCCACCCATGAGAGAGACCTGGATTGAGTTCCTGGCTTCCAGCT TTGCCCCAGCCCAGCCCCAGCTGTTGCAGACAGTTGGAGAGTAAACCAACAGATGGGAGTTCTCTCTCTT TCTCTCAAATAAATAAAAATGTAAATAATTAAAATAATAAAAAGAGAGAGTGGCCTCACAAATATGGGAA CAGCTGAGCAAGTGTTTTTTATTTATTTGAAAATAAATAGGAGAGAGAGAGAGGGAGAGAGAGATAGAAA GAGATCTTCCATCTGCTGATTCATTCCCCAGATGTCCACGACAGCTGGAGCTGGGCCAGGCAGAAGCCAG GAGCACCTTGAGGCAGGAAGCCCAGGGACATCCTCCACTGCTTTCCCAGACACATGAGCAGGGAGCTGGA TTAGAAGTGGAGTAGCCACGACTTGAACCCGTGCTCGTATGGGATGCCAGTGTTGCAGGCGGCAGCTTAG CCCCTTATGCCACAACACCAGCCCTCCCTGAGCAGATATTTTCTGTGAGCCAAGGAAGTGAGCCACATGC TCATCTTGGGCAAGATCACTCCTGGCCACAGGAAGTGGGAGAGCAGAACTGTGGAGGCACAGAGGGTGGC AGTAACAAGGAGGGATCCCAGGACAGTGAGACCCGGGCCAGGGAGCAGCCAGCCCACCCTGGGCTCTGAC CACCCCACCTCACCCCACCTGCAGATCAACAACCAGCGTTCAGGCCTGCCAGTCTCCCTGAGCAAGGACC GCCTGCGCGTGTATCAGCGCGGGACCCGGGCCGTGGTGGAGCTGGACTTCGGGCTGGTGGTCACCTACGA CTGGGACGCTCAGCTGACCGTGAGCCTGCCTGCCAAATTCCAAGACCAGGTGTGCGGGCTGTGTGGCAAC TACAATGGCAACCCCGCCGACGACTTCCTCACACCCGACTGGGTACAGGCCTCGGATGCCCTGGAGTTTG CCAACAGCTGGAAACTGGACGATGGGGATCCCCTGTGTGATGATGGTTGCCAGGGCAACTGTCCCTCCTG CACCGCAGCCCAGACCGAGCAGTACAAGGGCGACCATCTGTGCGGCATGCTGACCCTGGCTGAGGGCCCC TTTGCCCCCTGCCATGAGGTCCTGGAACCCCAGTCCTTCCTAGATGATTGTGTGTACGACCTGTGTGTGA CGGGCGGGGAGCGGCTCAGCCTGTGCCGCCTCCTCAGCACGTACGCCCAGGCCTGCCAGGAGCTCGGTGT CTCTGTCACGGACTGGAGATCGTCAGCCAGCTGCCGTGAGTGATGCCACTAGGGGCGCCCGGGGCACATG GGGATAGACAGGCGGGCCTCTTGGGTCTGCTTAGAATCTGAGCCCTTAGTTTGCTTGAGACTAATGCCGA GCCTATCTGGGGCACAAGGATGGCCAAGACAGCCAGGGTCACGGCAGGCATAGCAGTATACGGCGACACC CTGGAGCCGTCAGGCTGGGGGTGGCAGAGAGGTTGAGGCTGGGTTGGGGAAGTTCAATGGCATTGCAGGA GACACACAGTTCTTGATCTAGATGAGGGGTGTCAGGAAGTGTTTCCTAAAAAAAGGGGTGCCCAAGTTCA AAGCCACAGGAAGAAGTAGGAAAAAAGGAGGAGAAACTGGGTTCCTGGGGGACAGCACGTAGAGGCTTGG CAGGAGAGGAGATCTGCAGGATCCCAACAGAGAATTGTGCAGCCTCTTCCCACTCACCACCCTTGTGTGA CTCGCTTCTCCTCCCTGGATCAGGTCCAAGCCTTTTGGCCAGGTGTCATGCACTTCAGTCACTCACTCAT TCAGTAAATGAGCCTTCCTTGGGCCCCCTGCCTGGCCCTGCATCACCAGTGGGTTCGTCCATCTCCCTTC CCCCTTTCATTTCCACATCTGCCTCATTTCTGAGCACCTGCTGGGTGCCGGGCCCCTGTCCATGGTGCTG AAGACTCAGCAGTGACTGAGGCAGACCAGGTCCCCACTGCCACAAAACTTACGTGCCAGGGAGAGAAGGG GGAGACAGACAGCACGCAGGTAAAGTGTGAAATAGCTTCAGAGAGCAATAGGAGGAAAGTTTGCACGGTG GAAGTGGCTGCGAGACTCCTAGAGCAGGGATGGCCTTTGTGAGCAGGTGGCATTGGAGCTGAGATGGGGC GGGGGGCAGGCAAGGCAGGCAGCAGTGATGTTTGTGGAGCACTTCCACATCAATAACCCATTTAATCCTC ACAACAGCTCTGTGAGGCCGGTGCTATAGCATCCTATTTACCAACAGGGAAACCAGACAAGGGGAGATGG GAGTCATTTGCTCACCGTCACACAGCTAAGAAGGAGCAGAGCTGAGATCTGAACCCAGGCTGTCTGGGCT CCAGTTGGCATGCTCTGTGGATGCCGTGCTGAGGGAAGGGTACACCAGGCAGAGGGAACAGCCAGTGCAA AGGTCCTGAGGACGGAGGCCACTGTGACTGGGGCAGAGAGAGAGGGAGAGGAGATGAGAGCAAGGGAGAG GAGATGAGAGCAAGGGAGAGGAGATGAGAGCAAGGGAGAGGAGATGAGAGCAAGGGAGTGGTGGAACAGA TGGTGCAGGGCCTTGGGGTGACTGATGGAACCTCAGGAGGGCCCTAAGAGGGGACAAACCTGATCTGATT CAGGTGTCCCTGGCTGCTCAGGGCAGGCAGGTGGGAGTCCAGGCAGCAGGCAACATGCTGGATAGGTTTT GAATATGGAGTTCCCAGGACACACTGGCAGGTTGGTTGTCCAGTGGATGGCAGTGGAGTGGGAAGGGAGC TGCTCAAGGCAGAGCTGGGGGTTCGGGCCTGGGCCGTTGTCATTGACTGAGAGGATAGTGCTGAGTTTGC AGCCAGCAGAGGGGGGTTGCTGGGGGAGCCTGGACACTTGGCCTGACCCACCCTCATGTCTCCCCTGCAG CCTTGTCCTGCCCCGCCAACAGCAGCTATGAGCTCTGTGGCCCCGCCTGCCCCGCCACCTGCAACTCCGT CGCAGCACCGTCTAACTGCTCTGAGCGCCCGTGCGTGGAGGGCTGCGTGTGCCTTTCGGGTTTCGTGGCC AGCGGCGGCGCCTGCATCCCTGAGTCATCGTGCGGGTGCACCTTCGAGGGCCTCCTACTGGCACCTGGCC AGCAGGTATGGGCTGACACCCTGTGCAAACAGAGCTGCACCTGCGATGGCACCACCCACCAGGTGAGCTG CCAAGACACGCAGGGCTGCCCGGAAGGCGAGCGCTGCCGCGTGGAGAACAACCTCCTGGGATGCTACCCT GAAAGCTTTGGTAGCTGCCAGGCCTCTGGGGACCCGCACTATGTGAGCTTTGATGGCCGGCGCTTCGACT TCATGGGCACCTGCACCTACCTGCTGGCGGGCTCCTGTGGCCAGAACACAGCACTGCCCAGCTTCAGCGT GCTGGTGGAGAATGAGCACCGGGGCAGCCAGACCGTGAGCTACACAAGTGCCGTACAGCTGAAGGTCTAT GGGGTGGAAGTGGCCGTGAACCGGAAGTACCCTGGGCAAGTGCTGGTGAGTGACATGGGCCCAGAGCTGG GCAGAGGGGAGGGAGACCCCCGGGATGGGAGTTGGGGCCTGCTCCTCCTGGCCTGTGTGCCTTAGTCTTT CACTGCCTGAGTTTTGTCCCCTGTTGAGAAGCATGAGTGGGGGCAGTTCCCGGGCTGGTTGTGGGGACTT