Um total de 123 isolados de Pasteurella multocida provenientes de suínos foi avaliado através da PCR para pesquisa de genes codificadores de capsula, toxina dermonecrótica e outros fatores de virulência. As amostras foram caracterizadas como tipo capsular A (78,8 %) e tipo capsular D (21%). Nenhum dos isolados foi positivo para presença de toxina dermonecrótica. Os genes codificadores dos fatores de virulência pesquisados foram observados nas freqüências de 93,5 % para nanB, 92,7% para psl, 91,9% para oma87 e nanH, 87,8% para sodA,87% para hghA,83,7% para ompH, 82,9% para sodC, 79,7% para ptfA e exbBD tonB,73,2% para hgbB, 14,6% para pfhA e 4,9% para tbpA. Estes achados são compatíveis com o descrito na literatura internacional. / A total of 123 Pasteurella multocida strains from swine was evaluated through PCR to detect capsular, dermonecrotic toxin codifying genes and others virulence factors. The strains were identified as capsular type A (78.8 %) and capsular type D (21%). None of isolates were positive to dermonecrotic toxin gene. The virulence factors genes were detected in the following frequency: 93.5 % to nanB, 92.7% to psl, 91.9% to oma87 and nanH, 87.8% to sodA, 87% to hghA, 83.7% to ompH, 82.9% to sodC, 79.7% to ptfA and exbBD tonB, 73.2% to hgbB, 14.6% to pfhA and 4.9% to tbpA. These findings were in accordance with international literature.

Pasteurella multocida é um dos principais patógenos envolvidos nas broncopneumonias infecciosas em suínos. Apesar de ser considerada agente secundário à pneumonia enzoótica causada pelo Mycoplasma hyopneumoniae e por agentes virais como o vírus da influenza suína, há evidências do seu envolvimento como agente primário. Neste contexto, o primeiro estudo desenvolvido teve como objetivo desenvolver um método de reprodução experimental de pneumonia por P. multocida A cepa 11246 em suínos infectados com diferentes concentrações de inóculo. Um segundo estudo foi desenvolvido com o objetivo de demonstrar diferenças fenotípicas, moleculares e patogênicas entre cepas de P. multocida A isoladas de casos clínicos de pneumonia em granjas comerciais de suínos de vários estados brasileiros. No primeiro experimento os suínos foram desafiados por gotejamento intranasal lento com inóculo de diferentes concentrações de P. multocida A cepa 11246 [Grupo (G1): 108 Unidades Formadoras de Colônias (UFC)/ml; G2: 107 UFC/ml; G3: 106 UFC/ml e G4: 105 UFC/ml]. Foram utilizados dois suínos por grupo com aproximadamente 100 dias de idade. Neste, todas as concentrações de inóculo demonstraram a capacidade da bactéria em causar doença respiratória grave e septicemia nos animais inoculados. Utilizando-se a mesma metodologia de desafio, com inóculo de 107 UFC/ml, o segundo estudo, ao desafiar 64 suínos igualmente distribuídos em oito grupos (G1 a G8) com oito diferentes cepas de P. multocida A (uma cepa por grupo), os resultados demonstraram a presença de cepas muito patogênicas (G1-11246, G2-11229, G3-16614 e G7-17044); pouco patogênicas (G4-16618 e G5-16972); e apatogênicas (G6-17034 e G8-17078), de acordo com a gravidade das alterações clinico-patológicas desenvolvidas. Na avaliação patológica dos animais desafiados, observaram-se três padrões de lesões distintas, associadas ou não entre si: 1. broncopneumonia fibrinonecrótica cranioventral com pleurite fibrinosa (G1, G3, G7); 2. pleurite difusa uni ou bilateral, associada ou não com pericardite e peritonite (G3, G5, G7) e; 3. pleuropneumonia necrossupurativa focal, geralmente no lobo cardíaco (G1, G2; G3, G4, G7). Na análise genotípica, nos padrões de PFGE obtidos após a macro-restrição com a enzima ApaI, as cepas patogênicas (Nos 11246, 11229, 16614, 16618, 16972 e 17044) foram classificadas no mesmo grupo, com homologia variando de 67,3 a 100%, diferenciando-se das cepas apatogências (Nos 17034 e 17078), que pertenceram a outro grupo, com homologia de apenas 52,7% com as demais amostras. Coletivamente, os resultados demonstraram padrões distintos de patogenicidade de diferentes cepas de P. multocida, os quais podem estar associados à características genéticas das cepas. Adicionalmente o estudo demonstrou a atuação primária de algumas cepas de P. multocida em pneumonias, pleurites e septicemias em suínos. / Pasteurella multocida is one of the main pathogens involved in infectious bronchopneumonia in swine. Although considered a secondary agent to the enzootic pneumonia caused by Mycoplasma hyopneumoniae and viral agents as the swine influenza, there are evidences related to its involvement as a primary agent. In this context, the first study undertaken aimed at developing an experimental reproduction method of pneumonia caused by P. multocida A Strain 11246 in swine infected with different inoculum concentrations. A second study was conducted aiming demonstrating phenotypic, molecular