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1.
J Med Microbiol ; 68(10): 1408-1418, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31418679

RESUMO

Respiratory tract infections are responsible for over 2.8 million deaths per year worldwide. Colonization is the first step in the process of microbes occupying the respiratory tract, which may lead to subsequent infection. Carriage, in contrast, is defined as the occupation of microbial species in the respiratory tract. The duration of carriage may be affected by host immunity, the composition and interactions between members of the microbial community, and the characteristics of colonizing bacteria, including physiology associated with being present in a bacterial biofilm. Numerous vaccines have been implemented to control infections caused by bacteria that can colonize and be subsequently carried. Such vaccines are often species-specific and may target a limited number of strains thereby creating a vacant niche in the upper respiratory tract. Epidemiological changes of bacteria found in both carriage and disease have therefore been widely reported, since the vacant niche is filled by other strains or species. In this review, we discuss the use of carriage-prevalence studies in vaccine evaluation and argue that such studies are essential for (1) examining the epidemiology of carriage before and after the introduction of new vaccines, (2) understanding the dynamics of the respiratory tract flora and (3) identifying the disease potential of emerging strains. In an era of increasing antibiotic resistance, bacterial carriage-prevalence studies are essential for monitoring the impact of vaccination programmes.


Assuntos
Infecções Bacterianas/microbiologia , Vacinas Bacterianas/imunologia , Portador Sadio/microbiologia , Infecções Respiratórias/microbiologia , Animais , Infecções Bacterianas/epidemiologia , Infecções Bacterianas/imunologia , Infecções Bacterianas/prevenção & controle , Vacinas Bacterianas/administração & dosagem , Vacinas Bacterianas/genética , Portador Sadio/epidemiologia , Portador Sadio/imunologia , Portador Sadio/prevenção & controle , Humanos , Infecções Respiratórias/epidemiologia , Infecções Respiratórias/imunologia , Infecções Respiratórias/prevenção & controle , Vacinação
2.
APMIS ; 127(10): 671-680, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31344276

RESUMO

Regardless of the communal impact of Shiga toxins, till today neither a specific treatment nor licensed vaccine is available. Lactococcus lactis (L. lactis), generally regarded as safe organism, is well known to provide a valuable approach regarding the oral delivery of vaccines. This study was undertaken to evaluate the protective efficacy of Stx2a1 expressed in nisin-inducible L. lactis, against Shiga toxins (Stx1, Stx2) in mouse model. Oral immunization of BALB/c mice with LL-Stx2a1 elicited significant serum antibody titer with elevated fecal and serum IgA, along with minimized intestinal and kidney damage resulting in survival of immunized animals at 84% and 100% when challenged with 10 × LD50 of Escherichia coli O157 and Shigella dysenteriae toxins, respectively. HeLa cells incubated with immune sera and toxin mixture revealed high neutralizing capacity with 90% cell survivability against both the toxins. Mice immunized passively with both toxins and antibody mixture survived the observation period of 15 days, and the controls administered with sham sera and toxins were succumbed to death within 3 days. Our results revealed protective efficacy and toxin neutralization ability of LL-Stx2a1, proposing it as an oral vaccine candidate against Shiga toxicity mediated by E. coli O157 and S. dysenteriae.


Assuntos
Vacinas Bacterianas/administração & dosagem , Vacinas Bacterianas/imunologia , Escherichia coli O157/imunologia , Envenenamento/prevenção & controle , Toxina Shiga/imunologia , Toxina Shiga/toxicidade , Shigella dysenteriae/imunologia , Administração Oral , Animais , Anticorpos Antibacterianos/administração & dosagem , Anticorpos Antibacterianos/sangue , Anticorpos Neutralizantes/administração & dosagem , Anticorpos Neutralizantes/sangue , Antitoxinas/administração & dosagem , Antitoxinas/sangue , Vacinas Bacterianas/genética , Sobrevivência Celular/efeitos dos fármacos , Modelos Animais de Doenças , Portadores de Fármacos/administração & dosagem , Escherichia coli O157/genética , Vetores Genéticos/administração & dosagem , Células HeLa , Humanos , Lactococcus lactis/genética , Camundongos , Camundongos Endogâmicos BALB C , Toxina Shiga/genética , Shigella dysenteriae/genética , Análise de Sobrevida , Resultado do Tratamento , Vacinas Sintéticas/administração & dosagem , Vacinas Sintéticas/genética , Vacinas Sintéticas/imunologia
3.
J Microbiol Biotechnol ; 29(7): 1165-1176, 2019 Jul 28.
Artigo em Inglês | MEDLINE | ID: mdl-31280529

RESUMO

Botulinum neurotoxins (BoNTs), produced by Clostridium botulinum, are the most toxic substances known. However, the number of currently approved medical countermeasures for these toxins is very limited. Therefore, studies on therapeutic antitoxins are essential to prepare for toxin-related emergencies. Currently, more than 10,000 Halla horses, a crossbreed between the native Jeju and Thoroughbred horses, are being raised in Jeju Island of Korea. They can be used for equine antitoxin experiments and production of hyperimmune serum against BoNT/A1. Instead of the inactivated BoNT/A1 toxoid, Halla horse was immunized with the receptor-binding domain present in the C-terminus of heavy chain of BoNT/A1 (BoNT/A1-HCR) expressed in Escherichia coli. The anti-BoNT/A1-HCR antibody titer increased rapidly by week 4, and this level was maintained for several weeks after boosting immunization. Notably, 20 µL of the week 24 BoNT/A1-HCR(-immunized) equine serum showed an in vitro neutralizing activity of over 8 international unit (IU) of a reference equine antitoxin. Furthermore, 20 µL of equine serum and 100 µg of purified equine F(ab')2 showed 100% neutralization of 10,000 LD50 in vivo. The results of this study shall contribute towards optimizing antitoxin production for BoNT/A1, which is essential for emergency preparedness and response.