GGGGAGTTGGTCGTTGAGTGGTCTTTGAAAGAAGCCTGGGGGCCTGGCAGGAGCTCAGCAAATGTTGGCT ACTGCTTATTGTTGTTGTTGTTATGCACACTCGGAACTGTAGACCCGTGCGTTTTCTGTAGGATGCTGGT TTTTCAGGGTGCAGGTTGACATGTCGGGTGACAGGTGAGATGCCGGGAGCTGGAGGGGAGTGGATCACAG AGGTCCTTACCCGATGTCTCCAGGGATGCTGGTGGGGAAGGCCTCCCAGGGGCCCCAATGGTCCCGGGTT TCTGTCCAGAGGATCCTAGAGGGACTACTGCCCAGTGGGAGCCAAGGGCTACTGGCTTTGTGTTAGAAGG TAGACATGGAGACGTGGGACTGTTGTGGCTGGTATTTGGTACTGAGCAGTGGCCTGTAGCCTGGGGAGAG GGGTGGATGATGTGTCCAACACCACTCTAAACCCTTCATACATCTTAACTCATCACCCTCACGACAACCT CGGAATAAAGGAAATGCTGCCCCCAGAGAACACTCTAGAGAAACGGGACAGAATTTTGACTGTATTTCTA GTCACTGCTCTGAGATGACACTTGGGCTGAGGCTTGGAGAATACCAACCAACACATACTGGGTTAATTTA ATGTGCTGTATCCATATGCATCAACCTGTTTAATCTGTACCACAACCCTGTGAAGTAGCTGGTCTTCAGT GAGACTGGGCGGGGCTTCAGTGAGGATGGGCGGAGTTCGGCGAGACTGGGCGGGGATTCAGTGAGGCTGG GCGGAGTTCAGTGAGGCTGGGCGGAGTTCAGTGAGGCTGGGCAGGGCTTCAGTGAGGCTGGGTGGGGCTT TGGTAGAGTTGGGTGGGGCTTCGTGTGCTCAAGATGCCCGCCTGCCTGGAGTGGCAGGAGTTGGGGGTGG GCCATACTGGGGGGTTAAACTGGGGTTCTTTCAGGCCATTGTAAAGGGTTTGGATCAAAGCTGAACCTAA CAGGTGAGGTGGATGGAAGTGGTCCCGGGAAGAGCGATGAGGGCATAGCAAGTGCAGAGGTCCTGAGGTT GGGGATGGGAATGCATTTGATGTGCCCAGAGACACAACAAGAGGCCAGAGCGGCTGGGGCTGAGTGAGTG GTGTGGACACAGGAGTGGACAGGGCAGGGGTCAATCAGGACTTTATAGGGAAGGGGCCTGGATTGAAGGC AAATCCCAAAGGCGGGGAGGAGGGGGTAAGTGTGATGATCCTGAGGCCAGGCTGAGCTGGGGCAGCTGAG GGCTCCTGAGCAAGCCCACAGGGCTGGAGCAGAGGGAGGGGCAGAGTGGGAGGAGGGAAGCTCAGGGGGT GGCAGGGAGACAGAGCAGGCAGGCTTTGAGGGCCCTGAGTCAGAGGTTTGCATTTAAGCTGATGCCTGAA GAACCAGGTCAGTGGACGGCGTTCCAGGCAGAAGGAAACAGCAGGTGCCAAGGCCCTGAGGCAGAACTGA GCATGTTACCTTCCAGAGAGTAGCAAGGAGGCCAGGGAAGCTGGAGCCAAGTGGGAGGGGGGTGAGCCAT GGGGCCAGGAATGCCTGGCCTCTGCACCCTCCTGCCTCTCCCCCCAGGTGGATGGCGTCCTGAAGAACCT GCCCTTCCAAGCAGCCGATGGGCGGGTGCAGCTGTTCCGCCAGGGCAACAATGCTGTCGTGCGCACGGAC TTTGGCCTGACTGTCACCTACGACTGGGACGCCCTGGTGACCGTCAAGGTGCCCAGCAGCTACGCGAAGG CCCTGTGTGGACTCTGTGGGAACTTCAACGGGGACCCCAGCGATGACCTGGCTCTGCGCGATGGGAACCA GGCTGCCAATGCTCTGGACTTCGGGAACAGCTGGCAGGAGGGGACGAGACCTGGCTGTGGGGCGAGTGAC GCCGGGGACTGTCCCACGCTGGACTCGCAGGTGACCCAGCAGCTGCAGAGCAAGAAGGAGTGTGGGATCC TTGCTGACCCTGAAGGACCCTTCCGGGACTGTCACAAGAAGCTGGACCCCCAGGGTGCCTTGCGCGACTG TGTGTATGACCTCTGCCTGCTGCCTGGCCAGTCTGAGCTACTGTGTGATGCTTTGGCTACATACGCTGCT GAATGCCAGGCTGCCGGGGCCACCGTGGAGCCCTGGAGGAGCGAGGAGCTTTGCCGTGAGTACCAGAGTG GCGAGGATGTATGTATGCGTGAGCATGTCAATATCATTCATTCACTGAATCTTTAGAACAGCGCTGTGAT GCAGGGGCTGTGGTTCTACTCACTTAGGAGATGAGGAAAGTGAGGTTCAGCAAGGCAGGGCTGCAGGGTC ACCACAACCAGCAAGTCACAGATGGTAGGCGTGGCCGCCAATGTTTGTGAAATGACAGGTGACATCCAGC GGCCGCACGTCTGAAGCCCACGTGGCAGCTGTCACTCAGAGGGCATCAGCGGTGCTGCCTTAGAAGAGGC ACGGCCCCCATCCAGGTCCTCCTGGTCCCCAGCTGGCCTGCTCCACTCACCCCACCTGCCAGGCCCCTTG GGCAGCGCGTCTGAGAGCCTGGCTGTGGATGCGGGTGCAGGGATGACCTGCAAACGTTTTTGCTCACCTG TGCATTTGGAAAACCACGCTTCCCCTCACCTGATTTTTTTAAAAGTTTATTTGAGAGGTAGAGTTACAGA CTATGAGAAGGAGAGACAGAGAGAGAGGTCTTCCATCCATTGGTTCACTCCCCAAACGGCCACAACAGCT GGAGCTGAGCCCATCCGAAGCCAGGAGCCAGGATCCTTTTCTGTGTCTCCCACACAGGCGCAGGGGTCCA AACACTTGGGCCATCTTCCACTGCTTTCCCAGGCATAGCAGAGAGCTAGATTGGAAGAGGAGCAGCCAGG ACCAGAATCGGTGCCCATATGGGATGCCGGTGCCTCTGGCAGAGGATTAGCCTACTATGCCACAGTTCAG GCCTCACCCTCACCTGATTTTTAAAAATCTTGGGATACAATGTACATATTCAAAAAGACCTGGGTAAGGG AACCACTTGATCAGTTTTTCAGTAAGAGAGCGTATCTGAGTAGACAGCCCACGTTCAGAGAAAGAACAGG GGCGGGCGTTTGGCACAGTGGTTAAGATGTCACTTGGGATTCCTGTATCCCATATCATAGTGCCTGGGTT CAAGTCCTGACTCTGCTTCCGACACACCTTCCTGCTAATGTGCACCCTGGGAGGCAGCAGTGACAGCTCA AGTGCTTAGGTCGCTGCCAACCACATGAGAAACCCTGATGGAGTTCCTGGTTCCTGGTTTTGACCTGGTC CATCCCTGGCTGTTTCAGGATTTGGAGAGTGAGCCAGCAGATGGAAGATGTCTCTGTCTCTTTGTCTCAC TGTCTCTCAAATAAAAATGAAAATAAATAAATGTACAAAAATTTCAAATGAGCATACCAAGACCCCCATC CCAAGAGGTAACCAATATTTTGACTTCTAAAATTGTTGAACTTCATATAAATGGAAACATACATCATTAG CTTTCTTCTTTGGTGTAAATAATCACAAAAGATATAATTCCCAACAAATAGTAACTTTTTACTTTTAAAA TACATTTTATTATGGAAAAATTCCAACATACCCAAAAGTAGACCAGGATGATGAACCTGCATATATCCAC CAGAAAATTGCTACCATTATTAATATAATGTTGACATCTTAGCAGGCAACTGTTACTGATGTAACTCTCT