Bordetella pertussis 520 The bacterium contains a surface protein, filamentous hemagglutinin, which binds to sulfatides that are found on cilia of epithelial cells. Once anchored, the bacterium produces tracheal cytotoxin, which stops the cilia from beating. This prevents the cilia from clearing debris from the lungs, so the body responds by sending the host into a coughing fit. These coughs expel some bacteria into the air, which are free to infect other hosts. Bordetella pertussis has the ability to inhibit the function of the host's immune system. Two toxins, known as the pertussis toxin (or PTx) and adenylate cyclase (CyaA), are responsible for this inhibition. CyaA converts ATP to cyclic AMP, and PTx inhibits an intracellular protein that regulates this process. The end result is that phagocytes convert too much ATP to cyclic AMP, which can cause disturbances in cellular signaling mechanisms, and prevent phagocytes from correctly responding to an infection (Wiki: Bordetella pertussis). Whooping Cough Acellular pertussis vaccines are effective in providing immunity to whooping cough, by stimulating antibodies to pertussis toxins, as well as an adhesin (Salyers and Whitt., 2002). Animal models of pertussis include primates, rats, mice, and rabbits (Salyers and Whitt., 2002). Bordetella pertussis is a Gram-negative, aerobic coccobacillus of the genus Bordetella, and the causative agent of pertussis or whooping cough. Pertussis (or Whooping Cough), is an infection of the respiratory system and characterized by a “whooping” sound when the person breathes in. In the US it killed 5,000 to 10,000 people per year before a vaccine was available. Vaccination has transformed this and between 1985-88 fewer than 100 children died from pertussis. Worldwide in 2000, according to the WHO, around 39 million people were infected annually and about 297,000 died. Bordetella pertussis infects its host by colonizing lung epithelial cells. The infection occurs most with children under the age of one when they are unimmunized or children with faded immunity, normally around the age 11 through 18. The signs and symptoms are similar to a common cold: runny nose, sneezing, mild cough, and low-grade fever. The patient becomes most contagious during the catarrhal stage of infection, normally 2 weeks after the coughing begins. It may become airborne when the person coughs, sneezes, or laughs. Pertussis vaccine is part of the DTaP (diphtheria, tetanus, acellular pertussis) immunization. The paroxysmal cough precedes a crowing inspiratory sound characteristic of pertussis. After a spell, the patient might make a “whooping” sound when breathing in, or vomit. Adults have milder symptoms, like prolonged coughing without the “whoop.” Infants less than 6 months may not have the typical whoop. A coughing spell may last a minute or more, producing cyanosis, apnoea and seizures. However, when not in a coughing fit, the patient does not experience trouble breathing. This is because Bordetella pertussis inhibits the immune response and therefore very little mucus is generated in the lungs. A prolonged cough may be irritating and sometimes a disabling cough may go undiagnosed in adults for many months (Wiki: Bordetella pertussis). 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 Actacel Diphtheria, tetanus, acellular pertussis, Haemophilus influenzae type b conjugate vaccine Actacel Sanofi Pasteur Ltd VO_0010705 Subunit vaccine Licensed Intramuscular injection (i.m.) Canada Products: Proteins + Conjugate. Aluminum phosphate Refrigerate at 2° to 8°C. Intramuscular injection (i.m.) Adacel Tetanus Toxoid, Reduced Diphtheria Toxoid and Acellular Pertussis Vaccine, Adsorbed Adacel Sanofi Pasteur, Ltd (USA: License #1726) VO_0000005 Toxoid vaccine Licensed Intramuscular injection (i.m.) USA: License #1726; Canada It is a sterile liquid suspension of tetanus and diphtheria toxoids and acellular pertussis components adsorbed onto aluminum phosphate, for intramuscular administration. aluminum phosphate Adacel vaccine should be stored at 2° to 8°C (35° to 46°F). DO NOT FREEZE Clostridium tetani is grown in modified Mueller-Miller casamino acid medium without beef heart infusion. Tetanus toxin is detoxified with formaldehyde and purified by ammonium sulfate fractionation and diafiltration. Diphtheria and tetanus toxoids are individually adsorbed onto aluminum phosphate (FDA: Adacel). Intramuscular injection (i.m.) Pertussis Adacel-Polio Tetanus Toxoid, Reduced Diphtheria Toxoid and Acellular Pertussis Vaccine Adsorbed Combined with Inactivated Poliomyelitis Vaccine Adacel-Polio Sanofi Pasteur SA VO_0003085 Toxoid vaccine + Subunit vaccine + Inactivated or "killed" vaccine Licensed Intramuscular injection (i.m.) Canada ADACEL®-POLIO is a sterile, uniform, cloudy, white suspension of tetanus and diphtheria toxoids and acellular pertussis vaccine adsorbed separately on aluminum phosphate and combined with inactivated poliomyelitis vaccine (vero cell origin) types 1, 2 and 3, and suspended in water for injection. Acellular pertussis vaccine is composed of five purified pertussis antigens (PT, FHA, PRN and FIM). (Product Monograph: Adacel-Polio) Aluminum phosphate Store at 2° to 8°C (35° to 46°F), do not freeze. Intramuscular injection (i.m.) B. pertussis BrkA protein vaccine VO_0011377 Subunit vaccine Research Subcutaneous injection Subcutaneous injection B. pertussis brkA Recombinant protein preparation Fraction BS was applied to a Mono Q Sepharose (Amersham, Biosciences) (0.5 mg protein per ml resin) previously equilibrated with 25 mM Tris–HCl, pH 8.0. Proteins were eluted with a NaCl gradient (0–1 M) in 25 mM Tris–HCl, pH 8.0, in 0.5 ml fractions at a flow rate of 1 ml/min. Elution was monitored at A280 nm. The fractions showing the same peak profile were pooled and eluted again under the same chromatography conditions. Samples were submitted to sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) (T = 12.5% in 0.75 M Tris, 0.2% SDS, pH 8.8) and electrophoresis was performed at 60 mA in 25 mM Tris, 0.192 M glycine, 0.1% SDS, pH 8.3. The gel was stained with silver nitrate and fractions showing a similar molecular mass profile were pooled, concentrated by centrifugation at 440 × g in Centrifugal Ultrafree-20 tubes, 10 kDa (Millipore), and their protein concentration was evaluated. Four pools were formed (P1, P2, P3, P4), and used for immunization of mice (Cainelli et al., 2007). BALB/c Female BALB/c mice, 4–6 weeks old (Animal House of the Instituto Butantan) (9–15 mice/group) were subcutaneously injected three times at weekly intervals (days 0, 7, 14) with BS pools (P1, P2, P3, P4) (1 μg/0.1 ml/mouse), and two times (days 0 and 14) with 73 kDa or 60 kDa proteins (1 μg/0.1 ml/mouse) alone or mixed with Diphtheria-Pertussis-Tetanus (DPT) vaccine formulated without aluminum hydroxide (NA-DPT), (2 μl/mouse), (Instituto Butantan). Current DPT vaccine containing aluminum hydroxide (DPTBut) was used as control (2 μl/mouse) (Lot no. 0008147/0 and 0309132, Instituto Butantan). Non-immunized mice (injected with physiologic saline) were used as control (Cainelli et al., 2007). High levels of antibodies were induced, and a 78% protection rate of mice challenged with live B. pertussis was observed. The 73 kDa N-terminal alpha-domain of BrkA autotransporter protein, one protein identified in the fraction, stimulated antibodies against pertussis and induced a 42% protection rate against the challenge (Cainelli et al., 2007). Animals were challenged by intracerebral route (i.c.) with live B. pertussis (strain 18323, NIH, USA), 21 days after the first immunization. Each mouse was inoculated with 30,000 live bacteria. Deaths were recorded until day 15 (Cainelli et al., 2007). B. pertussis Cpn60 protein vaccine VO_0011357 Subunit vaccine Research Subcutaneous injection Subcutaneous injection B. pertussis cpn60/60 kDa chaperonin Recombinant protein preparation Fraction BS was applied to a Mono Q Sepharose (Amersham, Biosciences) (0.5 mg protein per ml resin) previously equilibrated with 25 mM Tris–HCl, pH 8.0. Proteins were eluted with a NaCl gradient (0–1 M) in 25 mM Tris–HCl, pH 8.0, in 0.5 ml fractions at a flow rate of 1 ml/min. Elution was monitored at A280 nm. The fractions showing the same peak profile were pooled and eluted again under the same chromatography