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1.
Pol J Vet Sci ; 24(3): 335-343, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34730312

RESUMO

The aim of the study was to determine the effects of feed addition of LAVIPAN PL5 probiotic preparation containing compositions of microencapsulated lactic acid bacteria (Leuconostoc mesenteroides, Lactobacillus casei, Lactobacillus plantarum, Pediococcus pentosaceus) on production parameters and post-vaccinal immune response in pigs under field condition. The study was performed on 400 pigs in total and 60 pigs from this group were used to evaluate the effect of the product tested on the post-vaccinal response. The animals were divided into two groups: control group, fed without additive of LAVIPAN PL5 and the study group, receiving LAVIPAN PL5 at doses recommended by manufacturer from weaning to the end of fattening. The following parameters were recorded: main production parameters, including weight gains, fattening time (slaughter age) and animal health status during the study (mortality), and specific humoral post-vaccinal response after vaccination against swine erysipelas. The results indicate that the application of LAVIPAN PL5 had positive influence on the animals` productivity and did not significantly affect the post-vaccinal antibody levels and the development and maintenance of the post-vaccinal response, albeit the levels of antibodies were slightly higher in the animal receiving the test preparation. The higher average daily weight gains (by over 3%) which resulted in a 2 kg higher average weight at slaughter and a reduction of the fattening period by 5 days, undoubtedly contributed to significant economic benefits.


Assuntos
Vacinas Bacterianas/imunologia , Suplementos Nutricionais , Composição de Medicamentos , Lactobacillaceae , Probióticos , Suínos , Ração Animal , Animais , Relação Dose-Resposta a Droga , Erisipela/prevenção & controle , Erisipela/veterinária , Aditivos Alimentares , Imunidade Humoral , Ganho de Peso
2.
Int J Mol Sci ; 22(19)2021 Sep 22.
Artigo em Inglês | MEDLINE | ID: mdl-34638530

RESUMO

Outer Membrane Vesicles (OMV) constitute a promising platform for the development of efficient vaccines. OMV can be decorated with heterologous antigens (proteins or polysaccharides), becoming attractive novel carriers for the development of multicomponent vaccines. Chemical conjugation represents a tool for linking antigens, also from phylogenetically distant pathogens, to OMV. Here we develop two simple and widely applicable conjugation chemistries targeting proteins or lipopolysaccharides on the surface of Generalized Modules for Membrane Antigens (GMMA), OMV spontaneously released from Gram-negative bacteria mutated to increase vesicle yield and reduce potential reactogenicity. A Design of Experiment approach was used to identify optimal conditions for GMMA activation before conjugation, resulting in consistent processes and ensuring conjugation efficiency. Conjugates produced by both chemistries induced strong humoral response against the heterologous antigen and GMMA. Additionally, the use of the two orthogonal chemistries allowed to control the linkage of two different antigens on the same GMMA particle. This work supports the further advancement of this novel platform with great potential for the design of effective vaccines.


Assuntos
Proteínas de Bactérias/imunologia , Vacinas Bacterianas/imunologia , Vesículas Extracelulares/imunologia , Proteínas de Protozoários/imunologia , Vacinas Protozoárias/imunologia , Animais , Anticorpos Antibacterianos/imunologia , Antígenos de Bactérias/imunologia , Proteínas de Bactérias/química , Vacinas Bacterianas/biossíntese , Feminino , Lipopolissacarídeos/imunologia , Camundongos , Neisseria meningitidis/imunologia , Plasmodium falciparum/imunologia , Proteínas de Protozoários/química , Vacinas Protozoárias/biossíntese , Salmonella typhimurium/imunologia , Shigella sonnei/imunologia
3.
Vet Res ; 52(1): 133, 2021 Oct 19.
Artigo em Inglês | MEDLINE | ID: mdl-34666827