TCAATGTATTCAACAGAGACACAGTACACAGTAGAGCCCACCACTGCCCCCTGCAGATTCCATGAGAAAT GGGTGGATGCCTTCAACCGTCCATCCACCCGTCCGTTCACTGATCAAATGCACTCGTGTACCATATAATG GTGTCTCAGTCAGCAGTGGGCTGCATATACGATAGTGTTTCTGTGAGACTGGCGGGGCCTTCACTGTGTT AGTTTGTGTTAGGGCACTTCATGGTGTTCACACAACTAAACTGCTCAATAATGCACCTCACAGAACATGT GCCTGTCATAATGTATTTGTTGGCCCTGTGCCACATCCCAGGCAGTAGGGGTATGACAGTCCTTTTTTAA AAGATTTATTAGAAAGAGTACAGAGAGAGAGAGAAAGAGACACTGGTTCACTCCCCAAACAGCTGCAACA GTCAGGTCTCGTCTAGGCCAAAGCCAGGAACCAGAAACTCCATCCAGATCTCCCATGTGAGTAGCAGAGG CCCAAACACTTGGGCCATGCTCTGCTCTTTCCCAGGCACCCAGCAGGGAGCTGGATCCGCAATGGGACAG CCAGGATTTGCACTGGCGCTCCAATATGGGGTCCGGTGTCGCAGATGGTGGCTTAACACCCTGCACCACA GTGCTGGCCCAGCAGTGAAAGCCTCTGTCTTCCTAAACAATGATTATTTGTTCTAAAAGAATTTTTAAGT GATTTTTTACCATTTGCTTATTCTTTATTTGAGGGAGGGAGGGAGGGAGGGAGAGAGAGAGAGAGAGATC TCCACTGATTTACTCCTCAAATGCCTGCAAAAGCCAGGGCTGGGACAGGCTAAAAGCTAGAAGCCTGGAA CCCGGTCCAGGTCTCCCACATATGTGGTAGGAACCCAACCGCTTTAGCCATCACCACTGCCTCCTAAGGT GCAAAGCTAGGATTTGAACCCGGGCACTCCCATGCGGGGTGCAGGCGTCCAAAACAGGAGCTTCATCATG GGACCAAGTGCCTAACCTAAAAGAGATCTTTCTTTTTTAAAAATGATTTATTTATTTGAAAGAGAGTTAC AGAGAGAGAAGGAGAGACAGAGAGATCTTCCTTCTGCTGATCCACTCCTCAAATGGCTACAACAGCCAGA GCTGCACCAGGCCAAAGCCAGGAGCTAGGAGCCAGGAGCCAGGAGCCAGGAGCTTCTTTGAGGTCTCCCG TGTGGGTAGCAGAGACCCAAGCACTTGGGTCATCCTCCGCTGTTTTCCAGGCACATTATCAGGGAGTGGG ATCTGAAGTGGAGTGACGGGGACTCAAACCGGTGCCCATATGGGATGCCAGTGTCAAAGGAGGTGGCTTA ACCCACTGCGCCACCTGCTGGCCCCAAAGATATCTTTCCATGAGACGAATGGGACTCTGCTTCACCAGTG TTTCACACACATTGTTAAAATGAGGCCGGGGCCCCCATCCAGGCTGTCCCAGGGCGCACTTTCGCAGGAA CAGGATTTTAAGCGGGTGGGGGTGGCCGGAATCCTGGCGAGACCTCTGTCCACTAGTTGAATCGCTTCTG AGTCACAGGGAAGGAGCACAGGACACTAGAAAATCCATGGGTGTTTTTGGTGTGCATGTGATTTTTGAGC GGCCGATTCTATCAGGCCCTTATTCCATCTTTTTGGGAGCAGAGAACTGGAAGGAATTTTTTGCCCATAA TGATGCATCACCCTTTGTCCTCACAACCTTAGTGACGTTTGCAACCATGTCCCTTTCTGTCCCTGCGAGT TCTCTCACCCCAGGGCGGCACTCCGGGGTGAGATTTGGGAGGAGAGGAGGCTGCACTGTTCTCCCCTGTC AAGTGGGAGCACGTGCTTGGGAAAGGACACTGGGATGCTGAGAAGCGGGGATGCCCCCTGTGCCGGCACA TCTCAGGCCGCCATTTAAGGAAGGGCCCGCATGGCGCTAGCTGGCGCTGGTGTAACCAGGCTCTGTTCTG GGGGCTTCATGTCGTCTTTGACTCCTCACTGTCACCCTGTGGGGCTGACTCTGTCCTGTTTCCATTGTAT AAGATGAAGAAGTGCCCAGAGATGGTGAGTAACTTGCCTGAGGTCACCCAGCATAGCACAGAGACTTGAG CCCAGCAAGTGTGTCCTGTGTCCTGTGAATTGCCACACTCGGTGATGCCTGTGCAAATGGACACTCTCTT ATTTCCTTTAACAGCTCTTGGCCCTTGCACCTTCAGAAGTTCTAGAAGGAGCAGGGCAGGGCCTGACCCT ACGCCCCCCAGCCTGAGCTTCTGTGGTCATTAGAACTATCTTCTGCCTCCTGTCACTCTTCATTTTTTCT GAAATATTCTAAAGCAAATTCTAGACATATGAGCTTTTCTATAAATACTTCAGCAAGTGCTTGCTATTCA GTGACAGAAAGGGGCTTTTTTTTTTTTTTTAAAGAAACTTCATTTATTTGAAAGGCAGAGTTACAGAGAG GTAGAGGCAGAGAGAGAGGTCTTCCATCTGCTGGTTCACTCATCAGATGGCCACAATGGCCAGAGCTGCG CCGATCCAAAGCTAGGATCCAGGAGCTTCTTCCGGGTCTCCCACATGGGTGCAGGGGCTTAAGGACTTGG GCCATCTTCCACTGCCTTCCCGGGCCACAGCAGAGAGCTGGACTAGAAGAGGAGCAACCGGGACTAGAAC CCGGCGCCCATATGGGATGCCGGTGCTGCAGGTGGAGGATTAACCTAGTGTGCCACTGTGCTGGCCCCTT TTAAGTCATTTTTATTCTGTAAAAACTTCCTTCCTTTCCCCCCAACACATGTGGGACTGCAAAAAAAGTT CATGGGAAATATGTATTATGAAAATAAAAACTGCACTCAAATAAGCTTTTCTTTTAATTCCACCTTCCAC GACCCTTCTGAAATGCCCTTATATCATTATGAAGTTTTTTAGATGTAAAGAAAAGTTGAAAGAATTTTAC AGTGATTGTCAATACCCCCCCAGCCCATGCTCCACAACCTATTTGCCCTCTACCTGCTGGCTCATTAGCT ACCACTGTCTACCCCCTTGCATCAGCCAGATTTTCGTCGCTATAGTGAAACACCTGGGGTAGGCATCTTT ATAAAGAGAGGAGGGTTATGTGGGGCCGCTGTTCTTGAGGTGCAAGGTGTAGGGGCTGCATCTGGTGAGG GCTGAAAGTAGCATGGGACATCACATGACAGGAGCCGGCCAGCATACTGGCAGCAGCATTTCCCACTTCC CCTCTGCTCTTTGGTTCTGCTCTGAACTGGCTGTTGGATCTAGAACCGTGCTGTGGGGCTGGCATTGAGG TGTAACGGGTGAAGCTGCCGTCTGCAATGCCAGTGTCCCATGTGGGTGCTGGTTCAAGTTCTGGCTGCTC TACTTCCAGTCCAGCTTTGTGACATGGCCTGGGAAAGCAGTAGAAGATGGCGCATGTGCTTGGGCCCTTG CACCTAGGTGGGAGGCCTGGAAGAAGCTCCTGGCATCCAGCTTTGGCCTGGCCCAGCTCTGGCCATTACA GCCATCTGGGGAGTGAACCAGCAGGTGGAAGTACTGTCTCTCTCTCTCTCTCTCTCTCTCTCTCTCTCTC CTAGTCTCCCTTTCAAATAAATAAATGTCTTTTAAAAATACACAAATAAATAAATAAATAAATAAAATTT GTAACTTATCACCAACCTACAGCCAAGTTAAACAGGACTGTTAAAGACATCACAGGCTGGCGCCGCGGCT