RESUMO
The objective of this field trial was to determine the efficacy of a recombinant toxoid vaccine against Shiga toxin 2e (Stx2e) in piglets suffering from edema disease (ED). Three farms with confirmed ED cases were selected for the field trials. On each farm, a total of 40 4-day-old pigs were randomly allocated to either the vaccinated or unvaccinated group, with 20 pigs per group (10 males and 10 females). A 1.0-mL dose of the recombinant toxoid vaccine was administered intramuscularly to pigs in the vaccinated groups in accordance with the manufacturer's recommendations at 4 d of age. A single 2.0-mL dose of phosphate-buffered saline was administered to unvaccinated pigs at the same age. Clinical signs of ED were observed in 12 piglets in the unvaccinated groups and 7 unvaccinated pigs died as a result of ED out of the total number of piglets on Farms A, B, and C. Vaccination had a positive effect on pig growth performance compared to that of unvaccinated pigs on 2 of the 3 farms. Seroconversion of neutralizing antibodies against Stx2e occurred in 70% of piglets in the vaccinated group on Farm A, 75% of vaccinated piglets on Farm B, and 55% of vaccinated piglets on Farm C, when detectable antibodies were measured at 17 d post-vaccination (dpv). Detectable antibodies were measured in 85% of vaccinated piglets on Farms A and B and in 90% of these piglets on Farm C at 37 dpv. These field trials determined that the ED recombinant toxoid vaccine successfully reduced clinical signs and mortality, improved average daily weight gain, and resulted in the production of neutralizing antibodies against Stx2e in pigs.
L'objectif de cette étude sur le terrain était de déterminer l'efficacité d'un vaccin à base d'anatoxine recombinante contre la toxine Shiga 2e (Stx2e) chez les porcelets souffrant de la maladie de l'oedème (ED). Trois fermes ayant des cas confirmés de ED ont été sélectionnées pour les études sur le terrain. Dans chaque ferme, un total de 40 porcs âgés de 4 jours ont été répartis au hasard dans le groupe vacciné ou non vacciné, avec 20 porcs par groupe (10 mâles et 10 femelles). Une dose de 1,0 ml du vaccin à base d'anatoxine recombinante a été administrée par voie intramusculaire aux porcs des groupes vaccinés conformément aux recommandations du fabricant à l'âge de 4 jours. Une dose unique de 2,0 ml de solution saline tamponnée au phosphate a été administrée aux porcs non vaccinés au même âge. Des signes cliniques de ED ont été observés chez 12 porcelets des groupes non vaccinés et 7 porcs non vaccinés sont morts des suites d'une maladie de l'oedème sur le nombre total de porcelets des fermes A, B et C. La vaccination a eu un effet positif sur les performances de croissance des porcs par rapport à celles des porcs non vaccinés dans 2 des 3 fermes. La séroconversion des anticorps neutralisants contre Stx2e s'est produite chez 70 % des porcelets du groupe vacciné de la ferme A, 75 % des porcelets vaccinés de la ferme B et 55 % des porcelets vaccinés de la ferme C, lorsque des anticorps détectables ont été mesurés 17 jours après la vaccination (dpv). Des anticorps détectables ont été mesurés chez 85 % des porcelets vaccinés des fermes A et B et chez 90 % de ces porcelets de la ferme C à 37 dpv. Ces études sur le terrain ont déterminé que le vaccin toxoïde recombinant ED réduisait avec succès les signes cliniques et la mortalité, améliorait le gain de poids quotidien moyen et entraînait la production d'anticorps neutralisants contre Stx2e chez les porcs.(Traduit par Docteur Serge Messier).
Assuntos
Vacinas Sintéticas , Animais , Suínos , Feminino , Vacinas Sintéticas/imunologia , Vacinas Sintéticas/administração & dosagem , Masculino , Doenças dos Suínos/prevenção & controle , Doenças dos Suínos/imunologia , Edematose Suína/prevenção & controle , Edematose Suína/imunologia , Infecções por Escherichia coli/veterinária , Infecções por Escherichia coli/prevenção & controle , Infecções por Escherichia coli/imunologia , Toxina Shiga II/imunologia , Vacinas contra Escherichia coli/imunologia , Vacinas contra Escherichia coli/administração & dosagem , Toxoides/imunologia , Vacinas Bacterianas/imunologia , Vacinas Bacterianas/administração & dosagemRESUMO
INTRODUCTION: Pigs without intestinal receptors for F4 fimbriae are congenitally resistant to F4 fimbriae-bearing enterotoxigenic Escherichia coli (ETEC F4). In general, 50 % and 100 % of piglets born to resistant (RR) sows crossed with hetero- or homozygous susceptible (SR, SS) boars, respectively, are susceptible but do not receive colostral antibodies against F4 fimbriae unless the sows have been vaccinated. The question arises as to whether resistant sows produce protective amounts of F4 antifimbrial antibodies after vaccination. The serum and colostrum antibody titres of 12 resistant and 12 susceptible vaccinated gilts were compared. The effect of the receptor status of the dam and sire on the preweaning performance of 5027 piglets was evaluated using Agroscope's recordings. The sows of the experimental herd, where ETEC F4 was circulating, were vaccinated against ETEC twice during the first pregnancy and once during each following pregnancy. The log2 transformed F4 antibody titres in the serum obtained after the second vaccine injection as well as in the colostrum of the 12 resistant animals were lower than the titres of the susceptible animals (serum: F4ab 11,19 ± 1,44 vs. 12,18 ± 1,33, P = 0,096; F4ac 10,03 ± 1,58 vs. 11,59 ± 1,43, P = 0,019; colostrum: F4ab 12,20 ± 2,41 vs. 14,02 ± 1,31, P = 0,033; F4ac 10,93 ± 2,46 vs. 13,03 ± 5,21, P = 0,006). The heat labile enterotoxin (LT) antibody titres after vaccination did not differ between susceptible and resistant animals (p > 0,10). Preweaning mortality in the offspring of RR sows × SS boars was slightly lower than in the offspring of SS sows × RR boars (P = 0,04), suggesting that the disease risk of susceptible piglets born to vaccinated resistant sows was not increased, even though they received colostrum with a slightly reduced content of antibody against F4 fimbriae.
