Actinobacillus pleuropneumoniae 715 Actinobacillus pleuropneumoniae interacts closely with epithelial cells in the lower respiratory tract and toxins produced during infection are delivered directly to the cell surface. This close association between A. pleuropneumoniae and respiratory epithelial cells may impair the binding of specific antibodies to the Apx toxins, resulting in development of necrosis and hemorrhage (Haesebrouck et al., 2004). porcine pleuropneumonia Protection is mediated by antibodies and mucosal immunity (Shin et al., 2007). Pigs are the main host, and mice can serve as a model of infection (Shin et al., 2007). The bacterium Actinobacillus pleuropneumoniae (App) was previously called Haemophilus pleuropneumoniae and there are at least twelve different strains, some of which produce no disease and are non pathogenic, but others cause very severe disease. Strains 1, 5, 9, 11 and 12 are highly virulent and strains 3 and 6 are very mild. The organism is carried in the tonsils and respiratory tract and the incubation period is very short, from as little as 12 hours through to three days. It is transmitted by droplet infection between one pig and another. The organism may survive in discharges, serum etc. for up to 5 days. Contact with dead stock is therefore important from biosecurity. It dies quickly if dried, but it may persist in water for 20 days or more. App can survive in the lungs and tonsils for long periods of at least 4 months. It is probably airborne for only 5 to 10 metres. Disease is dose dependent i.e. the more bacteria the pig is exposed to the more severe will be the disease. Infection is spread from one pig to another by nose to nose contact. Pigs may be infected with different serotypes simultaneously. PRRS and EP can make the disease worse. In a naïve herd up to 30% of animals may be affected. When App attacks the lungs the toxins produced cause severe damage to the tissues which turn blue to black (necrosis) with extensive pleurisy. The chest cavity rapidly fills up with fluid. The organism may affect the pig from weaning through to slaughter but usually the age is from 8 to 16 weeks, once maternal antibody has disappeared. Sudden death is often the only sign with blood and froth discharged from the nose. In the live pig a short cough may be heard with signs of severe breathing difficulties and blueing of the ears. Badly affected pigs are severely depressed. Body temperature is often high. Death is due to a combination of heart failure and the toxins produced by the organisms (ThePigSite Pig Health). 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 A. pleuropneumoniae apfA vaccine Subunit vaccine Research Intraperitoneal injection (i.p.) Marcol 52 (Esso)-based adjuvant (Zhou et al., 2013). Intraperitoneal injection (i.p.) Recombinant protein preparation Purified recombinant ApfA elicited an elevated humoral immune response and conferred robust protection against challenges with A. pleuropneumoniae serovar 1 strain 4074 and serovar 7 strain WF83 in mice (Zhou et al., 2013). A. pleuropneumoniae ApxIa and ApxIIa protein vaccine VO_0011384 Subunit vaccine Research Saccharomyces cerevisiae Oral immunization Oral immunization A. pleuropneumoniae ApxIa and ApxIIa Recombinant protein preparation The apxIIA gene was cloned from A. pleuropneumoniae serotype 5 isolated from the lungs of Korean pigs with pleuropneumonia. For the oral vaccine, S. cerevisiae expressing ApxIA antigen as well as the ApxIIA antigen were prepared (Shin et al., 2007). Recombinant protein preparation The apxIA gene was cloned from A. pleuropneumoniae serotype 5 isolated from the lungs of Korean pigs with pleuropneumonia. For the oral vaccine, S. cerevisiae expressing ApxIA antigen as well as the ApxIIA antigen were prepared (Shin et al., 2007). BALB/c Briefly, 15 mice per group were subcutaneously injected with 100 µg of protein extract after emulsifying with complete Freund's adjuvant (Sigma, USA). This was then followed by a boost immunization with the same amount of antigens after emulsifying with incomplete Freund's adjuvant (Sigma, USA) at 2 weeks after the initial immunization. The final immunization was performed in the same manner at 2 weeks after the boost immunization. All groups were immunized orally through an oral gavage with 4 doses of Saccharomyces cerevisiae expressing either ApxIA (group C) or ApxIIA (group D) alone or both (group E) at 10-day intervals (Shin et al., 2007). After the challenge, the mice in group E had a significantly lower infectious burden and a higher level of protection than the mice in the other groups (p < 0.05) (Shin et al., 2007). Mice in each group were challenged by intraperitoneal injection of a field isolate of A. pleuropneumoniae serotype 5 at 1.45 × 10^6 CFU (minimal lethal dose, MLD) in 10 days after their final immunization, and were then monitored every 6 h for up to 72 h (Shin et al., 2007). A. pleuropneumoniae ApxIA protein vaccine VO_0011356 Subunit vaccine Research Saccharomyces cerevisiae [Ref1006:Shin et al., 2007] Oral immunization Oral immunization ApxIA (Shin et al., 2007) Recombinant protein preparation The apxIA gene was cloned from A. pleuropneumoniae serotype 5 isolated from the lungs of Korean pigs with pleuropneumonia. For the oral vaccine, S. cerevisiae expressing ApxIA antigen were prepared (Shin et al., 2007) BALB/c Briefly, 15 mice per group were subcutaneously injected with 100 µg of protein extract after emulsifying with complete Freund's adjuvant (Sigma, USA). This was then followed by a boost immunization with the same amount of antigens after emulsifying with incomplete Freund's adjuvant (Sigma, USA) at 2 weeks after the initial immunization. The final immunization was performed in the same manner at 2 weeks after the boost immunization. All groups were immunized orally through an oral gavage with 4 doses of Saccharomyces cerevisiae expressing either ApxIA (group C) or ApxIIA (group D) alone or both (group E) at 10-day intervals (Shin et al., 2007). The immunogenicity of the rApxIA antigen derived from the yeast was confirmed by a high survival rate and an ApxIA-specific IgG antibody response (p <0.01) (Shin et al., 2007). Mice in each group were challenged by intraperitoneal injection of a field isolate of A. pleuropneumoniae serotype 5 at 1.45 × 106 CFU (minimal lethal dose, MLD) in 10 days after their final immunization, and were then