CACTGGGCTAATCCTCCGCCTGCGGCACCGACACCCCAGGTTCTAGTCCCGGTTGGGGTGCTGGATTCTG TCCTGGCTGCTCCTCTTCCAGTCCAGCTCTCTGCTGTGGCCCGGGAGTGCAGTGGAGGATGGCCCAGGTC CTTGGGCCCTGCACCTGCATGGGAGACCGGGAGGGGGCACCTGGCTCCTGGCTTCGGATCTGCGCAGCAT GCTGGCCGCAATGCACTGGCCGTGACGGCCACTTGGCGGGGTGAACCAACAGAAAATGGAGGACCTTTCT CTCTGTCTTCTCTCTCACTGTCTGACTCTGCCTGTCCAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAA AAAAGAAAGAAAGAAAGAAAGAAAAGACATCACAGATGATCCCAAACTGTGGTCAGACTGGAACAGAACT GCAGTGATCACAATCAGATAATCAGATTCACAATGGTCAAGTGTGTTCCCCAGGCCTCACTGGACCCAGG GGCTTCTAGTGTGTGTGTGTGTGCGTGTGCGTGTGTGTTCACGTTATGCACATGTATGTGTGTGAGTACA TGTTACACACATGTATATGTTGAGGGTCAGCCATGTCAGGCTGGGAGCAGGAAGTTTGACTGACGGCCTC TCTCTCTGCAGCACGGAGCTGTCCAGAGCACAGCCACTATGAGTCCTGTGCCCGCGGCTGCCCGCTGAGC TGCGGGGACCTCCCGGTGTCCGGGGGCTGTGGCTCAGAATGCTACGAGAGCTGCGTGTGCGATGAAGGCT TTGTGCTCAGCGGCGAGTCCTGCGTGCCCCTGGCCTCCTGTGGCTGTGTATACCAGGGCTCCTACTACCA GCCAGGCCAGACCTTCCACCCTGGCCCCGGGTGCGACTCCCTGTGCCACTGCCAGGAGGGTGGCCTGGTG TCCTGTGAGGACTCCTCCTGCGGCCCGCAAGAGGAGTGCCAGCTGTCTGGTGGCGTCCTGGGCTGCGTGG TTGTGGGCTCTGCCACGTGTCAGGCATCCGGAGACCCCCATTACGTCACATTCGATGGCAGCCGCTTTGA CTTCATGGGCACCTGTGTGTACGTGCTGGCTCAGACCTGCGGGACCCCGCCCGGCCGGCCCCAGTTCACC GTCCTGCAGGAGAACGAGGCCTGGGGCAACGGACAGGTCAGCGTGACCAAAGCAATCACGGTCCTCGTGG GCAACCACACCATACGTCTGGAGCAGAGTCAGCAGAAGGTCACGGTGAGAACCACGGCTTGCATGGGAGG GGCGGTGCTGGAGTGGGGGTGCGGCCTGATCTCCCCTGTCTGTGCCCCTCCACCTCTCCGCCTTCGGCCC CTCGGCCTACGCTGCACTGTCCTGTCTGAAGGCCTCTTCCACCCCCTCCTCCCTCCTTCTCCATCCTCTC GCCACCCCTCCCCTAACCCGTCCCAGCCCCCTCCTTCATCTCCCACCCTATCAGAGGTTGGGAAAGATCA GAGAGTGGGCAGGGTCCAAGGACAGAAGATGGGGTGTGGGGGTGACCCTGTCCCCGACTCGACAACCACA GTAGCTACAGACTTTGCAGGCTGAGCCCGGACCCTGCGTCGAGCCCACAGGTCACTCTGTCTTCCCTGTG GCAGCTGGAGGCACCACGATTAACTCTCTTTTTGTAGATGAGGAGGTCCGGCTGTTGGCCTAAGAAACTG GCATTTCGGCTGCACTGGAGGGGAGGGGACTTTCTCAGAGACCCCACTCCCACACAGCCACTGCTCTGGT CCTGTCCTGGATCAGTAGATGACTTCATCACACATGACATAGCTTAATACAGCCCCCAACCCAGCCCAGC TCTTAGAGCAGCGCCCCGACTGTGGTTTGCTCTAAGCTTCTTGTAATTGACATCTCACTACATCCCACCC CACCCCCGCTTCCCTGAGAAGTAGGAAGTATCATCCCCACTATGCAGAGGAGCAAGGCGAGGCACAGGTG AAGTCAGTTCTCTGCTTGGGAAGTCCAGCAGTTGGTTATGCTCTGTGGGGACAGACACAGCCAGGAACCC GCCTTTCTCCTGCCTCCTCCCCTGATTCCTCACACTCCAAAAGACTCCAGCGTGCACCACATCTGCCCCC ACGGAACGAGGAGCAAGTGGGTTAATCGGGGTGGGTTTGCACAGCTTTGCCAGTGGCCAGCAGCCATTGG CTGAAACCACGGGTCCACAGCTCTCGGGGCTGAAGGTCATTTGCCCAGGAATGTAGCTTGGCCTTCCAGC CTTCAGTGTTTAAAGCAAAAACCTTCAGTGGCCGCTCACCCGTTAAAATGAAGCCTTCCAGTCAGGGCTG GTGATCACCTGGATGCACGGCAGCCCCCCCCCCCCCACGCCTCCCCGCTCCTTCACGTTCACACGGCCCT CTGCTCTGTGTCTTCCGGCTTGTCACTGGATACAGGGCCCGCCCTAATCTCCTCTCCAGGTCATTCCCCT AATTATGTCCATGAAGATTCTTATTCCAAAGTCACATTCTGCTGTTGAAAAAACAATATTTATTTATTTG AAATAATTGCAGAGATAGAGAAAGAGAAAGAGAGAGAGAGAGAGAGAGAGAGAGATCTTCCATCCGCTGG GTCATGCCCCCAAATACCCACAACAGCCAGAGCTGGGCCAGGCTGAAGCCAGGAGCCTGGAACTCCATCC GGATCCTCCCACTTGGGTACAGGGGCCCAAGTACTTGGGCCATCCTCTGTTGCTTTCCCAGGCACTTAGC AGGAAGCTGGATCAGAAGCAGAACAGCTGGGACTCAAACCAGTGCTCACAGGGGATGCCGGCGCATCACA GGCAGTGGCTTAACATGCTGTGCCATGAGACGAGCCCCTAAAGTCACAGTCTGTGATTCTAAGTAGACAT ATATTTTGGAGACCAGCATCCAACCCCCTATAAGACTCTATTATTATACCCATTTCACAAATACAGAAAC CACAACTCAGGGAGGTGAGGCACCACAGACCCTCACTGTCGGGCAGGGGCTGTAGCGGGTGTGGCTGGGC CGAACCCACCCTCTGAGACCCTGCTCCTCCCGCCTCCCAGGTGGACGGCGTGGACCTCAAGCCGCCGGTG GAGCTGGACAAGGGCGAGATCCGCATCAACCAGCACGGCTCGGACGTGGTGATCGAGACCGACTTCGGCC TGCGCGTGGTCTACGACCTCATGTACTACGTGCGGGTCACTGTCCCGGGCAACTACTACCAGCAGATGTG TGGCCTCTGTGGTGATTACAACGGCAAGGCCGAGGACGACTTCCAGAAGCGCAACGGCTCACAGGCGGCC AACCCCAACGACTTCGGCAACTCCTGGGAGGAGGCCGTGCCGGGCTCGCCCTGCCTGCCGCCCCCTGAGT GCGACTCGGATGCAGATTGCAAGTGCACCCCCGAGCTGGAGGAGCAGTACAAGAAGGAGGAGTTCTGTGG GCTGCTCACCAGCTCCACGGGCCCGCTGTCCTCCTGCCACAAGCTGCTGGATCCTCAGAACTCCTTGCAA GACTGTGTCTTCGACCTCTGCCTGGGCGGCGGGAACGAGAGCATCTTGTGCGGCCACATCCACGCCTACG TGAGCGCCTGCCAGGCAGCTGGAGGCCAGGTTCAGCCCTGGAGGAATGAAAAGTTCTGTCGTGAGTGAGG