INTRODUCTION: Les porcs dépourvus de récepteurs intestinaux pour les fimbriae F4 sont congénitalement résistants aux Escherichia coli entérotoxinogènes porteurs de fimbriae F4 (ETEC F4). En général, 50 % et 100 % des porcelets nés de truies résistantes (RR) croisées avec des verrats hétéro- ou homozygotes sensibles (SR, SS), respectivement, sont sensibles mais ne reçoivent pas d'anticorps colostraux contre les fimbriae F4, à moins que les truies n'aient été vaccinées. La question se pose de savoir si les truies résistantes produisent des quantités protectrices d'anticorps antifimbriae F4 après la vaccination. Les titres d'anticorps dans le sérum et le colostrum de 12 truies reproductrices vaccinées résistantes et de 12 truies reproductrices vaccinées sensibles ont été comparés et l'effet du statut récepteur de la mère et du père sur les performances avant sevrage de 5027 porcelets a été évalué. Les truies du troupeau expérimental, où circulait ETEC F4, ont été vaccinées deux fois au cours de la première gestation et une fois au cours de chaque gestation suivante contre ETEC. Les titres d'anticorps F4 transformés en log2 dans le sérum obtenu après la deuxième injection de vaccin ainsi que dans le colostrum des 12 animaux résistants étaient inférieurs aux titres des animaux sensibles (sérum : F4ab 11,19 ± 1,44 vs. 12,18 ± 1,33, P = 0,096 ; F4ac 10,03 ± 1,58 vs. 11,59 ± 1,43, P = 0,019 ; colostrum : F4ab 12,20 ± 2,41 vs. 14,02 ± 1,31, P = 0,033 ; F4ac 10,93 ± 2,46 vs. 13,03 ± 5,21, P = 0,006). Les titres d'anticorps contre l'entérotoxine thermolabile (LT) après la vaccination ne différaient pas entre les animaux sensibles et résistants (p > 0,10). La mortalité avant sevrage dans la progéniture des truies RR × verrats SS était légèrement inférieure à celle de la progéniture des truies SS × verrats RR (P = 0,04), ce qui suggère que le risque de maladie des porcelets sensibles nés de truies résistantes vaccinées n'a pas été augmenté, même s'ils ont reçu du colostrum avec une teneur légèrement réduite en anticorps contre les fimbriae F4.
Assuntos
Escherichia coli Enterotoxigênica , Infecções por Escherichia coli , Vacinas contra Escherichia coli , Fímbrias Bacterianas , Doenças dos Suínos , Animais , Suínos , Infecções por Escherichia coli/veterinária , Infecções por Escherichia coli/prevenção & controle , Infecções por Escherichia coli/imunologia , Doenças dos Suínos/prevenção & controle , Doenças dos Suínos/imunologia , Doenças dos Suínos/microbiologia , Feminino , Vacinas contra Escherichia coli/imunologia , Vacinas contra Escherichia coli/administração & dosagem , Escherichia coli Enterotoxigênica/imunologia , Fímbrias Bacterianas/imunologia , Fímbrias Bacterianas/genética , Gravidez , Colostro/imunologia , Anticorpos Antibacterianos/sangue , DesmameRESUMO
Avian pathogenic Escherichia coli (APEC) is a notable pathogen that frequently leads to avian colibacillosis, posing a substantial risk to both the poultry industry and public health. The commercial vaccines against avian colibacillosis are primarily inactivated vaccines, but their effectiveness is limited to specific serotypes. Recent advances have highlighted bacterial membrane vesicles (MV) as a promising candidate in vaccine research. How to produce bacterial MVs vaccines on a large scale is a significant challenge for the industrialization of MVs. The msbB gene encodes an acyltransferase and has been implicated in altering the acylation pattern of lipid A, leading to a decrease in lipid A content in lipopolysaccharides (LPS). Here, we evaluated the immunoprotective efficacy of MVs derived from the LPS low-expressed APEC strain FY26ΔmsbB, which was an APEC mutant strain with a deletion of the msbB gene. The nitrogen cavitation technique was employed to extract APEC MVs, with results indicating a significant increase in MVs yield compared to that obtained under natural culture. The immunization effectiveness was assessed, revealing that FY26ΔmsbB MVs elicited an antibody response of laying hens and facilitated bacterial clearance. Protective efficacy studies demonstrated that immunization with FY26ΔmsbB MVs conferred the immune protection in chickens challenged with the wild-type APEC strain FY26. Notably, LPS low-carried MVs recovered from the mutant FY26ΔmsbB also displayed cross-protective capabilities, and effectively safeguarding against infections caused by O1, O7, O45, O78, and O101 serotypes virulent APEC strains. These findings suggest that MVs generated from the LPS low-expressed APEC strain FY26ΔmsbB represent a novel and empirically validated subunit vaccine for the prevention and control of infections by various APEC serotypes.
Assuntos
Galinhas , Infecções por Escherichia coli , Vacinas contra Escherichia coli , Escherichia coli , Doenças das Aves Domésticas , Vacinas de Subunidades Antigênicas , Animais , Doenças das Aves Domésticas/prevenção & controle , Doenças das Aves Domésticas/microbiologia , Doenças das Aves Domésticas/imunologia , Infecções por Escherichia coli/veterinária , Infecções por Escherichia coli/prevenção & controle , Infecções por Escherichia coli/imunologia , Escherichia coli/imunologia , Vacinas contra Escherichia coli/imunologia , Vacinas contra Escherichia coli/administração & dosagem , Vacinas de Subunidades Antigênicas/imunologia , Vacinas de Subunidades Antigênicas/administração & dosagem , Feminino , Proteção CruzadaRESUMO
Colibacillosis, a disease caused by Escherichia coli in broiler chickens has serious implications on food safety, security, and economic sustainability. Antibiotics are required for treating the disease, while vaccination and biosecurity are used for its prevention. This systematic review and meta-analysis, conducted under the COST Action CA18217-European Network for Optimization of Veterinary Antimicrobial Treatment (ENOVAT), aimed to assess the efficacy of E. coli vaccination in broiler production and provide evidence-based recommendations. A comprehensive search of bibliographic databases, including, PubMed, CAB Abstracts, Web of Science and Agricola, yielded 2,722 articles. Following a defined protocol, 39 studies were selected for data extraction. Most of the studies were experimental infection trials, with only three field studies identified, underscoring the need for more field-based research. The selected studies reported various types of vaccines, including killed (n = 5), subunit (n = 8), outer membrane vesicles/protein-based (n = 4), live/live-attenuated (n = 16), and CpG oligodeoxynucleotides (ODN) (n = 6) vaccines. The risk of bias assessment revealed that a significant proportion of studies reporting mortality (92.3%) or feed conversion ratio (94.8%) as outcomes, had "unclear" regarding bias. The meta-analysis, focused on live-attenuated and CpG ODN vaccines, demonstrated a significant trend favoring both vaccination types in reducing mortality. However, the review also highlighted the challenges in reproducing colibacillosis in experimental setups, due to considerable variation in challenge models involving different routes of infection, predisposing factors, and challenge doses. This highlights the need for standardizing the challenge model to facilitate comparisons between studies and ensure consistent evaluation of vaccine candidates. While progress has been made in the development of E. coli vaccines for broilers, further research is needed to address concerns such as limited heterologous protection, practicability for application, evaluation of efficacy in field conditions and adoption of novel approaches.