monitored every 6 h for up to 72 h (Shin et al., 2007). A. pleuropneumoniae DNA vaccine pcDNA-apxIA/pcDNA-apxIIA VO_0004544 DNA vaccine Research pcDNA3.1 [Ref1003:Chiang et al., 2009] Intramuscular injection (i.m.) Intramuscular injection (i.m.) DNA vaccine construction DNA vaccine construction Significant humoral immune responses were induced by this DNA vaccine through intramuscular immunization. The IgG subclass (IgG1 and IgG2a) analysis indicates that divalent DNA vaccine induces both Th1 and Th2 immune responses (Chiang et al., 2009). Animals immunized with divalent vaccine demonstrated 70% survival after challenge with a dose of 5 × 108 CFU of A. pleuropneumoniae serotype 1 ten days after 2nd boost. Survival was significantly higher than that of the negative control groups (P < 0.05). No protective efficacy was observed for pcDNA3.1 vector immunization group and PBS control group and all mice were died within 24 h (Chiang et al., 2009). Both IgG1 and IgG2a responses were induced by divalent DNA vaccine, with IgG1 slightly higher than IgG2a. The levels of IgG1 and IgG2a were also significant compared with the negative control groups (Chiang et al., 2009). Both IgG1 and IgG2a responses were induced by divalent DNA vaccine, with IgG1 slightly higher than IgG2a. The levels of IgG1 and IgG2a were also significant compared with the negative control groups (Chiang et al., 2009). A. pleuropneumoniae HbpA vaccine Subunit vaccine Research Intramuscular injection (i.m.) Alhydrogel (Chen et al., 2012). Intramuscular injection (i.m.) Recombinant protein preparation he coding sequence of candidate genes were amplified from the genomic DNA of A. pleuropneumoniae JL03. The PCR products were cloned into pET28a and transformed into E. coli DH5α. Positive clones were transformed into E. coli BL21 (DE3) for expression. HbpA induced relatively higher levels of antibody titers compared with the other proteins, reaching 40% protection in mice when challenged with A. pleuropneumoniae JL03(Chen et al., 2012). A. pleuropneumoniae HS93C-Ampr VO_0011385 Live, attenuated vaccine Research A. pleuropneumoniae serovar 7 strain HS93 Intramuscular injection (i.m.) Intramuscular injection (i.m.) A. pleuropneumoniae ApxII-activating protein, ApxIIC Gene mutation Site-specific mutagenesis of the apxIIC gene utilized the recombination plasmid pEP-CAmpr. Cesium chloride-purified pEP-CAmpr DNA was isolated from E. coli and linearized with ClaI. Following digestion, the DNA was purified by phenol-chloroform extraction and ethanol precipitated. A total of 3 μg of linearized DNA was electroporated (0.2-cm-diameter cuvettes; 400 Ω; 1.25 kV) into A. pleuropneumoniae HS93 (serovar 7, ApxII) (Prideaux et al., 1999). Nine 6-week-old pigs received 109 CFU of the A. pleuropneumoniae vaccine strain in 1 ml of growth medium, via intranasal inoculation on day 0, while nine control pigs received 1 ml of BHI. The vaccine was prepared by inoculating 10 ml of BHI-NAD (10 μg/ml) with a single colony of the vaccine strain and growing with shaking at 37°C until an OD600 of 0.8 was reached. The vaccination schedule was repeated on day 14. On day 28, the nine vaccinated and nine control pigs were divided into groups of six and three (Prideaux et al., 1999). Pigs vaccinated with live HS93C- Ampr via the intranasal route were protected against a cross-serovar challenge with a virulent serovar 1 strain of A. pleuropneumoniae (Prideaux et al., 1999). Two groups of six pigs (i.e., vaccinated and unvaccinated) were challenged with 2 × 10^9 A. pleuropneumoniae HS25 (serovar 1) in 2 ml of growth medium via the intranasal route, while the groups of three were given 2 ml of BHI broth in a similar manner. The challenge strain was prepared by inoculating a single colony of HS25 into BHI-NAD (10 μg/ml) and growing until an OD600 of 0.8 was reached. At this time the viable count was 10^9 CFU/ml. At 5 days postchallenge, pigs were euthanized, and the number and severity of lung lesions were recorded (Prideaux et al., 1999). A. pleuropneumoniae OmpW vaccine Subunit vaccine Research Intramuscular injection (i.m.) Alhydrogel (Chen et al., 2012). Intramuscular injection (i.m.) Recombinant protein preparation The coding sequence of candidate genes were amplified from the genomic DNA of A. pleuropneumoniae JL03. The PCR products were cloned into pET28a and transformed into E. coli DH5α. Positive clones were transformed into E. coli BL21 (DE3) for expression. OmpW induced relatively higher levels of antibody titers compared with the other proteins, and reached 40% protection in mice. All OmpW-vaccinated pigs except one developed very mild disease(Chen et al., 2012). A. pleuropneumoniae TonB2 vaccine Live, attenuated vaccine Research subcutaneous injection Complete Freund's adjuvant subcutaneous injection Recombinant protein preparation The tonB2 gene was cloned from Actinobacillus pleuropneumoniae JL01 (serovar 1) and expressed as a glutathione-S-transferase (GST) fusion protein in Escherichia coli BL21(DE3). Purified soluble GST-TonB2 was assessed for its ability to protect BALB/c mice against A. pleuropneumoniae infection. Mice were vaccinated with GST-TonB2 subcutaneously and challenged intraperitoneally with either ~4.0 × 10^5 colony-forming units (CFU) or ~1.0 × 10^6 CFU of A. pleuropneumoniae 4074 (Liu et al., 2011). Actinobacillus pleuropneumoniae apxIA mutant vaccine VO_0002766 Live, attenuated vaccine Research intranasal immunization intranasal immunization Gene mutation This apxIA mutant is from Actinobacillus pleuropneumoniae (Xu et al., 2006). An apxIA mutant is attenuated in pigs (Xu et al., 2006). An apxIA mutant offered a level of cross-serovar protection against A. pleuropneumoniae infection in pigs (Xu et al., 2006). An apxIA mutant is attenuated in mice (Xu et al., 2006). An apxIA mutant offered a level of cross-serovar protection against A. pleuropneumoniae infection in mice (Xu et al., 2006). Actinobacillus pleuropneumoniae ApxIC mutant vaccine VO_0002767 Live, attenuated vaccine Research intranasal immunization To construct an avirulent mutant strain by inactivation of ApxI toxin, the apxIC gene of A. pleuropneumoniae serovar 10 was inactivated by inserting a chloramphenicol resistance gene cassette into the downstream XhoI site of the apxIC gene for constructing the transfer plasmid. The transfer plasmid was introduced into the electrocompetent A. pleuropneumoniae serovar 