GGGACCCCGCAGGGCAGGGGCAGGGACATTGAGACCCAGACGGTGGGGCTCGTGCCGTGCTGCCCTTGCA GGGCTCTGACGGGTGCCCCCTCCTTGCAGCGATGGAGTGCCCCCCTCACAGCCACTACGAGCTGTGCGCA GACACCTGCTCCCTGGGCTGCTCGGCTCTCAGCGGCTCCGTGCAGTGCCCGGATGGCTGTGCTGAGGGCT GCCAGTGTGACCCTGACTTCTACTACAACGGTGAAGCCTGCGTGCCCATCCAGCAGTGTGGCTGCTACCA CAACGGTGTCTACTACGAGGTAGGATCGCGGACACCCCCCCTCCCTGGAGGGCCGCTCCTGGGACCTCGT CCTGAGCCCCCTCCCACCACCGCTCTTCCCCCAGTCTGTCCACTCCTGCCCACGCCTCTCGCTTGCCCAG CTCCTTTTCCCCACCTGGATCTCTCCTACCCCCATTTTCCGGCCTCTGGATGACCATCCATTTGCCAGTG GGGGAGCTCTTTCTAAATATGACTGTGGGCCCTGGGATACCCTTGCTGCCCACATCAAGTTGGGGCTTTG GGGCTCAGGCGTGGACAAAGGTGGCTCTTAGGACCACAAGGATGAGATTTGGTCTTTATCCCACCTGGCC AACTCCGCGTCCCTCGTCCACTCTCTCACTGTCGGTCCTTTTTAAAAAATGTTTTTATATATTTATTTTC ATTTTATATGAAAGGCAGAAAGAGAAACAGAGAGAAATCATCCATCCCCCTCCCCCTCCCCCTCTCCCTC TCTGTCTCCCTCTCCCTCTTCCTCTCTCTCTCCCTCTTCCTCTCTCTCTCCGTCTCTCTCCCTCTCTCTC TCTCTCTTTCTCTCTTTCTCATCCATCCACTGGTTCACTTCCCAAATGTCCACAACAGCCGCCAGAGCCA GGAGCCCAGAACTCCATCCAGGTCTCCTGAGTACTGGAGCCGGCACCTGTGGCCTCCCAGGGTGCACATT AGCAGGGAGCCAGACTGGAAGCGGAGGAGCCGGGACTTGAAGCAGGCAACTCTGATACGGGATGCAGGCG CCCCCGGCAGCCGCATAGACCCCGCTGGGCAAACACCCAGCCCTGTGTTAGTCCTCATTTCAGCTGAGTA GAGTTTGTCCGACGTGCATCTCCCTCACAGGGCTGTGAGCTCTACGAGGGCAGGGGCCTCTCTGTTCTCC TCCCATGCATAAGAGCAGTAACTCGTCCACAGTAAGCAGGAAACACGCGGATGGTGCTTCCTGGGTGCCC TTGCTGTGTGTATGTTTTACACGCACTGCCTATGGACGTAAGCTTTTTATTATGACGATGTTCAAACTTG CGAAAGTTCAGAGAACAATAGAACGAACCTCCACGTGTCTGAGCATCCCTGGGGCTGCCAAAGTTGACGT CTTCCCCAGTCGTGTTCTCTAGCCTCCTTCCATCTCCTACTGGGATGATTGGCCGGAAGCCTCTTTTCAT CCGACGTATACTTTCTATGTGCTGCTAACTCAGGCTTGCACGGGTAGGTGCTGTTGTTATCTGCAGATTG CAGGTGAGGAGACTGAGGCAGAACAAGGCTAAGTAATTTGCCCAGAGTATCATAGTCTGGAGACAGCAGA GACGGACTTCAGATGGCCCGCTCCGAATTCCCGCCACACTCTTTCTCCCACACTGCAGAGCTGAATGAAT GAGTGGAAGTGAATGTATGCATTGGGTCCCAAGGCCATGCTGTCCACAGGGTCCCTGATGGCCATGCCTT ATGTCCCTGCAGCCGGAGCAGACGGTACTGACTGACAACTGCCAGCAGCAGTGCGTGTGCCACTCAGGCA CAGGCGTGACGTGTCAGGAACACAGCTGCAAGCCGGGGCAGGTGTGCGAGCCCTCGGGAGGCGTCCTGAG CTGCGTCTCCAAAGGTACTGGGCTGGGGCTGGGGCTGGGACTGGCGAGGCACAGGGGACACGGGGCCAGG AGCCAAGAGGGGCGTGGCAGCGGTGTACATGGTGGGAGGTGCAGAAGACTGAGGATGAGGTCTCAGGCCC TGCATTGATCTTTCAGGGCCAGCAGCAGAGACTCCCTTGTCTTGGGGACCTTCCAGGCCAGGTTTCCCAG AGCACATGTCAGAGACCCTCAGTGAAAGGCAAATCTGGAGGCGCCTCCAAGGCCATGAGGCTGAAACACA GGGGCCCCAGGAAGCATGTTGGGACCCCTGCCACTGGTTCTTCCCAGGAAGTCCTCTAGGACCTTGGTGT TGGGCACAGAGAGCCCTAAGACGTGGGTCTCAGATGCAGAGAAGCCCACAGGGCTAGGACCTCAGCTATG GAGGAAGCTAGGGCCCAGGTCCCATATGGACACCCTGAGGCCGGCATCGCAGACACAGGCGCCCTCAGGG CTGGCATCGCAAACCCAAGGACTCCTGAGGTTCAGGTCTCAACCTAGGTCCCCTGCAAAGAAAACCCTGG GGACCCCGGGAGCTGGGTCTCAGATGTGGCAACTCTGGATGCTCATGTCTTAGACACAGCCTGGCCCAGG GCCTGAGTGCCAGACCTGGAGGACTCCCTGGGCCTGGTCTTAGAAACAGCATCTGAGCCAGCGCCATGGC TCACTAGGCTAATCCTCCGCCTAGCGGCGCCGGCACACCGGGTTCTAGTCCTGGTTGGGGTGCCGGATTC TGTCCCGGTTGCCCCTCTTCCAGCCCAGCTCTCTGCTGTGGCCAGGGAGTGCAGTGGAGGATGGCGCAGG TGCTTGGGCTCTGCACCCCATGGGAGACCAGGAAAAGCACCTGGCTCCTGGCTTCTGCCATCGGATCAGC GCGGTGCGCCGGCCGCAGCGCGCTGGCTGCGGCGGCCATTGGAGGGTGAACCAACGGCAAAGGAAGACCT TTCTCTCTGTCTCTCTCTCACTGTCCACTCTGCCTGTCAAAAAAAAAAAAAAAAAAAATATAAAGAAAGA AAGAACAGCATCTGTGGGATCTTAGAAGTAAACCTTGGATCTGCTCTCTCCTGTGGTAGTCCTCGGGGCC GGTGTCCCTGGCACAGCCTGAGGTCTTCTCTCCTCTGCCCCCAGACCCATGCCAGGGTGTCACGTGCCGG CCCCAGGAGACCTGCAAGGAGCAGGACGGCCAGGGTGTGTGTGTGCCCAACTACAACGCCACGTGCTGGC TGTGGGGCGACCCACACTACAACACCTTCGACGGCCGGGCCTTTGACTTCCAAGGCACCTGCAACTACAT TCTGGTGCAAGTTGGCTGCCCGGGGGTGGACGCCGAGGGCCTGACACCCTTTACCATCACCACCAAGAAT GAGAACCGGGGCAACCCCACCGTGTCCTATGTGAAGGAGGTCACCGTGTCTGTCCTGGGCACCAACATCT CCATCCACAAGGGCGAGACGGGCAAAGTCAGGGTATGTGTGGCAAGGTGGTCCCCTGAACCCCCAGGAGG GCTGGGGGAGCCCTGACAGCCCCAGTGAGGAGCCGAGGTTCTCTGTATTCCCCTAGGCCTGAACCAAATC AGCCACCGAACAAACAGGCTTAGCTCTGTGCTGAGCACTTCGGCATCTGCCTCTCAGTAGACTTGGGTTT GAATCCAAGCTCTGCTTCCCAGGTGCTGGTGGGTGGGCCATGTGCCCAGCTCAGAGTCTGGCCCAGATGA GCTCCAGAGAGCAGATTAAGAGGCCTGGAGACTCGGACCCAGAGGGAAATCCAGGGAGGTGAGGGCAGAG