conditions. Samples were submitted to sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) (T = 12.5% in 0.75 M Tris, 0.2% SDS, pH 8.8) and electrophoresis was performed at 60 mA in 25 mM Tris, 0.192 M glycine, 0.1% SDS, pH 8.3. The gel was stained with silver nitrate and fractions showing a similar molecular mass profile were pooled, concentrated by centrifugation at 440 × g in Centrifugal Ultrafree-20 tubes, 10 kDa (Millipore), and their protein concentration was evaluated. Four pools were formed (P1, P2, P3, P4), and used for immunization of mice (Cainelli et al., 2007). BALB/c Female BALB/c mice, 4–6 weeks old (Animal House of the Instituto Butantan) (9–15 mice/group) were subcutaneously injected three times at weekly intervals (days 0, 7, 14) with BS pools (P1, P2, P3, P4) (1 μg/0.1 ml/mouse), and two times (days 0 and 14) with 73 kDa or 60 kDa proteins (1 μg/0.1 ml/mouse) alone or mixed with Diphtheria-Pertussis-Tetanus (DPT) vaccine formulated without aluminum hydroxide (NA-DPT), (2 μl/mouse), (Instituto Butantan). Current DPT vaccine containing aluminum hydroxide (DPTBut) was used as control (2 μl/mouse) (Lot no. 0008147/0 and 0309132, Instituto Butantan). Non-immunized mice (injected with physiologic saline) were used as control (Cainelli et al., 2007). High levels of antibodies were induced, and a 78% protection rate of mice challenged with live B. pertussis was observed. The Cpn60/60 kDa chaperonin, one protein identified in the fraction, stimulated antibodies against pertussis and induced a 42% protection rate against the challenge (Cainelli et al., 2007). Animals were challenged by intracerebral route (i.c.) with live B. pertussis (strain 18323, NIH, USA), 21 days after the first immunization. Each mouse was inoculated with 30,000 live bacteria. Deaths were recorded until day 15 (Cainelli et al., 2007). B. pertussis CyaA protein vaccine VO_0011359 Subunit vaccine Research Subcutaneous injection Subcutaneous injection B. pertussis secreted adenylate cyclase (cyaA) Recombinant protein preparation The AC was purified from culture supernatants using a camodulin affinity chromatography. The preparation consisted of two polypeptides of 45 and 43 kDa that are structurally related as described by Ladant et al (Guiso et al., 1989). BALB/c For active immunizations, Balb/c mice were given, subcutaneously, 3,ug of purified AC adsorbed on aluminium hydroxide, three times, at one week intervals . The mice were bled 5 days after the last injection in order to assess the presence of circulating anti-AC antibodies . The lethal challenge was performed 9 days after the final injection (Guiso et al., 1989). Active immunization with purified B. pertussis secreted adenylate cyclase (cyaA) protect mice against a lethal respiratory challenge with B. pertussis or B. parapertussis (Guiso et al., 1989). Bacterial suspension (50 pl) was injected intranasally to groups of 10 3-week-old female Balb/c mice (CERJ, St Berthevin, France), weighing 16±1 g . The LD 50 for the challenge inocula was determined daily by recording the number of dead mice . Pulmonary edema was quantified by lung weight (Guiso et al., 1989). B. pertussis DNA vaccine encoding Prn VO_0011391 DNA vaccine Research DONR221 (Invitrogen, Carlsbad, CA) and pABB-CRS2 [Ref1021:Komatsu et al., 2010]. Subcutaneous injection Subcutaneous injection B. pertussis pertactin precursor prn2 DNA vaccine construction To construct a prn mutant, amplification of the region containing the whole prn2 gene of the CCHMC1 strain was performed using PRN-F GGCACAGGACCGGCGCGTGTTTCGCGCACGACTCT) and PRN-R (CGCGTGGTGCGCCTGAAAGGCGGCGATGCCTTCA) with attB adaptors. The PCR products were cloned into pDONR221 to obtain pDONR-PTXA1 and pDONR-PRN2 by site-specific recombination techniques using the Gateway cloning system (Invitrogen). The regions transferred into the pDONR221 plasmid were sequenced for verification. pDONR-PTXA1 or pDONR-PRN2 was mixed with pABB-CRS2 to obtain pABB-PTXA1 and pABB-PRN2 by using the Gateway cloning system. pABB-PTXA1 or pABB-PRN2 was introduced into E. coli SM10pir and mobilized into the B. pertussis strain Tohama by conjugation (Komatsu et al., 2010). BALB/c 3.5-week-old female BALB/c mice (Japan SLC, Hamamatsu) were immunized by two subcutaneous injections of 0.25 SHDs (0.125 ml) over a 2-week interval (Komatsu et al., 2010). While the vaccine was effective against all of the B. pertussis strains regardless of the allele expression pattern, the strain expressing ptxA1 and prn2 displayed a survival advantage over the other strains (Komatsu et al., 2010). Two weeks after the second immunization, 50 µl of a suspension containing approximately 6 x 10^6 CFU of B. pertussis was instilled intranasally into mice anesthetized by intraperitoneal injection with pentobarbital sodium (Nembutal; Abbott Laboratories, Abbott Park, IL). Two hours (day 0) or 2, 5, or 8 days after the challenge, the mice were euthanized by pentobarbital injection (Komatsu et al., 2010). B. pertussis DNA vaccine pcDNA/S1 VO_0004545 DNA vaccine Research pcDNA.3.1(+) [Ref2663:Kamachi et al., 2003] Gene gun Gene gun DNA vaccine construction Gene gun vaccination was employed for the delivery of pcDNA/S1, and the induction of IgG1 predominant antibody production was observed (Kamachi et al., 2003). For immunization, 0.5 mg of gold particles were coated with 2 μg of plasmid DNA and 0.5 mg gold per injection was used. Mice were immunized intradermally three times on days 0, 14, and 28 using a Helios Gene Gun at a helium gas pressure of 400 psi (Kamachi et al., 2003). In the pcDNA/S1-immune group, five out of 10 mice survived 24 hours after the challenge, whereas all of the mice in the pcDNA-immune group died within 24 hours (Kamachi et al., 2003). Immunized BALB/c mice were challenged intranasally with B. pertussis strain 18–323 (Kamachi et al., 2003). B. pertussis FhaB and 69 kDa OMP protein vaccine VO_0011498 Subunit vaccine Research Intramuscular injection (i.m.) 4.0 ml Alhydrogel (Novotny et al., 1991) Intramuscular injection (i.m.) Combination of the B. pertussis 69-kDa outer membrane protein and filamentous hemagglutinin (fhaB) Recombinant protein preparation A crystal clear supernatant of 5-day-old static cultures containing proteolysis inhibitor was purified. To remove impurities, the FHA was precipitated by overnight dialysis against 25-30 volumes of buffer A at 4 C, and the precipitate was collected by centrifugation. The precipitated FHA was dissolved in the smallest possible volume of 40 mM B-alanine buffer at pH 3.5, clarified by centrifugation, and applied at room temperature at a flow of 30 ml/h to a Superose 12 column. The retained highly purified FHA was eluted (Novotny et al., 1991). Groups of mice were injected intraperitoneally with 0.5 ml volumes of four concentrations (Novotny et al., 1991). A combination of the 69-kDa outer membrane protein and filamentous hemagglutinin (fhaB), both isolated from lymphocytosis promoting factor (LPF; pertussis toxin) minus mutants of Bordetella pertussis, is protective in the mouse intracerebral challenge potency (Kendrick) test (Novotny et al., 1991). Mice were challenged intracerebrally 14 days after antigen injection. The challenge dose contained 300-400 LD50, and a 1:1250 dilution of the challenge does contained ~ 10cfu. All mice were challenged within 90 minutes after the challenge suspension was thawed; the challenge was injected using a 1 ml syringe in a Hamilton PB600-I dispensor that reproducibly delivers 20-ul voumes (Novotny et al., 1991). B. pertussis PTx protein vaccine VO_0011361 Subunit vaccine Research Intraperitoneal injection (i.p.) Aluminum hydroxide Intraperitoneal injection (i.p.) B. pertussis pertussis toxin (PTx) Recombinant protein preparation Vaccine is prepared by chemically modifying purified PT from culture supernatants with tetranitromethane (TNM). The lot was adsorbed to aluminum hydroxide (Alhydogel; Superfos, Vedbaek, Denmark) at a concentration of 50 μg of protein adsorbed to 4 mg per 1.0 ml. Animal doses (2.5, 0.5, and 0.1 μg) were prepared by making fivefold serial dilutions in aluminum hydroxide (4 mg/ml) diluent and given in a volume of 50 μl (Bruss and Siber, 2002). Recombinant protein preparation Vaccine is prepared by chemically modifying purified PT from culture supernatants with tetranitromethane (TNM). The lot was adsorbed to aluminum hydroxide (Alhydogel; Superfos, Vedbaek, Denmark) at a concentration of 50 μg of protein adsorbed to 4 mg per 1.0 ml. Animal doses (2.5, 0.5, and 0.1 μg) were prepared by making fivefold serial dilutions in aluminum hydroxide (4 mg/ml) diluent and given in a volume of 50 μl (Bruss and Siber, 2002). Recombinant protein preparation Vaccine is prepared by chemically modifying purified PT from culture supernatants with tetranitromethane (TNM). The lot was adsorbed to aluminum hydroxide (Alhydogel; Superfos, Vedbaek, Denmark) at a concentration of 50 μg of protein adsorbed to 4 mg per 1.0 ml. Animal doses (2.5, 0.5, and 0.1 μg) were prepared by making fivefold serial dilutions in aluminum hydroxide (4 mg/ml) diluent and given in a volume of 50 μl (Bruss and Siber, 2002). Recombinant protein preparation Vaccine is prepared by chemically modifying purified PT from culture supernatants with tetranitromethane (TNM). The lot was adsorbed to aluminum hydroxide (Alhydogel; Superfos, Vedbaek, Denmark) at a concentration of 50 μg of protein adsorbed to 4 mg per 1.0 ml. Animal doses (2.5, 0.5, and 0.1 μg) were prepared by making fivefold serial dilutions in aluminum hydroxide (4 mg/ml) diluent and given in a volume of 50 μl (Bruss and Siber, 2002). Recombinant protein preparation Vaccine is prepared by chemically modifying purified PT from culture supernatants with tetranitromethane (TNM). The lot was adsorbed to aluminum hydroxide (Alhydogel; Superfos, Vedbaek, Denmark) at a concentration of 50 μg of protein adsorbed to 4 mg per 1.0 ml. Animal doses (2.5, 0.5, and 0.1 μg) were prepared by making fivefold serial dilutions in aluminum hydroxide (4 mg/ml) diluent and given in a volume of 50 μl (Bruss and Siber, 2002). BALB/c Mice were removed from their cages, weighed, and placed on a stainless steel rack that fits inside of the Plexiglas aerosol chamber (40 by 40 by 40 cm). The 21-h culture of B. pertussis was suspended in sterile PBS to a concentration of approximately 2 × 10^9 CFU/ml of inoculum. This inoculum was delivered to the mice using a standard nebulizer (model 647; Devilbis, Somerset, Pa.) with a set pressure of 1.5 kg/cm2. The chamber and the nebulizer were enclosed in a biosafety level-2 hood and certified prior to use to document that airflow barriers were maintained. Uniformity of aerosol in the chamber was maintained with the use of two PABST 900 series AC fans (Newark Supply, Newark, N.J.). The even dispersion of the aerosol was confirmed with a light laser (Bruss and Siber, 2002). BALB/c mice were immunized with PTx vaccine on day 6 of life and then challenged with B. pertussis using the aerosol challenge model. These primed mice were significantly better protected against leukocytosis, weight loss, and proliferation of B. pertussis in the lungs following aerosol challenge than the nonprimed group. This protection correlated with levels of anti-PT antibody in serum present on the day of aerosol challenge (Bruss and Siber, 2002). Mice were exposed to nebulization for 30 min and removed 30 min after termination of aerosol. The completion of the aerosol represented time 0. Mice were removed from the box and replaced into their cages. Cages were checked daily for mortality (Bruss and Siber, 2002). Boostrix Tetanus Toxoid, Reduced Diphtheria Toxoid and Acellular Pertussis Vaccine, Adsorbed Boostrix GlaxoSmithKline Biologicals VO_0000015 Toxoid vaccine Licensed Intramuscular injection (i.m.) USA (License #1617) BOOSTRIX (Tetanus Toxoid, Reduced Diphtheria Toxoid and Acellular Pertussis Vaccine, Adsorbed) is a noninfectious, sterile, vaccine for intramuscular administration. It contains tetanus toxoid, diphtheria toxoid, and pertussis antigens (inactivated pertussis toxin [PT] and formaldehyde-treated filamentous hemagglutinin [FHA] and pertactin). The antigens are the same as those in INFANRIX, but BOOSTRIX is formulated with reduced quantities of these antigens (FDA: Boostrix). Aluminum Phosphate Store refrigerated between 2º and 8ºC (36º and 46ºF). Do not freeze. Tetanus toxin is produced by growing Clostridium tetani in a modified Latham medium derived from bovine casein. Toxins are detoxified with formaldehyde, concentrated by ultrafiltration, and purified by precipitation, dialysis, and sterile filtration (FDA: Boostrix). Intramuscular injection (i.m.) Boostrix-Polio Combined diphtheria, tetanus, acellular pertussis (adsorbed) and inactivated poliomyelitis vaccine Boostrix-Polio GlaxoSmithKline VO_0003088 Toxoid vaccine + Subunit vaccine + Inactivated or "killed" vaccine Licensed Intramuscular injection (i.m.) Canada BOOSTRIX®-POLIO (combined diphtheria, tetanus, acellular pertussis and inactivated poliomyetitis) vaccine contains diphtheria toxoid, tetanus toxoid, three purified pertussis antigens [pertussis toxoid (PT), filamentous haemagglutinin (FHA) and pertactin (69 kDalton outer membrane protein)] adsorbed onto aluminum salts and inactivated polio virus types 1, 2 and 3. (GSK: Boostrix-Polio) Aluminum hydroxide Store at 2° to 8°C (35° to 46°F), do not freeze. Intramuscular injection (i.m.) Bordetella pertussis aroA mutant vaccine VO_0002807 Live, attenuated vaccine Research intracerebral challenge A DNA fragment encoding a kanamycin resistance determinant was used to insertionally inactivate the cloned aroA gene of Bordetella pertussis in Escherichia coli K-12, and a conjugative shuttle vector system based on the suicide vector pRTP1 was used to deliver the mutations from E. coli back into B. pertussis CN2992FS and BP1. The aroA mutation was introduced by allelic exchange into the chromosome of B. pertussis, resulting in otherwise isogenic parental and aroA mutant pairs. The B. pertussis aroA mutants grew well on laboratory medium supplemented with aromatic compounds but failed to grow on unsupplemented medium (Roberts et al., 1990). intracerebral challenge Gene mutation The B. pertussis aroA mutants expressed the normal B. pertussis extracellular, virulence-associated proteins (Roberts et al., 1990). Mice exposed to three separate aerosols of live B. pertussis aroA bacteria were protected against lung colonization after being exposed to an aerosol containing the virulent parental B. pertussis strain. High-level antibodies against B. pertussis rapidly appeared in the sera of mice immunized by aerosol with the B. pertussis aroA strains and challenged with the virulent parent (Roberts et al., 1990). Bordetella pertussis BPZE vectored vaccine VO_0004608 Recombinant vector vaccine Research Bordetella pertussis BPZE, which is attenuated for 3 different toxins: the pertussis toxin, the dermonecrotic toxin, and the tracheal cytotoxins [Ref2891:Mielcarek et al., 2006]. intranasal immunization This is an intranasal vaccine because pathogenic B. pertussis colonizes the respiratory tract of humans. The vaccine itself has been shown to only need one inoculation in order to elicit protection, making it a good candidate to be a vaccine vector for other diseases (Mielcarek et al., 2006). The pertussis toxin itself if extremely virulent, but after thorough and careful attenuation, the virulence is basically gone (Mielcarek et al., 2006). intranasal immunization The pertussis toxin gene, which encodes a highly virulent toxin (Mielcarek et al., 2006). The mice were vaccinated with highly-attenuated B. pertussis in order to prepare for challenge with virulent wild-type B. pertussis (Mielcarek et al., 2006). VO_0000287 A single intranasal inoculation of mice with the B. pertussis vaccine vector induced the same level of protection, if not higher, as two injections of the commercial acellular vaccine (Mielcarek et al., 2006) . After the mice had been inoculated with attenuated B. pertussis (which after a month had colonized the entire mouse respiratory tract) they were challenged with virulent wild-type B. pertussis (Mielcarek et al., 2006). Inoculation with the B. pertussis vaccine vector shows protective immunity which rivals that of the vaccines currently on the market. Bordetella pertussis dnt mutant vaccine VO_0002808 Live, attenuated vaccine Research intranasal immunization his strain was obtained by genetically inactivating pertussis toxin via two point mutations in the ptx gene, by deleting dnt encoding dermonecrotic toxin, and by replacing the B. pertussis ampG gene by