Assuntos
Anticorpos Antibacterianos/imunologia , Vacinas Bacterianas/imunologia , Antitoxina Botulínica/imunologia , Toxinas Botulínicas Tipo A/imunologia , Clostridium botulinum/imunologia , Fragmentos de Peptídeos/imunologia , Animais , Anticorpos Antibacterianos/sangue , Vacinas Bacterianas/química , Antitoxina Botulínica/sangue , Toxinas Botulínicas Tipo A/química , Feminino , Cavalos , Imunização/veterinária , Camundongos Endogâmicos BALB C , Testes de Neutralização/veterinária , Fragmentos de Peptídeos/química , Coelhos
4.
Vet Immunol Immunopathol ; 213: 109887, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31307668

RESUMO

Chlamydia abortus produces ovine enzootic abortion (OEA). Symptoms are not observed until the organism colonises the placenta, eventually causing abortion. Infected animals become carriers and will shed the organism in the following oestruses. This process suggests that sex hormones might play an important role in the physiopathology of OEA, affecting the success of chlamydial clearance and also jeopardising the effectiveness of vaccination. However, the mechanisms through which sex hormones are involved in chlamydial pathogenicity remain unclear. The aim of this study, therefore, was to determine the effect of progesterone on the immune response against C. abortus and on the protection conferred by an experimental inactivated vaccine in sheep. Eighteen sheep were ovariectomised and divided into four groups: vaccinated and progesterone-treated (V-PG), vaccinated and non-treated (V-NT), non-vaccinated and non-treated (NV-NT) and non-vaccinated and progesterone-treated sheep (NV-PG). Animals from both PG groups were treated with commercial medroxyprogesterone acetate impregnated intravaginal sponges before and during the vaccination (V-PG) or just before challenge (NV-PG). The animals from both V groups were subcutaneously immunised with an experimental inactivated vaccine, which was seen to confer high protection in previous studies. All sheep were challenged intratracheally with C. abortus strain AB7 and were sacrificed on day 8 post-infection. Morbidity was measured as the variation in rectal temperature and samples of sera were collected for antibody and cytokine (IFN-γ and IL-10) analysis by commercial ELISA. In addition, lung and lymph node samples were collected for chlamydial detection by qPCR and for histopathological and immunohistochemical analyses. Sheep from the V-PG group showed less severe or no lesions and lower morbidity than the other groups. They also had the highest abundance of regulatory T-cells. The sheep from V-NT also manifested high antibody levels against C. abortus and less severe lesions than those observed in non-vaccinated sheep, which showed high morbidity, low antibody levels and severe lesions, especially in NV-NT. These results confirm the effectiveness of the experimental vaccine employed and suggest that progesterone could enhance the effect.


Assuntos
Vacinas Bacterianas/uso terapêutico , Infecções por Chlamydia/veterinária , Imunidade Humoral , Progesterona/administração & dosagem , Doenças dos Ovinos/imunologia , Aborto Animal/imunologia , Aborto Animal/prevenção & controle , Animais , Anticorpos Antibacterianos/sangue , Vacinas Bacterianas/imunologia , Chlamydia/imunologia , Infecções por Chlamydia/imunologia , Ensaio de Imunoadsorção Enzimática , Feminino , Ovinos , Doenças dos Ovinos/microbiologia , Vacinas de Produtos Inativados/imunologia , Vacinas de Produtos Inativados/uso terapêutico
5.
Protein Pept Lett ; 26(5): 324-331, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31237198

RESUMO

Antimicrobial resistance (AMR) reported to increase globally at alarming levels in the recent past. A number of potential alternative solutions discussed and implemented to control AMR in bacterial pathogens. Stringent control over the clinical application of antibiotics for a reduction in uses is a special consideration along with alternative solutions to fight against AMR. Although alternatives to conventional antibiotics like antimicrobial peptides (AMP) might warrant serious consideration to fight against AMR, there is a thriving recognition for vaccines in encountering the problem of AMR. Vaccines can reduce the prevalence of AMR by reducing the number of specific pathogens, which result in cutting down the antimicrobial need and uses. However, conventional vaccines produced using live or attenuated microorganisms while the presence of immunologically redundant biological components or impurities might cause major side effects and health related problems. Here we discussed AMPs based vaccination strategies as an emerging concept to overcome the disadvantages of traditional vaccines while boosting the AMPs to control multidrug resistant bacteria or AMR. Nevertheless, the poor immune response is a major challenge in the case of peptide vaccines as minimal antigenic epitopes used for immunization in peptide vaccines.


Assuntos
Peptídeos Catiônicos Antimicrobianos/imunologia , Vacinas Bacterianas/imunologia , Adjuvantes Imunológicos , Animais , Peptídeos Catiônicos Antimicrobianos/química , Desenvolvimento de Medicamentos , Farmacorresistência Bacteriana Múltipla , Humanos , Imunidade Inata , Vacinas de Subunidades/imunologia
6.
J Vet Sci ; 20(3): e24, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31161742