AGGTGGGCCTCTGCTTCTGCCCAGGGAAGAGCCATGTGGGTCCACTCAGCAGACACTAAGATGGGCATGC GCACAGGAGTGCACAGAGAGTGTGTACGGCCAGTGGGGAGAGCCAGAGACAGAGAGGACAGTGACGGGAG GGAGTGCAGAGACCCAAAGAAAGAGGGAGAAGCGGAGGTCCAGCAAGAGAGCTAGACCCAGGTGAAGCAA CAGAGAGGGAGGAGAGAGCAATCCAGAGGAAGAAGCAGACACAAAGACGGGAACAGATGTTCATGACATT GTCAAACGGCTATACAACTTTCAGGCGGGGGGAAAGCCATGGCAGCTCCCAACCCCCGTCAGGACAAGGT GGGGAGTCGAGAGCTGGGGCCTCCCACCCTGAGTGACCCAGGCACCTGCTTCCCCCTCCGCCAGGTGAAC GGCGTGCTGACGACGCTGCCTGTCTCCGCGGCCGGCGGGCGGATTTACGTGTCCCATGGAGTGTGGAAGG CTGTGCTGGTGACAGACTTTGGGCTGCAGGTCACCTATGACTGGGACAATCGCGTGGAGGTGATCCTGCC CAGCAGCTATCACGGCGCCGTGTGCGGGCTCTGTGGAAACCTGGATGGCGACCCCAACAATGACCAAGTC TTTCCCAACGGCACAGCCGCTCCCTCCATACCCGCCTGGGGTGGCAGCTGGCGGGCCCCAGGCTGGGACC CACTGTGCTGGGACGAGTGCCAGGGCTCCTGCCCGACGTGTTCTGAGGACCTGCTGGAGAAGTACCAGGG CCCTGGCTTCTGCGGCCCCCTGGTCCCCGGGACCGAGAGCCCCTTCGCCGACTGCCTCGCCCACGTGTCG CCCGACAGCTACTTCCAGGGCTGTGTCCTGGACGTGTGCCTGAGTGGTGGGGCTCAGGACATACTTTGCC AGGCGCTGGCTAGCTATGCGGCTGCCTGCCAGGCCGCTGGCGTCGCCATCCAGGAATGGAGGGAGCAGGC CGGCTGTGGTGAGTGCCGGGGAGGGGGCAGAGGCTGGGGGTGGGGTCCTGTCTGCCAGGCGGGCTTGACT GCTCTCCAGCCCTTCTGGGTTCTTCTTGTATTTCTGTTCCCGAGCGCCTGTCTCTCGGCGCTTCTCTGTG TGTCTCCCTTTGGGTCTCTCTGTATCCCTCTCTGTGCCTCTTGCTCTCTCTCCTTCGGTCTCTGTCTCTC TTCCTCTCTCTGTCAGCCCCTTGGTTTCTGTATTTTGCCACCGTGTCCTTGGACCCCACCCCTAACATCC TTCCCTCTTTCTCCCTCTCCCACCCGCCCGCAGGGGTCTCCTGCCCTGAAAACAGCCACTACGAGCTCTG TGGCTCACCCTGCCCAGCCAGCTGCCCGGCTCCTGAGTCCACCAAGACCTCAGCCCTCTGTGAAGGTTCC TGCGTGGAGGGCTGCCAGTGCGACACGGGCTTCGTGTTGAGCGCTGGGCGCTGCGTGCCCCTGGAGGGCG GCTGCGGCTGCTGGGCCAACAGCACCTACTATGAGACCGGCAGCGAGTTCTGGACGGACGCCACATGCTC CCAGCGGTGCCGCTGTGGGGCTGAGGGCGGCTCGCTGGTCTGCACACCTGCCAGCTGCGCCAAGGGCGAG GCATGTGCCCTGCTGTCCTCGGGCCAGTACGGCTGCCAACCAGTGAGCACTGCGGAGTGCCAGGCCTGGG GTGACCCCCATTACGTCACCCTGGACGGGCACCGATTCGACTTCCAAGGCACCTGCGAGTACCTGCTGAG TGCACCCTGCTCTGAGCCGCCGGCCGGGACTGAGAATTTCACCGTCACCGTTGTCAACGAGCACCGGGGC AGCCAGGCTGTCAGCTACACCCGCAGTGTCACCCTGTATATCTACGACCACCGCCTGACCCTCAGCGCCC GCTGGCCTCGGCAGCTACAGGTGAGGAGGGCATGGGCCGCACAGGAGCAGGTGCCGGCCCTGGGGTTGCC TGGGACGGTAAGAGGTCCGCCAGGTCCCTGAACACCTTACAGCTTAGCTGGGACTTGATGGACGGGGTCT GGAGCATAGGCCTGGGAGCTGGATGGTGTGAGGCAGTGGCTCCCCCTCCCCCTGCGCTGAGCCTTAGTTT ATTCCTACGAGAAATGGGCCCAAGAAGTCATGTGCTGCAGGGTGGCGTCAAGAGCCTGTTGTTTTTACTA CAAGAAGCCCTGGACTCAGAGTCCCACAGCTCCTAGGTGGTGGAGACGGGCTTCGAACCTGACTGGCCCG CCCCGCCCTGCCCCACGCCCGCAGGTGGACGGCGAGTTCGTGACGCTGCCCTTCCAGCTGGACTCGCGCC TGAACGCGTATGTGAGCAGCGCCGACGTGGTGGTGACCACGGCCGCCGGGATCTCGCTCAGTTTCGACGG GGACAGCTTCGTGCGCCTCCGCGTGCCGGCGGCCTACGCGGGCGCCCTCTGCGGCCTGTGCGGGGACTAC AACGAGAACTCGGCCGACGACCTGGCAGCGGTGAACGGGAAGCCCGAGGGCTGGCAGGTGGGCGGTGAGC CGGGCTGCGAAAAGTGCGAGCCCGAGCCGTGCCCGGAGCCGTGCACGCCCGAGGAGCAGGAGCCCTTCGG CGGCCCCGACGCCTGCGGGGTGATCATGTCCCGCAAAGGCCCGCTGGGGCCCTGCCACTGCATCGTGCCG CCGGAGCAGTACTTCCAGGCCTGCCTGCTGGACGCCTGCCAGGCCCAGGGCCATCCGGGAGGCTTCTGCC CTGCGGTGGCCGCCTATGTGGCTGCCTGTCAGGCCGCCGGGGCCGAGATCGGCGAATGGAGGCTGCCGGA CTTCTGTTGTGAGTACTGGCCCTTGCACGTTCACAAAGCAGGCGCCTCCTCCTCTCCCCAGCTTCTTCCC TCTTCCTGGGCTCAGGGACCAGCGAGGTGTCTGTTAGACTATGCGCGGCGACAGACTGGTCAGGTACACC TACGGTCAGGGCTCTGAGGACCCCAAACAGCTGCCTAAGACAGGGTCCGGGAGTCCCTGCAGTTCCTTTT GGACAGATAGATCTCCTCGGTCAGGTGCATCCTGGCAGCTTCAACAACCAGACCTAGTTGTAGTCCCCGC ACAGGCCGCAGAGGGCGCCCGCGTAGGCCGCCGGCACGCGGAGGCGCACGAAGCTGTCCCCGTCGAAACT CTGTGGGTCAGAGTCACACCCTAAAACAAACGGAGTCGGGGAGACTCCAGCAGGTGCTCGGACACCCACG CCAGGCACAGCCCCACAGGCGCACGCCCCGGGATACCTGTGGCTGATCCTAACCCTTGTATCCTGGTCAC ACATCCATGACCAGACACTCACTGGACACTTAGAAGTTTTAGGGTGTGACACACACCTGGTCAGAGGGTG TTGCCCCCACCCCGTGGGAGGTGCTGGGTCCGATCCTGGTACCTGGGTGTGTTGTCCCAGGGGAAGCCTC ACCCTCGTCCCGTCTCACCCCCGCAGCCATCCAGTGTCCAGCCAACAGCCACTACGAGCTCTGCGGCAAC TCCTGCCCCGTGAGCTGCCCCAGCCTCTCGGCGCCCGAAGGCTGCGAGCCAACCTGCCGCGAAGGTTGCT ACTGCGACGCCGGCTACGTGCTCAGCGGTGACACATGCGTCCCCCTGGGCCAGTGCGGCTGCCTCCACGA