and pathogenic differences between the strains of P. multocida A isolated from clinical cases of pneumonia in commercial swine farms in several Brazilian states. In the first experiment, swine were challenged by slow intranasal drip with different inoculum concentrations of P. multocida A strain 11246 [Group (G1): 108 Colony Forming Units (CFU)/ml; G2: 107 CFU/ml; G3: 106 CFU/ml and G4: 105 CFU/ml]. Two swine per group with approximately 100 days of age were used. In these animals all inoculum concentrations demonstrated the bacteria capability to cause severe respiratory disease and septicemia in the inoculated animals. Using the same challenge methodology inoculating 107 CFU/ml at the second study when challenging 64 swine equally distributed into eight groups (G1 to G8) with eight different strains of P. multocida A (one strain per group) results showed the presence of highly pathogenic strains (G1-11246, G2- 11229, G3-16614 e G7-17044); less pathogenic (G4-16618 e G5-16972); and apathogenic (G6-17034 e G8-17078), according to the severity of the clinical and pathological alterations developed. In the pathologic evaluation of challenged animals, we observed three distinct patterns of injuries associated or not with each other: 1. Cranioventral fibrinonecrotic bronchopneumonia with fibrinous pleuritis (G1, G3, G7); 2. Difuse uni or bilateral pleuritis pleuritis, associated or not with pericarditis and peritonitis (G3, G5, G7) and; 3. Necrosuppurative focal pleuropneumonia, generally in the cardiac lobe (G1, G2, G3, G4, G7). In genotypic analysis, the PFGE patterns obtained after the macro-restriction with ApaI enzyme, the pathogenic strains (# 11246, 11229, 16614, 16618, 16972 and 17044) were classified in the same group, with homology ranging from 67.3 to 100%, differing from the apathogenic strains (# 17034 and 17078), which belonged to another group, with only 52.7% homology with the other samples. Collectively, the results showed distinct patterns in different pathogenic strains of P. multocida, which may be associated with the genetic features of the strains. Additionally, the reasearch demonstrated the primary role of some strains of P. multocida in pneumonia, pleuritis and septicemia in swine.

As afecções bucais em gatos domésticos são causas frequentes de atendimento clínico. São enfermidades multifatoriais, cuja etiopatogenia ainda não foi elucidada. Contudo, acredita-se que o desequilíbrio da microbiota bucal e da resposta imune local resulte num processo inflamatório, que a longo prazo poderá interferir no comportamento do animal, ocasionar perda de dentes e levar até a morte. A microbiota bucal é composta por diferentes gêneros bacterianos, dentre estes destacam-se Staphylococcus spp. e a Pasteurella spp. O tratamento das afecções bucais é baseado no uso de antimicrobianos e anti-inflamatórios, porém há uma alta taxa de insucesso. Adicionalmente, como a escolha dos antimicrobianos na maioria das vezes é feita de maneira empírica e indiscriminada, existe a possibilidade de surgimento de bactérias multirresistentes. Desta maneira, nos últimos anos vários esforços foram realizados com intuito de superar o advento da resistência bacteriana e os produtos naturais possuem potencial para isto, dentre estes destacam-se os óleos essenciais de plantas. Visto isso, o presente estudo objetivou isolar e identificar cepas de Staphylococcus spp. e Pasteurella spp. de amostras da cavidade bucal de gatos domésticos sadios e com gengivite. Posteriormente, os isolados foram submetidos ao teste de sensibilidade antimicrobiana frente a seis óleos essenciais (OEs): Citrus bergamia (bergamota), Anthemis nobile (camomila romana), Cymbopogon citratus (capim-limão), Copaifera officinalis (Copaiba), Eugenia caryophyllus (cravo) e Melaleuca alternifólia (tea tree ou melaleuca). Os resultados mostraram que Staphylococcus spp. e Pasteurella spp. estão presentes tanto na cavidade bucal de gatos sadios, quanto em animais com gengivite. Os OEs com melhor efetividade antimicrobiana frente a maioria dos isolados foram capim limão, cravo, melaleuca e camomila romana. Os achados obtidos no presente estudo foram similares a outras investigações anteriores. Já os OEs de copaíba e bergamota não apresentaram nenhuma ação antimicrobiana. As discrepâncias observadas podem ser explicadas, principalmente, pelas diferenças de composição química, de concentração dos compostos químicos, pelo sinergismo entre eles, pela origem fitogeográfica e condições de cultivo da planta utilizada para obtenção dos OEs. / The oral affections in domestic cats are frequent causes of clinical care. These are multifactorial diseases, which etiopathogenesis has not been elucidated yet. However, believes that imbalanced oral microbiota and a immune response local results in the inflammatory process, which