10 for homologous recombination by electroporation. The mutant strain was obtained and identified by PCR and Southern blotting (Xu et al., 2007). intranasal immunization Gene mutation Actinobacillus pleuropneumoniae apxIIC and apxIVA double deletion mutant vaccine VO_0002769 Live, attenuated vaccine Research Intraperitoneal injection (i.p.) Plasmid pENT1 was used to introduce the ΔapxIVA deletion into A. pleuropneumoniae single mutant ΔapxIIC via the single-step transconjugation system. The colonies with the correct PCR profile were confirmed by Southern blot and sequencing assays (Liu et al., 2007). Intraperitoneal injection (i.p.) Gene mutation Gene mutation BALB/c The LD50 data shown that the double mutant ΔapxIICΔapxIVA was attenuated by three-fold, compared with the single mutant HB04C− (Liu et al., 2007). Two weeks after secondary immunization, all mice were challenged with 10 LD50 of homologous (WF83) (6.0 × 107) and heterologous (1.8 × 106) (S4074) virulent A. pleuropneumonaie by intraperitoneal route. There was no mouse died in groups 1 and 2, which shown a protection efficiency of 100% against homologous challenge (Liu et al., 2007). Actinobacillus pleuropneumoniae apxIIIB and apxIIID double mutant vaccine VO_0002771 Live, attenuated vaccine Research intranasal immunization An apxIIIBD mutant (1536∆B∆D) was selected and the correct mutation was verified by PCR using three primer pairs. The X3BD-F2 and X3BD-R2 primer pair was designed to produce products of 3720 and 4365 bps from the wild-type 1536 and 1536∆B∆D genomes, respectively (Park et al., 2009). intranasal immunization Gene mutation Gene mutation The LD50 of 1536∆B∆D in mice was 6.9 x 10^8 CFU, while that of the wild-type was 4.0 x 10^8 CFU, showing that the mutation of the apxIIIBD genes attenuates the lethality of A. pleuropneumoniae in mice (Park et al., 2009). To evaluate the ability of the mutant 1536∆B∆D strain to protect mice against lethal challenge, mice were immunized with 1536∆B∆D twice and challenged with a lethal dose of wild-type A. pleuropneumoniae 1536. Eight of the nine mice immunized with 1536∆B∆D survived for more than 72 hr after lethal challenge (89% protection), while all eight of the unimmunized mice died by 72 hr after challenge (Park et al., 2009). Actinobacillus pleuropneumoniae HS93Tox-/pIG-T1K vectored vaccine VO_0004607 Recombinant vector vaccine Research A mutant form of Actinobacillus pleuropneumoniae serovar strain HS93, known as HS93Tox- which lacks the genes ApxA (structural toxin) and ApxC (post-translational activating protein) [Ref2889:Prideaux et al., 1998]. Intramuscular injection (i.m.) The HS93Tox-/pIG-T1K vector strain, using an Actinobacillus pleuropneumoniae to express the AxpA gene, was shown to protect mice against Actinobacillus pleuropneumoniae challenges (Prideaux et al., 1998). ApxA gene encodes an A. pleuropneumoniae structural toxin (Prideaux et al., 1998). Because the toxin has been attenuated, this greatly decreases the potential virulence of the vaccine. The HS93Tox- mutant of the serovar 7 strain of Actinobacillus pleuropneumoniae lacks the genes encoding the toxin ApxA and the post-translational activating protein ApxC, but still has genes required for secretion, making it a good vector. A plasmid vector was created to express the ApxA gene inside the HS93Tox- mutant of A. pleuropneumoniae, so that the bacterium acts as a vector for its own natural toxin (Prideaux et al., 1998). Intramuscular injection (i.m.) The inoculation with HS93Tox-/pIG-T1K induced antibodies specific to the Apx gene, and this response was boosted when the mice were re-inoculated (Prideaux et al., 1998). VO_0001030 The mice vaccinated with the HS93Tox-/pIG-T1K strain were protected against both the serovar 7 and serovar 1 challenges, but the mice only inoculated with the HS93Tox- strain not expressing the gene for the AxpA toxin received no protection against the heterologous serovar 1 challenge (Prideaux et al., 1998). The mice inoculated with HS93Tox-/pIG-T1K strain expressing the toxin gene and the HS93Tox- not expressing the toxin gene were challenged with homologous wild-type serovar 7 and heterologous serovar 1 strains of A. pleuropneumoniae (Prideaux et al., 1998). Actinobacillus pleuropneumoniae ureC and apxIIA double mutant deletion vaccine VO_0002768 Live, attenuated vaccine Research aerosol immunization To construct the A. pleuropneumoniae serotype 2 isogenic mutant, 12 clinical isolates were tested initially with respect to their amenability to genetic manipulation via conjugation and cointegration of pBMKUΔ1 (Tonpitak et al., 2002). aerosol immunization Gene mutation Gene mutation In all pigs, an immune response could be detected in the detergent extract enzyme-linked immunosorbent assay (ELISA), and only in the wild-type group six of seven pigs showed elevated levels (>10 ELISA units [EU]) in the ApxIIA ELISA 3 weeks after challenge. These results showed that the A. pleuropneumoniae double-mutant strain is highly attenuated and that the group infected with the mutant strain can be discriminated from the wild-type-infected group based on the ApxIIA ELISA (Tonpitak et al., 2002). A single aerosol application of the attenuated double mutant resulted in protection from clinical disease comparable to that obtained with two applications by using a conventional bacterin vaccine. In addition, immunized pigs were protected significantly from colonization of the lungs (Tonpitak et al., 2002). APP HflX vaccine Subunit vaccine Research subcutaneous injection (Zhang et al., 2016) subcutaneous injection HS93Tox-/pIG-T1K VO_0004637 Recombinant vector vaccine Research Intramuscular injection (i.m.) HS93Tox-/pIG-T1K, expresses the Apx structural protein in a non-activated form (Prideaux et al., 1998). Intramuscular injection (i.m.) Recombinant vector construction HS93Tox-/pIG-T1K, expresses the Apx structural protein in a non-activated form (Prideaux et al., 1998). Mice were vaccinated with alive strain of HS93Tox-/pIG-T1K (Prideaux et al., 1998). VO_0003057 Live vaccination of mice with HS93Tox-/pIG-T1K offered protection against homologous wild-type serovar 7 challenge, and also heterologous challenge with a serovar 1 strain (Prideaux et al., 1998). Mice were challenged with a wild-type serovar 7, and a serovar 1 strain (Prideaux et al., 1998). mixture of Salmonella strains delivering ApxIA, ApxIIA, ApxIIIA and OmpA of A. pleuropneumoniae Recombinant vector vaccine Research intranasal immunization (Hur et al., 2016) intranasal immunization Recombinant vector construction An attenuated Salmonella Typhimurium was used to express ApxIA (Hur et al., 2016). Recombinant vector construction An attenuated Salmonella Typhimurium was used to express OmpA (Hur et al., 2016). Recombinant vector construction An attenuated Salmonella Typhimurium was used to express ApxIIA (Hur et al., 2016). Recombinant vector construction An attenuated Salmonella Typhimurium was used to express ApxIIIA (Hur et al., 2016). The splenic lymphocyte proliferation and the levels of IL-4, IL-6 and IL-12 of the inoculated mice were significantly increased, and the T- and B-cell populations were also elevated. Collectively, the candidate may efficiently induce the Th1- and Th2-type immune responses.