RESUMO

Porcine proliferative enteropathy (PPE) caused by Lawsonia intracellularis (LI) is a global cause for substantial economic losses in the swine industry. Here, we constructed live attenuated Salmonella typhimurium (ST) mutant strains expressing and secreting 4 selected immunogenic LI antigens, namely, optA, optB, Lawsonia flagellin (LfliC), and Lawsonia hemolysin (Lhly); the resultant recombinant strains were designated Sal-optA, Sal-optB, Sal-LfliC, or Sal-Lhly, respectively. Using the BALB/c mouse model, we demonstrate that mice vaccinated once orally, either with a mixture of all 4 recombinant strains or with an individual recombinant strain, show significant (p < 0.05) production of LI-specific systemic immunoglobulin (Ig) G and mucosal IgA responses compared to the Salmonella alone group. Upon restimulation of vaccinated splenocytes with the LI-specific antigens, significant (p < 0.05) and comparable production of interferon-γ responses are found in all vaccinated groups, except the Sal-Lhly group, which shows non-significant levels. Challenge studies were performed in C57BL/6 vaccinated mice. On challenge with the LI (106.9 50% tissue culture infectious dose) 14 days post-vaccination, 20% (1/5) of mice in all vaccinated groups, except Sal-Lhly group, show the presence of the LI-specific genomic DNA (gDNA) in stool samples. In contrast, 40% (2/5) and 60% (3/5) of mice vaccinated with the Sal-Lhly strain and the attenuated Salmonella alone, respectively, were found positive for the LI-specific gDNA. Furthermore, 0% mortality was observed in mice vaccinated against the ST challenge compared to the 30% mortality observed in the unvaccinated control group. In conclusion, we demonstrate that the Salmonella-based LI-vaccines induce LI-specific humoral and cell-mediated immunities, and encompass the potential to offer dual protection against PPE and salmonellosis.


Assuntos
Antígenos de Bactérias/imunologia , Vacinas Bacterianas/imunologia , Infecções por Desulfovibrionaceae/prevenção & controle , Lawsonia (Bactéria)/imunologia , Infecções por Salmonella/prevenção & controle , Vacinas contra Salmonella/imunologia , Animais , Anticorpos Antibacterianos/sangue , Vacinas Bacterianas/administração & dosagem , Células Cultivadas , DNA Bacteriano/análise , Infecções por Desulfovibrionaceae/imunologia , Infecções por Desulfovibrionaceae/mortalidade , Modelos Animais de Doenças , Fezes/microbiologia , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Infecções por Salmonella/mortalidade , Vacinas contra Salmonella/administração & dosagem , Suínos , Doenças dos Suínos/imunologia , Doenças dos Suínos/mortalidade , Doenças dos Suínos/prevenção & controle , Vacinas Atenuadas/imunologia
7.
J Anim Sci ; 97(7): 2739-2749, 2019 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-31069378

RESUMO

The goal of this study was to compare the cell-mediated immune responses of highly commingled, sale-barn origin calves (STR; n = 10) to those of single source calves that had been weaned for 60 d (UNS; n = 10). Peripheral blood mononuclear cells and neutrophils (PMNs) were isolated from jugular venous blood of each calf. Peripheral blood mononuclear cells were stimulated with Concanavalin A (ConA), BVDV-1, BVDV-2, BHV-1, Mannheimia haemolytica, and Pasteurella multocida and evaluated for clonal proliferation and secretion of IL-8 into cell culture supernatants. The native functional capacities of PMNs were evaluated in response to stimulation with heat-killed Escherichia coli and Staphylococcus aureus. Complete blood counts and serum biochemical profiles were performed for each animal at the time of sample collection. Compared with STR calves, UNS calves had greater lymphocyte proliferative responses following stimulation BVDV1 (P = 0.041), BVDV2 (P = 0.002), BHV-1 (P = 0.001), M. haemolytica (P = 0.016), and P. multocida (P = 0.049). In addition, PMNs isolated from UNS calves had a greater ability to phagocytose E. coli (P = 0.001) and S. aureus (P = 0.003) when compared with STR calves. Serum nonesterified fatty acids were higher in STR calves (P < 0.001). Serum ß-hydroxybutyrate was lower in STR calves (P < 0.003). These data suggest that immunologic and physiologic differences exist between STR and UNS calves. Although the underlying mechanisms for these differences are not clear, it is possible that combinations of energy imbalances, stress-induced immunosuppression, and general immune naiveté may predispose STR calves to an increased risk of morbidity and mortality due to bovine respiratory disease.


Assuntos
Vacinas Bacterianas/imunologia , Doenças dos Bovinos/imunologia , Imunidade Celular , Vacinas Virais/imunologia , Animais , Bovinos , Doenças dos Bovinos/prevenção & controle , Concanavalina A/imunologia , Vírus da Diarreia Viral Bovina/imunologia , Escherichia coli/imunologia , Herpesvirus Bovino 1/imunologia , Leucócitos Mononucleares/imunologia , Masculino , Mannheimia haemolytica/imunologia , Neutrófilos/imunologia , Pasteurella multocida/imunologia , Distribuição Aleatória , Staphylococcus aureus/imunologia , Estresse Fisiológico , Vacinas Atenuadas/imunologia , Desmame
8.
Microb Pathog ; 133: 103559, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31132417

RESUMO

Aeromonas salmonicida, the oldest known fish pathogen and currently endemic throughout most of the world in both fresh and marine waters, causes severe economic losses to the salmon farming industry. Although there have been many studies on the prevention of furunculosis over the past few decades, it is still prevalent in many fisheries. In this study, a recombinant adenovirus vaccine candidate harboring the highly immunogenic Vapa gene (pAd-easy-cmv-Vapa) was successfully constructed and tested. The immune protection rate and specific antibody levels in the peripheral blood were then determined after immunizing rainbow trout. In addition, relative levels of IgM and IgT in the head kidney and hindgut before and after immunization were measured by quantitative reverse transcription PCR. Western blotting results indicated that the recombinant adenovirus could infect HEK-293 cells and express the A layer protein (encoded by Vapa). Further, survival analysis of fish 28 days after challenge showed that immunization significantly lowered the mortality rate (40%) compared to that in the control group (76.6%) and empty vector group (73.6%). This also led to an increase in specific antibodies in peripheral serum. In addition, levels of IgM and IgT in the head kidney and hindgut were increased to varying degrees. In conclusion, our research provides a candidate vaccine for the prevention of Aeromonas salmonicida A450 infection in rainbow trout and lays the foundation for future research on adaptive immune mechanisms associated with rainbow trout antibodies.