Assuntos
Galinhas , Infecções por Escherichia coli , Doenças das Aves Domésticas , Vacinação , Animais , Galinhas/microbiologia , Infecções por Escherichia coli/prevenção & controle , Infecções por Escherichia coli/veterinária , Doenças das Aves Domésticas/prevenção & controle , Doenças das Aves Domésticas/microbiologia , Vacinação/veterinária , Escherichia coli/imunologia , Vacinas contra Escherichia coli/imunologia , Vacinas contra Escherichia coli/administração & dosagemRESUMO
BACKGROUND: Neonatal and post-weaning diarrhea is a concern disease caused by enterotoxigenic Escherichia coli fimbriae F4 (F4+ETEC) in pig farms. Diarrhea outbreaks are often severe and costly due to the high prevalence and spread of the disease within the same herd. Vaccine is one of strategic solution in protecting pig against F4+ETEC infection in particular pig farm. In present study, we conducted two trials of vaccination with crude F4 fimbriae extract vaccine in pregnant sow and nursery pigs. METHODS: In experiment 1 (20 sows; non-vaccinated control, n=10), we vaccinated pregnant sows (n=10) twice at 4 wk and 2 wk before farrowing and evaluated impact of vaccination on maternal immunity. The sow serum and colostrum were collected before vaccination, 2 and 4 weeks after vaccination, 6 hours after farrowing, respectively, and the piglet's serum from both groups (2 piglet/sow, 10 piglets from each group) were also collected on 3 days old to measure F4 specific IgG, F4 specific IgA using in house ELISA kit. In experiment 2, to optimize doses and dosage of candidate vaccine in piglets, 18 piglets (3 piglets/group) were allocated into five immunized groups and one control group (unimmunized group), we immunized piglets twice at 4 and 6 weeks old with difference doses (i.e., 0, 50, 100, 150, 200 µg), and for a dose 150 µg, we immunized with two dosages at 1 ml and 2 ml. Piglets were challenged with a 3 ml dose of 3 × 109 CFU/ml bacterial culture of enterotoxigenic Escherichia coli (F4+ETEC) in order to evaluate the efficacy of vaccine. After challenging, the clinical sign of the piglets was daily observed and the rectal swab was performed every day for investigation of the fecal shedding of Escherichia coli (F4+ETEC) by using PCR technique. Serum were collected before, 2 and 4 weeks after vaccination and 1 week after challenge to measure F4 specific IgG, F4 specific IgA using in house ELISA kit and cytokines levels (i.e., IL-1 beta, IL-6, IL-8 and TNF alpha) before and 1 week after challenge using commercial ELISA kit. RESULTS: The levels of antibody results showed that in experiment 1, the anti-F4 antibody levels both F4 specific IgG and F4 specific IgA in serum and colostrum of vaccinated sow increased significantly after vaccination. The piglets of immunized sows have antibody level both F4 specific IgG and F4 specific IgA in their serum higher than those piglets of unimmunized sows significantly (p < 0.01). In experiment 2, irrespective of different doses and dosage, there is no difference in term of F4 specific IgG and F4 specific IgA levels among immunized groups. However, all of vaccinated piglets showed F4 specific IgG and F4 specific IgA levels higher and the elimination of Escherichia coli (F4+ETEC) in feces post challenge faster (< 3 days) than unvaccinated group (> 5 days). For cytokines levels, a higher level of IL-1 beta, IL-6, IL-8 and TNF alpha at 1 week after challenge in vaccinated groups was found when compared with the levels in non-vaccinated group. CONCLUSIONS: Our results suggest that crude F4 fimbriae extract autogenous vaccine is a candidate vaccine for protecting piglets against diarrhea disease caused by enterotoxigenic Escherichia coli (F4+ETEC) and vaccination the pregnant sow twice before farrowing is one of strategies to provide maternal derived antibody to the newborn piglets for against enterotoxigenic Escherichia coli (F4+ETEC) during early life.
Assuntos
Anticorpos Antibacterianos , Escherichia coli Enterotoxigênica , Infecções por Escherichia coli , Vacinas contra Escherichia coli , Doenças dos Suínos , Animais , Suínos , Feminino , Infecções por Escherichia coli/prevenção & controle , Infecções por Escherichia coli/veterinária , Infecções por Escherichia coli/imunologia , Doenças dos Suínos/prevenção & controle , Doenças dos Suínos/imunologia , Doenças dos Suínos/microbiologia , Escherichia coli Enterotoxigênica/imunologia , Vacinas contra Escherichia coli/imunologia , Vacinas contra Escherichia coli/administração & dosagem , Gravidez , Anticorpos Antibacterianos/sangue , Colostro/imunologia , Imunoglobulina A/sangue , Vacinação/veterinária , Imunoglobulina G/sangue , Fímbrias Bacterianas/imunologia , Diarreia/prevenção & controle , Diarreia/veterinária , Diarreia/microbiologia , Diarreia/imunologia , Animais Recém-Nascidos/imunologia , Imunidade Materno-AdquiridaRESUMO
The present study investigated the expression of cytokines and cellular changes in chickens following vaccination with irradiated avian pathogenic Escherichia coli (APEC) and/or challenge. Four groups of 11-week-old pullets, each consisting of 16 birds were kept separately in isolators before they were sham inoculated (N), challenged only (C), vaccinated (V) or vaccinated and challenged (V+C). Vaccination was performed using irradiated APEC applied via aerosol. For challenge, the homologous strain was administered intratracheally. Birds were sacrificed on 3, 7, 14 and 21 days post challenge (dpc) to examine lesions, organ to body weight ratios and bacterial colonization. Lung and spleen were sampled for investigating gene expression of cytokines mediating inflammation by RT-qPCR and changes in the phenotype of subsets of mononuclear cells by flow cytometry. After re-stimulation of immune cells by co-cultivation with the pathogen, APEC-specific IFN-γ producing cells were determined. Challenged only birds showed more severe pathological and histopathological lesions, a higher probability of bacterial re-isolation and higher organ to body weight ratios compared to vaccinated and challenged birds. In the lung, an upregulation of IL-1ß and IL-6 following vaccination and/or challenge at 3 dpc was observed, whereas in the spleen IL-1ß was elevated. Changes were observed in macrophages and TCR-γδ+ cells within 7 dpc in spleen and lung of challenged birds. Furthermore, an increase of CD4+ cells in spleen and a rise of Bu-1+ cells in lung were present in vaccinated and challenged birds at 3 dpc. APEC re-stimulated lung and spleen mononuclear cells from only challenged pullets showed a significant increase of IFN-γ+CD8α+ and IFN-γ+TCR-γδ+ cells. Vaccinated and challenged chickens responded with a significant increase of IFN-γ+CD8α+ T cells in the lung and IFN-γ+TCR-γδ+ cells in the spleen. Re-stimulation of lung mononuclear cells from vaccinated birds resulted in a significant increase of both IFN-γ+CD8α+ and IFN-γ+TCR-γδ+ cells. In conclusion, vaccination with irradiated APEC caused enhanced pro-inflammatory response as well as the production of APEC-specific IFN-γ-producing γδ and CD8α T cells, which underlines the immunostimulatory effect of the vaccine in the lung. Hence, our study provides insights into the underlying immune mechanisms that account for the defense against APEC.