(Hur et al., 2016) PleuroStar APP PleuroStar APP Novartis Animal Health VO_0000889 Recombinant vector vaccine Licensed Intramuscular injection (i.m.) Recombinant ApxII, TbpB, CysL, OmlA(1), and OmlA(2) proteins (Van et al., 2001) Intramuscular injection (i.m.) Porcilis APP Porcilis APP Intervet VO_0001158 Recombinant vector vaccine Licensed Intramuscular injection (i.m.) Extracted ApxI, ApxII, ApxIII, and outer membrane proteins (Chiers et al., 1998). Intramuscular injection (i.m.) rS.C-APP-ApxI/ApxII VO_0004785 Recombinant vector vaccine Research Oral immunization The surface-displayed ApxIIA#5 expressing S. cerevisiae and the ApxIA expressing S. cerevisiae (Shin et al., 2013). Oral immunization Recombinant vector construction S. cerevisiae expressing either ApxI or ApxII (Shin et al., 2013). Recombinant vector construction S. cerevisiae expressing either ApxI or ApxII (Shin et al., 2013). Three groups were designated as the untreated pigs (n = 5, control), the pigs fed with the vector-only S. cerevisiae (n = 5, vector control), and the experimental pigs fed with the ApxIA expressing S. cerevisiae and the surface-displayed ApxIIA#5 expressing S. cerevisiae at a time (n = 10, vaccinated group), respectively. The yeast vaccines were followed by three-time administrations with ApxIA (1.5 × 109 CFU) and ApxIIA (1.5 × 109 CFU) with one week interval (Shin et al., 2013). VO_0003057 The vaccinated pigs showed higher specific IgG- and IgA-related antibody activities than the non-treated control and vector control pigs. Additionally, the induced immune responses were found to protect pigs infected with A. pleuropneumoniae according to the analysis of clinical signs and the gross and microscopic pulmonary lesions (Shin et al., 2013). The pigs were challenged intranasally one week after final vaccination with a dose (1.5 × 10^9 CFU) of A. pleuropneumoniae serotype 5 Korean isolate from a pig with porcine pleuropneumonia (Shin et al., 2013). rS.C-APP-ApxIIA VO_0004786 Recombinant vector vaccine Research Oral vaccination (Kim et al., 2010) A neutralizing epitope fragment of ApxIIA toxin was expressed and immobilized on the cell surface of Saccharomyces cerevisiae for efficient vaccine development. Oral vaccination Recombinant vector construction A neutralizing epitope fragment of ApxIIA toxin was expressed on the cell surface of Saccharomyces cerevisiae (Kim et al., 2010). Oral immunization was preceded by overnight fasting of the mice (water was provided ad libitum). Freshly harvested 2.5 x 10^7 or 2.5 x 10^8 cells were dissolved into 1ml of 0.9% saline and orally administered at 200 µl/mouse through an oral gavage at 10 day intervals, 4 times (Kim et al., 2010). VO_0003057 The mice fed the recombinant epitope-expressing yeast were protected from injection of a lethal dose of A. pleuropneumoniae (Kim et al., 2010). The immunized mice were injected intraperitoneally with 200 ml of an A. pleuropneumoniae preparation (about 1 x 10^8 CFU) or buffer control 10 days after the final immunization (Kim et al., 2010). apfA Actinobacillus pleuropneumoniae AAO64346 CDD:331644 228399 major type IV fimbrial subunit precursor 7.91 15710.73 259 ApfA >AAO64346.1 major type IV fimbrial subunit precursor [Actinobacillus pleuropneumoniae serovar 1 str. 4074] MQKLSLIRPLTNAFTLIELMIVIAIIAILATVAIPSYNSYTQKAALSELLAASASYKTDVEICIYNTGDS KNCSGGQNGVRKMTELRQAKYLNAITVEGGTITVTGKGNLQEYGYTMTPIHNGSTISWETKCKGEDLSLF PANFCASN Protective antigen Purified recombinant ApfA elicited an elevated humoral immune response and conferred robust protection against challenges with A. pleuropneumoniae serovar 1 strain 4074 and serovar 7 strain WF83 in mice [Ref4865:Zhou et al., 2013]. apxIA Actinobacillus pleuropneumoniae VO_0011019 312899 CDD:308152 CDD:225483 CDD:311996 GOA:P55128 InterPro:IPR001343 InterPro:IPR003995 InterPro:IPR011049 InterPro:IPR013550 InterPro:IPR018504 InterPro:IPR018511 UniProtKB/Swiss-Prot:P55128 754346 ? 5.41 104857.1 1100 RTX N-terminal domain; pfam02382 >CAA51548.1 apxIA [Actinobacillus pleuropneumoniae serovar 9] MANSQLDRVKGLIDSLNQHTKSAAKSGAGALKNGLGQVKQAGQKLILYIPKDYQASTGSSLNDLVKAAEA LGIEVHRSEKNGTALAKELFGTTEKLLGFSERGIALFAPQFDKLLNKNQKLSKSLGGSSEALGQRLNKTQ TALSALQSFLGTAIAGMDLDSLLRRRRNGEDVSGSELAKAGVDLAAQLVDNIASATGTVDAFAEQLGKLG NALSNTRLSGLASKLNNLPDLSLAGPGFDAVSGILSVVSASFILSNKDADAGTKAAAGIEISTKILGNIG KAVSQYIIAQRVAAGLSTTAATGGLIGSVVALAISPLSFLNVADKFERAKQLEQYSERFKKFGYEGDSLL ASFYRETGAIEAALTTINSVLSAASAGVGAAATGSLVGAPVAALVSAITGIISGILDASKQAIFERVATK LANKIDEWEKKHGKNYFENGYDARHSAFLEDTFELLSQYNKEYSVERVVAITQQRWDVNIGELAGITRKG SDTKSGKAYVDFFEEGKLLEKEPDRFDKKVFDPLEGKIDLSSINKTTLLKFVTPVFTAGEEIRERKQTGK YEYMTELFVKGKEKWVVTGVQSHNAIYDYTNLIQLAIDKKGEKRQVTIESHLGEKNDRIYLSSGSSIVYA GNGHDVAYYDKTDTGYLTFDGQSAQKAGEYIVTKELKADVKVLKEVVKTQDISVGKRSEKLEYRDYELSP FELGNGIRAKDELHSVEEIIGSNRKDKFFGSRFTDIFHGAKGDDEIYGNDGHDILYGDDGNDVIHGGDGN DHLVGGNGNDRLIGGKGNNFLNGGDGDDELQVFEGQYNVLLGGAGNDILYGSDGTNLFDGGVGNDKIYGG LGKDIYRYSKEYGRHIIIEKGGDDDTLLLSDLSFKDVGFIRIGDDLLVNKRIGGTLYYHEDYNGNALTIK DWFKEGKEGQNNKIEKIVDKDGAYVLSQYLTELTAPGRGINYFNGLEEKLYYGEGYNALPQLRKDIEQII SSTGAFTGDHGKVSVGSGGPLVYNNSANNVANSLSYSLAQAA Protective antigen The ApxI antigen is an important factor in the protection against Actinobacillus pleuropneumoniae serotype 5 infection; therefore, the protective immunity in mice following oral immunization with Saccharomyces cerevisiae expressing either ApxIA (group C) or ApxIIA (group D) alone or both (group E) was compared with that in two control groups (group A and B). The immunogenicity of the rApxIA antigen derived from the yeast was confirmed by a high survival rate