in a long term can cause various physical changes in the animal. The oral microbiota is composed of different bacterial genera, among these highlighting Staphylococcus spp. and the Pasteurella spp. The treatment of these affections is based on the use of antimicrobials and anti- inflammatories, but there is a high failure rate. In addition, the choice of antimicrobials is mostly done in a empirical and indiscriminate way, these is a possibility of appearance of multiresistant bacteria. In this way, in the last years several efforts have been made to overcome the advent bacterial resistance and natural products have potential for this. Among there are the essential oils. Then, the present study aimed to isolate and identify strains of Staphylococcus spp. e Pasteurella spp. Of samples of oral cavity of healthy domestic cats and with gingivitis. Posteriorly, the isolates were submmited to the antimicrobial susceptibility test before the six essential oils (EOs): Citrus bergamia (bergamot), Anthemis nobile (roman chamomile), Cymbopogon citratus (lemongrass), Copaifera officinalis (Copaiba), Eugenia caryophyllus (clove) e Melaleuca alternifólia (tea tree or melaleuca). The results showed that the Staphylococcus spp. and the Pasteurella spp are presented as soon in the oral cavity of healthy cats, as in animals with gingivitis. The EOs with better antimicrobial effectiveness against of the most of the isolates were Cymbopogon citratus (lemongrass), Eugenia caryophyllus (cloves), Melaleuca alternifólia (tea tree or melaleuca) and Anthemis nobile (roman chamomile). The findings obtained in the present study were similar to the others investigations. Then, the EOs of Copaifera officinalis (Copaiba) and Citrus bergamia (bergamot) did not present any antimicrobial action. The discrepancies can be explained, mainly, by differences in the chemical compositions, concentration of chemical compounds, by synergism among them, by phytogeographic origen and conditions of culture of plant utilized to obtain of EOs.

Pasteurella multocida é o agente causador de muitas doenças de importância econômica em medicina veterinária e tem sido descrita como um agente de alto potencial zoónotico. No Brasil, ao contrário do que se observa na literatura internacional, informações sobre a frequência deste agente em animais de companhia como cães, gatos e coelhos são inexistentes. O presente estudo teve como proposta isolar cepas de Pasteurella multocida a partir de cães, gatos e coelhos, avaliar a freqüência deste agente nestas espécies animais, caracterizar os isolados de acordo com o tipo capsular e genes codificadores de fatores de virulência através da reação em cadeia pela polimerase, avaliar o perfil de resistência a antimicrobianos dos isolados obtidos e caracterizar as amostras através da PFGE. Foram examinados 640 animais, sendo 191 gatos, 309 cães e 140 coelhos. Dentre os animais examinados 8,1% foram positivos para o isolamento de P. multocida, sendo 10,4% dos gatos, 0,9% dos cães e 20,7% dos coelhos avaliados. Dentre as 93 cepas selecionadas 22,5% foram sensíveis a todas as drogas testadas, 77,4% das cepas foram resistentes a pelo menos uma droga utilizada e 5,3% foram apresentavam resistência a três ou mais drogas. Através da PFGE foram observados 39 pulsotipos com índice discriminatório igual a 0,97. Todos os genes codificadores de fatores de virulência foram detectados em pelo menos um isolado, sendo que nenhum destes esteve presente em 100% das cepas avaliadas. / Pasteurella multocida is the causative agent of many diseases of economic importance in veterinary medicine and has been described as an agent a high zoonotic potential. In Brazil, contrary to what is observed in the international literature, information about the frequency of this agent in animals such as dogs, cats and rabbits are nonexistent. This study proposes isolate strains of Pasteurella multocida from dogs, cats and rabbits, evaluate the frequency of this agent in these animal species, characterize the isolates according to the capsular type, and genes encoding virulence factors through the reaction polymerase chain, evaluate the antimicrobial resistance profiles of isolates and characterize the samples by PFGE. We examined 640 animals, 191 cats, 309 dogs and 140 rabbits. Among the animals examined were positive 8.1% for the isolation of P. multocida, and 10.4% of cats, dogs 0.9% and 20.7% of the rabbits studied. Among the 93 selected strains 22.5% were susceptible to all drugs tested, 77.4% of strains were resistant to at least one drug were used and 5.3% showed resistance to three or more drugs. Through PFGE were observed 39 pulsotipos discriminatory index equal to 0.97. All genes encoding virulence factors were detected in at least one isolated, none of which was present in 100% of the strains evaluated.