GGGCCGCTACTACCCACTGGGCGCAGCCTTCTACCCAGGGCCCGAGTGCGAGAGACGCTGTGAGTGCGGC CCAGGGGGCCAAGTCAGCTGCAAGGAGGGTGCGGCCTGCGGGCCTTACGAGGAGTGCCGGCTGGAGGACG GCGTCCAGGCCTGTCACCCCAAAGGCTGCGGCCGCTGCCTGGCCGACGGAGGCATCCACTACCTCACCCT GGACGGACGCGTCTACGACCTGCACGGCTCCTGCTCCTACATCTTGGCCCAGGTCTGTGACCCGCAGCCC GGGGATGAGGACTTCACCATCGTCCTGGAGAAGAACGCGGCTGGAGAACCGCAGCGCGTGCTGGTTACCG TGGCTGGCCAGGTCGTGGGCCTGGCCCGGGGACCGGAGGTGAGTGGCCCGCCCAGGGACCCAGGGAGACA CAGCCAAGTCCTGGGCTTCTGGAGGTTCTGTGAGCCACTCACCCGCCCCTTCCTCCCGTGCAGGTCACCA TCGACGGCGAGGTGGTGGACCTGCCCGTGGCCGTGGGCCATGTGCGGGTGACCTCCGAGGGCCGAAACCT GATCCTGCAGACAACCGAGGGGCTGCGGCTTCTCTTTGACGGCGACGCCCACGTCCTCATCTCCATCCCC AGCCCCTTCCACGGTCGGCTCTGCGGCCTGTGCGGCAACTTCAACGGCAACTGGAGCGACGACTTCGAGC TACCCGACGGCTCGGTGGCCCCCAGCGTGGAGGACTTCGGGGCGGCGTGGCGGGCACCCGGCTCCCCCCA GGACTGCACCGAGGGCTGTGGGGCCCAAGGCTGCCCCGTGTGCCGGGCGGAGGAGACGGCACCCTACGAG AGCAGCGAGCTCTGTGGGCGGCTGCTCGACCCCAGCGGCCCCTGGGCCGCCTGCCACGAGGTGCTGAGTC CTTCCGAGTACTTCCGCCAGTGCGTGTACGACCTGTGCGCCCAGAAGGGCGACCAGGCCTTCCTCTGCCG CAGCCTGGCCGCCTACACAGCCGACTGTCAGGCGGCCGGCGTGGCCGTGAAGCCCTGGAGGACAGACAGC TTCTGCCGTGAGTGTCGGGGGCGGGGGTGGGGTGGGGTGGTGCCTGGGAGGTCTCCCGCCCGCCACGCCC CGCCCTCCTCCGTCTGCATCTCAGGAGCAGCCCAGCCCCCTCCTGCGAAAGCTCCTCCCACGCCCGCTGC TCGCCTGGCGGCTCCCCTCTGCCCCCTCTGACCGCCCCCTTTCTCCTCAAAGCGCTTCACATCTTCCCTG GGCCTCCATCCTGGGCACTTTCTCACCTTGCAGCCTGAGTCTGTGGCTTGCCAGCCCCCTGGGGGCAACA CCGGCTCCCCTCAGAGCACCCAGGACAAAGCTGCAGGCCGTTGGGCCCCCAAACCAGGGCTGTCCCTCTC CCCCAAATCTCCTGCTGCAAGGACATGCCCCTCCCCAACCTAGGCTCTGCAGGAAAAGGCCATGGCCGAG TTTGCTTCGGTCTCCTCAGAGCAGGACCCCTACCCAGGGCCTTATAGGCTTCACAGCCTTGGCCTTGTCC TCAGCGGGGACAGTGGAGCCTGTCTCCTGCTCCGAGCTCTCTCCTGACTGCCAGCCCCAGGGGTCCAGTG TGAGCGCGTTCCCTCCAGCATCCTCACAATGTCTTGCACCTGCTGTGTTCCCAGACGACATCAGCGCCTC ACCCCAAGCCAGTCCTCCTTCCCCTGGCCCCCCCGTGTCCCGGCACTGGGCAGCCACAGCAGCCACCAGT TCTCAGCCAGAGCCCAGGACCTCACCCCGAATGCTTCCCCTGGGTCCTCCCAGCCCCCTGTGTTTCACTT GCCCCGGCCCTGAGCCCCAAGCCTGACCTTGCCCAATGCAGCACAGCCACATGGGCCCCTCATGGCCTGT CCCTCCGGTTTGAGCTCTGCAGGGCAGAGTTTGGGGCTGTCTGCGTCATTTGGGTCATCAGCGCAGCCCA CGCCCGGGCTGGCTGTATAGAAGCTCTTGTGGCCGTCCATGGAGGCGTGACCCCAGCCCGCCATGTCTCT CTCCACAGCGCTGCAGTGCCCAGCTAACAGCCACTACTCCGTCTGCACCTACTCCTGCCAGGGCTCCTGC ACAGCGCTCTCTGGCCTCACGGGCTGCACCAGCCACTGCTTCGAGGGCTGTGAGTGTGACGACCGCTTCC TGCTCGCCCAGGGCGTCTGCGTCCCCTCCCAGGAGTGTGGCTGCACCTACAATGGCCGGTACTTGCCTGT GAGTAGGGGCTCGAGGTGGGCAGGGAGGGCGGGAGGGAGTCTAACCTCCCCGAGGACTGGGACAGGGGTG CCGCTGCCATCTCCCAGCTGGGACACTTGCTGTGTGTGATGCTGCTGACCTCCAACCTGGTAGTCTAACA CGGAAGCAATGTGTTCTCCCACCATTCCGGAAATCAGTACCCCCACGCTGGAGGCAGGCTGCCCCCAGCC CCCCCCCCCCCCGCAGTCTAACTGCTCCCTGCAGCTTCTGGGGGCTGCCAGCATCCCGTGCCTTGGGGCT GCATCCCTGCAGTATCGGCCTGTGTGTGTCAGGAACGCTCCCTCCAGCTTCCTCTTGGGAGGACACCCGG ATAATCCAGCATGAATTCTCCACTTCCAAGTCCTCGGTTTAACACCGCTGCAAACACCTTTTTCCCACAG AAGGGGATGTTTACTTGGTCCCAGGGATTGGGATCTGATGTCTGTGAGGGACCACACTTGGCCTGCCATG GTCCCCACCCTGAACCTCATTTTCTCCACCTGTAAGATGGGGGTAGTCATTGTCCTTGCACCACAGGTGT GTAAGGGAAGGTGTGATTGTGTGGAAGACGCCAGCTGTGCCCTGGGCCTGGCACTCCCTGCGCATCCCAC TCAGGGAAAGGAATAGGAACTTAGACGGTGCTCTAGGCAGCCCCCAACCATCACTTACTCTGCAAACTGA AATGCAATCCTTGATTTATTCGTGTTAACAGTATTTTTTTGGGCTCTTGCTCTGCACTGGTTGTTATGGG TGTTTAAAGATTTAGTTATTTATTCGAAGAGGAGAGAGAGAGAGAGATTTTTCATCTGCTGGTTCACTCC CCAAAGGACCACAAGACTGGGACTGGTCCAGCTCAAAACCAAGAGCCTGGAGCTCCATCCTGGTCTCCCA CATGGGAGGCAGGGCCCCAACTACCTGGGCCGTCCTCTGCTGCCTTCCCAGGTGCATTTAGGGAGCTGGA TCAGAAGTGGAGCTGCTGGGACTTATTGGCGCTATTGCTGTTTCCCCCTGTTACAGAGCCATCCCTGTAA CCCCCCAACCTCTTACCTGCCCCCTTCTGCACACAGGTGAACTCCTCCCTCCTGTCCTCAGACTGCAACG AGCTCTGCTACTGCTCCCCAGACGCAGACCTGCAGTGCTATGAGGCCAGCTGCAAGGCGGGCAGCGTCTG CGAGGTCCAGAACGGGGTTCGGGTCTGCCAGGCCTCCGGCGCCCAGTGTACCCTCTCCGCAGGCTCCAAC CTCACCACCTTTGATGGGGCCCTCAGTGCCTTCAACTCCTCTGGTGTCTATGAGCTCTCCTTCCGCTGCC CAGGACTACAGACCCCCTGGTATCGTGTGGTGGCAGCCATCCAGCCCTGCGCTGGCACAGCTGAGACGGT GGGCCAGCTCCACGTCTTCTTCGAGGACGGGATAGTCACCGTGACCCGAGACGGGGGCGTGTGGGTAAGC