and an ApxIA-specific IgG antibody response (p < 0.01) [Ref1006:Shin et al., 2007]. apxIA Actinobacillus pleuropneumoniae L20 4850247 126208908 APL_1444 CP000569 YP_001054133 416269 1652926 1655994 - RTX-I toxin determinant A 5.34 104673.05 1022 pubmed:8359891 >gi|126207488:1652926-1655994 Actinobacillus pleuropneumoniae L20, complete genome CTTAAGCAGATTGTGTTAAATAATTACTGAAAGCATTCGGTATGCTATTCGGTGAATTGCTGTAAGCTAA TGGACCGCCTGCTCCCACTAAAACTTGTCCGTGTTCACCGGTAAGTGCACCAGTAGATGAAATGATTTGT TCAATATCTTTTCTGAGTTGAGGAAGTGCATTATATCCTTCTCCATAATACAATTTTTCTTCTAACCCAT TAAAGTAATTGATACCTCTTCCAGGAGCTGTCAGTTCAGTCAGATATTGGCTTAAAACATAAGCTCCATC TTTATCAACGATTTTTTCAATTTTATTATTTTGTCCTTCTTTACCTTCCTTGAACCAATCTTTAATCGTG AGCGCATTCCCATTGTAATCTTCATGGTAATACAGTGTTCCTCCGATTCTTTTATTCACAAGAAGATCAT CACCGATTCTGATAAATCCTACATCTTTAAAACTAAGATCCGATAACAATAACGTATCATCATCACCGCC TTTCTCAATAATGATATGACGACCGTACTCCTTACTGTAGCGATAAATATCCTTACCTAAACCACCGTAG ATTTTGTCATTGCCTACACCACCGTCAAATAAGTTAGTACCATCGCTGCCATACAGAATGTCATTACCCG CACCACCTAATAATACGTTGTATTGACCCTCAAAGACCTGCAACTCATCGTCACCATCACCGCCATTAAG GAAATTATTACCTTTTCCGCCGATTAATCGGTCGTTTCCGTTACCACCAACAAGATGGTCGTTACCGTCA CCGCCATGGATTACATCATTACCGTCGTCTCCGTATAAGATATCGTGGCCGTCATTACCGTAGATTTCAT CATCGCCTTTCGCACCATGGAAAATATCGGTAAAGCGACTACCAAAGAATTTGTCTTTACGATTACTACC GATAATTTCTTCAACAGAATGTAATTCATCTTTAGCTCTGATACCGTTCCCAAGTTCGAATGGGCTTAAC TCATAATCACGATATTCTAATTTTTCACTGCGTTTTCCAACTGAAATATCCTGAGTTTTAACCACTTCTT TTAAAACTTTTACATCAGCTTTAAGTTCTTTAGTGACAATATATTCACCGGCTTTCTGTGCACTTTGTCC GTCAAATGTTAAGTAACCTGTATCGGTTTTATCGTAATATGCTACATCATGTCCGTTACCCGCATATACG ATAGATGAACCGGATGAAAGATATATACGATCATTTTTCTCACCCAAATGAGATTCAATGGTCACTTGAC GTTTTTCACCTTTTTTATCTATCGCTAATTGGATAAGATTCGTATAGTCATAAATCGCATTATGTGACTG CACACCGGTTACCACCCATTTTTCTTTACCTTTAACGAATAATTCGGTCATATATTCGTATTTACCGGTT TGCTTACGCTCACGAATCTCTTCACCTGCGGTAAAAACCGGTGTAATAAATTTCAATAAAGTGGTTTTGT TAATTGAAGAAAGGTCGATTTTGCCTTCAAGCGGATCAAACACTTTTTTATCAAAACGATCCGGATCTTT CTCTAACAATTTTCCTTCTTCAAAGAAATCGACATAAGCCTTACCGCTTTTCGCATCCGCACCTTTACGC GTGATACCGGCAAGTTCCCCGATATTGACATCCCAACGTTGTTGCGTAATAGCAACGACACGCTCTACCG AATACTCTTTATTGTATTGTGATAACAATTCAAAGGTATCTTCTAAGAATGCGGAATGGCGGGCGTCATA ACCGTTTTCAAAATAGTTTTTACCGTGTTTTTTCTCCCATTCGTCAATCTTATTCGCTAATTTCGTTGCA ACTCGTTCGAAGATTGCCTGTTTAGAAGCATCTAAAATACCTGAAATAATACCGGTGATTGCACTAACTA AAGCTGCTACCGGCGCACCGACTAATGAGCCGGTTGCAGCAGCCCCAACACCTGCGGAAGCCGCACTTAA CACACTGTTAATCGTGGTTAATGCCGCTTCAATCGCACCGGTTTCACGGTAGAATGAAGCTAATAAACTA TCACCTTCATAACCGAACTTTTTAAAGCGCTCCGAATATTGTTCAAGCTGTTTCGCACGTTCAAACTTAT CCGCAACATTTAAGAACGAAAGCGGGCTAATCGCTAATGCTACGACCGAACCGATTAAACCACCGGTTGC CGCAGTTGTGGATAAGCCTGCCGCCACACGTTGCGCAATAATATATTGAGAAACCGCTTTACCGATATTG CCTAAGATTTTAGTTGAGATTTCAATACCTGCCGCCGCTTTTGTACCTGCATCGGCATCTTTATTACTTA AAATGAATGAAGCCGAAACAACAGATAAGATACCTGATACGGCATCAAACCCAGGTCCTGCAAGGCTTAA ATCTGGAAGGTTATTTAACTTACTTGCTAAACCGCTTAAGCGAGTGTTAGATAAGGCATTGCCCAATTTA CCTAATTGTTCGGCAAACGCATCCACCGTACCCGTTGCACTTGCAATGTTATCCACTAACTGAGCGGCTA GATCCACACCCGCTTTAGCTAATTCCGAACCACTGACGTCCTCACCGTTTCTACGGCGACGAAGCAGGCT ATCAAGATCCATACCCGCAATAGCCGTACCTAAGAAACTTTGTAAGGCTGAAAGTGCCGTTTGCGTTTTA TTTAAACGTTGTCCTAATGCTTCCGATGAACCGCCGAGCGATTTACTTAATTTTTGGTTCTTATTCAGTA ACTTATCAAACTGAGGTGCAAATAATGCGATGCCTCGTTCCGAGAAACCTAATAGTTTTTCCGTTGTACC GAATAATTCTTTCGCTAGTGCGGTACCGTTTTTTTCCGAGCGATGTACTTCGATCCCTAAAGCCTCCGCC GCTTTCACTAAATCATTAAGACTTGAGCCGGTACTAGCTTGATAATCTTTCGGAATATATAAAATTAATT TCTGCCCTGCTTGCTTCACCTGTCCCAAACCATTTTTTAATGCGCCGGCACCTGATTTAGCTGCACTTTT TGTATGTTGATTAAGTGAATCAATCAATCCTTTGACTCTATCGAGCTGAGAGTTAGCCA >gi|126208908|ref|YP_001054133.1| RTX-I toxin determinant A [Actinobacillus pleuropneumoniae L20] MANSQLDRVKGLIDSLNQHTKSAAKSGAGALKNGLGQVKQAGQKLILYIPKDYQASTGSSLNDLVKAAEA LGIEVHRSEKNGTALAKELFGTTEKLLGFSERGIALFAPQFDKLLNKNQKLSKSLGGSSEALGQRLNKTQ TALSALQSFLGTAIAGMDLDSLLRRRRNGEDVSGSELAKAGVDLAAQLVDNIASATGTVDAFAEQLGKLG NALSNTRLSGLASKLNNLPDLSLAGPGFDAVSGILSVVSASFILSNKDADAGTKAAAGIEISTKILGNIG KAVSQYIIAQRVAAGLSTTAATGGLIGSVVALAISPLSFLNVADKFERAKQLEQYSERFKKFGYEGDSLL ASFYRETGAIEAALTTINSVLSAASAGVGAAATGSLVGAPVAALVSAITGIISGILDASKQAIFERVATK LANKIDEWEKKHGKNYFENGYDARHSAFLEDTFELLSQYNKEYSVERVVAITQQRWDVNIGELAGITRKG ADAKSGKAYVDFFEEGKLLEKDPDRFDKKVFDPLEGKIDLSSINKTTLLKFITPVFTAGEEIRERKQTGK YEYMTELFVKGKEKWVVTGVQSHNAIYDYTNLIQLAIDKKGEKRQVTIESHLGEKNDRIYLSSGSSIVYA GNGHDVAYYDKTDTGYLTFDGQSAQKAGEYIVTKELKADVKVLKEVVKTQDISVGKRSEKLEYRDYELSP FELGNGIRAKDELHSVEEIIGSNRKDKFFGSRFTDIFHGAKGDDEIYGNDGHDILYGDDGNDVIHGGDGN DHLVGGNGNDRLIGGKGNNFLNGGDGDDELQVFEGQYNVLLGGAGNDILYGSDGTNLFDGGVGNDKIYGG LGKDIYRYSKEYGRHIIIEKGGDDDTLLLSDLSFKDVGFIRIGDDLLVNKRIGGTLYYHEDYNGNALTIK DWFKEGKEGQNNKIEKIVDKDGAYVLSQYLTELTAPGRGINYFNGLEEKLYYGEGYNALPQLRKDIEQII SSTGALTGEHGQVLVGAGGPLAYSNSPNSIPNAFSNYLTQSA Virmugen The mutant strain, with deletion of apxIA gene, obtained in this study offered a level of cross-serovar protection against A. pleuropneumoniae infection in mice and pigs [Ref1800:Xu et al., 2006]. ApxIC Actinobacillus pleuropneumoniae 1477456 CDD:154216 715 ? 172 RTX toxin acyltransferase family; cl01131 >gi|1477456|gb|AAB17219.1| apxIC [Actinobacillus pleuropneumoniae] MSKKINGFEVLGEVAWLWASSPLHRKWPLSLLAINVLPAIESNQYVLLKRDGFPIAFCSWANLNLENEIK YLDDVASLVADDWTSGDRRWFIDWIAPFGDSAALYKHMRDNFPNELFRAIRVDPDSRVGKISEFHGGKID KKLASKIFQQYHFELMSELKNKQNFKFSLVNS Virmugen In the intra-peritoneal mouse model, the virulence of the mutant strain decreased at least 100 fold compared with the parent strain. The mutant was evaluated as a potential vaccine using a vaccination-challenge trial. The death number and lung lesion score in the vaccinated pigs given the serovar 1 challenge were obviously lower than those in the unvaccinated pigs [Ref1041:Xu et al., 2007]. apxIIA Actinobacillus pleuropneumoniae VO_0011020 52630374 CDD:280531 CDD:225483 CDD:305016 CDD:285531 715 ? ApxIIA 5.5 96615.24 1024 biovar: 1 >AAU84700.1 ApxIIA [Actinobacillus pleuropneumoniae] MSKITLSSLKSSLQQGLKNGKNKLNQAGTTLKNGLTQTGHSLQNGAKKLILYIPQGYDSGQGNGVQDLVK AANDLGIEVWREERSNLDIAKTSFDTTQKILGFTDRGIVLFAPQLDNLLKKNPKIGNTLGSASSISQNIG KANTVLGGIQSILGSVLSGVNLNELLQNKDPNQLELAKAGLELTNELVGNIASSVQTVDAFAEQISKLGS HLQNVKGLGGLSNKLQNLPDLGKASLGLDIISGLLSGASAGLILADKEASTEKKAAAGVEFANQIIGNVT KAVSSYILAQRVASGLSSTGPVAALIASTVALAVTPLSFLNVADKFKQADLIKSYSERFQKLGYDGDRLL ADFHRETGTIDASVTTINTALAAISGGVGAASAGSLVGAPVALLVAGVTGLITTILEYSKQAMFEHVANK VHDRIVEWEKKHNKNYFEQGYDSRHLADLQDNMKFLINLNKELQAERVVAITQQRWDNQIGDLAAISRRT DKISSGKAYVDAFEGGQHQSYDSSVQLDNKNGIINISNTNRKTQSVLFRTPLLTPGEENRERIQEGKNSY ITKLHIQRVDSWTVTDGDASSSVDFTNVVQRIAVKFDDAGNIIESKDTKIIANLGAGNDNVFVGSSTTVI DGGDGHDRVHYSRGEYGALVIDATAETEKGSYSVKRYVGDSKALHETIATHQTNVGNREEKIEYRREDDR