RESUMO

Streptococcus suis is an important swine pathogen responsible for economic losses to the swine industry worldwide. There is no effective commercial vaccine against S. suis. The use of autogenous ("bacterin") vaccines to control S. suis outbreaks is a frequent preventive measure in the field, although scientific data on immunogenicity and reduction in mortality and morbidity are scarce. The goal of our study is to experimentally evaluate the immunogenicity and protective efficacy against homologous challenge in weaned piglets of a S. suis serotype 2 bacterin-based vaccine formulated with six different commercial adjuvants (Alhydrogel®, Emulsigen®-D, Quil-A®, Montanide™ ISA 206 VG, Montanide™ ISA 61 VG, and Montanide™ ISA 201 VG). The vaccine formulated with Montanide™ ISA 61 VG induced a significant increase in anti-S. suis antibodies, including both IgG1 and IgG2 subclasses, protected against mortality and significantly reduced morbidity and severity of clinical signs. Vaccines formulated with Montanide ISA 206 VG or Montanide ISA 201 VG also induced a significant increase in anti-S. suis antibodies and showed partial protection and reduction of clinical signs severity. Vaccines formulated with Alhydrogel®, Emulsigen®-D, or Quil-A® induced a low and IgG1-shifted antibody response and failed to protect vaccinated piglets against a homologous challenge. In conclusion, the type of adjuvant used in the vaccine formulation significantly influenced the immune response and efficacy of the vaccine against a homologous challenge.


Assuntos
Adjuvantes Imunológicos/farmacologia , Vacinas Bacterianas/administração & dosagem , Infecções Estreptocócicas/veterinária , Streptococcus suis/imunologia , Doenças dos Suínos/imunologia , Adjuvantes Imunológicos/administração & dosagem , Animais , Vacinas Bacterianas/imunologia , Infecções Estreptocócicas/imunologia , Infecções Estreptocócicas/microbiologia , Sus scrofa , Suínos , Doenças dos Suínos/microbiologia , Desmame
4.
Sci Rep ; 11(1): 17626, 2021 09 02.
Artigo em Inglês | MEDLINE | ID: mdl-34475453

RESUMO

Antigen identification is an important step in the vaccine development process. Computational approaches including deep learning systems can play an important role in the identification of vaccine targets using genomic and proteomic information. Here, we present a new computational system to discover and analyse novel vaccine targets leading to the design of a multi-epitope subunit vaccine candidate. The system incorporates reverse vaccinology and immuno-informatics tools to screen genomic and proteomic datasets of several pathogens such as Trypanosoma cruzi, Plasmodium falciparum, and Vibrio cholerae to identify potential vaccine candidates (PVC). Further, as a case study, we performed a detailed analysis of the genomic and proteomic dataset of T. cruzi (CL Brenner and Y strain) to shortlist eight proteins as possible vaccine antigen candidates using properties such as secretory/surface-exposed nature, low transmembrane helix (< 2), essentiality, virulence, antigenic, and non-homology with host/gut flora proteins. Subsequently, highly antigenic and immunogenic MHC class I, MHC class II and B cell epitopes were extracted from top-ranking vaccine targets. The designed vaccine construct containing 24 epitopes, 3 adjuvants, and 4 linkers was analysed for its physicochemical properties using different tools, including docking analysis. Immunological simulation studies suggested significant levels of T-helper, T-cytotoxic cells, and IgG1 will be elicited upon administration of such a putative multi-epitope vaccine construct. The vaccine construct is predicted to be soluble, stable, non-allergenic, non-toxic, and to offer cross-protection against related Trypanosoma species and strains. Further, studies are required to validate safety and immunogenicity of the vaccine.


Assuntos
Biologia Computacional/métodos , Vacinas/imunologia , Vacinologia/métodos , Vacinas Bacterianas/imunologia , Doença de Chagas/imunologia , Doença de Chagas/prevenção & controle , Cólera/imunologia , Cólera/prevenção & controle , Epitopos de Linfócito B/imunologia , Epitopos de Linfócito T/imunologia , Humanos , Malária Falciparum/imunologia , Malária Falciparum/prevenção & controle , Plasmodium falciparum/imunologia , Vacinas Protozoárias/imunologia , Trypanosoma cruzi/imunologia , Vibrio cholerae/imunologia
5.
J Fish Dis ; 44(12): 1937-1950, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34392540