Assuntos
Infecções por Escherichia coli , Vacinas contra Escherichia coli , Animais , Galinhas , Feminino , Vacinas contra Escherichia coli/administração & dosagem , Vacinas contra Escherichia coli/imunologia , Infecções por Escherichia coli/imunologia , Infecções por Escherichia coli/prevenção & controle , Infecções por Escherichia coli/veterinária , Doenças das Aves Domésticas/imunologia , Doenças das Aves Domésticas/prevenção & controle , AerossóisRESUMO
Enterotoxigenic Escherichia coli (ETEC) strains are a leading cause of children's and travelers' diarrhea. Developing effective vaccines against this heterologous group has proven difficult due to the varied nature of toxins and adhesins that determine their pathology. A multivalent candidate vaccine was developed using a multi-epitope fusion antigen (MEFA) vaccinology platform and shown to effectively elicit broad protective antibody responses in mice and pigs. However, direct protection against ETEC colonization of the small intestine was not measured in these systems. Colonization of ETEC strains is known to be a determining factor in disease outcomes and is adhesin-dependent. In this study, we developed a non-surgical rabbit colonization model to study immune protection against ETEC colonization in rabbits. We tested the ability for the MEFA-based vaccine adhesin antigen, in combination with dmLT adjuvant, to induce broad immune responses and to protect from ETEC colonization of the rabbit small intestine. Our results indicate that the candidate vaccine MEFA antigen elicits antibodies in rabbits that react to seven adhesins included in its construction and protects against colonization of a challenge strain that consistently colonized naïve rabbits.
Assuntos
Antígenos de Bactérias/administração & dosagem , Diarreia/prevenção & controle , Escherichia coli Enterotoxigênica/crescimento & desenvolvimento , Escherichia coli Enterotoxigênica/imunologia , Epitopos/imunologia , Infecções por Escherichia coli/prevenção & controle , Vacinas contra Escherichia coli/administração & dosagem , Animais , Anticorpos Antibacterianos/sangue , Antígenos de Bactérias/genética , Antígenos de Bactérias/imunologia , Diarreia/sangue , Diarreia/microbiologia , Modelos Animais de Doenças , Escherichia coli Enterotoxigênica/genética , Epitopos/genética , Infecções por Escherichia coli/sangue , Infecções por Escherichia coli/microbiologia , Vacinas contra Escherichia coli/genética , Vacinas contra Escherichia coli/imunologia , Humanos , Imunização , Intestino Delgado/imunologia , Intestino Delgado/microbiologia , CoelhosRESUMO
Enterotoxigenic Escherichia coli (ETEC) is a leading cause of mortality and morbidity in children in low-income countries. We have tested an oral ETEC vaccine, ETVAX, consisting of inactivated E coli overexpressing the most prevalent colonization factors and a toxoid, LCTBA, administered together with a mucosal adjuvant, double-mutant heat-labile toxin (dmLT), for capacity to induce mucosal immune responses and immunological memory against the primary vaccine antigens, ie, colonization factors, heat-labile toxin B-subunit and O antigen. The studies show that ETVAX could induce strong intestine-derived and/or fecal immune responses in a majority of vaccinated Swedish adults and in different age groups, including infants, in Bangladesh.
Assuntos
Escherichia coli Enterotoxigênica/imunologia , Infecções por Escherichia coli/prevenção & controle , Proteínas de Escherichia coli , Vacinas contra Escherichia coli/administração & dosagem , Imunidade nas Mucosas , Adolescente , Adulto , Anticorpos Antibacterianos , Criança , Enterotoxinas , Humanos , Lactente , Pessoa de Meia-IdadeRESUMO
A series of studies was undertaken in specific-pathogen-free white leghorn chickens for the development of a chicken model of avian pathogenic Escherichia coli (APEC) peritonitis. Once established, this model was then used to measure the effectiveness of a siderophore receptor and porin proteins (SRP®) APEC vaccine. Initially, five pilot studies were performed to compare the E. coli serotype, challenge route, and dose of inoculum that resulted in pathologies characteristic of the peritonitis observed in commercial layer facilities, such as widespread organ infection, atrophy, discoloration, corrugation of yolk sacs, and the presence of caseous exudate. Isolates of serotypes O1, O2, and O78 were tested by intravenous, intravaginal, intratracheal, and intraperitoneal routes and were compared at various levels of challenge inoculum. Daily observations of mortality and morbidity were made, and at necropsy, gross lesion scores were collected and bacterial colonization of internal organs determined. Outcomes varied from a complete lack of mortality or detectable pathology and low, or no, organ colonization in the case of intravaginal and intratracheal routes with each E. coli serotype to moderate to high levels of mortality, pathology, and colonization after challenge via the intravenous and intraperitoneal routes with O2 and O78 serotypes, respectively. The O78 serotype was found to result in pathologies consistent with field observations of peritonitis, and therefore, subsequent studies were performed only with O78. In addition to the relative failure with both the intratracheal and intravaginal routes of challenge, the intravenous route was found to be inconsistent and often resulted in lameness not observed with the intraperitoneal route. A final pilot study confirmed that the dose (â¼ 8 log 10 CFU) administered by the intraperitoneal route replicated peritonitis, and therefore, all vaccination/challenge studies were conducted in this manner. Five vaccination/challenge studies are reported here in which variables of chicken age, vaccination interval, and vaccination to challenge interval were examined. In all studies, vaccine effectiveness was dramatic and was shown to completely protect against mortality and substantially against tissue colonization and pathology typical of APEC infections. The vaccine elicited a rapid onset of immunity with both narrow and broad vaccination intervals and in both young and mature chickens. Additionally, the vaccine was demonstrated to sustain robust effectiveness against mortality over 3 months. The SRP APEC vaccine should provide effective protection of young and mature chickens from E. coli under broadly flexible conditions of use in commercial operations.