FHTGYTVTDSLKSVEEIIGSQFNDIFKGSQFDDVFHGGNGVDTIDGNDGDDHLFGGAGDDVIDGGNGNNF LVGGTGNDIISGGKDNDIYVHKTGDGNDSITDSGGQDKLAFSDVNLKDLTFKKVDSSLEIINQKGEKVRI GNWFLEDDLASTVANYKATNDRKIEEIIGKGGERITSEQVDKLIKEGNNQISAEALSKVVNDYNTSKDRQ NVSNSLAKLISPVGSFTSSSDFRNNLGTYVPSSIDVSNNIQLARAA Protective antigen The levels of local and systemic antibodies specific to the Apx antigens were investigated in mice orally immunized with Apx antigen-expressing yeast. Specific IgA responses to ApxIA or ApxIIA in the intestines and lungs from mice immunized with yeast expressing Apx antigens were significantly higher than those in the control groups after the second and third immunizations, respectively (p < 0.05). All mice were monitored for up to 72 h after challenge with the MLD of an A. pleuropneumoniae field isolate. Overall, the final survival rates of the vaccinated groups were higher than those of the control groups at each time point [Ref1006:Shin et al., 2007]. apxIIA Actinobacillus pleuropneumoniae serotype 2 255959000 APL_0956 CP000569 YP_001053657 CDD:111291 CDD:116920 715 1095617 1098487 - RTX-II toxin determinant A 5.34 96054.51 956 RTX N-terminal domain; pfam02382 >gi|126207488:1095617-1098487 Actinobacillus pleuropneumoniae L20, complete genome ATTAAGCGGCTCTAGCTAATTGAATATTATTCGAGACATCTATTGATGAAGGAACATATGTTCCTAAATT ATTCCTAAAGTCTGAGGAAGACGTAAAGCTCCCGACTGAAGAAATCAATTTTGCTAAGCTATTAGATACG TTCTGTCTATCTTTACTCGTATTGTAATCATTCACAACTTTGGATAATGCTTCTGCAGAGATTTGATTGT TACCCTCCTTAATCAGTTTATCAACTTGTTCTGATGTAATACGTTCTCCTCCTTTACCAATAATTTCCTC AATTTTTCGGTCATTCGTAGCTTTATAGTTAGCAACTGTGCTAGCCAAATCATCTTCTAAGAACCAATTC CCAATACGAACTTTTTCTCCTTTTTGATTAATGATTTCGAGAGAAGAATCTACTTTCTTAAAGGTGAGGT CTTTAAGATTTACATCCGAAAATGCCAGTGTATCTTGTCCGCCAGAGTCTGTAATAGAATCATTTCCATC GCCTGTTTTATGGACATATATATCATTATCTTTACCTCCCGAGATAATATCATTACCGGTTCCTCCAACA AGGAAATTGTTACCGTTTCCTCCATCGATAACATCATCGCCTGCGCCACCAAATAAATGATCGTCACCAT CGTTACCATCAATAGTGTCTACACCATTACCACCATGGAACACATCATCAAATTGGCTTCCTTTGAAAAT ATCATTAAATTGTGAACCAATGATCTCTTCAACTGATTTGAGTGAGTCCGTCACAGTATAACCAGTATGA AAACGATCATCTTCACGACGATATTCAATTTTTTCTTCACGATTACCAACATTTGTTTGGTGGGTGGCAA TTGTTTCATGTAATGCTTTACTGTCTCCGACATAGCGTTTTACTGAATATGAGCCTTTTTCTGTCTCGGC TGTAGCATCAATAACTAATGCGCCATATTCTCCTCTACTGTAGTGAACTCGATCATGTCCGTCCCCGCCA TCAATAACGGTAGTACTTGACCCAACAAATACATTATCGTTACCAGCACCTAAATTTGCGATAATTTTAG TATCTTTAGATTCGATAATGTTACCTGCATCATCAAATTTCACAGCGATTCGTTGTACTACATTAGTGAA ATCTACGCTTGAGCTAGCATCACCATCTGTTACAGTCCAACTGTCAACTCTTTGTATATGTAATTTTGTA ATATAAGAATTTTTACCTTCCTGAATACGTTCCCGATTCTCTTCACCTGGAGTTAGTAATGGAGTTCTGA ATAAAACACTTTGTGTCTTTCTATTTGTATTACTAATATTAATAATACCGTTTTTGTTATCTAGCTGTAC GGATGAATCGTAGGACTGGTGTTGCCCCTCCTCAAAAGCATCCACATAAGCTTTTCCACTGGAAATTTTA TCCGTTCTACGGCTAATTGCCGCTAGGTCTCCAATTTGGTTATCCCATCTTTGTTGGGTAATAGCTACTA CGCGTTCAGCCTGAAGTTCTTTATTTAAATTGATAAGAAACTTCATATTGTCTTGTAAATCAGCTAAATG ACGAGAATCATAACCTTGCTCAAAATAGTTTTTATTATGTTTTTTCTCCCATTCAACTATTCTGTCATGA ACCTTATTTGCAACATGTTCAAACATGGCTTGTTTAGAATATTCTAGAATAGTTGTAATAAGTCCCGTAA CACCAGCAACGAGTAACGCAACTGGAGCTCCGACTAGAGAACCCGCGCTTGCAGCTCCAACTCCACCGGA GATAGCTGCTAAAGCAGTGTTAATTGTTGTTACAGAAGCATCAATAGTTCCTGTCTCACGGTGAAAATCA GCTAATAAACGATCTCCATCATATCCTAATTTTTGGAAGCGTTCAGAATATGATTTGATTAAATCAGCTT GTTTAAACTTATCAGCTACATTTAAGAATGAAAGAGGGCTAACAGCTAGTGCAACTGTAGATGCGATTAA TGCAGCGACAGGACCAGTTGAAGACAAACCTGAAGCGACTCGTTGGGCAAGAATGTAAGATGAGACCGCT TTTGTTACATTACCTATAATTTGGTTAGCAAATTCTACACCTGCGGCAGCTTTCTTTTCTGTTGAAGCCT CTTTATCTGCTAAAATGAGACCTGCAGATGCTCCAGAAAGTAAACCAGAGATAATGTCCAAACCTAAACT TGCTTTTCCTAGATCTGGTAGATTTTGTAATTTATTACTCAATCCTCCTAATCCTTTCACATTCTGTAAA TGTGAACCTAGTTTAGATATTTGTTCTGCAAATGCATCTACAGTTTGCACCGAGCTAGCAATATTACCAA CTAATTCATTAGTCAGTTCTAGCCCTGCTTTTGCAAGTTCTAATTGATTAGGATCTTTATTTTGAAGTAA TTCATTCAGATTTACTCCAGATAAAACAGATCCTAAAATAGATTGAATACCACCTAATACAGTATTGGCT TTACCTATATTTTGTGAGATGCTAGAAGCACTTCCTAATGTATTGCCAATTTTAGGATTCTTCTTTAATA AATTATCTAGCTGAGGTGCAAATAATACAATTCCTCTATCAGTAAAACCTAGAATTTTCTGAGTTGTATC AAAGCTAGTTTTTGCAATGTCCAAATTGCTGCGTTCTTCTCGCCATACTTCAATACCTAAATCATTAGCA GCTTTAACTAAATCTTGAACTCCATTTCCTTGACCCGAATCATAGCCTTGAGGAATATATAAGATTAATT TTTTAGCCCCATTCTGTAGAGAATGACCAGTTTGAGTTAAACCATTCTTCAGTGTTGTACCTGCTTGATT TAACTTGTTTTTCCCATTTTTCAATCCTTGTTGTAAGGACGATTTTAATGATGACAAAGTGATTTTTGAC A >gi|255959000|gb|ACU43588.1| RTX-II toxin determinant A [Actinobacillus pleuropneumoniae] MSKITLSSLKSSLQQGLKNGKNKLNQAGTTLKNGLTQTGHSLQNGAKKLILYIPQGYDSGQGNGVQDLVK AANDLGIEVWREERSNLDIAKTSFDTTQKILGFTDRGIALFAPQLDNLLKKNPKIGNTLGSASSISQNIG KANTVLGGIQSILGSVLSGVNLNELLQNKDPNQLELAKAGLELTNELVGNIASSVQTVDAFAEQISKLGS HLQNVKGLGGLSNKLQNLPDLGKASLGLDIISGLLSGASAGLILADKEASTEKKAAAGVEFANQIIGNVT KAVSSYILAQRVASGLSSTGPVAALIASTVALAVSPLSFLNVADKFKQADLIKSYSERFQKLGYDGDRLL ADFHRETGTIDASVTTINTALAAISGGVGAASAGSLVGAPVALLVAGVTGLITTILEYSKQAMFEHVANK VHDRIVEWEKKHNKNYFEQGYDSRHLADLQDNMKFLINLNKELQAERVVAITQQRWDNQIGDLAAISRRT DKISSGKAYVDAFEEGQHQSYDSSVQLDNKNGIINISNTNRKTQSVLFRTPLLTPGEENRERIQEGKNSY ITKLHIQRVDSWTVTDGDASSSVDFTNVVQRIAVKFDDAGNIIESKDTKIIANLGAGNDNVFVGSSTTVI DGGDGHDRVHYSRGEYGALVIDATAETEKGSYSVKRYVGDSKALHETIATHQTNVGNREEKIEYRREDDR FHTGYTVTDSLKSVEEIIGSQFNDIFKGSQFDDVFHGGNGVDTIDGNDGDDHLFGGAGDDVIDGGNGNNF LVGGTGNDIISGGKDNDIYVHKTGDGNDSITDSGGQDKLAFSDVNLKDLTFKKVDSSLEIINQKGEKVRI GNWFLEDDLASTVANYKATNDRKIEEIIGKGGERITSEQVDKLIKEGNNQISAEALSKVVNDYNTSKDRQ NVSNSLAKLISSVGSFTSSSDFRNNLGTYVPSSIDVSNNIQLARAA Virmugen Deletion in ureC and apxIIA genes of Actinobacillus pleuropneumoniae serotype 2 prototype provides attenuation and protection in pigs against challenge with the virulent parent strain of A. pleuropneumoniae [Ref1042:Tonpitak et al., 2002]. ApxIIC Actinobacillus pleuropneumoniae 52630373 CDD:154216 715 ? ApxIIC 160 biovar: 1 >gi|52630373|gb|AAU84699.1| ApxIIC [Actinobacillus pleuropneumoniae] MMLKNDFNVLGQIAWLWANSPMHRNWSVSLLMKNVIPAIENDQYLLLVDDGFPIAYCSWAKLTLESEARY VKDTNSLKIDDWNAGDRIWIIDWIAPFGDSSLLYKHMRQRFPYDIGRAIRIYPSKKDTGKIIYLKGGKIT KKVAEKTFLQYEQELITALQ Virmugen In the present study, the gene encoding the ApxII-activating protein, apxIIC, was insertionally inactivated on the chromosome of a serovar 7 strain, HS93. Pigs vaccinated with live HS93C-Ampr via the intranasal route were protected against a cross-serovar challenge with a virulent serovar 1 strain of A. pleuropneumoniae [Ref1040:Prideaux et al., 1999]. apxIIIA Actinobacillus pleuropneumoniae CAA48711 CDD:308152 CDD:225483 CDD:311996 GOA:P55131 InterPro:IPR001343 InterPro:IPR003995 InterPro:IPR011049 InterPro:IPR013550 InterPro:IPR018504 InterPro:IPR018511 UniProtKB/Swiss-Prot:P55131 715 ApxIIIA 5.56 107581.37 1123 RTX