El propósito de este estudio fue determinar la variabilidad genética de cepas de Gallibacterium anatis aisladas en aves comerciales del Perú. El trabajo experimental consistió en aislar Gallibacterium anatis de muestras clínicas de aves comerciales con sintomatología respiratoria desde el 2007 al 2011, y caracterizarlos mediante pruebas bioquímicas. Se obtuvieron 96 cepas de G. anatis. Luego, se identificaron mediante técnicas moleculares y se determino la variabilidad genética de estas cepas de G. anatis mediante ERIC-PCR. Los resultados demostraron que existen 10 biovares circulando en el Perú los cuales son en un 45,83 % del biovar 4, 12,50 % del Biovar 1, 11,45 % del Biovar 3, 7,30 % del Biovar 11, 6,25% del Biovar NI, 4,17% del Biovar 12, 15 y 20 cada uno, y 2,08 % del Biovar 19 y 24 cada uno. El mayor porcentaje de aislados de G. anatis y de biovares se encontró en Lima en 64,58 %, La Libertad 28,13 % y en menor porcentaje Ica, Arequipa, Ucayali y Madre de Dios. Palabras Clave: Variabilidad genética, Gallibacterium anatis, Aves comerciales, ERIC-PCR, Biovares, Peru. / Tesis

Pasteurella multocida causes diseases in many animal species including fowl cholera, a septicemic disease of poultry and other birds. Pathogenesis of the disease has been studied by many investigators by the systemic administration of the organism in poultry. However, only a few studies have been done as to the respiratory pathogenesis of the organism. The objective of the study was to investigate the fate of P. multocida after the intratracheal administration in turkeys The fate of four strains of Pasteurella multocida was studied after their intratracheal inoculation in young adult turkeys. Viable bacterial counts were made in respiratory tissues as well as in the liver, spleen and blood at 6 and 9 hrs after the inoculation of approximately 10⁹ viable organisms of each strain. A virulent, encapsulated strain, P-1059, invaded systemically by 6 hrs postinoculation (PI) and multiplied vigorously in all tissues and organs examined. A blue colony mutant of P-1059, T-325, which does not possess a thick layer of capsule, as well as CU vaccine strain, invaded the parenchymal organs, but did not show significant increase in viable counts at 9 hrs PI compared with at 6 hrs PI. Another vaccine strain, M-9, also invaded blood and internal organs by 6 hrs PI, however, its viable counts showed no significant change between 6 and 9 hrs PI, or in some tissues significant decrease at 9 hrs PI. The results indicate that all the four strains possess high capacity to invade respiratory tissues with varying capacity to persist in host tissues. The lesions caused by two strains of Pasteurella multocida (P-1059 and M-9) were observed after their intratracheal inoculation in young adult turkeys. The lesions were observed in the respiratory organs at 0, 0.25, 0.5, 1, 2, 3, and 6 hrs after inoculation of approximately 10⁹ viable organisms of each strain. Both virulent strain, P-1059 and non-virulent vaccine strain, M-9, have capacity to invade and multiply in the tissues examined. Macroscopicly, the lesions in the lung and in the airsac were found as early as 1 hr PI, including the infected lung was foamy and the airsac became cloudy. They became more severe by 2 to 6 hrs PI. Microscopicly, hecerophiles were present, occasionally, in the lung, trachea and airsac by 0 to 1 hr after inoculation. Then they became more severe by 2 to 6 hrs PI. By 6 hrs PI, there were diffuse heterophiles infiltration in the trachea, lung, anc airsac. The lung vascular was edema. The trachea ciliate and mucous gland was cystic or hyperplasia, and the airsac shewed increased in thickness and cloudiness. These results of study indicate that the lesion caused by P-1059 and vaccine strain, M-9, were not significantly different. / Graduation date: 1992