Assuntos
Adenoviridae/genética , Aeromonas salmonicida/imunologia , Doenças dos Peixes/prevenção & controle , Infecções por Bactérias Gram-Negativas/imunologia , Infecções por Bactérias Gram-Negativas/veterinária , Imunização , Vacinas Sintéticas/imunologia , Imunidade Adaptativa , Vacinas contra Adenovirus , Aeromonas salmonicida/genética , Sequência de Aminoácidos , Animais , Anticorpos , Antígenos de Bactérias/genética , Antígenos de Bactérias/imunologia , Vacinas Bacterianas/genética , Vacinas Bacterianas/imunologia , Doenças dos Peixes/imunologia , Doenças dos Peixes/microbiologia , Infecções por Bactérias Gram-Negativas/microbiologia , Células HEK293 , Interações Hospedeiro-Patógeno , Humanos , Imunoglobulina M , Rim/imunologia , Oncorhynchus mykiss , Vacinação , Vacinas Sintéticas/genética
9.
mSphere ; 4(3)2019 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-31043512

RESUMO

Campylobacter jejuni is among the most common causes of diarrheal disease worldwide and efforts to develop protective measures against the pathogen are ongoing. One of the few defined virulence factors targeted for vaccine development is the capsule polysaccharide (CPS). We have developed a capsule conjugate vaccine against C. jejuni strain 81-176 (CPS-CRM) that is immunogenic in mice and nonhuman primates (NHPs) but only moderately immunogenic in humans when delivered alone or with aluminum hydroxide. To enhance immunogenicity, two novel liposome-based adjuvant systems, the Army Liposome Formulation (ALF), containing synthetic monophosphoryl lipid A, and ALF plus QS-21 (ALFQ), were evaluated with CPS-CRM in this study. In mice, ALF and ALFQ induced similar amounts of CPS-specific IgG that was significantly higher than levels induced by CPS-CRM alone. Qualitative differences in antibody responses were observed where CPS-CRM alone induced Th2-biased IgG1, whereas ALF and ALFQ enhanced Th1-mediated anti-CPS IgG2b and IgG2c and generated functional bactericidal antibody titers. CPS-CRM + ALFQ was superior to vaccine alone or CPS-CRM + ALF in augmenting antigen-specific Th1, Th2, and Th17 cytokine responses and a significantly higher proportion of CD4+ IFN-γ+ IL-2+ TNF-α+ and CD4+ IL-4+ IL-10+ T cells. ALFQ also significantly enhanced anti-CPS responses in NHPs when delivered with CPS-CRM compared to alum- or ALF-adjuvanted groups and showed the highest protective efficacy against diarrhea following orogastric challenge with C. jejuni This study provides evidence that the ALF adjuvants may provide enhanced immunogenicity of this and other novel C. jejuni capsule conjugate vaccines in humans.IMPORTANCE Campylobacter jejuni is a leading cause of diarrheal disease worldwide, and currently no preventative interventions are available. C. jejuni is an invasive mucosal pathogen that has a variety of polysaccharide structures on its surface, including a capsule. In phase 1 studies, a C. jejuni capsule conjugate vaccine was safe but poorly immunogenic when delivered alone or with aluminum hydroxide. Here, we report enhanced immunogenicity of the conjugate vaccine delivered with liposome adjuvants containing monophosphoryl lipid A without or with QS-21, known as ALF and ALFQ, respectively, in preclinical studies. Both liposome adjuvants significantly enhanced immunity in mice and nonhuman primates and improved protective efficacy of the vaccine compared to alum in a nonhuman primate C. jejuni diarrhea model, providing promising evidence that these potent adjuvant formulations may enhance immunogenicity in upcoming human studies with this C. jejuni conjugate and other malaria and HIV vaccine platforms.


Assuntos
Vacinas Bacterianas/imunologia , Infecções por Campylobacter/prevenção & controle , Imunogenicidade da Vacina , Lipídeo A/análogos & derivados , Saponinas/administração & dosagem , Adjuvantes Imunológicos/administração & dosagem , Animais , Anticorpos Antibacterianos/sangue , Infecções por Campylobacter/imunologia , Campylobacter jejuni/imunologia , Citocinas/imunologia , Feminino , Humanos , Imunoglobulina G/imunologia , Lipídeo A/administração & dosagem , Lipossomos/administração & dosagem , Lipossomos/química , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Primatas , Células Th1/imunologia , Células Th2/imunologia , Vacinas Conjugadas/administração & dosagem
10.
Fish Shellfish Immunol ; 90: 317-327, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31039442