RESUMO

The protective effects of autogenous and commercial ERM immersion vaccines (bacterins based on Yersinia ruckeri, serotype O1, biotypes 1 and 2) for rainbow trout (Oncorhynchus mykiss) were compared in order to evaluate whether the use of local pathogen strains for immunization can improve protection. In addition, the effect of the bacterin concentration was established for the commercial product. Following sublethal challenge of vaccinated and non-vaccinated control fish with live bacteria, we followed the bacterial count in the fish (gills, liver and spleen). The expression of genes encoding immune factors (IL-1ß, IL-6, IL-8, IL-10, IFN-γ, MHCI, MHCII, CD4, CD8, TCRß, IgM, IgT, IgD, cathelicidins 1 and 2, SAA and C3) and densities of immune cells in organs were recorded. Both vaccines conferred protection as judged from the reduced bacterial load in exposed fish. Innate immune genes were upregulated in all groups following bacterial challenge but significantly more in non-vaccinated naive fish in which densities of SAA-positive immune cells increased. Immunoglobulin genes were upregulated on day 5 post-challenge, and fish vaccinated with the high commercial bacterin dosage showed increased IgM levels by ELISA on day 14 post-challenge, reflecting that the vaccine dosage was correlated to protection. In conclusion, both vaccine types offered protection to rainbow trout when exposed to live Y. ruckeri and no significant difference between commercial and autogenous vaccines was established.


Assuntos
Vacinas Bacterianas/imunologia , Doenças dos Peixes/imunologia , Yersiniose/veterinária , Animais , Doenças dos Peixes/microbiologia , Imersão , Oncorhynchus mykiss , Vacinação , Yersiniose/imunologia , Yersinia ruckeri
6.
Biochem Pharmacol ; 192: 114720, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34363796

RESUMO

Manganese (Mn2+) has been reported to activate macrophages and NK cells, and to induce the production of type-I interferons (IFNs) by activating the cGAS-STING pathway. Few studies have been conducted on its adjuvanticity to microbial vaccines, and on the involvement of the interferon regulatory factor (IRF) 5 signaling pathway in the adjuvanticity. In this study, we demonstrated that Mn2+ could facilitate various microbial vaccines to induce enhanced antibody responses, and facilitate the influenza virus vaccine to induce protective immunity against the influenza virus challenge. When formulated in vaccines, Mn2+ could activate murine CD4+ T cells, CD8+ T cells, B cells and DCs, and induce the expression and phosphorylation of TANK-binding kinase 1 (TBK1) and IRF5 in the splenocytes of the immunized mice, resulting in the increased expression of type-I IFNs, TNF-α, B cell-activating factor of the TNF family (BAFF) and B lymphocyte-induced maturation protein-1 (Blimp-1). The induced TBK1 could recruit and bind the IRF5. Furthermore, the Mn2+ induced expression of IRF5 and Blimp-1 was prohibited by a IRF5 interfering oligonucleotide. The data suggest the Mn2+ could be used as a novel type of adjuvants for microbial vaccines, and the activation of IRF5 signaling pathway might involve in the adjuvanticity.


Assuntos
Vacinas Bacterianas/administração & dosagem , Vacinas Bacterianas/metabolismo , Fatores Reguladores de Interferon/metabolismo , Manganês/administração & dosagem , Transdução de Sinais/fisiologia , Animais , Vacinas Bacterianas/imunologia , Cloretos/administração & dosagem , Feminino , Fatores Reguladores de Interferon/imunologia , Compostos de Manganês/administração & dosagem , Camundongos , Camundongos Endogâmicos ICR , Transdução de Sinais/efeitos dos fármacos
7.
Biomolecules ; 11(6)2021 06 15.
Artigo em Inglês | MEDLINE | ID: mdl-34203937

RESUMO

Bacterial secretory systems are essential for virulence in human pathogens. The systems have become a target of alternative antibacterial strategies based on small molecules and antibodies. Strategies to use components of the systems to design prophylactics have been less publicized despite vaccines being the preferred solution to dealing with bacterial infections. In the current review, strategies to design vaccines against selected pathogens are presented and connected to the biology of the system. The examples are given for Y. pestis, S. enterica, B. anthracis, S. flexneri, and other human pathogens, and discussed in terms of effectiveness and long-term protection.