N-terminal domain; pfam02382 >CAA48711.1 apxIIIA [Actinobacillus pleuropneumoniae] MSTWSSMLADLKKRAEEAKRQAKKGYDVTKNGLQYGVSQAKLQALAAGKAVQKYGNKLVLVIPKEYDGSV GNGFFDLVKAAEELGIQVKYVNRNELEVAHKSLGTADQFLGLTERGLTLFAPQLDQFLQKHSKISNVVGS STGDAVSKLAKSQTIISGIQSVLGTVLAGINLNEAIISGGSELELAEAGVSLASELVSNIAKGTTTIDAF TTQIQNFGKLVENAKGLGGVGRQLQNISGSALSKTGLGLDIISSLLSGVTASFALANKNASTSTKVAAGF ELSNQVIGGITKAVSSYILAQRLAAGLSTTGPAAALIASSISLAISPLAFLRVADNFNRSKEIGEFAERF KKLGYDGDKLLSEFYHEAGTIDASITTISTALSAIAAGTAAASAGALVGAPITLLVTGITGLISGILEFS KQPMLDHVASKIGNKIDEWEKKYGKNYFENGYDARHKAFLEDSFSLLSSFNKQYETERAVLITQQRWDEY IGELAGITGKGDKLSSGKAYVDYFQEGKLLEKKPDDFSKVVFDPTKGEIDISNSQTSTLLKFVTPLLTPG TESRERTQTGKYEYITKLVVKGKDKWVVNGVKDKGAVYDYTNLIQHAHISSSVARGEEYREVRLVSHLGN GNDKVFLAAGSAEIHAGEGHDVVYYDKTDTGLLVIDGTKATEQGRYSVTRELSGATKILREVIKNQKSAV GKREETLEYRDYELTQSGNSNLKAHDELHSVEEIIGSNQRDEFKGSKFRDIFHGADGDDLLNGNDGDDIL YGDKGNDELRGDNGNDQLYGGEGNDKLLGGNGNNYLSGGDGNDELQVLGNGFNVLRGGKGDDKLYGSSGS DLLDGGEGNDYLEGGDGSDFYVYRSTSGNHTIYDQGKSSDLDKLYLSDFSFDRLLVEKVDDNLVLRSNES SHNNGVLTIKDWFKEGNKYNHKIEQIVDKNGRKLTAENLGTYFKNAPKADNLLNYATKEDQNESNLSSLK TELSKIITNAGNFGVAKQGNTGINTAALNNEVNKIISSANTFATSQLGGSGMGTLPSTNVNSMMLGNLAR AA Protective antigen The splenic lymphocyte proliferation and the levels of IL-4, IL-6 and IL-12 of the inoculated mice were significantly increased, and the T- and B-cell populations were also elevated. Collectively, the candidate may efficiently induce the Th1- and Th2-type immune responses.[Ref4696:Hur et al., 2016] apxIIIB Actinobacillus pleuropneumoniae serovar 2 470686 CDD:30270 CDD:162558 CDD:186074 CDD:73011 34063 ? RTX toxin A sub-family of peptidase C39 which contains Cyclolysin and Hemolysin processing peptidases. Peptidase family C39 mostly contains bacteriocin-processing endopeptidases from bacteria. The cysteine peptidases in family C39 cleave the 'double-glycine'...; cd02417 >gb|L12145.1|ACNNON:3943-6078 Actinobacillus pleuropneumoniae (serotype 2) RTX toxin III (apxIII CABD) genes, complete cds ATGGAGTCACAAATGCCTTTTAACGAAAAAATAGATTACGGATTACATGCATTGGTAATTCTCGCGCAAT ATCACAATGTTGCCGTAAACCCTGAAGAGGTAAAACATAAATTTGATCTTGATGGCAAAGGATTGGATCT TGTTGCTTGGTTATTAGCAGCAAAATCATTAGAATTAAAAGTCAAACGAGTAAAAAAGAGTATTGAGCGT TTACCATTTATTCATCTTCCTGCTTTAATCTGGCGAGATGATGGTCAACACGTTATTTTGATGAAAATTG ACACCCAAACTAACCGTTACCTTATTTTTGACTTAGAAGAACGAAACCCTAAAGTACTAAGTGCGGCTGA ATTTCACGAAATTTTTCAAGGTGGTATGATTCTTATTACTTCACGAGCTTCTATTATGGGGCAATTGGCG AAGTTTGATTTCACTTGGTTTATCCCCGCAGTAATTAAATACCGTAAAATTTTTGTAGAAACTATTATTG TTTCTATTTTTTTGCAGCTTTTTGCACTAATTACTCCCTTATTTTTCCAAGTTGTGATGGATAAAGTTCT TGTCCATCGTGGATTTTCTACACTTAATGTTATCACGGTTGCATTATCTGTAGTGGTTATCTTTGAAATT GTATTAAGCGGTCTACGGACTTATATATTTTCCCATAGCACTAGCCGAATTGATGTAGAACTTGGTGCAA AATTATTTCGTCACTTGTTAGCGTTACCTATTTCTTATTTCGAAAATAGACGTGTAGGTGACACAGTTGC TCGAGTACGAGAATTGGATCAAATACGCAATTTTTTAACAGGTCAGGCACTTACCTCTGTATTAGATCTC TTATTCTCTTTTATTTTCTTTGCAGTGATGTGGTATTACAGCCCAAAACTAACTATTGTGATTTTACTTT CATTACCTTGTTATATCGCATGGTCAATATTTATTAGCCCAATATTACGTCGTCGTCTAGATGAAAAATT TGCTCGTAATGCTGATAATCAATCTTTTTTAGTTGAATCTGTTTCTGCAATAGACACGATCAAGGCTCTT GCTGTAACACCTCAAATGACAAATATTTGGGATAAACAGTTAGCAAGTTATGTATCAGCAGATTTTAGAG TGACAGTATTGGCAACTATTGGACAGCAAGGTGTACAACTTATCCAAAAAACAGTAATGATAATTAATTT ATGGTTAGGTGCACATTTAGTAATTTCAGGGGATCTTAGCATTGGACAATTAATTACTTTTAATATGCTT TCAGGACAAGTTATTGCACCTGTAGTTCGTTTAGCACAATTGTGGCAAGACTTTCAACAAGTAGGAATTT CTATTACACGATTGGGAGATGTCTTAAATTCACCTACAGAAAATTATCAAGGTAAGCTTTCACTACCAGA AATCTTTGGGGATATCGCATTTAAACATATTCGCTTTCGCTATAAGCCCGATGCTCCAATCATTTTAGAT GATGTAAATTTATCGGTTAAACAGGGGGAAGTTATTGGGATAGTAGGACGTTCAGGTTCAGGTAAAAGTA CTCTCACTAAATTATTACAACGTTTTTATATTCCGGAAAATGGCCAAGTATTGATTGATGGTCACGATCT TGCGCTTGCTGATCCTAATTGGTTACGTCGTCAAATTGGTGTTGTTTTACAAGATAATGTGTTATTAAAC CGTAGTATTCGCGATAATATCGCACTCACTGATCCAAGCATGTCTATGGAACGTGTTATCTATGCGGCAA AATTAGCAGGGGCACATGATTTTATTTCTGAATTACGTGAAGGTTACAATACTATTGTAGGAGAGCTTGG TGCAGGCTTATCTGGTGGACAACGTCAACGGATTGCTATTGCACGAGCTTTAGTCAATAACCCTAGGATT TTGATTTTTGATGAGGCGACAAGTGCATTAGATTATGAATCTGAACATATCATTATGCAAAATATGCAAA AAATCTGCCATGGACGGACAGTAATCATTATTGCCCACCGTCTTTCTACAGTAAAAAATGCGGATCGCAT TATTGTTATGGAAAAGGGACATATTGTAGAGCAAGGTAAACATAACCAATTACTGGAAAATGAAAATGGA CTCTATTATTACCTCAACCAACTACAATCAAATTAA Virmugen An apxIIIB mutant, in combination with an apxIIID mutation, is highly attenuated in pigs and induces significant protection from challenge with wild type A. pleuropneumoniae. The mutant also was slightly attenuated in mice and induced protection in mice against challenge from the parent strain [Ref1907:Park et al., 2009]. apxIIID Actinobacillus pleuropneumoniae serovar 2 470687 CDD:130902 34063 ? RTX toxin type I secretion membrane fusion protein, HlyD family; TIGR01843 >gb|L12145.1|ACNNON:6090-7523 Actinobacillus pleuropneumoniae (serotype 2) RTX toxin III (apxIII CABD) genes, complete cds ATGAAGTTATGGATTCTAGGACTTGGGGAATTTTTTCAACGTTATCGTAATATTTGGCGTGAAATATGGA AAATCCGCAAACAATTAGATACCCCAGCAAGACAAAAAGATGAAAACGAATTTTTGCCTCGGCATTTAGA GTTAATTGAGACACCTATTTCAAAAAAGCCACGGCTGATCGCTTATTTGATAATGCTATTTCTATTTTTA GCTATTGTAATTTCCATTATTAGTAAAGTAGAAATTGTTGCTAGTGCTACAGGTAAGTTGGTATTTAGTG GACATAGTAAAGAAATAAAGCCTATTGAGAATGCTTTAGTAAAAGACATTTTTGTTAAAGATGGACAATT TGTTGAAAAAGGACAATTATTATTAAATCTCACCGCACTTGGCTGCGATGCAGACAAACAAAAAACTAAA GTATCGTTAGGATTGGAAAGATTAGATGGTTACCGATATAAGTCATTGTTATATAGCATTGAACACAATA GATTACCTTTATTGGATTTTAACCAAGCTGATTTTGATTCTGTTCAGGAAGAAGATAAGACTGGCGCACG TCATTTAATTACCGAACAATTTGAGACTTGGCAAAAACAAAAATATCAGAAGGAATTAGCGTATCAACGT AAACAAGCTGAAAAACAAACAGTATTAGCAAATATCCGTAAATATGAAAGCGCTAGTCGTATTGAAAAGG AGAAATTAAGTGATTTAAAAAAATTATATGATGTAAAGTCTATTTCTAAGCATGAGTTGTTAGCACAAGA AAATAGATATGTTGAAGCTAGTAATGAATTGTCTGTTTATCAATCTCATCTCAAAGAAGTAGAAAGTGAC TTGCTTAAAGCACAAGAAGATTTAAAGCTTGTTACTCAATTATTTAAGAGTGATATTTTGGAAAAACTAC AGCAAAATATACAACGCGAAAAGCAGCTCACTTTAGAACTTGAGAAAAATGAACAACGTCAATTAGCCTC TATCATTAGGGCGCCAGTATCAGGCACAGTCCAACAATTAAAAACTCATACTAAAGGTGGCGTAGTAACT ACTGCAGAAACCTTAATGGTCATTGCTCCTGAGGATGACGTGTTGGAAGTAAGTGCTTTAATTCAAAACA AAGATGTTGGTTTTGTTGAAATTGGACAGGAAGCAGTTATTAAAGTGGAAACTTTTCCCTACACAAGATA TGGTTATCTCTATGGAAAAGTAAAAACTATTACTCTTGATGCTATTGAGCACCCTCAGCTTGGTTTAGTT TTCAATTCTATTATTGAGATTAACAAGAAAACATTAACAGATGGTGATAAAGAAATTCAATTAGGTTCTG GAATGAGCGTTATTGCAGAAATTAAAACAGGAGAACGCAGTGTTATCAGTTTCCTACTCAGTCCATTAGA AGAATCTATTACTGAAAGTCTAAGAGAACGTTAA Virmugen An apxIIID mutant, in combination with an apxIIIB mutation, is highly attenuated in pigs and induces significant protection from challenge with wild type A. pleuropneumoniae. The mutant also was slightly attenuated in mice and