Escherichia coli ampG, resulting in the removal of tracheal cytotoxin (Feunou et al., 2008). intranasal immunization Gene mutation The dnt mutant in B. pertussis yielded a highly attenuated strain that was still able to transiently colonize the mouse respiratory tract [Ref1805:Feunou et al., 2008. A single intranasal administration of BPZE1(dnt mutant vaccine) induced full protection in adult mice (8 weeks old), as well as in infant mice (3 weeks old), whereas commercial acellular pertussis vaccine (aPV) only partially protected infant mice, even after repetitive doses (Feunou et al., 2008). DAPTACEL Diphtheria and Tetanus Toxoids and Acellular Pertussis Vaccine Adsorbed DAPTACEL Sanofi Pasteur, Ltd. VO_0000029 Toxoid vaccine Licensed Intramuscular injection (i.m.) USA (License #1726) DAPTACEL is a vaccine indicated for active immunization against diphtheria, tetanus and pertussis as a five-dose series in infants and children 6 weeks through 6 years of age. aluminum phosphate Should be stored at 2° to 8°C (35° to 46°F). DO NOT FREEZE. Clostridium tetani is grown in modified Mueller-Miller casamino acid medium without beef heart infusion. Tetanus toxin is detoxified with formaldehyde and purified by ammonium sulfate fractionation and diafiltration (FDA: DAPTACEL). Intramuscular injection (i.m.) Isotonic suspension of pertussis antigens and diphtheria and tetanus toxoids (FDA: DAPTACEL). Infanrix Diphtheria and Tetanus Toxoids and Acellular Pertussis Vaccine Adsorbed Infanrix GlaxoSmithKline Biologicals VO_0000064 Toxoid vaccine Licensed Intramuscular injection (i.m.) USA (License #1617 ) The vaccine is an noninfectious, sterile combination of diphtheria and tetanus toxoids and 3 pertussis antigens [inactivated pertussis toxin (PT), filamentous hemagglutinin (FHA), and pertactin (69 kiloDalton outer membrane protein)] adsorbed onto aluminum hydroxide (FDA: Infanrix). Aluminum Hydroxide Store INFANRIX refrigerated between 2° and 8°C (36° and 46°F). Do not freeze. Tetanus toxin is produced by growing Clostridium tetani in a modified Latham medium derived from bovine casein. The toxin is detoxified with formaldehyde, concentrated by ultrafiltration, and purified by precipitation, dialysis, and sterile filtration (FDA: Infanrix). Intramuscular injection (i.m.) Diphtheria and tetanus toxoids and 3 pertussis antigens [inactivated pertussis toxin (PT), filamentous hemagglutinin (FHA), and pertactin (69 kiloDalton outer membrane protein)] (FDA: Infanrix). Infanrix -IPV/Hib Diphtheria, tetanus, pertussis (acellular component), poliomyelitis (inactivated) and Haemophilus type b conjugate vaccine (adsorbed) Infanrix -IPV/Hib GlaxoSmithKline VO_0010722 Subunit vaccine + Inactivated or "killed" vaccine Licensed Intramuscular injection (i.m.) Canada Products: Proteins + killed virus + conjugate. Other components: Formaldehyde Polysorbate 80, Lactose. Aluminum Hydroxide Store in a refrigerator (2°C – 8°C). Intramuscular injection (i.m.) Infanrix-hexa Combined diphtheria and tetanus toxoids, acellular pertussis, hepatitis B (recombinant), inactivated poliomyelitis and adsorbed conjugated Haemophilus influenzae type b vaccine Infanrix-hexa GlaxoSmithKline VO_0010719 Subunit vaccine + Inactivated or "killed" vaccine Licensed Intramuscular injection (i.m.) Canada Products: Proteins + killed viruses + conjugate. Other components: Yeast protein Formaldehyde, Lactose, Polysorbate 20 and 80. Aluminum phosphate and aluminum hydroxide Should be stored at 2° to 8°C (35° to 46°F). Intramuscular injection (i.m.) Infanrix-IPV Diphtheria, tetanus, pertussis (acellular, component) and poliomyelitis (inactivated) vaccine (adsorbed) Infanrix-IPV GlaxoSmithKline VO_0010721 Subunit vaccine + Inactivated or "killed" vaccine Licensed Intramuscular injection (i.m.) Canada Products: Proteins + killed virus. Other components: Formaldehyde, Polysorbate 80. Aluminum hydroxide Store in a refrigerator (2°C - 8°C). Intramuscular injection (i.m.) Infanrix/Hib Combined diphtheria, tetanus, acellular pertussis (DTPa) and Haemophilus influenza type b vaccine Infanrix/Hib GlaxoSmithKline VO_0010720 Subunit vaccine Licensed Intramuscular injection (i.m.) Canada Products: Proteins + conjugate. Other components: Formaldehyde, Lactose. Aluminum hydroxide Refrigerated stored between +2°C and +8°C. Intramuscular injection (i.m.) KINRIX Diphtheria and Tetanus Toxoids and Acellular Pertussis Adsorbed and Inactivated Poliovirus Vaccine KINRIX GlaxoSmithKline VO_0000067 Toxoid vaccine + Subunit vaccine + Inactivated or "killed" vaccine Licensed Intramuscular injection (i.m.) USA A single dose of KINRIX is indicated for active immunization against diphtheria, tetanus, pertussis, and poliomyelitis as the fifth dose in the diphtheria, tetanus, and acellular pertussis (DTaP) vaccine series and the fourth dose in the inactivated poliovirus vaccine (IPV) series in children 4 through 6 years of age whose previous DTaP vaccine doses have been with INFANRIX and/or PEDIARIX for the first three doses and INFANRIX for the fourth dose. (FDA: KINRIX) Aluminum hydroxide Store refrigerated between 2° and 8°C (36° and 46°F), do not freeze. The diphtheria toxin is produced by growing Corynebacterium diphtheriae in Fenton medium containing a bovine extract. After, they are detoxified with formaldehyde, concentrated by ultrafiltration, and purified by precipitation, dialysis, and sterile filtration. Intramuscular injection (i.m.) licensed Pertussis human vaccine Generic Unknown VO_0000765 Toxoid vaccine Licensed A generic representation of vaccines used to prevent whooping cough (pertussis) in humans, most commonly based on inactivated pertussis toxin (toxoid) and sometimes combined with other bacterial components. These vaccines stimulate immunity without causing disease by exposing the immune system to detoxified pertussis toxin. Pediacel Diphtheria and Tetanus Toxoids and Acellular Pertussis Vaccine Adsorbed Combined with Inactivated Poliomyelitis Vaccine and Haemophilus b Conjugate Vaccine (Tetanus Protein – Conjugate) Pediacel Sanofi Pasteur Ltd VO_0010730 Subunit vaccine + Inactivated or "killed" vaccine Licensed Intramuscular injection (i.m.) Canada Products: Proteins, killed virus + conjugate. Other components: Bovine serum Formaldehyde, Polysorbate 80. Aluminum phosphate Store at 2° to 8°C (35° to 46°F). Intramuscular injection (i.m.) Pediarix Diphtheria and Tetanus Toxoids and Acellular Pertussis Adsorbed, Hepatitis B (Recombinant) and Inactivated Poliovirus Vaccine Combined Pediarix GlaxoSmithKline Biologicals VO_0000082 Toxoid vaccine Licensed Intramuscular injection (i.m.) United States It contains diphtheria and tetanus toxoids, 3 pertussis antigens (inactivated pertussis toxin [PT] and formaldehyde-treated filamentous hemagglutinin [FHA] and pertactin [69 kiloDalton outer membrane protein]), hepatitis B surface antigen, plus poliovirus Type 1 (Mahoney), Type 2 (MEF-1), and Type 3 (Saukett) (FDA: Pediarix). Aluminum hydroxide The vaccine should be refrigerated between 2º and 8ºC (36º and 46ºF). Do not freeze. The diphtheria toxin is produced by growing Corynebacterium diphtheriae in Fenton medium containing a bovine extract. The diphtheria, tetanus, and pertussis antigens are individually adsorbed onto aluminum hydroxide then diluted and combined to produce the final formulated vaccine (FDA: Pediarix). Intramuscular injection (i.m.) Pentacel Diphtheria and Tetanus Toxoids and Acellular Pertussis Adsorbed, Inactivated Poliovirus and Haemophilus b Conjugate (Tetanus Toxoid Conjugate) Vaccine Pentacel Sanofi Pasteur Limited VO_0000084 Subunit vaccine + Inactivated or "killed" vaccine Licensed Intramuscular injection (i.m.) USA (License #1726), Canada It consists of a Diphtheria and Tetanus Toxoids and Acellular Pertussis Adsorbed and Inactivated Poliovirus (DTaP-IPV) component and an ActHIB® vaccine component. Pentacel vaccine is indicated for active immunization against diphtheria, tetanus, pertussis, poliomyelitis and invasive disease due to Haemophilus influenzae type b (FDA: Pentacel). Aluminum phosphate Store at 2° to 8°C (35° to 46°F). Do not freeze. Corynebacterium diphtheriae is grown in modified Mueller’s growth medium. After purification by ammonium sulfate fractionation, the diphtheria toxin is detoxified with formaldehyde and diafiltered (FDA: Pentacel). Intramuscular