RESUMO

Mycobacteriosis is a chronic progressive disease affecting teleost fishes all over the world. No vaccine is commercially available against its main etiological agent, Mycobacterium marinum. The mycobacterial gene responsible for invasion and intracellular persistence, iipA, is known to modulate M. marinum pathology. The innate and adaptive immune responses in sea bass (Dicentrarchus labrax) vaccinated with M. marinum iipA::kan mutant with (and without) the use of adjuvant, with (and without) a booster vaccination were monitored. The adjuvanted vaccine induced enhanced immune responses. TNF-α transcription levels were extremely high in spleen of the fish vaccinated with the addition of adjuvant in both fish vaccinated once and twice, followed by an IgM response highly specific for M. marinum. Also, histologically, granulomas started appearing in spleen and head-kidney tissues (but with no visible bacteria) within a month after vaccination, mainly with the adjuvanted vaccine. This was followed by reduction in pathology, as demonstrated by the lower number of granulomas (with visible bacteria), indicating that even heat-killed bacteria were able to elicit granulomatous formations. Adhesion of the internal organs and moderate pigmentation were observed in the perivisceral adipose tissue of nearly all vaccinated fish. Although the adjuvanted heat-killed avirulent iipA::kan mutant clearly induced a strong humoral and adaptive immune response, the booster treatment did not seem to have produced a significantly higher degree of protection from the disease compared to fish that received a single vaccination.


Assuntos
Vacinas Bacterianas/imunologia , Bass , Doenças dos Peixes/prevenção & controle , Infecções por Mycobacterium/veterinária , Mycobacterium marinum/imunologia , Vacinação/veterinária , Imunidade Adaptativa , Adjuvantes Imunológicos , Animais , Imunidade Inata , Imunização Secundária/veterinária , Infecções por Mycobacterium/prevenção & controle , Distribuição Aleatória
11.
Fish Shellfish Immunol ; 90: 431-439, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31082516

RESUMO

The effectiveness of ionotropic gelation method (by combining alginate and chitosan) vaccine against Lactococcus garvieae and Streptococcus iniae was examined in rainbow trout. Fish were separated into four groups and fed the distinctive examined feeds. Our groups were included: A) fish immunized by chitosan-alginate coated vaccine, B) fish immunized by non-coated vaccine, C) fish feed by chitosan-alginate coated pellets without vaccine and D) fish feed by basic diet (non-coated and without vaccine). In groups A and B, the vaccination was carried out for 14 days. Fish of group C, like groups A and B were fed 14 days with pellets covered with chitosan-alginate without vaccine and a short time later they were fed with control diet. On day 0, 20, 40 and 60 of the trial, serum samples were extracted. Fish were challenged with L. garvieae and S. iniae after 60 days of research. Innate immunity components containing complement activity, total protein and IgM appeared no significant changes nearly in all groups during the 60 days that the examination finished. Although, bactericidal activity and lysozyme activity demonstrated a significant increase on days 20, 40 and 60 in group A compared to control groups (C and D) (P < 0.05) and similar results about the blood respiratory burst activity just on days 20 and 40 were obtained. Also, the relative expression of IL-6 of group A, was significantly higher compared to all of other groups (B, C and D) on days 20 and 60 of experiment (P < 0.05). The same results were obtained about the relative expression of IgM. The serum ELISA antibody titer against L. garvieae, increased significantly on days 20 and 40 of experiment in fish immunized by chitosan-alginate coated vaccine (Group A) compared to control groups (C and D)(P < 0.05) while the result of ELISA test against S. iniae was significantly higher on days 40 and 60 of experiment in group A compared to groups B, C and D (P < 0.05). After challenge with these two live bacteria (S. iniae and L. garvieae), a survival rates of 76.67 ±â€¯5.77% (challenged with S. iniae) and 66.67 ±â€¯5.77% (challenged with L. garvieae) were seen in group immunized with chitosan-alginate coated vaccine (Group A), which were higher than survival rates gotten in other trial groups (P < 0.05). The consequences of the present experiment show that the oral vaccination of rainbow trout with improved chitosan-alginate (via ionotropic procedure) (group A) properly secures this important fish against Lactococcus garvieae and Streptococcus iniae.


Assuntos
Vacinas Bacterianas/imunologia , Doenças dos Peixes/prevenção & controle , Infecções por Bactérias Gram-Positivas/veterinária , Lactococcus/imunologia , Oncorhynchus mykiss/imunologia , Streptococcus iniae/imunologia , Administração Oral , Alginatos/farmacologia , Animais , Quitosana/farmacologia , Infecções por Bactérias Gram-Positivas/prevenção & controle , Infecções Estreptocócicas/prevenção & controle , Infecções Estreptocócicas/veterinária , Vacinas Estreptocócicas/imunologia
12.
J Fish Dis ; 42(7): 1057-1064, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31087342

RESUMO

Lumpfish (Cyclopterus lumpus), a native fish of the North Atlantic Ocean, is utilized as cleaner fish to biocontrol sea lice infestations in Atlantic salmon aquaculture. However, bacterial infections are affecting cleaner fish performance. Vibrio anguillarum, the aetiological agent of vibriosis, is one of the most frequent bacterial infections in lumpfish, and effective vaccine programmes against this pathogen have been identified as a high priority for lumpfish. Vibrogen-2 is a commercial polyvalent bath vaccine that contains formalin-inactivated cultures of V. anguillarum serotypes O1 and O2, and Vibrio ordalii. In this study, we evaluated Vibrogen-2 efficacy in lumpfish against a local isolated V. anguillarum strain. Two groups of 125 lumpfish were bath-immunized, bath-boost-immunized at four weeks post-primary immunization, and intraperitoneally (i.p.) boost-immunized at eight weeks post-primary immunization. The control groups were i.p. mock-immunized with PBS. Twenty-seven weeks post-primary immunization, the fish were i.p. challenged with 10 or 100 times the V. anguillarum J360 LD50 dose. After the challenge, survival was monitored daily, and samples of tissues were collected at ten days post-challenge. Commercial vaccine Vibrogen-2 reduced V. anguillarum tissue colonization and delayed mortality but did not confer immune protection to C. lumpus against the V. anguillarum i.p. challenge.