Los objetivos de la presente tesis doctoral han sido la caracterización de los mecanismos de captación de hierro de Pasteurella multocida, con el fin de contribuir al diseño de una vacuna contra este patógeno basada en la sobreexpresión de proteínas de membrana externa, receptoras de hemoglobina y/o hemina, o en la expresión constitutiva de las proteínas de membrana reguladas por hierro (IROMPs).Se ha identificado el gen fur de P. multocida y se ha estudiado el perfil electroforético de las proteínas de membrana externa de dicho patógeno, descubriéndose un control de la expresión de una proteína mayoritaria de membrana (OmpH) por parte de la proteína Fur. Se ha construido un mutante fur y se ha demostrado que la mutación de este gen no presenta ningún efecto sobre la virulencia de la cepa.Así mismo, se ha caracterizado la región cromosómica de P. multocida que contiene los genes exbB, exbD y tonB, detectándose la existencia de promotores internos en dicha región y por lo tanto la expresión independiente de cada uno de los tres genes del sistema. Se ha estudiado la regulación de la expresión de todos ellos, demostrándose que pertenecen al regulón Fur, y se han construido mutantes en los genes exbB, exbD y tonB. Se ha calculado la dosis letal 50 (DL50) de cada una de las cepas construidas, determinándose que cada uno de estos genes es imprescindible para el desarrollo normal de una infección por P. multocida, ya que en todos los casos se obtuvo un incremento de la DL50 superior a los tres órdenes de magnitud con respecto la cepa salvaje.Por otro lado, se ha analizado el genoma de P. multocida Pm70 y se han estudiado 9 proteínas que, por similitud con los receptores descritos en el banco de datos, podrían actuar como receptores de hemoglobina y/o hemina. Así se ha podido determinar que algunas de ellas son capaces de unir hemoglobina y hemina (PM0040, PM0236, PM0300, PM0741, PM1081 y PM1428), mientras que otras tan sólo interaccionan con la hemoglobina (PM0576) o la hemina (PM1282), y que otra (PM1078) no reconoce ninguna de estas fuentes de hierro.De entre todas estas proteínas se ha elegido la PM0300, que se ha denominado HgbA, para realizar un estudio más detallado de este tipo de receptores de membrana. Así, se ha demostrado que el gen hgbA forma una unidad transcripcional con los genes PM0298 y PM0299. Estos genes presentan similitud con hugX y hugZ de Plesiomonas shigelloides respectivamente, y están implicados en procesos de detoxificación de hierro. Se ha demostrado que, en P. multocida, las proteínas PM0298 y PM0299 son esenciales para la viabilidad de la cepa. Por otro lado, se ha determinado que el gen hgbA se expresa en las primeras dos horas de la infección y que, in vitro, su expresión se induce en ausencia de hierro. Además, se ha construido un mutante deficiente para esta proteína y se ha comprobado que no presenta disminuida ni su capacidad de unir hemoglobina in vitro ni su virulencia. Por otro lado, se ha comprobado la distribución prácticamente universal de este gen en cepas de P. multocida de distintos serotipos y orígenes animales, hecho que propone a esta proteína como candidata para el desarrollo de un método de identificación rápido y específico de este microorganismo.Por último, se ha analizado la capacidad inmunogénica y protectora de los receptores de hemina y/o hemoglobina. Así, se ha demostrado que por lo menos tres de estas proteínas (PM0236, PM0741 y HgbA) son inmunogénicas. Sin embargo, la inoculación en ratones de las proteínas HgbA y PM0741, ya sea de forma individual o conjunta, no induce protección ante un enfrentamiento homólogo. / In the present work, the Pasteurella multocida iron uptake mechanisms have been characterised. These results could be use to the obtention of one vaccine against this pathogen. The P. multocida fur gene has been identified and it has been demonstrated that the porine OmpH is under the control of the Fur protein. On the other hand, a P. multocida Fur mutant was constructed and its LD50 was calculated demonstrating that a mutation in this gene has no effect in the virulence of the strain.Moreover, the region which contains P. multocida exbB, exbD and tonB genes has been characterised. The results obtained demonstrate that these three genes do not constitute a single transcriptional unit, but all these genes possess its own promoter which is under the Fur-Fe(II) regulation. It has been obtained a ExbB, ExbD and TonB mutants