injection (i.m.) Quadracel Diphtheria and Tetanus Toxoids and Acellular Pertussis Vaccine Adsorbed Combined with Inactivated Poliomyelitis Vaccine Quadracel Sanofi Pasteur Ltd VO_0010736 Subunit vaccine + Inactivated or "killed" vaccine Licensed Intramuscular injection (i.m.) Canada Aluminum phosphate Store at 2 to 8C (35 to 46F). Do not freeze. Intramuscular injection (i.m.) rBCG-S1PT VO_0004790 Recombinant vector vaccine Licensed Intramuscular injection (i.m.) Intramuscular injection (i.m.) BCG vaccine with S1 subunit of detoxified B. pertussis toxin; PT-9K/129G (Nascimento et al., 2008). Mice were immunized with 50μl of one-tenth dose of an adult mouse of DTP at day 5 (or day 12 as specified) or 10^5 CFU of BCG or rBCG-S1PT on day 5 according to different regimens (Nascimento et al., 2008). VO_0003057 A single dose of rBCG-S1PT at day 5 led to a 100% survival of mice, and even at an extremely high challenge dose (300 times the lethal adult dose) rBCG-S1PT still induced 50% survival of neonate-immunized mice. Mice immunized with BCG alone experienced a protective effect of 80%, however at a higher challenge dose, this effect was reduced to 50%. Mice immunized with DTP showed no protection (Nascimento et al., 2008). Mice were subjected to intracerebral inoculation with a lethal dose of B. pertussis with approximately 3 x 10^4, 3 x 10^5, or 9 x 10^5 CFU (in 30μl) on day 21 after birth. S. gordonii-PT VO_0004670 Recombinant vector vaccine Research Intramuscular injection (i.m.) (Lee et al., 1999) Intramuscular injection (i.m.) Tripacel Pertussis Vaccine-Acellular, Combined with Diphtheria and Tetanus Toxoids (Adsorbed) Tripacel Sanofi Pasteur Ltd VO_0010742 Subunit vaccine Licensed Intramuscular injection (i.m.) Canada Aluminum phospate Store at at 2° to 8°C. Intramuscular injection (i.m.) Tripedia Diphtheria and Tetanus Toxoids and Acellular Pertussis Vaccine Adsorbed Tripedia Sanofi Pasteur, Inc. VO_0000112 Toxoid vaccine Licensed Intramuscular injection (i.m.) USA (FDA License #1725) Tripedia vaccine combines diptheria and tetanus toxoids with purified pertussis antigens. It consists of 3 doses administered at intervals of 4-8 weeks (FDA: Tripedia). aluminum potassium sulfate Store between 2 and 8 degrees Celsius. DO NOT FREEZE. Intramuscular injection (i.m.) VC-TetC/Tcf VC expressing B. pertussis TetC/Tcf VO_0004781 Recombinant vector vaccine Research intranasal immunization An attenuated strain of Vibrio cholerae was used as a carrier for the expression of heterologous antigens such as fragment C from tetanus toxin (TetC) and tracheal colonization factor from Bordetella pertussis (Tcf) (Chen et al., 1998). intranasal immunization Recombinant protein preparation An attenuated strain of Vibrio cholerae was used as a carrier for the expression of heterologous antigens such as fragment C from tetanus toxin (TetC) and tracheal colonization factor from Bordetella pertussis (Tcf) (Chen et al., 1998). VO_0000287 Mice vaccinated with IEM101 expressing Tcf experienced significant reduction in bacterial colonization of their tracheas (Chen et al., 1998). Mice were challenged with wild-type B. pertussis (Chen et al., 1998). aroA 144037 CDD:179423 CDD:30129 520 ? 442 3-phosphoshikimate 1-carboxyvinyltransferase; Provisional >gi|144037|gb|AAA22968.1| 5-enolpyruvylshikimate-3-phosphate synthase (EC 2.5.1.19) [Bordetella pertussis] MSGLAYLDLPAARLARGEVALPGSKSISNRVLLLAALAEGSTEITGLLDSDDTRVMLAALRQLGVSVGEV ADGCVTIEGVARFPTEQAELFLGNAGTAFRPLTAALALMGGDYRLSGVPRMHERPIGDLVDALRQFGAGI EYLGQAGYPPLRIGGGSIRVDGPVRVEGSVSSQFLTALLMAAPVLARRSGQDITIEVVGELISKPYIEIT LNLMARFGVSVRRDGWRAFTIARDAVYRGPGRMAIEGDASTASYFLALGAIGGGPVRVTGVGEDSIQGDV AFAATLAAMGADVRYGPGWIETRGVRVAEGGRLKAFDADFNLIPDAAMTAATLALYADGPCRLRNIGSWR VKETDRIHAMHTELEKLGAGVQSGADWLEVAPPEPGGWRDAHIGTWDDHRMAMCFLLAAFGPAAVRILDP GCVSKTFPDYFDVYAGLLAARD Virmugen An aroA mutant is highly attenuated in mice and induces significant protection from challenge with wild type B. pertussis [Ref1660:Roberts et al., 1990]. brkA Bordetella pertussis VO_0011036 562026 CDD:332715 CDD:238653 CDD:273608 520 ? BrkA 7.12 96022.08 1066 Domain of Unknown Function (DUF1522); cl27894 >AAA51646.1 BrkA [Bordetella pertussis] MYLDRFRQCPSSLQIPRSAWRLHALAAALALAGMARLAPAAAQAPQPPVAGAPHAQDAGQEGEFDHRDNT LIAVFDDGVGINLDDDPDELGETAPPTLKDIHISVEHKNPMSKPAIGVRVSGAGRALTLAGSTIDATEGG IPAVVRRGGTLELDGVTVAGGEGMEPMTVSDAGSRLSVRGGVLGGEAPGVGLVRAAQGGQASIIDATLQS ILGPALIADGGSISVAGGSIDMDMGPGFPPPPPPLPGAPLAAHPPLDRVAAVHAGQDGKVTLREVALRAH GPQATGVYAYMPGSEITLQGGTVSVQGDDGAGVVAGAGLLDALPPGGTVRLDGTTVSTDGANTDAVLVRG DAARAEVVNTVLRTAKSLAAGVSAQHGGRVTLRQTRIETAGAGAEGISVLGFEPQSGSGPASVDMQGGSI TTTGNRAAGIALTHGSARLEGVAVRAEGSGSSAAQLANGTLVVSAGSLASAQSGAISVTDTPLKLMPGAL ASSTVSVRLTDGATAQGGNGVFLQQHSTIPVAVALESGALARGDIVADGNKPLDAGISLSVASGAAWHGA TQVLQSATLGKGGTWVVNADSRVQDMSMRGGRVEFQAPAPEASYKTLTLQTLDGNGVFVLNTNVAAGQND QLRVTGRADGQHRVLVRNAGGEADSRGARLGLVHTQGQGNATFRLANVGKAVDLGTWRYSLAEDPKTHVW SLQRAGQALSGAANAAVNAADLSSIALAESNALDKRLGELRLRADAGGPWARTFSERQQISNRHARAYDQ TVSGLEIGLDRGWSASGGRWYAGGLLGYTYADRTYPGDGGGKVKGLHVGGYAAYVGDGGYYLDTVLRLGR YDQQYNIAGTDGGRVTADYRTSGAAWSLEGGRRFELPNDWFAEPQAEVMLWRTSGKRYRASNGLRVKVDA NTATLGRLGLRFGRRIALAGGNIVQPYARLGWTQEFKSTGDVRTNGIGHAGAGRHGRVELGAGVDAALGK GHNLYASYEYAAGDRINIPWSFHAGYRYSF Protective antigen A soluble fraction obtained from Bordetella pertussis was evaluated as adjuvant for the pertussis component of the Diphtheria-Pertussis-Tetanus (DPT) vaccine. High levels of antibodies were induced, and a 78% protection rate of mice challenged with live B. pertussis was observed. Two proteins were identified as the 73 kDa N-terminal alpha-domain of BrkA autotransporter protein and the Cpn60/60 kDa chaperonin. Both stimulated antibodies against pertussis and induced a 42% protection rate against the challenge [Ref1024:Cainelli et al., 2007]. cpn60 Bordetella pertussis VO_0011035 968920 CDD:234573 CDD:239460 520 ? Cpn60 (GroEL) 4.81 52145.9 605 chaperonin GroEL; Reviewed; PRK00013 >AAA74967.1 Cpn60 (GroEL) [Bordetella pertussis] MAAKQVLFADEARVRIVRGVNVLANAVKTTLGPKGRNVVLERSFGAPTVTKDGVSVAKEIELKDKFENIG AQLVKDVASKTSDNAGDGTTTATVLAQAVVQEGLKYVAAGFNPIDLKRGIDKAVAAAVEELKKLSKPVTT SKEIAQVGSISANSDASIGQIIADAMDKVGKEGVITVEDGKSLENELDVVEGMQFDRGYLSPYFINSPEK QVAALDDPYVLIYDKKVSNIRDLLPVLEQVAKSSRPLLIIAEDVEGEALATLVVNNIRGILKTTAVKAPG FGDRRKAMLEDIAILTGGTVISEETGMSLEKATLQDLGQAKRIEVAKENTTIIDGAGDGKSIEARVKQIR AQIEEATSDYDREKLQERVAKLAGGVAVIRVGAATEVEMKEKKARVEDALHATRAAVEEGVVPGGGVALL RAKQAITGLKGDTADQNAGIKLILRAVEEPLRTIVTNAGDEASVVVNTVLNGKGNYGYNAATGEYGDLVE QGVLDPTKVTRTALQNAASVASLLLTAEAAVVELMENKPAAAPAMPGGMGGMGGMDF Protective antigen A soluble fraction obtained from Bordetella pertussis was evaluated as adjuvant for the pertussis component of the Diphtheria-Pertussis-Tetanus (DPT) vaccine. High levels of antibodies were induced, and a 78% protection rate of mice challenged with live B. pertussis was observed. Two proteins were identified as the 73 kDa N-terminal alpha-domain of BrkA autotransporter protein and the Cpn60/60 kDa chaperonin. Both stimulated antibodies against pertussis and induced a 42% protection rate against the challenge [Ref1024:Cainelli et al., 2007]. CyaA Bordetella pertussis VO_0011031 580668 2COL CDD:281494 CDD:280531 CDD:225483 CDD:305016 520 ? adenylate cyclase 4.36 164358.59 1785 Anthrax toxin LF subunit; pfam03497 >CAA01202.1 adenylate cyclase [Bordetella pertussis] MQQSHQAGYANAADRESGIPAAVLDGIKAVAKEKNATLMFRLVNPHSTSLIAEGVATKGLGVHAKSSDWG LQAGYIPVNPNLSKLFGRAPEVIARADNDVNSSLAHGHTAVDLTLSKERLDYLRQAGLVTGMADGVVASN HAGYEQFEFRVKETSDGRYAVQYRRKGGDDFEAVKVIGNAAGIPLTADIDMFAIMPHLSNFRDSARSSVT SGDSVTDYLARTRRAASEATGGLDRERIDLLWKIARAGARSAVGTEARRQFRYDGDMNIGVITDFELEVR NALNRRAHAVGAQDVVQHGTEQNNPFPEADEKIFVVSATGESQMLTRGQLKEYIGQQRGEGYVFYENRAY GVAGKSLFDDGLGAAPGVPSGRSKFSPDVLETVPASPGLRRPSLGAVERQDSGYDSLDGVGSRSFSLGEV SDMAAVEAAELEMTRQVLHAGARQDDAEPGVSGASAHWGQRALQGAQAVAAAQRLVHAIALMTQFGRAGS TNTPQEAASLSAAVFGLGEASSAVAETVSGFFRGSSRWAGGFGVAGGAMALGGGIAAAVGAGMSLTDDAP AGQKAAAGAEIALQLTGGTVELASSIALALAAARGVTSGLQVAGASAGAAAGALAAALSPMEIYGLVQQS HYADQLDKLAQESSAYGYEGDALLAQLYRDKTAAEGAVAGVSAVLSTVGAAVSIAAAASVVGAPVAVVTS LLTGALNGILRGVQQPIIEKLANDYARKIDELGGPQAYFEKNLQARHEQLANSDGLRKMLADLQAGWNAS SVIGVQTTEISKSALELAAITGNADNLKSVDVFVDRFVQGERVAGQPVVLDVAAGGIDIASRKGERPALT FITPLAAPGEEQRRRTKTGKSEFTTFVEIVGKQDRWRIRDGAADTTIDLAKVVSQLVDANGVLKHSIKLD VIGGDGDDVVLANASRIHYDGGAGTNTVSYAALGRQDSITVSADGERFNVRKQLNNANVYREGVATQTTA YGKRTENVQYRHVELARVGQVVEVDTLEHVQHIIGGAGNDSITGNAHDNFLAGGSGDDRLDGGAGNDTLV