Artíclo regularVacuna para prevenir la peritonitis de gallina de postura. Se llevó a cabo una serie de estudios en aves tipo Leghorn blancas libres de patógenos específicos para el desarrollo de un modelo en pollo para la peritonitis causada por Escherichia coli patógena aviar (APEC). Una vez establecido, este modelo se utilizó para medir la eficacia de una vacuna con proteínas del receptor de sideróforo y de porina (SRP®) de E. coli patógena aviar. Inicialmente, se realizaron cinco estudios piloto para comparar el serotipo de E. coli, la ruta de desafío y la dosis de inóculo que resultaron en patologías características de las peritonitis observadas en instalaciones comerciales de ponedoras, como la infección generalizada de órganos, atrofia, decoloración, ondulación de saco vitelino y la presencia de exudado caseoso. Los aislamientos de los serotipos O1, O2 y O78 se analizaron por vías intravenosa, intravaginal, intratraqueal e intraperitoneal y se compararon a varios niveles de inóculo de desafío. Se realizaron observaciones diarias de mortalidad y morbilidad, en la necropsia, se registraron puntuaciones de lesiones macroscópicas y se determinó la colonización bacteriana de los órganos internos. Los resultados variaron desde una ausencia total de mortalidad o patología detectable y una colonización de órganos baja o nula en el caso de las rutas intravaginal e intratraqueal con cada serotipo de E. coli hasta niveles de mortalidad, patología y colonización de moderados a altos después del desafío por vía intravenosa e intraperitoneal con los serotipos O2 y O78, respectivamente. Se encontró que el serotipo O78 dio como resultado patologías consistentes con las observaciones de campo de la peritonitis y por lo tanto, los estudios posteriores se realizaron solo con el serotipo O78. Además del fracaso relativo con las rutas de desafío intratraqueal e intravaginal, se descubrió que la vía intravenosa era inconsistente y a menudo, provocaba cojera que no se observaba con la vía intraperitoneal. Un estudio piloto final confirmó que la dosis (â¼8 log10 UFC) administrada por vía intraperitoneal reproducía la peritonitis y por lo tanto, todos los estudios de vacunación/desafío se realizaron de esta manera. En este estudio se reportan cinco estudios de vacunación/desafío en los que se examinaron las variables de edad del pollo, intervalo de vacunación e intervalo de vacunación al desafío. En todos los estudios, la eficacia de la vacuna fue muy evidente y se demostró que protege completamente contra la mortalidad y sustancialmente contra la colonización de tejidos y la patología típica de las infecciones por E. coli patógena aviar. La vacuna provocó un rápido inicio de la inmunidad con intervalos de vacunación tanto estrechos como amplios y tanto en aves jóvenes como maduras. Además, se demostró que la vacuna mantiene una sólida eficacia contra la mortalidad durante tres meses. La vacuna con proteínas del receptor de sideróforo y de porina de E. coli patógena aviar debería proporcionar una protección eficaz de las aves jóvenes y maduras contra E. coli en condiciones de uso ampliamente flexibles en operaciones comerciales.
Assuntos
Galinhas , Infecções por Escherichia coli/veterinária , Vacinas contra Escherichia coli/administração & dosagem , Escherichia coli/imunologia , Peritonite/veterinária , Doenças das Aves Domésticas/prevenção & controle , Animais , Infecções por Escherichia coli/microbiologia , Infecções por Escherichia coli/prevenção & controle , Feminino , Masculino , Peritonite/microbiologia , Peritonite/prevenção & controle , Projetos Piloto , Doenças das Aves Domésticas/microbiologiaRESUMO
There are no vaccines licensed for enterotoxigenic Escherichia coli (ETEC), a leading cause of diarrhea for children in developing countries and international travelers. Virulence heterogeneity among strains and difficulties identifying safe antigens for protective antibodies against STa, a potent but poorly immunogenic heat-stable toxin which plays a key role in ETEC diarrhea, are challenges in ETEC vaccine development. To overcome these challenges, we applied a toxoid fusion strategy and a novel epitope- and structure-based multiepitope fusion antigen (MEFA) vaccinology platform to construct two chimeric multivalent proteins, toxoid fusion 3xSTaN12S-mnLTR192G/L211A and adhesin CFA/I/II/IV MEFA, and demonstrated that the proteins induced protective antibodies against STa and heat-labile toxin (LT) produced by all ETEC strains or the seven most important ETEC adhesins (CFA/I and CS1 to CS6) expressed by the ETEC strains causing 60 to 70% of diarrheal cases and moderate to severe cases. Combining two proteins, we prepared a protein-based multivalent ETEC vaccine, MecVax. MecVax was broadly immunogenic; mice and pigs intramuscularly immunized with MecVax developed no apparent adverse effects but had robust antibody responses to the target toxins and adhesins. Importantly, MecVax-induced antibodies were broadly protective, demonstrated by significant adherence inhibition against E. coli bacteria producing any of the seven adhesins and neutralization of STa and cholera toxin (CT) enterotoxicity. Moreover, MecVax protected against watery diarrhea and provided over 70% and 90% protection against any diarrhea from an STa-positive or an LT-positive ETEC strain in a pig challenge model. These results indicated that MecVax induces broadly protective antibodies and prevents diarrhea preclinically, signifying that MecVax is potentially an effective injectable vaccine for ETEC. IMPORTANCE Enterotoxigenic Escherichia coli (ETEC) bacteria are a top cause of children's diarrhea and travelers' diarrhea and are responsible for over 220 million diarrheal cases and more than 100,000 deaths annually. A safe and effective ETEC vaccine can significantly improve public health, particularly in developing countries. Data from this preclinical study showed that MecVax induces broadly protective antiadhesin and antitoxin antibodies, becoming the first ETEC vaccine candidate to induce protective antibodies inhibiting adherence of the seven most important ETEC adhesins and neutralizing the enterotoxicity of not only LT but also STa toxin. More importantly, MecVax is shown to protect against clinical diarrhea from STa-positive or LT-positive ETEC infection in a pig challenge model, recording protection from antibodies induced by the protein-based, injectable, subunit vaccine MecVax against ETEC diarrhea and perhaps the possibility of intramuscularly administered protein vaccines for protection against intestinal mucosal infection.