Assuntos
Vacinas Bacterianas/uso terapêutico , Doenças dos Peixes/prevenção & controle , Peixes/microbiologia , Vibrioses/veterinária , Vibrio/imunologia , Animais , Aquicultura , Vacinas Bacterianas/imunologia , Agentes de Controle Biológico , Doenças dos Peixes/imunologia , Imersão , Dose Letal Mediana , Vacinação/métodos , Vacinas de Produtos Inativados/imunologia , Vacinas de Produtos Inativados/uso terapêutico , Vibrioses/imunologia , Vibrioses/prevenção & controle
13.
Mol Immunol ; 111: 182-197, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31078054

RESUMO

The type VI secretion system (T6SS) has recently emerged as a new pattern of protein secretions in Campylobacter jejuni (C. jejuni). Within the T6SS cluster, hemolysin co-regulated protein (hcp) is considered as a hallmark of functional T6SS and holds key role in bacterial virulence. As poultry is the primary reservoir of C. jejuni and the major sources for human infection, we evaluated the capacity of recombinant hcp (rhcp) immunization in blocking C. jejuni colonization in chickens with an aim to control bacterial transmission to humans via poultry food chain. Considering the mucosal route is the primary portal for C. jejuni entry and gut mucosa offers the apposite site for C. jejuni adherence, we investigated the immune-protective potential of intra-gastric administration of rhcp using chitosan-based nanoparticles. To achieve this goal, full length coding sequence of hcp gene from C. jejuni was cloned and expressed in E. coli. Purified rhcp was entrapped in chitosan-Sodium tripolyphosphate nanoparticles (CS-TPP NPs) and orally gavaged in chickens. Our results suggest that intra-gastric immunization of CS-TPP-rhcp induces consistent and steady increase in intestinal (sIgA) and systemic antibody (IgY) response against rhcp with significant reduction in cecal load of C. jejuni. The protection afforded by rhcp associated cellular responses with Th1 and Th17 profile in terms of increased expression of NFkB, IL-1ß, IL-8, IL-6, IFN-γ and IL-17 A genes. Though systemic immunization of rhcp with IFA resulting in a robust systemic (IgY) and local (sIgA) antibody response, mucosal administration of rhcp loaded CS-TPP NPs was found to be superior in terms of bacterial clearance. Altogether, present study suggests that chitosan based intra-gastric delivery of rhcp have several advantages over the injectable composition and could be a promising vaccine approach to effectively control C. jejuni colonization in chickens.


Assuntos
Formação de Anticorpos/imunologia , Campylobacter jejuni/imunologia , Galinhas/imunologia , Mucosa Gástrica/imunologia , Proteínas com Ferro-Enxofre/imunologia , Proteínas Recombinantes/imunologia , Sistemas de Secreção Tipo VI/imunologia , Animais , Proteínas de Bactérias/imunologia , Vacinas Bacterianas/imunologia , Ceco/imunologia , Ceco/microbiologia , Galinhas/microbiologia , Escherichia coli/imunologia , Mucosa Gástrica/microbiologia , Proteínas Hemolisinas/imunologia , Imunização/métodos , Doenças das Aves Domésticas/imunologia , Doenças das Aves Domésticas/microbiologia , Células Th1/imunologia , Células Th17/imunologia
14.
Mol Immunol ; 111: 198-204, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31078966

RESUMO

Group B Streptococcus (GBS) represents one of the most common causes of bacterial infection in neonates; it is also associated with premature childbirth and stillbirth. A vaccine against GBS is needed, but no approved vaccines are yet available. The Surface Immunogenic Protein (SIP) of GBS is conserved in all serotypes and had been reported to be a good vaccine prototype in a mouse model of GBS infection. Also, we have previously shown that both subcutaneous and oral immunization with rSIP can induce an efficient immune response that decreases GBS vaginal colonization in mice. In this study, we show that a vaccine based on a mixture of rSIP and AbISCO-100 adjuvant reduces GBS vaginal colonization in mice and induces antibodies with opsonophagocytic activities. Moreover, the passive transfer of sera and total T-cells from mice immunized with rSIP mixed with AbISCO-100 to unvaccinated mice decreases vaginal GBS colonization in an infected mouse. This is the first report of cellular immunity associated with rSIP-based vaccine testing in a mouse model of GBS infection.


Assuntos
Formação de Anticorpos/imunologia , Imunidade Celular/imunologia , Infecções Estreptocócicas/imunologia , Streptococcus/crescimento & desenvolvimento , Adjuvantes Imunológicos/farmacologia , Animais , Anticorpos Antibacterianos/imunologia , Vacinas Bacterianas/imunologia , Feminino , Imunização/métodos , Camundongos , Camundongos Endogâmicos C57BL , Vacinação/métodos
15.
Curr Top Microbiol Immunol ; 421: 1-19, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31123883

RESUMO

It has been over 30 years since a link was established between H. pylori infection of the gastric mucosa and the development of chronic gastric diseases. Research in rodent models supported by data from human tissue demonstrated that the host immune response to H. pylori is limited by host regulatory T cells. Immunization has been shown to induce a potent Th1- and Th17-mediated immune response capable of eradicating or at least significantly reducing the bacterial load of H. pylori in the stomach in small animal models. These results have not translated well to humans. Clinical trials employing many of the strategies used in rodents for oral immunization including the use of a mucosal adjuvant such as Escherichia coli LT or delivery by attenuated enteric bacteria have failed to limit H. pylori infection and have highlighted the potential toxicity of exotoxin-based mucosal adjuvants. A recent study, however, utilizing a recombinant fusion protein of H. pylori urease and the subunit B of E. coli LT, was performed on over 4000 children. Efficacy of over 70% was demonstrated against naturally acquired infection compared to control volunteers one year post-immunization. Efficacy was reduced, but still above 50% at three years. This study provided new insight into the strategies for developing an improved vaccine for widespread use in countries with high infection rates and where gastric cancer (GC) remains one of the most common causes of death due to cancer.