Assuntos
Bactérias , Infecções Bacterianas , Proteínas de Bactérias/imunologia , Vacinas Bacterianas , Bactérias/imunologia , Bactérias/patogenicidade , Infecções Bacterianas/imunologia , Infecções Bacterianas/prevenção & controle , Sistemas de Secreção Bacterianos , Vacinas Bacterianas/imunologia , Vacinas Bacterianas/uso terapêutico , Humanos , Virulência/imunologia
8.
Sci Rep ; 11(1): 14215, 2021 07 09.
Artigo em Inglês | MEDLINE | ID: mdl-34244557

RESUMO

Clostridium difficile is a spore-forming gram-positive bacterium, recognized as the primary cause of antibiotic-associated nosocomial diarrhoea. Clostridium difficile infection (CDI) has emerged as a major health-associated infection with increased incidence and hospitalization over the years with high mortality rates. Contamination and infection occur after ingestion of vegetative spores, which germinate in the gastro-intestinal tract. The surface layer protein and flagellar proteins are responsible for the bacterial colonization while the spore coat protein, is associated with spore colonization. Both these factors are the main concern of the recurrence of CDI in hospitalized patients. In this study, the CotE, SlpA and FliC proteins are chosen to form a multivalent, multi-epitopic, chimeric vaccine candidate using the immunoinformatics approach. The overall reliability of the candidate vaccine was validated in silico and the molecular dynamics simulation verified the stability of the vaccine designed. Docking studies showed stable vaccine interactions with Toll-Like Receptors of innate immune cells and MHC receptors. In silico codon optimization of the vaccine and its insertion in the cloning vector indicates a competent expression of the modelled vaccine in E. coli expression system. An in silico immune simulation system evaluated the effectiveness of the candidate vaccine to trigger a protective immune response.


Assuntos
Vacinas Bacterianas/imunologia , Vacinas Bacterianas/uso terapêutico , Clostridioides difficile/imunologia , Clostridioides difficile/patogenicidade , Infecções por Clostridium/tratamento farmacológico , Infecções por Clostridium/imunologia , Biologia Computacional/métodos , Escherichia coli/metabolismo , Humanos
9.
ACS Appl Mater Interfaces ; 13(28): 32703-32715, 2021 Jul 21.
Artigo em Inglês | MEDLINE | ID: mdl-34251169

RESUMO

Drug resistance of Klebsiella pneumoniae severely threatens human health. Overcoming the mechanisms of K. pneumoniae resistance to develop novel vaccines against drug-resistant K. pneumoniae is highly desired. Here, we report a technology platform that uses high pressure to drive drug-resistant K. pneumoniae to pass through a gap, inducing the formation of stable artificial bacterial biomimetic vesicles (BBVs). These BBVs had little to no bacterial intracellular protein or nucleic acid and had high yields. BBVs were efficiently taken up by dendritic cells to stimulate their maturation. BBVs as K. pneumoniae vaccines had the dual functions of inducing bacteria-specific humoral and cellular immune responses to increase animals' survival rate and reduce pulmonary inflammation and bacterial loads. We believe that BBVs are new-generation technology for bacterial vesicle preparation. Establishment of this BBV vaccine platform can maximally expand preparation technology for vaccines against drug-resistant K. pneumoniae.


Assuntos
Vacinas Bacterianas/uso terapêutico , Materiais Biomiméticos/uso terapêutico , Vesículas Extracelulares/imunologia , Infecções por Klebsiella/terapia , Klebsiella pneumoniae/imunologia , Animais , Vacinas Bacterianas/síntese química , Vacinas Bacterianas/imunologia , Vacinas Bacterianas/toxicidade , Materiais Biomiméticos/síntese química , Materiais Biomiméticos/toxicidade , Fracionamento Celular/métodos , Farmacorresistência Bacteriana Múltipla/efeitos dos fármacos , Feminino , Imunidade Celular/efeitos dos fármacos , Imunidade Humoral/efeitos dos fármacos , Klebsiella pneumoniae/química , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos ICR , Pressão
10.
Vet Res ; 52(1): 100, 2021 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-34225787