CTGGGCGTGGCGGCGGGCGGGCGGGGGTCGGGGTGATGTGCAGTGTCCTTGCATTGTTGCCTGCCTGTCT TGCTGTCTCTTTCCTCTGCAATTTGATCTCTGGATTGGTATTTGCCTCAGTATTTCAGCTGAGTTCGTGG GAGGCAGAACGCATTCAAGGAACGTCATAGTTTTGATATTAGCGTCAATCAGGACTCCATTGGTTGCAGG TGACAGAAAAACCGAGCTCAAACTTCCTGAGAAGCAGAAGTGAATTGATTGGCCCACGGAACTAGAAAAC TCAGGGTCAGGACTATAGGCCTCTATGTTTTAGATGTGCTGGTCACCAAGTCGGCTTGATTCTCCGGCTT TCCTCTCGCAGACCCACACCGCACTGGTTTAGCTACGCTGGACCAGTTTGGGCCCTTGCCTATCCCTGGA ACCAGTCACCATGGCCTTGGGGATGGAATGCTGTGATTGGTCAGGTGGTTTTTATTGGAGGGGGTAGGGC TGGTCACCCAGGCAGCTCTGCCTAGCACATGCCAAACGTCAGGCTCCCGGAAGGAAGCTGCGGAAGCTGC ACCTTGCATCAGCTCCGGAACCTGAGCCCTGGGTGCGCAGGGATCCTGTCTGTCCCCGTCACCCCTTTAT TCCCAGTCCCCAGATCCAGGCCTGGCACCTGGACCCCGGAAAAGTCGGGTTTGGTGACTCAGCTCAGCCC CGCCCCTCTGAGTCAGGCTGGGAGCCGACTCCCACTCCAGGGCCGACTCGAACCCAGTTCTCATACTCAG GAAGCAGCCGGGAGAGGCTTCCCCTGCCCCGCCCCGCCCCTCCTGGCTGTCTCCATCCTCCCTCCCTTTC TCCCTCCTCCCTTCTTTCCTCCCTCCCCCCCATCTCAGCTCCACACCTACTTTTCCCATCAGTCTGCCTG TCTCTCCAGTCACCCGACAGAGGCAGACTCAGATACAAAAGCATTTCGGGAAAAAAAGAGAACTTCTGTT TAAAAGCAATTTTTGCTAGAGAGACTAACTTTAGAAGGATGAACTTACCAACAAAAACAAACAACACTTG TTTCAAGGGAAAAAAAACTCCCGACGTCGCTGAGTCTGCAACCCAGGACGAGGAAGCAGGCATCTCCTCA CAGGCCTATTATATTTGCTATGCTCACTACTTATCTTTAGACACCAGCATTACAATGATAAGGGATAAAC TCTCCTCTTGGGGAAGCAGTAACAGAGAACATGCTCCTCAGAGGCCTTTTGTTTTGAAAAGTAGACCCCA ACAGGGTGGCCCTGAGGTTGGTTGGTTGGGATGGGCCTCTGGTACAAAGTCCCTCCCACCCCCGACCCTG GGACACTGCGTGGGTCCCCCAATCCCTTTCTCCATCCGCCCAGTCTCCAGCTATCTCCCCGAGTCTGTCT GGCCACACGCAGCCTCCATCCGGGTCTTCATGGCTTTCAGAACCTGCTCCTTGCTTTAGTTCCTGAACTC ATGACCTCGCTCGGGGTCTCCGTCCTGGTAACTCGCCGGCTGCGCTGCGGCTCCGGCCTCACCTGTGTCT GCCCGCCTCCATCGCCAGGTGAATGGTCGCCAGGTGGACCTCCCAGCTGAAGTGTTGACATCGGTGTCCG TGACGCGCAACAGCGACAACTCCATACTTGTCCACCAAAAGGATGGGCTTTGGGTGTGGCTGGGCGCCGA TGGGCAGCTGACCGTGACGGTGGACAGTGGCCGCGCTGGCCAGCTGTGTGGGGCCTGCGGAAACTTTGAC GGAGACCCGACCAACGACAAGTCGGTCACGGAGAGCTGGACAGCACCGGACCTTTCCCCATGGTGAGGAT GTGGCGGGGAAGCCGGGCTTCTCGGGCGCGAGGGCGTTGGATGCTCACGGGAACGGGCAGTGGACGCGTG GGCAAGAGGAGGTGCTGAGTGTCTGTCTCTTGCAGTGAGGACTG Vaximmutor Aktar et al., 2016 journal Aktar A, Rahman MA, Afrin S, Faruk MO, Uddin T, Akter A, Sami MIN, Yasmin T, Chowdhury F, Khan AI, Leung DT, LaRocque RC, Charles RC, Bhuiyan TR, Mandlik A, Kelly M, Kováč P, Xu P, Calderwood SB, Harris JB, Qadri F, Ryan ET 2016 23 5 427-435 Clinical and vaccine immunology : CVI Eko et al., 2000 journal Eko FO, Mayr UB, Attridge SR, Lubitz W 2000 83 1-2 115-123 Journal of biotechnology Ekong et al., 2009 journal Ekong EE, Okenu DN, Mania-Pramanik J, He Q, Igietseme JU, Ananaba GA, Lyn D, Black C, Eko FO 2009 55 2 280-291 FEMS immunology and medical microbiology FDA: Vaxchora website https://www.fda.gov/downloads/BiologicsBloodVaccines/Vaccines/ApprovedProducts/UCM506235.pdf Kirn and Taylor, 2005 journal Kirn TJ, Taylor RK 2005 73 8 4461-4470 Infection and immunity Osek et al., 1994 journal Osek J, Jonson G, Svennerholm AM, Holmgren J 1994 62 7 2901-2907 Infection and immunity Product Monograph: Dukoral website http://healthsensetravelclinic.ca/wp-content/uploads/dukoral.pdf Ravichandran et al., 2006 journal Ravichandran M, Ali SA, Rashid NH, Kurunathan S, Yean CY, Ting LC, Bakar AS, Lalitha P, Zainuddin ZF 2006 24 18 3750-3761 Vaccine Sharma et al., 2008 journal Sharma MK, Singh NK, Jani D, Sisodia R, Thungapathra M, Gautam JK, Meena LS, Singh Y, Ghosh A, Tyagi AK, Sharma AK 2008 27 2 307-318 Plant cell reports Vishwakarma et al., 2015 journal Vishwakarma V, Sahoo SS, Das S, Ray S, Hardt WD, Suar M 2015 33 15 1880-1889 Vaccine WHO: Cholera website http://www.who.int/topics/cholera/about/en/index.html Xu et al., 2009 journal Xu G, Wang S, Zhuang L, Hackett A, Gu L, Zhang L, Zhang C, Wang H, Huang Z, Lu S 2009 27 29 3821-3830 Vaccine Yu et al., 2005 journal Yu F, Qi G, Liu Y, Gao S, Kan B 2005 29 3 191-196 Molecular biotechnology