Assuntos
Diarreia/microbiologia , Diarreia/prevenção & controle , Escherichia coli Enterotoxigênica/imunologia , Infecções por Escherichia coli/prevenção & controle , Vacinas contra Escherichia coli/imunologia , Animais , Anticorpos Antibacterianos/imunologia , Anticorpos Neutralizantes/imunologia , Antígenos de Bactérias/imunologia , Toxinas Bacterianas/imunologia , Diarreia/imunologia , Modelos Animais de Doenças , Epitopos/imunologia , Proteínas de Escherichia coli/imunologia , Vacinas contra Escherichia coli/administração & dosagem , Vacinas contra Escherichia coli/efeitos adversos , Camundongos , Proteínas Recombinantes de Fusão/imunologia , Suínos , Vacinas Combinadas/genética , Vacinas Combinadas/imunologiaRESUMO
Vaccines against enteric diseases could improve global health. Despite this, only a few oral vaccines are currently available for human use. One way to facilitate such vaccine development could be to identify a practical and relatively low cost biomarker assay to assess oral vaccine induced primary and memory IgA immune responses in humans. Such an IgA biomarker assay could complement antigen-specific immune response measurements, enabling more oral vaccine candidates to be tested, whilst also reducing the work and costs associated with early oral vaccine development. With this in mind, we take a holistic systems biology approach to compare the transcriptional signatures of peripheral blood mononuclear cells isolated from volunteers, who following two oral priming doses with the oral cholera vaccine Dukoral®, had either strong or no vaccine specific IgA responses. Using this bioinformatical method, we identify TNFRSF17, a gene encoding the B cell maturation antigen (BCMA), as a candidate biomarker of oral vaccine induced IgA immune responses. We then assess the ability of BCMA to reflect oral vaccine induced primary and memory IgA responses using an ELISA BCMA assay on a larger number of samples collected in clinical trials with Dukoral® and the oral enterotoxigenic Escherichia coli vaccine candidate ETVAX. We find significant correlations between levels of BCMA and vaccine antigen-specific IgA in antibodies in lymphocyte secretion (ALS) specimens, as well as with proportions of circulating plasmablasts detected by flow cytometry. Importantly, our results suggest that levels of BCMA detected early after primary mucosal vaccination may be a biomarker for induction of long-lived vaccine specific memory B cell responses, which are otherwise difficult to measure in clinical vaccine trials. In addition, we find that ALS-BCMA responses in individuals vaccinated with ETVAX plus the adjuvant double mutant heat-labile toxin (dmLT) are significantly higher than in subjects given ETVAX only. We therefore propose that as ALS-BCMA responses may reflect the total vaccine induced IgA responses to oral vaccination, this BCMA ELISA assay could also be used to estimate the total adjuvant effect on vaccine induced-antibody responses, independently of antigen specificity, further supporting the usefulness of the assay.
Assuntos
Antígeno de Maturação de Linfócitos B/genética , Vacinas contra Cólera/administração & dosagem , Cólera/prevenção & controle , Escherichia coli Enterotoxigênica/imunologia , Infecções por Escherichia coli/prevenção & controle , Vacinas contra Escherichia coli/administração & dosagem , Imunidade Humoral/genética , Imunoglobulina A/imunologia , Biologia de Sistemas/métodos , Vacinação/métodos , Vibrio cholerae/imunologia , Administração Oral , Adulto , Linfócitos B/imunologia , Biomarcadores , Células Cultivadas , Cólera/microbiologia , Vacinas contra Cólera/imunologia , Infecções por Escherichia coli/microbiologia , Vacinas contra Escherichia coli/imunologia , Voluntários Saudáveis , Humanos , Memória Imunológica , TranscriptomaRESUMO
Enterotoxigenic Escherichia coli (ETEC) is estimated to cause approximately 380,000 deaths annually during sporadic or epidemic outbreaks worldwide. Development of vaccines against ETEC is very challenging due to the vast heterogeneity of the ETEC strains. An effective vaccines would have to be multicomponent to provide coverage of over ten ETEC strains with genetic variabilities. There is currently no vaccine licensed to prevent ETEC. Nanobodies are successful new biologics in treating mucosal infectious disease as they recognize conserved epitopes on hypervariable pathogens. Cocktails consisting of multiple nanobodies could provide even broader epitope coverage at a lower cost compared to monoclonal antibodies. Identification of conserved epitopes by nanobodies can also assist reverse engineering of an effective vaccine against ETEC. By screening nanobodies from immunized llamas and a naïve yeast display library against adhesins of colonization factors, we identified single nanobodies that show cross-protective potency against eleven major pathogenic ETEC strains in vitro. Oral administration of nanobodies led to a significant reduction of bacterial colonization in animals. Moreover, nanobody-IgA fusion showed extended inhibitory activity in mouse colonization compared to commercial hyperimmune bovine colostrum product used for prevention of ETEC-induced diarrhea. Structural analysis revealed that nanobodies recognized a highly-conserved epitope within the putative receptor binding region of ETEC adhesins. Our findings support further rational design of a pan-ETEC vaccine to elicit robust immune responses targeting this conserved epitope.
Assuntos
Diarreia/prevenção & controle , Escherichia coli Enterotoxigênica/imunologia , Infecções por Escherichia coli/prevenção & controle , Vacinas contra Escherichia coli/administração & dosagem , Anticorpos de Domínio Único/administração & dosagem , Animais , Anticorpos Antibacterianos/administração & dosagem , Anticorpos Antibacterianos/imunologia , Anticorpos Neutralizantes/administração & dosagem , Anticorpos Neutralizantes/imunologia , Células CACO-2 , Camelídeos Americanos , Proteção Cruzada , Diarreia/imunologia , Diarreia/microbiologia , Modelos Animais de Doenças , Desenho de Fármacos , Mapeamento de Epitopos , Epitopos/imunologia , Infecções por Escherichia coli/imunologia , Proteínas de Escherichia coli/antagonistas & inibidores , Proteínas de Escherichia coli/imunologia , Vacinas contra Escherichia coli/imunologia , Proteínas de Fímbrias/antagonistas & inibidores , Proteínas de Fímbrias/imunologia , Humanos , Imunoconjugados/administração & dosagem , Imunoconjugados/imunologia , Masculino , Camundongos , Anticorpos de Domínio Único/imunologiaRESUMO
Extraintestinal pathogenic Escherichia coli (ExPEC) has presented a major clinical infection emerged in the past decades. O-polysaccharide (OPS)-based glycoconjugate vaccines produced using the bacterial glycosylation machinery can be utilized to confer protection against such infection. However, constructing a low-cost microbial cell factory for high-efficient production of OPS-based glycoconjugate vaccines remains challenging. Here, we engineered a glyco-optimized chassis strain by reprogramming metabolic network. The yield was enhanced to 38.6 mg L-1, the highest level reported so far. MS analysis showed that designed glycosylation sequon was modified by target polysaccharide with high glycosylation efficiency of 90.7 % and 76.7 % for CTB-O5 and CTB-O7, respectively. The glycoconjugate vaccines purified from this biosystem elicited a marked increase in protection against ExPEC infection in mouse model, compared to a non-optimized system. The glyco-optimized platform established here is broadly suitable for polysaccharide-based conjugate production against ExPEC and other surface-polysaccharide-producing pathogens.