RESUMO

Glässer's disease is caused by the agent Glaesserella parasuis and is difficult to prevent and control. Candidate screening for subunit vaccines contributes to the prevention of this disease. Therefore, in this study, the inactivated G. parasuis reference serovar 5 strain (G. parasuis-5) was used to generate specific monoclonal antibodies (mAbs) to screen subunit vaccine candidates. Six mAbs (1A12, 3E3, 4C6, 2D1, 3E6, and 4B2) were screened, and they all reacted with the G. parasuis serovar 5 strain according to laser confocal microscopy and flow cytometry (FCM). Indirect enzyme-linked immunosorbent assay (ELISA) showed that one mAb 2D1, can react with all 15 reference serovars of G. parasuis. Protein mass spectrometry and Western blot analysis demonstrated that mAb 2D1 specifically reacts with Fe (3+) ABC transporter substrate-binding protein. A complement killing assay found that the colony numbers of bacteria were significantly reduced in the G. parasuis-5 group incubated with mAb 2D1 (p < 0.01) in comparison with the control group. Opsonophagocytic assays demonstrated that mAb 2D1 significantly enhanced the phagocytosis of 3D4/21 cells by G. parasuis (p < 0.05). RAW264.7 cells with stronger phagocytic ability were also used for the opsonophagocytic assay, and the difference was highly significant (p < 0.01). Passive immunization of mice revealed that mAb 2D1 can eliminate the bacteria in the blood and provide protection against G. parasuis-5. Our study found one mAb that can be used to prevent and control G. parasuis infection in vivo and in vitro, which may suggest that Fe (3+) ABC transporter substrate-binding protein is an immunodominant antigen and a promising candidate for subunit vaccine development.


Assuntos
Anticorpos Antibacterianos/imunologia , Anticorpos Monoclonais/imunologia , Vacinas Bacterianas/imunologia , Infecções por Haemophilus/veterinária , Haemophilus parasuis/imunologia , Animais , Anticorpos Antibacterianos/sangue , Anticorpos Monoclonais/sangue , Feminino , Infecções por Haemophilus/imunologia , Infecções por Haemophilus/microbiologia , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos ICR , Vacinas de Subunidades/imunologia
11.
Infect Immun ; 89(11): e0039621, 2021 10 15.
Artigo em Inglês | MEDLINE | ID: mdl-34310892

RESUMO

To develop an effective Pseudomonas aeruginosa outer-membrane-vesicle (OMV) vaccine, we eliminated multiple virulence factors from a wild-type (WT) P. aeruginosa strain, PA103, to generate a recombinant strain, PA-m14. Strain PA-m14 was tailored with a pSMV83 plasmid carrying the pcrV-hitAT fusion gene to produce OMVs. The recombinant OMVs (termed OMV-PH) enclosed increased amounts of the PcrV-HitAT bivalent antigen (PH) and exhibited lower toxicity than did the OMVs from PA103. Intramuscular vaccination with OMV-PH from PA-m14(pSMV83) afforded 70% protection against intranasal challenge with 6.5 × 106 CFU (∼30 50% lethal doses [LD50]) of PA103, while immunization using OMVs without the PH antigen (termed OMV-NA) or the PH antigen alone failed to offer effective protection against the same challenge. Further immune analysis showed that OMV-PH immunization significantly stimulated potent antigen-specific humoral and T-cell (Th1/Th17) responses over those with PH or OMV-NA immunization in mice and that these more-potent responses can effectively hinder P. aeruginosa infection. Undiluted antisera from OMV-PH-immunized mice displayed significantly more opsonophagocytic killing of WT PA103 than antisera from PH antigen- or OMV-NA-immunized mice. Moreover, OMV-PH immunization afforded significant antibody-independent cross-protection to mice against PAO1 and the AMC-PA10 clinical isolate. Taking our findings together, the recombinant P. aeruginosa OMV delivering the bivalent PH antigen exhibits high immunogenicity and may be a promising next-generation vaccine candidate against P. aeruginosa infection.


Assuntos
Proteínas da Membrana Bacteriana Externa/imunologia , Vacinas Bacterianas/imunologia , Infecções por Pseudomonas/prevenção & controle , Pseudomonas aeruginosa/imunologia , Animais , Anticorpos Antibacterianos/sangue , Feminino , Humanos , Imunização , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Fagocitose , Receptor 4 Toll-Like/fisiologia , Vacinas Sintéticas/imunologia
12.
J Zoo Wildl Med ; 52(2): 755-762, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34130423