Assuntos
Vacinas Bacterianas/imunologia , Mucosa Gástrica/microbiologia , Infecções por Helicobacter/imunologia , Infecções por Helicobacter/patologia , Helicobacter pylori/imunologia , Helicobacter pylori/patogenicidade , Animais , Anticorpos Antibacterianos/imunologia , Vacinas Bacterianas/química , Escherichia coli/imunologia , Mucosa Gástrica/imunologia , Mucosa Gástrica/patologia , Infecções por Helicobacter/microbiologia , Infecções por Helicobacter/prevenção & controle , Humanos , Inflamação/imunologia , Inflamação/microbiologia , Inflamação/patologia
16.
Fish Shellfish Immunol ; 89: 498-504, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30981887

RESUMO

Pseudomonas plecoglossicida is well-known as the cause of viscera granulomas disease in fish. In this study, a cspA1 knock-down strain was constructed and tested in Epinephelus coioides to observe the changes in virulence and evaluate its potential as an attenuated live vaccine. The results showed that the cspA1 knock-down strain caused a significant reduction in the ability of biofilm formation, motility, adhesion and virulence. E. coioides vaccinated with cspA1 knock-down strain were more tolerant of the infection by wild-type P. plecoglossicida. The relative percent survival value of E. coioides vaccinated with cspA1 knock-down strain reached 80% after challenging with wild-type P. plecoglossicida. In the meanwhile, the expression level of genes associated with immunity, including IL-1ß, IgM, MHC-I and MHC-II, was up-regulated after vaccination, indicating that the cspA1 knock-down strain can induce effective and durable immune response in E. coioides and it may be an effective attenuated live vaccine candidate for the prevention of infections by P. plecoglossicida.


Assuntos
Vacinas Bacterianas/imunologia , Bass , Doenças dos Peixes/imunologia , Infecções por Pseudomonas/veterinária , Pseudomonas/imunologia , Vacinação/veterinária , Animais , Proteínas de Bactérias/imunologia , Doenças dos Peixes/prevenção & controle , Infecções por Pseudomonas/imunologia , Infecções por Pseudomonas/prevenção & controle , Vacinas Atenuadas/imunologia
17.
Zoonoses Public Health ; 66(5): 470-479, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-30942554

RESUMO

An epidemiological investigation was conducted in an unvaccinated dairy farming enterprise in which three workers on one of the milking herds (Herd 1) were diagnosed with leptospirosis due to serovars Hardjo (H) (n = 2) and Pomona (P) (n = 1) between January and March 2015. Blood and urine samples were collected from milking cows in Herd 1 (N = 230) and Herd 2 (N = 400), rising one- (R1, N = 125) and rising two-year-old (R2, N = 130) replacement heifers, and four pigs associated with Herd 1, in March 2015. Sera were tested using the MAT for serovars H, P, Copenhageni (C), Ballum (B) and Tarassovi (T), and urine samples were tested by qPCR. Seventy-five per cent of 109 cows in Herd 1 and 36% of 121 in Herd 2 were seropositive (≥48), predominantly to H and P, and 23% of 74 cows in Herd 1 and 1% of 90 cows in Herd 2 were qPCR positive. Fifty-five per cent of 42 R2 heifers were seropositive to T. No R1 and 17% of 42 R2 heifers were qPCR positive. Subsequently, all cattle were vaccinated for H and P, and Herds 1 and 2 were given amoxicillin. After the booster vaccination, 7% of 91 in Herd 1, 2% of 82 in Herd 2 and 11% of 38 R1 heifers (sampled as R2) were PCR positive. After the amoxicillin treatment, no cows in Herd 1 and 5% of 62 cows in Herd 2 were urine PCR positive. Calves and pigs were seropositive to H, P, C and B. Vaccination and antibiotic treatment appeared effective in reducing the risk of exposure of workers to vaccine serovars. However, evidence of non-vaccine serovars indicated that workers likely remain at risk of exposure to Leptospira.


Assuntos
Doenças dos Bovinos/microbiologia , Leptospira/classificação , Leptospirose/veterinária , Criação de Animais Domésticos , Animais , Vacinas Bacterianas/imunologia , Bovinos , Doenças dos Bovinos/epidemiologia , Indústria de Laticínios , Feminino , Humanos , Leptospirose/epidemiologia , Leptospirose/microbiologia , Leptospirose/prevenção & controle , Estudos Soroepidemiológicos , Suínos , Doenças dos Suínos/microbiologia
18.
Microb Pathog ; 132: 208-214, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30980881

RESUMO

Pasteurella multocida (PM) causes a varity of clinical manifestation in domestic animals, even acute death. Vaccination is among effective strategy to prevent and control PM-related diseases. Bacterial ghosts (BGs) are empty bacterial envelopes, which sustain subtle antigenic comformation in bacterial outer-membrane and exhibit higher efficacy compared to inactivated vaccines. Here, a BG vaccine generated from the porcine PM reference strain CVCC446 (serotype B:2) was prepared upon lysis by E protein of bacteriophage PhiX174, and the safety and immunogenicity were evaluated its in a mouse model. Lysis rate was in 99.99% and the BG vaccine was completely inactivated by addition of freeze-dry procedure. Mice were immunized subcutaneously twice in 2-week intervals with BGs, or BGs plus adjuvant, or formalin-inactivated PM or an adjuvant control. Mice inoculated twice with BGs vaccines generated higher titer of antibodies, interleukin 4 and gamma interferon than those in the inactivated vaccine group or adjuvant placebo group (P < 0.05). CD4+ and CD8+ T lymphocyte levels in spleen were higher in both BG groups than inactivated vaccine group or adjuvant group. Mice administered with the BGs plus adjuvant were completely protected against intraperitoneal challenge with 10 × LD50 dose of virulent isolate and exhibited decreased tissue lesion and lower bacterial loads, which was superior to the inactivated vaccine. The results demonstrated safety of the BG vaccine and primary immunogenicity in a mouse model, suggesting a potential of further evaluation in a pig model and vaccine candidate.