induced protection in mice against challenge from the parent strain [Ref1907:Park et al., 2009]. ApxIVA Actinobacillus pleuropneumoniae 6671152 CDD:164328 CDD:116920 715 ? ApxIVA 130 Peptidase M10 serralysin C terminal; cl12108 >gi|6671152|gb|AAF23114.1| ApxIVA [Actinobacillus pleuropneumoniae] DWGRNSVIDAGAGNDTVNGGYGDDTLIGGKGNDILKGSYGADTYLFSKGHGQDVIYEYSNSASSTSDIDT LKFTDIGLSELWFSRENNDLIIKSLLSEDKVTVQNWYSHQDHKIENIRLSNEQMLVSTQV Virmugen A precisely defined DeltaapxIICDeltaapxIVA double-deletion mutant of A. pleuropneumoniae was constructed based on HB04C(-) by transconjugation and counterselection. The results demonstrated that the DeltaapxIICDeltaapxIVA double mutant strain was less virulent than HB04C(-). Despite attenuation of virulence, the DeltaapxIICDeltaapxIVA double mutant remains immunogenic and conferred a similar level of protective immunity to pigs against challenge with a lethal dose of a heterologous fully virulent standard serovar 1 strain of A. pleuropneumoniae [Ref1043:Liu et al., 2007]. hbpA Actinobacillus pleuropneumoniae ABN75084 CDD:223818 CDD:173858 416269 Heme-binding protein A 6.89 57811.6 643 ABC-type transport system, periplasmic component [Amino acid transport and metabolism]; COG0747 >ABN75084.1 Heme-binding protein A [Actinobacillus pleuropneumoniae serovar 5b str. L20] MKLANLTKVSAAVLAVLALAACDDKNADGKTTAKPAAEKTFVNCVSRSPQYFSPALAMDGISYNASSQQV YNRLVEFKRGSTEIEPALAESWDISEDGLTYTFHLRKGVKFHSNKEFTPSRDFNADDVVFSFNRQLDPNH PYHTVSKATYPYFKAMKFPTLLKSVEKVDDHTVKFTLTKRDATFVSSLGMDFTSIYSAEYADAMLKAGKP ETIDTTPIGTGPFAFTGYVLDQASRYVAYKDYWKGKADFDRLIFEIVPDATARYAKLQAGQCDLIDFPNA TDIEKMKTDPKVQLLSQPGLNIAYVAFNTEKAPFDNVKVRQALNLAVDKKAIIDVVYQGAGIAAKNPLPP TIWGYNDSLAESEFNIEKAKQLLAEAGYPNGFETELWVQPVVRASNPNPRRMSEIIQADWAKIGVKAKLV TYEWGDYIKRTKAGELTAGTYGWSGDNGDPDNFLSPLFGSANVGNSNYARFNSPELDALLDKALGLSDKA ERTKLYEQAQALLREQAPWINVAHSINFAPTSKRVQDYKQSPFGYTYLYGTKLAD Protective antigen Three of these proteins (APJL_0126, HbpA and OmpW) were further tested in the natural host (swine) by homologous and heterologous challenges. The results showed that these proteins could induce high titers of antibodies[Ref4928:Chen et al., 2012] Ighg1 Mus musculus 16017 AC160982 Vaximmutor Ighv1-9 Mus musculus 668478 AC073561 10090 12 114583568 114583861 immunoglobulin heavy variable V1-9 Also known as Igg2a; Gm16697 >gi|372099098:114583568-114583861 Mus musculus strain C57BL/6J chromosome 12, GRCm38 C57BL/6J GTCTTGCACAGTAATAGATGGCAGAGTCCTCAGTTGTCAGGCTGCTGAGTTGCATGTAGGCTGTGTTGGA GGATGTATCTGCAGTGAATGTGGCCTTGCCCTTGAACTTCTCATTGTAGTTAGTACTACCACTTCCAGGT AAAATCTCTCCAATCCACTCAAGGCCATGTCCAGGCCTCTGCTTTACCCACTCTATCCAGTAGCCAGTGA ATGTGTAGCCAGTAGCCTTGCAGGAAAGCTTCACTGAGGCCCCAGGCTTCATCAGCTCAGCTCCAGACTG CTGCAGCTGAACCT Vaximmutor ompA Actinobacillus pleuropneumoniae ABV82725 ATCC:27088 CDD:332966 CDD:143586 715 OmpA 5.45 26230.02 286 Peptidoglycan binding domains similar to the C-terminal domain of outer-membrane protein OmpA; cl28145 >ABV82725.1 OmpA [Actinobacillus pleuropneumoniae] MQIDFSKLKLQQQESEDSQWLPVSDLMSGLMILFLFIAVSFILNAKRVADNYQDNQEKIYQALQTEFSPK LKDWKAKIDKDTLTFIFTDPEVLFETGRSDLNAPFKKILDDFFPRYMKVVDNYKTSISEIRIEGHTSTEW DHKSSDDMAYFLNMQLSQDRTRSVLIYLYQLENIAQYRDWIKSNLSAVGLSSSKTIKNTQGIEDKEASKR VTFRIITNAEEQLRKLSEIK Protective antigen The splenic lymphocyte proliferation and the levels of IL-4, IL-6 and IL-12 of the inoculated mice were significantly increased, and the T- and B-cell populations were also elevated. Collectively, the candidate may efficiently induce the Th1- and Th2-type immune responses.[Ref4696:Hur et al., 2016] ompW Actinobacillus pleuropneumoniae ASU14913 CDD:328747 715 Outer membrane protein W 8.7 21467.67 291 Porin superfamily. These outer membrane channels share a beta-barrel structure that differ in strand and shear number. Classical (gram-negative) porins are non-specific channels for small hydrophillic molecules and form 16 beta-stranded barrels (16,20)...; cl21487 >ASU14913.1 Outer membrane protein W [Actinobacillus pleuropneumoniae] MKKAVLAAVLGGALLADSAMAHQAGDVIFRAGAIGVIANSSSDYQTGADVNLDVNNNIQLGLTGTYMLSD NLGLELLAATPFSHKITGKLGATDLGEVAKVKHLPPSLYLQYYFFDSNATVRPYVGAGLNYTRFFSAESL KPQLVQNLRVKKHSVAPIANLGVDVKLTDNLSFNAAAWYTRIKTTADYDVPGLGHVSTPITLDPVVLFSG ISYKF Protective antigen APJL_0126, HbpA and OmpW were further tested in the natural host (swine) by homologous and heterologous challenges., showing that these proteins could induce high titers of antibodies, but vaccination with each protein individually elicited low protective immunity against A. pleuropneumoniae.[Ref4928:Chen et al., 2012] tonB2 Actinobacillus pleuropneumoniae serovar 2 str. S1537 AAR95695 CDD:330347 CDD:281534 715 TonB2 10.26 28571.46 343 TonB N-terminal region; cl25526 >AAR95695.1 TonB2 [Actinobacillus pleuropneumoniae] MKKKHSRIGLTGSILIHTAIFGGLASMVTHSHSDDLPQEETMSMELVAALLEQPQVAVAQEEPAPPEPEK VEVEPEPEPEAEAIPELKPQPKPKEKPKEKPKEKPKPKEPPKPKEKEKPKKEKVKDKPIKALEKGPEAKQ GIVAKAIPNAVQGTQLRAGIPNGKPEGNPNGLSANGSQNGAVGGSGSGASGSEIGAYKAALQRALQRRAN NAYPTREKMMRKTGVVTIGFTVSSSGELINVKVLNSSGNGNLDNAAVKAAQSTKVSPPPAGFPSNVTVPV KFSIE Protective antigen The survival rate of the TonB2-vaccinated mice was significant higher than that of the mice given recombinant GST or adjuvant alone.[Ref4699:Liu et al., 2011] ureC Actinobacillus pleuropneumoniae serovar 2 303253439 CDD:183894 CDD:30031 754254 ? urease subunit alpha 572 urease subunit alpha; Reviewed; PRK13207 >gi|303253439|ref|ZP_07339581.1| urease subunit alpha [Actinobacillus pleuropneumoniae serovar 2 str. 4226] MALIIPRSQYVATYGPTVGDKVRLGDTDLWATIEQDFLTKGDECKFGGGKSVRDGMAQSSTATRDNPNVL DFALTNVMIIDAKLGIIKADIGIRDGRIVGIGQAGNPDTMDNVTPNMIIGASTEVHNGAHLIATAGGIDT HIHWICPQQAQHAIENGITTMIGGGSGPADGTHATTCTPGKFNIERMFQACEALPVNIGFFGKGNCSMLE PLKEQVVAGALGLKIHEDWGATPAVIDAALKVADEMDVQVAIHTDTLNESGFLEDTMKAINGRVIHTFHT EGAGGGHAPDIIKAAMYPNVLPASTNPTRPFTVNTIDEHLDMLMVCHHLDKRVPEDVAFADSRIRPETIA AEDILHDMGVFSIMSSDSQAMGRVGEVVTRTWQTADKMKAQRGALGDEGNDNFRIKRYIAKYTINPAIAH GICQYVGSLEVGKLADIVLWKPQFFGVKPEFVMKKGFISFAKMGDPNASIPTPQPVFYRPMFGANAKANT ESAVYFVSQASVDANIKAQYGIQKETLAVKGCRDVGKKDLVHNNATPEITVDPERYEVRVDGEHITCEPA TKVPLAQRYFLF Virmugen Deletions were introduced into the ureC and apxIIA genes of an Actinobacillus pleuropneumoniae serotype 2 strain by homologous recombination and counterselection. The double-mutant contains no foreign DNA, is highly attenuated, protects pigs from homologous challenge upon a single aerosol application [Ref1042:Tonpitak et al., 2002]. 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