GGEGQNTVIGGAGDDVFLQDLGVWSNQLDGGAGVDTVKYNVHQPSEERLERMGDTGIHADLQKGTVEKWP ALNLFSVDHVKNIENLHGSRLNDRIAGDDQDNELWGHDGNDTIRGRGGDDILRGGLGLDTLYGEDGNDIF LQDDETVSDDIDGGAGLDTVDYSAMIHPGRIVAPHEYGFGIEADLSREWVRKASALGVDYYDNVRNVENV IGTSMKDVLIGDAQANTLMGQGGDDTVRGGDGDDLLFGGDGNDMLYGDAGNDTLYGGLGDDTLEGGAGND WFGQTQAREHDVLRGGDGVDTVDYSQTGAHAGIAAGRIGLGILADLGAGRVDKLGEAGSSAYDTVSGIEN VVGTELADRITGDAQANVLRGAGGADVLAGGEGDDVLLGGDGDDQLSGDAGRDRLYGEAGDDWFFQDAAN AGNLLDGGDGRDTVDFSGPGRGLDAGAKGVFLSLGKGFASLMDEPETSNVLRNIENAVGSARDDVLIGDA GANVLNGLAGNDVLSGGAGDDVLLGDEGSDLLSGDAGNDDLFGGQGDDTYLFGVGYGHDTIYESGGGHDT IRINAGADQLWFARQGNDLEIRILGTDDALTVHDWYRDADHRVEIIHAANQAVDQAGIEKLVEAMAQYPD PGAAAAAPPAARVPDTLMQSLAVNWR Protective antigen A study demonstrated that passive immunization with specific anti-B. pertussis adenylate cyclase antibodies or active immunization with purified B. pertussis secreted adenylate cyclase (cyaA) protect mice against a lethal respiratory challenge with B. pertussis or B. parapertussis. Results suggest that adenylate cyclase might be the primary cytotoxin responsible for mouse pulmonary lesions during respiratory tract infection with B. pertussis or with the related species B. parapertussis and is a protective antigen of B. pertussis [Ref1019:Guiso et al., 1989]. dnt Bordetella pertussis Tohama I 2666936 33594321 BP3439 BX640421 NP_881965 257313 3647083 3651477 + dermonecrotic toxin 6.49 150126.42 1464 Previously sequenced as Bordetella pertussis dermonecrotic toxin Dnt TR:Q45336 (EMBL:U10527) (1451 aa) fasta scores: E(): 0, 100% id in 1451 aa. Almost identical to Bordetella bronchiseptica dermonecrotizing toxin TR:Q9S5D5 (EMBL:AB020025) (1464 aa) fasta scores: E(): 0, 98.97% id in 1464 aa >gi|33591275:3647083-3651477 Bordetella pertussis Tohama I, complete genome CGTGGATAAAGATGAATCGGCATTGCGGCAACTTGTCGACATGGCGCTTGTAGGCTACGACGGCGTGGTG GAAGAGTTGCTGGCGCTGCCCTCGGAAGAGTCCGGGGATCTTGCGGGTGGACGGGCCAAACGAGAGAAGG CCGAATTCGCGCTGTTTAGCGAAGCGCCCAACGGGGATGAACCCATCGGCCAGGATGCTCGTACATGGTT CTATTTTCCCAAGTACCGCCCGGTGGCGGTTTCCAATTTGAAGAAAATGCAGGTGGCGATTCGTGCTCGT CTCGAGCCTGAGTCATTGATCCTGCAGTGGTTGATCGCACTCGATGTCTATCTCGGCGTGTTGATCGCCG CCTTGTCCCGCACTGTGATCAGCGACCTGGTATTCGAGTATGTCAAGGCGCGCTACGAGATCTACTACCT ACTGAATCGCGTGCCGCATCCGCTGGCGACGGCGTACCTCAAGCGCCGCCGCCAGCGTCCGGTGGATCGT TCGGGACGTCTGGGCTCGGTGTTCGAACACCCGCTATGGTTCGCCTACGACGAATTGGCCGGCACCGTCG ATCTGGATGCCGACATCTACGAGCAGGCGCTCGCCGAAAGCATCGAACGCCGCATGGACGGAGAGCCGGA CGACGGCAGTCTGGATACCGCCGAACACGACGTATGGCGTTTGTGCCGCGACGGCATCAATCGGGGCGAG CAGGCGATTTTCCAGGCATCCGGCCCATATGGCGTGGTCGCGGATGCAGGGTATATGCGCACCGTTGCCG ATCTGGCGTATGCCGATGCATTGGCGGATTGCCTGCATGCCCAACTGCGCATCCGGGCGCAAGGCTCGGT CGATAGCCCGGGAGACGAGATGCCACGCAAACTTGATGCGTGGGAAATCGCCAAGTTTCATCTGGCCGCG ACCCAGCAGGCGCGGGTTGATCTGCTCGAGGCGGCGTTCGCGCTCGACTACGCCGCCTTGCGCGATGTGC GCGTCTACGGCGATTACCGCAATGCGCTGGCTCTTCGGTTCATCAAGCGCGAGGCCTTGCGGTTGCTGGG GGCGCGGCGCGGCAACGCCTCTACGATGCCGGCGGTTGCGGCTGGCGAGTACGACGAAATCGTGGCCAGT GGAGCAGCCAATGACGCGGCTTATGTATCCATGGCCGCCGCGTTGATCGCGGGCGTGCTCTGCGATCTCG AGAGCGCGCAGCGCACGTTGCCCGTCGTATTGGCCAGGTTTCGGCCCCTTGGCGTGCTTGCGCGATTCAG AAGGCTGGAGCAGGAAACCGCGGGCATGCTGCTTGGCGACCAGGAGCCGGAGCCTCGGGGCTTCATCAGT TTTACCGATTTTCGCGATAGCGACGCGTTCGCCAGCTACGCGGAGTATGCGGCCCAGTTCAACGACTATA TCGATCAATACAGCATACTCGAGGCGCAGCGGCTGGCGCGGATTCTGGCCCTGGGCTCGCGGATGACGGT CGATCAATGGTGCCTTCCCCTGCAGAAAGTACGGCACTACAAGGTGCTGACATCGCAGCCAGGGCTGATC GCGCGTGGAATCGAAAATCACAACAGGGGCATTGAATATTGCCTGGGGCGGCCGCCGCTGACCGATCTGC CGGGTCTTTTCACCATGTTCCAGCTCCATGATTCCAGCTGGCTGTTGGTATCGAACATCAACGGTGAGCT TTGGTCTGATGTCCTTGCGAACGCTGAGGTGATGCAGAATCCTACGCTGGCCGCCCTTGCCGAGCCGCAA GGCCGCTTTCGAACCGGCCGTCGAACGGGCGGGTGGTTTCTCGGCGGCCCCGCGACTGAAGGGCCAAGTC TGCGCGACAACTACCTCCTCAAATTGAGGCAGAGCAATCCGGGGCTGGATGTCAAGAAATGCTGGTATTT CGGGTATCGGCAAGAGTACAGGCTGCCCGCAGGCGCGCTGGGTGTGCCGCTATTCGCTGTTTCCGTTGCC CTGAGGCACAGTCTGGACGACCTCGCGGCGCACGCGAAGTCCGCTTTGTACAAACCCAGCGAATGGCAGA AGTTCGCCTTCTGGATCGTGCCGTTCTACCGGGAAATATTCTTTTCGACCCAGGATCGTTCCTATCGGGT CGATGTGGGGAGCATCGTCTTTGATTCGATTTCCTTGCTTGCCTCGGTGTTCAGCATAGGAGGGAAGTTG GGCAGTTTCACCCGTACCCAGTATGGCAACCTGCGCAATTTCGTGGTGCGGCAACGCATCGCGGGGTTGA GCGGGCAGCGCTTGTGGCGTTCGGTGCTCAAGGAGCTTCCGGCATTGATCGGAGCCAGCGGGTTGCGCCT GTCGCGTTCGCTGCTCGTCGATCTGTATGAGATCTTCGAGCCCGTGCCTATCCGTCGGCTTGTCGCGGGA TTCGTGAGCGCCACTACGGTCGGCGGGCGTAACCAGGCCTTCCTGCGGCAGGCATTCTCCGCTGCCAGTT CCTCGGCCGGGCGCACGGGGGGCCAATTGGCAAGCGAATGGCGGATGGCCGGCGTGGACGCCACCGGTTT GGTCGAGTCCACGTCGGGCGGCAGGTTTGAGGGCATCTACACGCGCGGCTTGGGACCGTTGAGCGAGTGC ACCGAGCACTTCATCGTCGAATCCGGGAATGCCTACAGAGTCATCTGGGATGCATACACGCATGGTTGGC GCGTGGTCAATGGGCGTTTGCCGCCGAGGCTGACCTATACCGTTCCGGTTCGGCTGAACGGGCAAGGCCA CTGGGAGACGCATCTGGATGTCCCTGGCCGGGGTGGGGCGCCGGAAATCTTCGGACGCATCCGCACGCGT AATCTGGTCGCCCTTGCCGCCGAGCAGGCCGCGCCGATGCGCCGCCTGCTCAACCAGGCGAGGCGTGTGG CGCTCAGGCATATCGATACCTGCAGGAGCAGGCTTGCGTTGCCGCGCGCTGAATCCGATATGGACGCGGC GATCCGGATTTTCTTCGGAGAGCCGGACGCCGGCCTTCGCCAGCGCATCGGGCGACGCCTGCAGGAGGTC AGGGCCTATATCGGCGATCTGAGTCCGGTCAATGACGTGCTGTACCGGGCGGGATATGACCTCGACGATG TCGCAACGCTGTTTAACGCAGTGGACCGGAACACGTCGCTGGGCAGGCAGGCTCGGATGGAGTTGTATCT GGATGCCATTGTCGATTTGCATGCCAGGCTCGGCTATGAAAATGCGCGTTTTGTCGACCTGATGGCGTTC CACCTGCTCAGCCTGGGCCATGCCGCGACGGCCAGTGAGGTCGTGGAGGCCGTTTCGCCCCGGCTGCTGG GCAATGTGTTCGATATCTCGAACGTCGCCCAGCTCGAACGCGGTATCGGGAATCCCGCCAGCACCGGTCT TTTCGTCATGCTGGGCGCCTATTCGGAATCGTCGCCCGCGATATTCCAGTCGTTCGTGAACGATATATTT CCCGCATGGCGACAGGCTTCCGGCGGGGGGCCGCTGGTATGGAACTTCGGTCCTGCCGCCATCAGCCCGA CGCGCCTGGATTACGCAAATACCGATATCGGATTGCTCAACCATGGGGATATTTCCCCGCTGCGCGCCAG GCCGCCATTGGGCGGCAGGCGCGACATCGATCTTCCTCCGGGGCTGGATATTTCGTTCGTGCGTTACGAC CGCCCGGTGCGCATGTCCGCGCCGCGTGCGCTCGACGCCAGCGTCTTCAGGCCGGTCGACGGGCCTGTCC ATGGCTATATTCAATCGTGGACGGGGGCTGAGATCGAATATGCGTACGGCGCGCCCGCAGCGGCACGCGA GGTCATGCTGACCGACAATGTGCGGATCATCAGCATCGAGAACGGCGATGAAGGGGCGATCGGGGTGCGC GTGAGGCTCGACACTGTTCCCGTCGCGACGCCGCTCATCCTGACTGGCGGCTCCTTGAGCGGGTGCACGA CGATGGTTGGGGTCAAGGAGGGCTACCTGGCCTTCTACCACACTGGCAAGTCGACCGAACTCGGGGATTG GGCGACTGCGCGCGAAGGCGTACAGGCGCTTTACCAGGCCCATTTGGCGATGGGGTACGCGCCGATCTCA ATCCCGGCGCCGATGCGCAATGACGACTTGGTCAGCATCGCCGCGACCTACGACCGGGCGGTCATTGCCT ATCTGGGCAAGGATGTGCCGGGAGGCGGCAGTACGCGCATAACGCGTCACGATGAGGGGGCGGGCAGTGT GGTTTCGTTCGACTACAACGCAGCAGTCCAGGCGTCGGCCGTTCCCCGCCTCGGCCAGGTATACGTTCTG ATTTCCAACGACGGACAAGGGGCGCGAGCCGTCCTGCTGGCGGAGGATCTGGCCTGGGCAGGCAGCGGCA GTGCCTTGGATGTGTTGAACGAACGATTGGTGACGTTGTTTCCGGCGCCGGTCTG >gi|33594321|ref|NP_881965.1| dermonecrotic toxin [Bordetella pertussis Tohama I] MDKDESALRQLVDMALVGYDGVVEELLALPSEESGDLAGGRAKREKAEFALFSEAPNGDEPIGQDARTWF YFPKYRPVAVSNLKKMQVAIRARLEPESLILQWLIALDVYLGVLIAALSRTVISDLVFEYVKARYEIYYL LNRVPHPLATAYLKRRRQRPVDRSGRLGSVFEHPLWFAYDELAGTVDLDADIYEQALAESIERRMDGEPD DGSLDTAEHDVWRLCRDGINRGEQAIFQASGPYGVVADAGYMRTVADLAYADALADCLHAQLRIRAQGSV DSPGDEMPRKLDAWEIAKFHLAATQQARVDLLEAAFALDYAALRDVRVYGDYRNALALRFIKREALRLLG ARRGNASTMPAVAAGEYDEIVASGAANDAAYVSMAAALIAGVLCDLESAQRTLPVVLARFRPLGVLARFR RLEQETAGMLLGDQEPEPRGFISFTDFRDSDAFASYAEYAAQFNDYIDQYSILEAQRLARILALGSRMTV DQWCLPLQKVRHYKVLTSQPGLIARGIENHNRGIEYCLGRPPLTDLPGLFTMFQLHDSSWLLVSNINGEL WSDVLANAEVMQNPTLAALAEPQGRFRTGRRTGGWFLGGPATEGPSLRDNYLLKLRQSNPGLDVKKCWYF GYRQEYRLPAGALGVPLFAVSVALRHSLDDLAAHAKSALYKPSEWQKFAFWIVPFYREIFFSTQDRSYRV DVGSIVFDSISLLASVFSIGGKLGSFTRTQYGNLRNFVVRQRIAGLSGQRLWRSVLKELPALIGASGLRL SRSLLVDLYEIFEPVPIRRLVAGFVSATTVGGRNQAFLRQAFSAASSSAGRTGGQLASEWRMAGVDATGL VESTSGGRFEGIYTRGLGPLSECTEHFIVESGNAYRVIWDAYTHGWRVVNGRLPPRLTYTVPVRLNGQGH WETHLDVPGRGGAPEIFGRIRTRNLVALAAEQAAPMRRLLNQARRVALRHIDTCRSRLALPRAESDMDAA IRIFFGEPDAGLRQRIGRRLQEVRAYIGDLSPVNDVLYRAGYDLDDVATLFNAVDRNTSLGRQARMELYL DAIVDLHARLGYENARFVDLMAFHLLSLGHAATASEVVEAVSPRLLGNVFDISNVAQLERGIGNPASTGL FVMLGAYSESSPAIFQSFVNDIFPAWRQASGGGPLVWNFGPAAISPTRLDYANTDIGLLNHGDISPLRAR PPLGGRRDIDLPPGLDISFVRYDRPVRMSAPRALDASVFRPVDGPVHGYIQSWTGAEIEYAYGAPAAARE VMLTDNVRIISIENGDEGAIGVRVRLDTVPVATPLILTGGSLSGCTTMVGVKEGYLAFYHTGKSTELGDW ATAREGVQALYQAHLAMGYAPISIPAPMRNDDLVSIAATYDRAVIAYLGKDVPGGGSTRITRHDEGAGSV VSFDYNAAVQASAVPRLGQVYVLISNDGQGARAVLLAEDLAWAGSGSALDVLNERLVTLFPAPV Virmugen A live attenuated B. pertussis vaccine strain BPZE1 that protects mice upon a single intranasal administration was developed by deleting dnt gene [Ref1805:Feunou et al., 2008]. fhaB Bordetella pertussis VO_0011030 3980256 1RWR CDD:289765 CDD:283510 CDD:293785 CDD:290071 CDD:292650 GOA:Q45365 InterPro:IPR008619 InterPro:IPR008638 InterPro:IPR010069 InterPro:IPR011050 InterPro:IPR011102 InterPro:IPR012334 UniProtKB/TrEMBL:Q45365 520 ? filamentous hemagglutinin 9.21 332849.05 3704 Extended Signal Peptide of Type V secretion system; pfam13018 >CAA36409.1 filamentous hemagglutinin [Bordetella pertussis] MNTNLYRLVFSHVRGMLVPVSEHCTVGNTFCGRTRGQARSGARATSLSVAPNALAWALMLACTGLPLVTH AQGLVPQGQTQVLQGGNKVPVVNIADPNSGGVSHNKFQQFNVANPGVVFNNGLTDGVSRIGGALTKNPNL TRQASAILAEVTDTSPSRLAGTLEVYGKGADLIIANPNGISVNGLSTLNASNLTLTTGRPSVNGGRIGLD VQQGTVTIERGGVNATGLGYFDVVARLVKLQGAVSSKQGKPLADIAVVAGANRYDHATRRATPIAAGARG AAAGAYAIDGTAAGAMYGKHITLVSSDSGLGVRQLGSLSSPSAITVSSQGEIALGDATVQRGPLSLKGAG VVSAGKLASGGGAVNVAGGGAVKIASASSVGNLAVQGGGKVQATLLNAGGTLLVSGRQAVQLGAASSRQA LSVNAGGALKADKLSATRRVDVDGKQAVALGSASSNALSVRAGGALKAGKLSATGRLDVDGKQAVTLGSV ASDGALSVSAGGNLRANELVSSAQLEVRGQREVALDDASSARGMTVVAAGALAARNLQSKGAIGVQGGEA VSVANANSDAELRVRGRGQVDLHDLSAARGADISGEGRVNIGRARSDSDVKVSAHGALSIDSMTALGAIG VQAGGSVSAKDMRSRGAVTVSGGGAVNLGDVQSDGQVRATSAGAMTVRDVAAAADLALQAGDALQAGFLK SAGAMTVNGRDAVRLDGAHAGGQLRVSSDGQAALGSLAAKGELTVSAARAATVAELKSLDNISVTGGERV SVQSVNSASRVAISAHGALDVGKVSAKSGIGLEGWGAVGADSLGSDGAISVSGRDAVRVDQARSLADISL GAEGGATLGAVEAAGSIDVRGGSTVAANSLHANRDVRVSGKDAVRVTAATSGGGLHVSSGRQLDLGAVQA RGALALDGGAGVALQSAKASGTLHVQGGEHLDLGTLAAVGAVDVNGTGDVRVAKLVSDAGADLQAGRSMT LGIVDTTGDLQARAQQKLELGSVKSDGGLQAAAGGALSLAAAEVAGALELSGQGVTVDRASASRARIDST GSVGIGALKAGAVEAASPRRARRALRQDFFTPGSVVVRAQGNVTVGRGDPHQGVLAQGDIIMDAKGGTLL LRNDALTENGTVTISADSAVLEHSTIESKISQSVLAAKGDKGKPAVSVKVAKKLFLNGTLRAVNDNNETM SGRQIDVVDGRPQITDAVTGEARKDESVVSDAALVADGGPIVVEAGELVSHAGGIGNGRNKENGASVTVR TTGNLVNKGYISAGKQGVLEVGGALTNEFLVGSDGTQRIEAQRIENRGTFQSQAPAGTAGALVVKAAEAI VHDGVMATKGEMQIAGKGGGSPTVTAGAKATTSANKLSVDVASWDNAGSLDIKKGGAQVTVAGRYAEHGE VSIQGDYTVSADAIALAAQVTQRGGAANLTSRHDTRFSNKIRLMGPLQVNAGGPVSNTGNLKVREGVTVT AASFDNETGAEVMAKSATLTTSGAARNAGKMQVKEAATIVAASVSNPGTFTAGKDITVTSRGGFDNEGKM ESNKDIVIKTEQFSNGRVLDAKHDLTVTASGQADNRGSLKAGHDFTVQAQRIDNSGTMAAGHDATLKAPH LRNTGQVVAGHDIHIINSAKLENTGRVDARNDIALDVADFTNTGSLYAEHDATLTLAQGTQRDLVVDQDH ILPVAEGTLRVKAKSLTTEIETGNPGSLIAEVQENIDNKQAIVVGKDLTLSSAHGNVANEANALLWAAGE LTVKAQNITNKRAALIEAGGNARLTAAVALLNKLGRIRAGEDMHLDAPRIENTAKLSGEVQRKGVQDVGG GEHGRWSGIGYVNYWLRAGNGKKAGTIAAPWYGGDLTAEQSLIEVGKDLYLNAGARKDEHRHLLNEGVIQ AGGHGHIGGDVDNRSVVRTVSAMEYFKTPLPVSLTALDNRAGLSPATWNFQSTYELLDYLLDQNRYEYIW GLYPTYTEWSVNTLKNLDLGYQAKPAPTAPPMPKAPELDLRGHTLESAEGRKIFGEYKKLQGEYEKAKMA VQAVEAYGEATRRVHDQLGQRYGKALGGMDAETKEVDGIIQEFAADLRTVYAKQADQATIDAETDKVAQR YKSQIDAVRLQAIQPGRVTLAKALSAALGADWRALGHSQLMQRWKDFKAGKRGAEIAFYPKEQTVLAAGA GLTLSNGAIHNGENAAQNRGRPEGLKIGAHSATSVSGSFDALRDVGLEKRLDIDDALAAVLVNPHIFTRI GAAQTSLADGAAGPALARQARQAPETDGMVDARGLGSADALASLASLDAAQGLEVSGRRNAQVADAGLAG PSAVAAPAVGAADVGVEPVTGDQVDQPVVAVGLEQPVATVRVAPPAVALPRPLFETRIKFIDQSKFYGSR YFFEQIGYKPDRAARVAGDNYFDTTLVREQVRRALGGYESRLPVRGVALVAKLMDSAGTVGKALGLKVGV APTAQQLKQADRDFVWYVDTVIDGQKVLAPRLYLTEATRQGITDQYAGGGALIASGGDVTVNTDGHDVSS VNGLIQGRSVKVDAGKGKVVVADSKGAGGGIEADDEVDVSGRDIGIEGGKLRGKDVRLKADTVKVATSMR YDDKGRLAARGDGALDAQGGQLHIEAKRLETAGATLKGGKVKLDVDDVKLGGVYEAGSSYENKSSTPLGS LFAILSSTTETNQSAHANHYGTRIEAGTLEGKMQNLEIEGGSVDAAHTDLSVARDARFKAAADFAHAEHE KDVRQLSLGAKVGAGGYEAGFSLGSESGLEAHAGRGMTAGAEVKVGYRASHEQSSETEKSYRNANLNFGG GSVEAGNVLDIGGADINRNRYGGAAKGNAGTEEALRMRAKKVESTKYVSEQTSQSSGWSVEVASTASARS SLLTAATRLGDSVAQNVEDGREIRGELMAAQVAAEATQLVTADTAAVALSAGISADFDSSHSRSTSQNTQ YLGGNLSIEATEGDATLVGAKFGGGDQVSLKAAKSVNLMAAESTFESYSESHNFHASADANLGANAVQGA VGLGLTAGMGTSHQITNETGKTYAGTSVDAANVSIDAGKDLNLSGSRVRGKHVVLDVEGDINATSKQDER NYNSSGGGWDASAGVAIQNRTLVAPVGSAGFNFNTEHDNSRLTNDGAAGVVASDGLTGHVKGDANLTGAT IADLSGKGNLKVDGAVNAQNLKDYRDKDGGSGGLNVGISSTTLAPTVGVAFGRVAGEDYQAEQRATIDVG QTKDPARLQVGGGVKGTLNQDAAQATVVQRNKHWAGGGSEFSVAGKSLKKKNQVRPVETPTPDVVDGPPS RPTTPPASPQPIRATVEVSSPPPVSVATVEVVPRPKVETGSAASASAGGAQVVPVTPPKVEVAKVEVVPR PKVETAQPLPPRPVVAEKVTTPAVQPQLAKVETVQPVKPETTKPLPKPLPVAKVTKAPPPVVETAQPLPP VKPQKATPGPVAEVGKATVTTVQVQSAPPKPAPVAKQPAPAPKPKPKPKPKAERPKPGKTTPLSGRHVVQ QQVQVLQRQASDINNTKSLPGGKLPKPVTVKLTDENGKPQTYTINRREDLMKLNGKVLSTKTTLGLEQTF RLRVEDIGGKNYRVFYETNK Protective antigen A combination of the 69-kDa outer membrane protein and filamentous hemagglutinin (fhaB), both isolated from lymphocytosis promoting factor (LPF; pertussis toxin) minus mutants of Bordetella pertussis, is protective in the mouse intracerebral challenge potency (Kendrick) test [Ref1017:Novotny et al., 1991]. Prn Bordetella pertussis Tohama I VO_0011033 2664290 33592195 BP1054 BX470248 NP_879839 257313 1098090 1100822 + pertactin autotransporter 9.61 86606.91 910 Identical to the previously sequenced Bordetella pertussis pertactin precursor Prn or Omp69A SW:PERT_BORPE (P14283) (910 aa) fasta scores: E(): 0, 100% id in 910 aa, and to Bordetella bronchiseptica pertactin precursor Prn SW:PERT_BORBR (Q03035) (911 aa) fasta scores: E(): 1.4e-160, 91.31% id in 921 aa >NC_002929.2:1098090-1100822 Bordetella pertussis Tohama I chromosome, complete genome AATGAACATGTCTCTGTCACGCATTGTCAAGGCGGCGCCCCTGCGCCGCACCACGCTGGCCATGGCGCTG GGCGCGCTGGGCGCCGCCCCGGCGGCGCATGCCGACTGGAACAACCAGTCCATCGTCAAGACCGGTGAGC GCCAGCATGGCATCCATATCCAGGGCTCCGACCCGGGCGGCGTACGGACCGCCAGCGGAACCACCATCAA GGTAAGCGGCCGTCAGGCCCAGGGCATCCTGCTAGAAAATCCCGCGGCCGAGCTGCAGTTCCGGAACGGC AGTGTCACGTCGTCGGGACAGTTGTCCGACGATGGCATCCGGCGCTTTCTGGGCACCGTCACCGTCAAGG CCGGCAAGCTGGTCGCCGATCACGCCACGCTGGCCAACGTTGGCGACACCTGGGACGACGACGGCATCGC GCTCTATGTGGCCGGCGAACAGGCCCAGGCCAGCATCGCCGACAGCACCCTGCAGGGCGCTGGCGGCGTG CAGATCGAGCGCGGCGCCAATGTCACGGTCCAACGCAGCGCCATCGTCGACGGGGGCTTGCATATCGGCG CCCTGCAGTCATTGCAGCCGGAAGACCTTCCGCCCAGCCGGGTGGTGCTGCGCGACACCAACGTGACCGC CGTGCCCGCCAGCGGCGCGCCCGCGGCGGTGTCTGTGTTGGGGGCCAGTGAGCTTACGCTCGACGGCGGG CACATCACCGGCGGGCGGGCAGCGGGGGTGGCGGCCATGCAAGGGGCGGTCGTGCATCTGCAGCGCGCGA CGATACGGCGCGGGGACGCGCCTGCCGGCGGTGCGGTTCCCGGCGGTGCGGTTCCCGGTGGTGCGGTTCC CGGCGGCTTCGGTCCCGGCGGCTTCGGTCCCGTCCTCGACGGCTGGTATGGCGTGGACGTATCGGGCTCC AGCGTGGAGCTCGCCCAGTCGATCGTCGAGGCGCCGGAGCTGGGCGCCGCAATCCGGGTGGGCCGCGGCG CCAGGGTGACGGTGTCGGGCGGCAGCTTGTCCGCACCGCACGGCAATGTCATCGAGACCGGCGGCGCGCG TCGCTTTGCGCCTCAAGCCGCGCCCCTGTCGATCACCTTGCAGGCCGGCGCGCATGCCCAGGGGAAAGCG CTGCTGTACCGGGTCCTGCCGGAGCCCGTGAAGCTGACGCTGACCGGGGGCGCCGATGCGCAGGGCGACA TCGTCGCGACGGAGCTGCCCTCCATTCCCGGCACGTCGATCGGGCCGCTCGACGTGGCGCTGGCCAGCCA GGCCCGATGGACGGGCGCTACCCGCGCGGTCGACTCGCTGTCCATCGACAACGCCACCTGGGTCATGACG GACAACTCGAACGTCGGTGCGCTACGGCTGGCCAGCGACGGCAGCGTCGATTTCCAGCAGCCGGCCGAAG CTGGGCGGTTCAAGGTCCTGACGGTCAATACGCTGGCGGGTTCGGGGCTGTTCCGCATGAATGTCTTCGC GGACCTGGGGCTGAGCGACAAGCTGGTCGTCATGCAGGACGCCAGCGGCCAGCACAGGCTGTGGGTCCGC AACAGCGGCAGCGAGCCGGCCAGCGCCAACACCCTGCTGCTGGTGCAGACGCCACTAGGCAGCGCGGCGA CCTTTACCCTTGCCAACAAGGACGGCAAGGTCGATATCGGTACCTATCGCTATCGATTGGCCGCCAACGG CAATGGGCAGTGGAGCCTGGTGGGCGCGAAGGCGCCGCCGGCGCCCAAGCCCGCGCCGCAGCCGGGTCCC CAGCCGCCGCAGCCGCCGCAGCCGCAGCCGGAAGCGCCGGCGCCGCAACCGCCGGCGGGCAGGGAGTTGT CCGCCGCCGCCAACGCGGCGGTCAACACGGGTGGGGTGGGCCTGGCCAGCACGCTCTGGTACGCCGAAAG CAATGCGTTGTCCAAGCGCCTGGGCGAGTTGCGCCTGAATCCGGACGCCGGCGGCGCCTGGGGCCGCGGC TTCGCGCAACGCCAGCAGCTGGACAACCGCGCCGGGCGGCGCTTCGACCAGAAGGTGGCCGGCTTCGAGC TGGGCGCCGACCACGCGGTGGCGGTGGCCGGCGGACGCTGGCACCTGGGCGGGCTGGCCGGCTATACGCG CGGCGACCGCGGCTTCACCGGCGACGGCGGCGGCCACACCGACAGCGTGCATGTCGGGGGCTATGCCACA TATATCGCCGACAGCGGTTTCTACCTGGACGCGACGCTGCGCGCCAGCCGCCTGGAGAATGACTTCAAGG TGGCGGGCAGCGACGGGTACGCGGTCAAGGGCAAGTACCGCACCCATGGGGTGGGCGCCTCGCTCGAGGC GGGCCGGCGCTTTACCCATGCCGACGGCTGGTTCCTCGAGCCGCAGGCCGAGCTGGCGGTATTCCGGGCC GGCGGCGGTGCGTACCGCGCGGCCAACGGCCTGCGGGTGCGCGACGAAGGCGGCAGCTCGGTGCTGGGTC GCCTGGGCCTGGAGGTCGGCAAGCGCATCGAACTGGCAGGCGGCAGGCAGGTGCAGCCATACATCAAGGC CAGCGTGCTGCAGGAGTTCGACGGCGCGGGTACGGTACACACCAACGGCATCGCGCACCGCACCGAACTG CGCGGCACGCGCGCCGAACTGGGCCTGGGCATGGCCGCCGCGCTGGGCCGCGGCCACAGCCTGTATGCCT CGTACGAGTACTCCAAGGGCCCGAAGCTGGCCATGCCGTGGACCTTCCACGCGGGCTACCGGTACAGCTG GTA >NP_879839.1 pertactin autotransporter [Bordetella pertussis Tohama I] MNMSLSRIVKAAPLRRTTLAMALGALGAAPAAHADWNNQSIVKTGERQHGIHIQGSDPGGVRTASGTTIK VSGRQAQGILLENPAAELQFRNGSVTSSGQLSDDGIRRFLGTVTVKAGKLVADHATLANVGDTWDDDGIA LYVAGEQAQASIADSTLQGAGGVQIERGANVTVQRSAIVDGGLHIGALQSLQPEDLPPSRVVLRDTNVTA VPASGAPAAVSVLGASELTLDGGHITGGRAAGVAAMQGAVVHLQRATIRRGDAPAGGAVPGGAVPGGAVP GGFGPGGFGPVLDGWYGVDVSGSSVELAQSIVEAPELGAAIRVGRGARVTVSGGSLSAPHGNVIETGGAR RFAPQAAPLSITLQAGAHAQGKALLYRVLPEPVKLTLTGGADAQGDIVATELPSIPGTSIGPLDVALASQ ARWTGATRAVDSLSIDNATWVMTDNSNVGALRLASDGSVDFQQPAEAGRFKVLTVNTLAGSGLFRMNVFA DLGLSDKLVVMQDASGQHRLWVRNSGSEPASANTLLLVQTPLGSAATFTLANKDGKVDIGTYRYRLAANG NGQWSLVGAKAPPAPKPAPQPGPQPPQPPQPQPEAPAPQPPAGRELSAAANAAVNTGGVGLASTLWYAES NALSKRLGELRLNPDAGGAWGRGFAQRQQLDNRAGRRFDQKVAGFELGADHAVAVAGGRWHLGGLAGYTR GDRGFTGDGGGHTDSVHVGGYATYIADSGFYLDATLRASRLENDFKVAGSDGYAVKGKYRTHGVGASLEA GRRFTHADGWFLEPQAELAVFRAGGGAYRAANGLRVRDEGGSSVLGRLGLEVGKRIELAGGRQVQPYIKA SVLQEFDGAGTVHTNGIAHRTELRGTRAELGLGMAAALGRGHSLYASYEYSKGPKLAMPWTFHAGYRYSW Protective antigen