Assuntos
Vacinas Bacterianas/imunologia , Imunogenicidade da Vacina/imunologia , Infecções por Pasteurella/imunologia , Infecções por Pasteurella/prevenção & controle , Pasteurella multocida/imunologia , Adjuvantes Imunológicos , Animais , Anticorpos Antibacterianos/sangue , Anticorpos Antibacterianos/imunologia , Carga Bacteriana , Vacinas Bacterianas/administração & dosagem , Modelos Animais de Doenças , Imunização , Interferon gama/metabolismo , Interleucina-4/metabolismo , Dose Letal Mediana , Camundongos , Baço/imunologia , Suínos , Vacinas de Produtos Inativados/administração & dosagem , Vacinas de Produtos Inativados/imunologia , Proteínas Virais/genética , Proteínas Virais/imunologia
19.
Drug Des Devel Ther ; 13: 909-924, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30936684

RESUMO

Vaccines for Pseudomonas aeruginosa have been of longstanding interest to immunologists, bacteriologists, and clinicians, due to the widespread prevalence of hospital-acquired infection. As P. aeruginosa becomes increasingly antibiotic resistant, there is a dire need for novel treatments and preventive vaccines. Despite intense efforts, there currently remains no vaccine on the market to combat this dangerous pathogen. This article summarizes current and past vaccines under development that target various constituents of P. aeruginosa. Targeting lipopolysaccharides and O-antigens have shown some promise in preventing infection. Recombinant flagella and pili that target TLR5 have been utilized to combat P. aeruginosa by blocking its motility and adhesion. The type 3 secretion system components, such as needle-like structure PcrV or exotoxin PopB, are also potential vaccine targets. Outer membrane proteins including OprF and OprI are newer representatives of vaccine candidates. Live attenuated vaccines are a focal point in this review, and are also considered for novel vaccines. In addition, phage therapy is revived as an effective option for treating refractory infections after failure with antibiotic treatment. Many of the aforementioned vaccines act on a single target, thus lacking a broad range of protection. Recent studies have shown that mixtures of vaccines and combination approaches may significantly augment immunogenicity, thereby increasing their preventive and therapeutic potential.


Assuntos
Vacinas Bacterianas/imunologia , Terapia por Fagos , Infecções por Pseudomonas/imunologia , Infecções por Pseudomonas/terapia , Pseudomonas aeruginosa/imunologia , Animais , Vacinas Bacterianas/química , Humanos , Lipopolissacarídeos/antagonistas & inibidores , Fenômenos Mecânicos , Testes de Sensibilidade Microbiana , Infecções por Pseudomonas/microbiologia , Infecções por Pseudomonas/virologia , Pseudomonas aeruginosa/química
20.
Fish Shellfish Immunol ; 90: 65-72, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30946958

RESUMO

Edwardsiella piscicida is the aetiological agent of fish edwardsiellosis, causing huge economic losses in aquaculture industries. The use of a live attenuated vaccine (LAV) will be an effective strategy to control the disease in farmed fish. Thus, methods facilitating exploration of targets used for construction of an LAV will be of great significance. Previously, we devised an algorithm termed pattern analysis of conditional essentiality (PACE) to perform genome-wide analysis of the temporal dynamic behaviour of E. piscicida mutants colonizing turbot. Here, we correlated the conditional essentiality patterns of the PACE-derived colonization determinants with that of the aroC gene encoding chorismate synthase, the established target for LAV construction in E. piscicida, and identified ETAE_0023 as a novel valuable LAV target. ETAE_0023 encodes an uncharacterized DcrB family protein. Deletion of ETAE_0023 dramatically impaired E. piscicida invasion capability in ZF4 cells as well as colonization in fish and resulted in in vivo clearance at ∼30 days post-infection. ΔETAE_0023 showed an ∼2500-fold higher 50% lethal dose (LD50) than that of the wild type strain. Vaccination with ΔETAE_0023 by intraperitoneal (i.p.) injection upregulated expression of immune factors, i.e., IL-1ß, IgM, MHC-I and MHC-II, and produced significantly high levels of E. piscicida-specific IgM as well as serum bactericidal capacities in turbot. Moreover, a single i.p. inoculation with ΔETAE_0023 generated significant protection comparable to the established WED LAV strain in turbot against challenge with the wild type strain after 5 weeks of vaccination. Taken together, we demonstrated a PACE-based method for heuristic identification of targets for LAV construction and presented ΔETAE_0023 as a new LAV candidate against edwardsiellosis.


Assuntos
Vacinas Bacterianas/imunologia , Edwardsiella/imunologia , Edwardsiella/patogenicidade , Infecções por Enterobacteriaceae/veterinária , Doenças dos Peixes/imunologia , Linguados , Algoritmos , Animais , Edwardsiella/genética , Infecções por Enterobacteriaceae/imunologia , Vacinas Atenuadas/imunologia , Virulência/genética
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