Assuntos
Engenharia Celular/métodos , Infecções por Escherichia coli/prevenção & controle , Vacinas contra Escherichia coli/biossíntese , Escherichia coli Extraintestinal Patogênica/imunologia , Glicoconjugados/biossíntese , Antígenos O/biossíntese , Sequência de Aminoácidos , Animais , Animais não Endogâmicos , Anticorpos Antibacterianos/biossíntese , Sequência de Carboidratos , Infecções por Escherichia coli/imunologia , Infecções por Escherichia coli/microbiologia , Infecções por Escherichia coli/mortalidade , Vacinas contra Escherichia coli/administração & dosagem , Vacinas contra Escherichia coli/genética , Vacinas contra Escherichia coli/imunologia , Escherichia coli Extraintestinal Patogênica/patogenicidade , Feminino , Glicoconjugados/administração & dosagem , Glicoconjugados/genética , Glicoconjugados/imunologia , Glicosilação , Imunização , Imunogenicidade da Vacina , Imunoglobulina G/biossíntese , Redes e Vias Metabólicas/genética , Camundongos , Antígenos O/genética , Antígenos O/imunologia , Plasmídeos/química , Plasmídeos/metabolismo , Análise de Sobrevida , Vacinas ConjugadasRESUMO
Colibacillosis disease has an important economic impact on poultry production worldwide. It is one of the most common causes of mortality in commercial layer and breeder chickens. Avian pathogenic Escherichia coli (APEC) is the main cause of this disease. Nanoparticles have been widely used in vaccine design as both adjuvants and antigen delivery vehicles. The present study aimed to produce an efficient vaccine from E. coli serogroups O1 and O78 to help in controlling colibacillosis in chicken using two forms of chitosan (CS) and ascorbate chitosan (AsCS) nanoparticles. Nanovaccines has been prepared through loading and encapsulation of outer membrane and flagellar antigen on CS and AsCS nanoparticles with loading efficiency 86, 63,55, 48% for CS-loaded-, Cs-capsulated-, AsCS-loaded- and AsCS-capsulated-E. coli Antigen, respectively. Two hundred specific pathogens free (SPF) 3-weeks old broiler chickens were used and divided into four groups to investigate the immune response of nanovaccines. The immune response was measured by the microagglutination, ELISA, and challenge test. From results, it could be concluded that generally adding chitosan NPs is capable of improving vaccine efficacy via the induction of strong immunity. Moreover, we recommend the production of the nanovaccine CS-capsulated -antigen from E. coli O1 and O78 serotypes to be used as a potent vaccine to aid in controlling colibacillosis. Also, the ascorbate chitosan is a great alternate for the initiation of a potent immune response in critical infection cases.
Assuntos
Galinhas/imunologia , Quitosana/química , Infecções por Escherichia coli/veterinária , Vacinas contra Escherichia coli/administração & dosagem , Escherichia coli/imunologia , Nanopartículas/química , Doenças das Aves Domésticas/prevenção & controle , Testes de Aglutinação , Animais , Antígenos de Bactérias/imunologia , Proteínas da Membrana Bacteriana Externa/metabolismo , Fenômenos Químicos , Vacinas contra Escherichia coli/imunologia , Imunidade , Imunidade Humoral , Nanotecnologia , Doenças das Aves Domésticas/microbiologia , Espectroscopia de Infravermelho com Transformada de FourierRESUMO
The objective of the present study was to evaluate the efficacy of a J-5 Escherichia coli vaccine in a mild to moderate inflammatory challenge model using primiparous dairy cows for inoculation only. We hypothesized a clinical difference between placebo and J-5 E. coli vaccinated animals with the mild to moderate inflammatory challenge model. In case the null hypothesis could not be confirmed, the alternate hypothesis was no clinical difference between both treatment groups. Therefore, 23 primiparous cows in mo 7 of pregnancy were randomly assigned to 1 of 2 treatment groups: J-5 E. coli vaccine (n = 12) or placebo (n = 11). Animals were vaccinated 3 times at 56 (±7) and 28 (±7) d before expected calving date and within 14 d postcalving (DIM 5 ± 3). All cows were challenged by infusion with E. coli P4:O32 into 2 left mammary quarters between 14 and 28 d postparturition, at least 10 d after the 3rd vaccination, immediately after the morning milking. Clinical observations and blood and milk samples were collected at several time points from 7 d pre-challenge until 13 d post-challenge. Primiparous cows responded mild to moderately to intramammary E. coli challenge with little clinical difference between treatment groups. Rectal temperature increased earlier in the vaccinated animals, which also eliminated bacteria faster during the early hours after intramammary E. coli challenge. At post-infusion hour 9, the bacterial population was significantly lower in the infected quarters of the vaccinated animals. Blood leukocyte number was only numerically higher in the vaccinated animals, in combination with a numerically higher percentage of late immature polymorphonuclear leukocytes (band cells) in circulation. Even in the nonvaccinated animals, the E. coli challenge in the primiparous cows elicited only a mild to moderate response. The absence of a pronounced clinical difference between vaccinated and nonvaccinated animals was therefore not surprising.
Assuntos
Infecções por Escherichia coli/veterinária , Vacinas contra Escherichia coli/uso terapêutico , Mastite Bovina/prevenção & controle , Animais , Bovinos , Escherichia coli/imunologia , Infecções por Escherichia coli/prevenção & controle , Vacinas contra Escherichia coli/administração & dosagem , Feminino , Contagem de Leucócitos , Mastite Bovina/microbiologia , Leite/microbiologia , Neutrófilos/imunologia , Paridade , Gravidez , Vacinação/veterináriaRESUMO
The present study was performed on 180-day-old commercial Cobb chicks to assess the effects of the probiotic candidate Enterococcus faecalis-1, the Poulvac Escherichia coli vaccine, and their combination on growth parameters, intestinal microbial composition, immune response, and protection against challenge with the avian pathogen E. coli O78. The experimental groups were as follows: G1, basal diet; G2, basal diet and challenge with O78 at 28 days of growth; G3, basal diet, vaccination with Poulvac (1 and 15 days), and challenge with O78 at 28 days of growth; G4, basal diet, E. faecalis-1 supplementation for the first 3 days of growth, and challenge with O78 at 28 days of growth; G5, basal diet, E. faecalis-1 supplementation for the first 3 days of growth, vaccination with Poulvac (1 and 15 days), and challenge with O78 at 28 days of growth; G6, basal diet and E. faecalis-1 supplementation for the first 3 days of growth. The results showed that E. faecalis-1 in drinking water significantly improved the growth performance and immune response, increased the total Enterococcus counts, reduced the mortality, and decreased the visceral invasion by O78 in challenged broilers. While the effect of the Poulvac vaccine alone or with E. faecalis-1 was not significant compared with that of the E. faecalis-1 supplement, the vaccine improved the growth rate and decreased the mortality and visceral invasion by APEC O78 in challenged broilers. These results showed that E. faecalis-1 supplementation and routine vaccination with the Poulvac vaccine could improve the growth performance and immune response of broiler chickens and protect against challenge with APEC O78.