Researchers constructed isogenic mutants of B. pertussis Tohama expressing the alleles ptxA1 or ptxA2 and prn1 or prn2 and compared the efficacies of an acellular pertussis vaccine against the mutants in a mouse model. While the vaccine was effective against all of the B. pertussis strains regardless of the allele expression pattern, the strain expressing ptxA1 and prn2 displayed a survival advantage over the other strains [Ref1021:Komatsu et al., 2010]. PtxA Bordetella pertussis Tohama I VO_0011034 2665068 33594638 BP3783 BX470248 NP_882282 257313 3988257 3989066 + pertussis toxin subunit 1 7.54 27989.63 269 Previously sequenced as Bordetella pertussis pertussis toxin subunit 1 precursor, NAD-dependent ADP-ribosyltransferase, PtxA SW:TOX1_BORPE (P04977) (269 aa) fasta scores: E(): 1.5e-110, 100% id in 269 aa >NC_002929.2:3988257-3989066 Bordetella pertussis Tohama I chromosome, complete genome GATGCGTTGCACTCGGGCAATTCGCCAAACCGCAAGAACAGGCTGGCTGACGTGGCTGGCGATTCTTGCC GTCACGGCGCCCGTGACTTCGCCGGCATGGGCCGACGATCCTCCCGCCACCGTATACCGCTATGACTCCC GCCCGCCGGAGGACGTTTTCCAGAACGGATTCACGGCGTGGGGAAACAACGACAATGTGCTCGACCATCT GACCGGACGTTCCTGCCAGGTCGGCAGCAGCAACAGCGCTTTCGTCTCCACCAGCAGCAGCCGGCGCTAT ACCGAGGTCTATCTCGAACATCGCATGCAGGAAGCGGTCGAGGCCGAACGCGCCGGCAGGGGCACCGGCC ACTTCATCGGCTACATCTACGAAGTCCGCGCCGACAACAATTTCTACGGCGCCGCCAGCTCGTACTTCGA ATACGTCGACACTTATGGCGACAATGCCGGCCGTATCCTCGCCGGCGCGCTGGCCACCTACCAGAGCGAA TATCTGGCACACCGGCGCATTCCGCCCGAAAACATCCGCAGGGTAACGCGGGTCTATCACAACGGCATCA CCGGCGAGACCACGACCACGGAGTATTCCAACGCTCGCTACGTCAGCCAGCAGACTCGCGCCAATCCCAA CCCCTACACATCGCGAAGGTCCGTAGCGTCGATCGTCGGCACATTGGTGCGCATGGCGCCGGTGATAGGC GCTTGCATGGCGCGGCAGGCCGAAAGCTCCGAGGCCATGGCAGCCTGGTCCGAACGCGCCGGCGAGGCGA TGGTTCTCGTGTACTACGAAAGCATCGCGTATTCGTTCTA >NP_882282.1 pertussis toxin subunit 1 [Bordetella pertussis Tohama I] MRCTRAIRQTARTGWLTWLAILAVTAPVTSPAWADDPPATVYRYDSRPPEDVFQNGFTAWGNNDNVLDHL TGRSCQVGSSNSAFVSTSSSRRYTEVYLEHRMQEAVEAERAGRGTGHFIGYIYEVRADNNFYGAASSYFE YVDTYGDNAGRILAGALATYQSEYLAHRRIPPENIRRVTRVYHNGITGETTTTEYSNARYVSQQTRANPN PYTSRRSVASIVGTLVRMAPVIGACMARQAESSEAMAAWSERAGEAMVLVYYESIAYSF Protective antigen BALB/c mice were immunized with PTx vaccine on day 6 of life and then challenged with B. pertussis using the aerosol challenge model. These primed mice were significantly better protected against leukocytosis, weight loss, and proliferation of B. pertussis in the lungs following aerosol challenge than the nonprimed group. This protection correlated with levels of anti-PT antibody in serum present on the day of aerosol challenge [Ref1025:Bruss and Siber, 2002]. ptxB Bordetella pertussis VO_0011037 225311180 CDD:308828 CDD:280986 GOA:C0MPK7 InterPro:IPR003899 InterPro:IPR005138 InterPro:IPR008992 InterPro:IPR016187 InterPro:IPR020063 UniProtKB/TrEMBL:C0MPK7 520 ? pertussis toxin subunit 2 precursor 8.37 23698.772 302 Aerolysin/Pertussis toxin (APT) domain; pfam03440 >CAX52304.1 pertussis toxin subunit 2 precursor [Bordetella pertussis] MPIDRKTLCHLLSVLPLALLGSHVARASTPGIVIPPQEQITQHGGPYGRCANKTRALTVAELRGSGDLQE YLRHVTRGWSIFALYDGTYLGGEYGGVIKDGTPGGAFDLKTTFCIMTTRNTGQPATDHYYSNVTATRLLS STNSRLCAVFVRSGQPVIGACTSPYDGKYWSMYSRLRKMLYLIYVAGISVRVHVSKEEQYYDYEDATFET YALTGISICNPGSSLC Protective antigen BALB/c mice were immunized with PTx vaccine on day 6 of life and then challenged with B. pertussis using the aerosol challenge model. These primed mice were significantly better protected against leukocytosis, weight loss, and proliferation of B. pertussis in the lungs following aerosol challenge than the nonprimed group. This protection correlated with levels of anti-PT antibody in serum present on the day of aerosol challenge [Ref1025:Bruss and Siber, 2002]. ptxC Bordetella pertussis VO_0011038 225311183 CDD:308828 CDD:280986 GOA:Q546I1 InterPro:IPR003899 InterPro:IPR005138 InterPro:IPR008992 InterPro:IPR016187 InterPro:IPR020063 UniProtKB/TrEMBL:Q546I1 520 ? pertussis toxin subunit 3 precursor 8.76 24184.712 303 Aerolysin/Pertussis toxin (APT) domain; pfam03440 >CAX52307.1 pertussis toxin subunit 3 precursor [Bordetella pertussis] MLINNKKLLHHILPILVLALLGMRTAQAVAPGIVIPPKALFTQQGGAYGRCPNGTRALTVAELRGNAELQ TYLRQITPGWSIYGLYDGTYLGQAYGGIIKDAPPGAGFIYRETFCITTIYKTGQPAADHYYSKVTATRLL ASTNSRLCAVFVRDGQSVIGACASPYEGRYRDMYDALRRLLYMIYMSGLAVRVHVSKEEQYYDYEDATFQ TYALTGISLCNPAASIC Protective antigen BALB/c mice were immunized with PTx vaccine on day 6 of life and then challenged with B. pertussis using the aerosol challenge model. These primed mice were significantly better protected against leukocytosis, weight loss, and proliferation of B. pertussis in the lungs following aerosol challenge than the nonprimed group. This protection correlated with levels of anti-PT antibody in serum present on the day of aerosol challenge [Ref1025:Bruss and Siber, 2002]. ptxD Bordetella pertussis VO_0011032 225311181 CDD:286372 GOA:C0MPK8 InterPro:IPR008992 InterPro:IPR015355 UniProtKB/TrEMBL:C0MPK8 520 ? pertussis toxin subunit 4 precursor 10.82 15542.962 227 Pertussis toxin S4 subunit; pfam09275 >CAX52305.1 pertussis toxin subunit 4 precursor [Bordetella pertussis] MLRRFPTRTTAPGQGGARRSRVRALAWLLASGAMTHLSPALADVPYVLVKTNMVVTSVAMKPYEVTPTRM LVCGIAAKLGAAASSPDAHVPFCFGKDLKRPGSSPMEVMLRAVFMQQRPLRMFLGPKQLTFEGKPALELI RMVECSGKQDCP Protective antigen BALB/c mice were immunized with PTx vaccine on day 6 of life and then challenged with B. pertussis using the aerosol challenge model. These primed mice were significantly better protected against leukocytosis, weight loss, and proliferation of B. pertussis in the lungs following aerosol challenge than the nonprimed group. This protection correlated with levels of anti-PT antibody in serum present on the day of aerosol challenge [Ref1025:Bruss and Siber, 2002]. ptxE Bordetella pertussis VO_0011039 225311182 CDD:286373 GOA:C0MPK9 InterPro:IPR008992 InterPro:IPR015356 UniProtKB/TrEMBL:C0MPK9 520 ? pertussis toxin subunit 5 precursor 6.49 14292.102 207 Pertussis toxin S5 subunit; pfam09276 >CAX52306.1 pertussis toxin subunit 5 precursor [Bordetella pertussis] MQRQAGLPLKANPMHTIASILLSVLGIYSPADVAGLPTHLYKNFTVQELALKLKGKNQEFCLTAFMSGRS LVRACLSDAGHEHDTWFDTMLGFAISAYALKSRIALTVEDSPYPGTPGDLLELQICPLNGYCE Protective antigen BALB/c mice were immunized with PTx vaccine on day 6 of life and then challenged with B. pertussis using the aerosol challenge model. These primed mice were significantly better protected against leukocytosis, weight loss, and proliferation of B. pertussis in the lungs following aerosol challenge than the nonprimed group. This protection correlated with levels of anti-PT antibody in serum present on the day of aerosol challenge [Ref1025:Bruss and Siber, 2002]. S1 Bordetella pertussis Tohama 3152313 CDD:111768 GOA:Q599G4 HSSP:P04977 InterPro:IPR003898 UniProtKB/TrEMBL:Q599G4 520 ? toxin subunit S1 7.49 28321.94 326 Pertussis toxin, subunit 1; pfam02917 >CAA06899.1 toxin subunit S1 [Bordetella pertussis] MRCTRAIRQTARTGWLTWLAILAVTAPVTSPAWADDPPATVYRYDSRPPEDVFQNGFTAWGNNDNVLDHL TGRSCQVGSSNSAFVSTSSSRRYTEVYLEHRMQEAVEAERAGRGTGHFIGYIYEVRADNNFYGAASSYFE YVDTYGDNAGRILAGALATYQSEYLAHRRIPPENIRRVTRVYHNGITGETTTTEYSNARYVSQQTRANPN PYTSRRSVASIVGTLVRMAPVIGACMARQAESSEAMAAWSERAGEAMVLVYYESIAYSF Protective antigen TcfA Bordetella pertussis 282766137 CDD:154874 520 ? tracheal colonization factor 5.91 62423.78 631 Autotransporter beta-domain; cl02365 >gi|282766137|gb|ADA85103.1| tracheal colonization factor [Bordetella pertussis] MHIYGNMNRATPCRGAVRALALALLGAGMWTLSPPSAWALKLPSLLTDDELKLVLPTGMSLEDFKRSLQE SAPSALATPPSSSPPVAKPGPGSVAEAPSGSGHKDNPSPPVVGVGPGMAESSGGHNPGVGGGTHENGLPG IGKVGGSAPGPDTSTGSGPDAGMASGAGSTSPGASGGAGKDAMPPSEGERPDSGMSDSGRGGESSAGGLN PDGAGKPPREEGEPGSKSPADGGQDGPPPPRDGGDADPQPPRDDGNGEQQPPKGGGDEGQRPPPAAGNGG NGGNGNAQLPERGDDAGPKPPEGEGGDEGPQPPQGGGEQDAPEVPPVAPAPPAGNGVYDPGTHTLTTPAS AAVSLASSSHGVWQAEMNALSKRMGELRLTPVAGGVWGRAFGRRQDVDNRVSREFRQTISGFELGADTAL PVADGRWHVGAVAGYTNGRIKFDRGGTGDDDSVHVGAYATYIEDGGFYMDGIVRVSRIRHAFKVDDAKGR RVRGQYRGNGVGASLELGKRFTWPGAWYVEPQLEVAAFHAQGADYTASNGLRIKDDGTNSMLGRLGLHVG RQFDLGDGRVVQPYMKLSWVQEFDGKGTVRTNDIRHKVRLDGGRTELAVGVASQLGKHGSLFGSYEYAKG S Other Intranasal administration of IEM101 expressing Tcf induced a significant reduction in bacterial colonization of the tracheas of mice challenged with wild-type B. pertussis. These data are in agreement with the putative role of Tcf in Bordetella tracheal colonization [Ref1027:Chen et al., 1998]. 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