and these mutants present a decrease in their virulence to increase their LD50 by more than three orders of magnitude when were inoculated via intraperitoneal. These data demonstrate that exbB, exbD and tonB genes are essential to P. multocida infectious process.Furthermore, the P. multocida Pm70 genome was analysed and nine putative haemin and haemoglobin-binding proteins have been identified by similarity with the same molecules of other bacterial pathogens. Quantitative binding assays have demonstrated that PM0040, PM0236, PM0300, PM0741, PM1081 and PM1428 bind both haemin and haemoglobin, whereas PM0576 and PM1282 only bind either haemoglobin or haemin, respectively. PM1078, despite presents similarity with a Yersinia enterocolitica haemin receptor, does not recognize none of these iron sources.PM0300 was named hgbA and it has been demonstrate that this gene and the PM0298 and PM0299 ORFs, which present similarity with hugX and hugZ of Plesiomonas shigelloides, respectively, constitute a single transcriptional unit. PM0298 and PM0299 are essential to the viability of P. multocida cells. The hgbA gene is expressed in vivo within the two first hours post-inoculation, and in vitro is repressed by iron. Moreover, a HgbA mutant binds haemoglobin to the same extent as the wild-type strain and, in agreement with this, virulence of the P. multocida hgbA cells was no affected. On the other hand, the hgbA gene is present in almost all the strains of P. multocida analysed, independently of their serotype or their animal source. This result propose hgbA as a putative candidate to develop a fast and specific method to identify this pathogen.Finally, the immumogenicity and the ability to induce protection of all these haemin and haemoglobin receptors were analysed. The results obtained have demonstrated that, despite PM0236, PM0741 and HgbA are immunogens, inoculation of mice with any single one of these binding proteins alone is not protective against P. multocida infection.

Pasteurella multocida serotype A:3 is a gram-negative bacterial pathogen which is one of the causative agents of shipping fever in cattle. In this study, ompH and two fragments of plpE gene (plpEN and plpEC) were cloned from the genomic DNA of P. multocida P-1062 (ATCC 15743, serotype A:3) and plpEN-ompH and plpEC-ompH fusions were constructed. In vitro expression of the genes was shown in HEK-293 cells. Later, full-length plpE gene was cloned and the recombinant proteins were expressed in E. coli and purified. Three DNA vaccine formulations, namely pCMV-ompH, pCMV-plpEN-ompH and pCMV-plpEC-ompH and five recombinant protein based vaccines, PlpEN-OmpH, PlpEC-OmpH, OmpH, PlpEC and PlpE were generated. Recombinant proteins were formulated with at least one of the adjuvants: alum, CpG, alum-CpG, oil based and oil based-CpG. BALB/c mice were immunized with these vaccine formulations and their sera were used for the evaluation of antibody and serum IFN-&gamma / titers. Protective capacities of the vaccines were also evaluated via challenge of mice with 10 LD50 of P. multocida A:3. DNA vaccines induced immune responses, but did not provide protection. All protein vaccine formulations increased antibody levels and CpG containing formulations enhanced serum IFN-&gamma / titers. 100 &micro / g of PlpEC-OmpH protein adsorbed on alum adjuvant conferred 40% protection while no protection was obtained with PlpEN-OmpH. Next, the effects of CpG, or its alum and oil based combinations as adjuvants were investigated on PlpEC-OmpH mediated protection. The vaccine formulation composed of PlpEC-OmpH and oil based-CpG adjuvant conferred 100% protection. Finally, the mice were vaccinated with recombinant OmpH, PlpEC and PlpE formulated with oil based-CpG adjuvant. OmpH, PlpEC and PlpE formulations provided 50%, 60% and 100% protection, respectively. These findings implicated that recombinant PlpE and PlpEC-OmpH fusion proteins when formulated with oil based-CpG adjuvant are potent acellular vaccine formulation candidates against shipping fever.

No description available.

Frankfurt (Main), Universiẗat, Diss., 2008. / Dateien im PDF-Format.