Assuntos
Galinhas , Infecções por Escherichia coli , Vacinas contra Escherichia coli , Microbioma Gastrointestinal , Imunidade , Doenças das Aves Domésticas/prevenção & controle , Probióticos/administração & dosagem , Animais , Galinhas/crescimento & desenvolvimento , Galinhas/imunologia , Galinhas/microbiologia , Infecções por Escherichia coli/prevenção & controle , Infecções por Escherichia coli/veterinária , Vacinas contra Escherichia coli/administração & dosagem , Vacinas contra Escherichia coli/imunologiaRESUMO
Enterotoxigenic Escherichia coli (ETEC) is a major cause of diarrheal disease among children in developing countries, and there are no licensed vaccines to protect against ETEC. Passive immunization by oral delivery of ETEC-specific secretory IgAs (sIgAs) could potentially provide an alternative approach for protection in targeted populations. In this study, a series of physiochemical techniques and an in vitro gastric digestion model were used to characterize and compare key structural attributes and stability profiles of 3 anti-heat-labile enterotoxin mAbs (sIgA1, sIgA2, and IgG1 produced in CHO cells). The mAbs were evaluated in terms of primary structure, N-linked glycan profiles, size and aggregate content, relative apparent solubility, conformational stability, and in vitro antigen binding. Compared to IgG1 mAb, sIgA1 and sIgA2 mAbs showed increased sample heterogeneity, especially in terms of N-glycan composition and the presence of higher molecular weight species. The sIgA mAbs showed overall better physical stability and were more resistant to loss of antigen binding activity during incubation at low pH, 37°C with pepsin. These results are discussed in terms of future challenges to design stable, low-cost formulations of sIgA mAbs as an oral supplement for passive immunization to protect against enteric diseases in the developing world.
Assuntos
Anticorpos Monoclonais/química , Escherichia coli Enterotoxigênica/imunologia , Proteínas de Escherichia coli/química , Vacinas contra Escherichia coli/química , Imunização Passiva , Imunoglobulina A Secretora/química , Administração Oral , Animais , Anticorpos Monoclonais/administração & dosagem , Células CHO , Cricetulus , Diarreia/prevenção & controle , Composição de Medicamentos , Estabilidade de Medicamentos , Infecções por Escherichia coli/prevenção & controle , Vacinas contra Escherichia coli/administração & dosagem , Imunoglobulina GRESUMO
A new HPV-16/18 bivalent vaccine expressed by the Escherichia coli has been proven to be efficacious in adult women. A randomized, immunogenicity noninferiority study of this candidate vaccine was conducted in December 2015 in China. Girls aged 9-14 years were randomized to receive 2 doses at months 0 and 6 (n=301) or 3 doses at months 0, 1 and 6 (n=304). Girls aged 15-17 years (n=149) and women aged 18-26 years (n=225) received 3 doses. The objectives included noninferiority analysis of the IgG geometric mean concentration (GMC) ratio (95% CI, lower bound>0.5) to HPV-16 and HPV-18 at month 7 in girls compared with women. In the per-protocol set, the GMC ratio of IgG was noninferior for girls aged 9-17 years receiving 3 doses compared with women (1.76 (95% CI, 1.56, 1.99) for HPV-16 and 1.93 (95% CI, 1.69, 2.21) for HPV-18) and noninferior for girls aged 9-14 years receiving 2 doses compared with women (1.45 (95% CI, 1.25, 1.62) for HPV-16 and 1.17 (95% CI, 1.02, 1.33) for HPV-18). Noninferiority was also demonstrated for neutralizing antibodies. The immunogenicity of the HPV vaccine in girls receiving 3 or 2 doses was noninferior compared with that in young adult women.
Assuntos
Vacinas contra Escherichia coli/administração & dosagem , Papillomavirus Humano 16/imunologia , Papillomavirus Humano 18/imunologia , Infecções por Papillomavirus/prevenção & controle , Vacinas contra Papillomavirus/administração & dosagem , Adolescente , Adulto , Anticorpos Neutralizantes/metabolismo , Criança , China , Relação Dose-Resposta à Radiação , Escherichia coli/metabolismo , Vacinas contra Escherichia coli/efeitos adversos , Feminino , Humanos , Imunogenicidade da Vacina , Vacinas contra Papillomavirus/efeitos adversos , Resultado do TratamentoRESUMO
TRIAL REGISTRATION: ClinicalTrials.gov ClinicalTrials.gov, Project ID: NCT02870751.
Assuntos
Linfócitos T CD4-Positivos/imunologia , Escherichia coli Enterotoxigênica/imunologia , Enterotoxinas/imunologia , Infecções por Escherichia coli/imunologia , Infecções por Escherichia coli/prevenção & controle , Vacinas contra Escherichia coli/administração & dosagem , Vacinas contra Escherichia coli/imunologia , Adulto , Anticorpos Antibacterianos/sangue , Proteínas da Membrana Bacteriana Externa/imunologia , Contagem de Colônia Microbiana , Diarreia/microbiologia , Diarreia/prevenção & controle , Proteínas de Escherichia coli/imunologia , Feminino , Temperatura Alta , Humanos , Imunoglobulina A/sangue , Imunoglobulina G/sangue , Masculino , Metaloproteases , Voluntários , Adulto JovemRESUMO
Vaccination against coliform mastitis has become part of mastitis control programs in the past 3 decades, as a means of reducing the severity of clinical mastitis. Our study objective was to evaluate the effect of 2 commercially available vaccines on clinical, behavioral, and antibody response following Escherichia coli intramammary challenge in cows near peak lactation. Cows (n = 12 per group) were vaccinated with vaccine 1 (V1) or vaccine 2 (V2) at dry-off, 21 d pre-calving, and 14 d post-calving. Twelve cows served as unvaccinated controls (CTL). Cows were challenged with E. coli in a rear quarter at approximately 100 d in milk. Milk samples were collected pre- and post-challenge to enumerate E. coli and determine somatic cell count. Serum was collected before each vaccination and at d 0, 1, 2, 3, 6, 30, and 60 relative to challenge, to study antibody response. Milk IgA and tumor necrosis factor-α concentrations were determined in whey. Vaginal temperature, cow activity, and milk yield and components were monitored post-challenge. Bacterial count, somatic cell score, milk yield and component decline, vaginal temperature, activity measures, and antibody and cytokine response were analyzed for treatment differences. The effects of parity, breed, and a repeated measure of time were also tested. Seven cows had to be removed from the study post-challenge for antibiotic treatment (CTL and V1, n = 3 each; V2, n = 1), 2 of which were euthanized (both CTL). Vaccinated cows exhibited fever (vaginal temperature ≥39.4°C) 3 h earlier than CTL cows, but we found no differences between treatments for bacterial count, somatic cell score, or milk yield reduction. Vaccinated cows spent more time lying per rest bout 2 d post-challenge, but total daily lying time was not different from CTL cows during the 7 d post-challenge. The vaccines differed in antibody response: V1 cows had greater serum IgG1 and IgG2 post-challenge. A parity effect was also evident: primiparous cows had lower bacterial counts, somatic cell score and a smaller milk yield decline than multiparous cows, but also had lower antibody production. Immunization with either J5 bacterin did not reduce clinical signs of mastitis in cows challenged at 100 d in milk, demonstrating that the effects of J5 vaccination had diminished at peak lactation.