RESUMO

A multiparous pygmy hippopotamus (Choeropsis liberiensis) dam produced three consecutive calves that died acutely at 13-15 wk of age from bacterial sepsis, for which diagnostic and therapeutic intervention was not possible. Streptococcus iniae (Cases 1 and 3), Escherichia coli (Case 2), and an unidentified member of the family Pasteurellaceae (Case 1) were identified in postmortem tissues through bacterial culture followed by standard and molecular identification methods. After the loss of two calves, a series of vaccinations were administered to the dam during the third pregnancy to enhance transplacental and colostral transfer of antibodies to the calf. The third calf did not survive, and the source of the bacterial infection in these three calves was undetermined. Prior to and after the birth of the fourth calf, nutritional and nutraceutical supplements were provided to the dam and calf. Additionally, pest control around the barn was enhanced. The fourth calf survived. Pygmy hippopotamus calves at the age of 13-15 wk may have increased susceptibility to bacterial infection, possibly due to waning maternally derived immunity. The findings in these cases, combined with a previous association of S. iniae in pygmy hippopotamus deaths, suggest that this bacterium is an especially important pathogen of the endangered pygmy hippopotamus.


Assuntos
Artiodáctilos , Infecções Bacterianas/veterinária , Endotoxemia/veterinária , Infecções por Escherichia coli/veterinária , Sepse/veterinária , Infecções Estreptocócicas/veterinária , Criação de Animais Domésticos , Animais , Animais de Zoológico , Infecções Bacterianas/prevenção & controle , Vacinas Bacterianas/imunologia , Endotoxemia/microbiologia , Escherichia coli , Infecções por Escherichia coli/patologia , Feminino , Masculino , Sepse/microbiologia , Infecções Estreptocócicas/microbiologia , Infecções Estreptocócicas/patologia , Streptococcus iniae
13.
Int J Mol Sci ; 22(9)2021 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-34066555

RESUMO

Traditional antimicrobial treatments consist of drugs which target different essential functions in pathogens. Nevertheless, bacteria continue to evolve new mechanisms to evade this drug-mediated killing with surprising speed on the deployment of each new drug and antibiotic worldwide, a phenomenon called antimicrobial resistance (AMR). Nowadays, AMR represents a critical health threat, for which new medical interventions are urgently needed. By 2050, it is estimated that the leading cause of death will be through untreatable AMR pathogens. Although antibiotics remain a first-line treatment, non-antibiotic therapies such as prophylactic vaccines and therapeutic monoclonal antibodies (mAbs) are increasingly interesting alternatives to limit the spread of such antibiotic resistant microorganisms. For the discovery of new vaccines and mAbs, the search for effective antigens that are able to raise protective immune responses is a challenging undertaking. In this context, outer membrane vesicles (OMV) represent a promising approach, as they recapitulate the complete antigen repertoire that occurs on the surface of Gram-negative bacteria. In this review, we present Escherichia coli and Pseudomonas aeruginosa as specific examples of key AMR threats caused by Gram-negative bacteria and we discuss the current status of mAbs and vaccine approaches under development as well as how knowledge on OMV could benefit antigen discovery strategies.


Assuntos
Farmacorresistência Bacteriana , Escherichia coli/fisiologia , Pseudomonas aeruginosa/fisiologia , Animais , Vacinas Bacterianas/imunologia , Infecções por Escherichia coli/epidemiologia , Infecções por Escherichia coli/imunologia , Infecções por Escherichia coli/microbiologia , Humanos , Infecções por Pseudomonas/epidemiologia , Infecções por Pseudomonas/imunologia , Infecções por Pseudomonas/microbiologia
14.
Vet J ; 273: 105676, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34148599

RESUMO

Lyme disease (LD), the most common tick-borne disease of canines and humans in N. America, is caused by the spirochete Borreliella burgdorferi. Subunit and bacterin vaccines are available for the prevention of LD in dogs. LD bacterin vaccines, which are comprised of cell lysates of two strains of B. burgdorferi, contain over 1000 different proteins and cellular constituents. In contrast, subunit vaccines are defined in composition and consist of either outer surface protein (Osp)A or OspA and an OspC chimeritope. In this study, we comparatively assessed antibody responses to OspA and OspC induced by vaccination with all canine bacterin and subunit LD vaccines that are commercially available in North America. Dogs were administered a two-dose series of the vaccine to which they were assigned (3 weeks apart): Subunit-AC, Subunit-A, Bacterin-1, and Bacterin-2. Antibody titers to OspA and OspC were determined by ELISA and the ability of each vaccine to elicit antibodies that recognize diverse OspC proteins (referred to as OspC types) assessed by immunoblot. While all of the vaccines elicited similar OspA antibody responses, only Subunit-AC triggered a robust and broadly cross-reactive antibody response to divergent OspC proteins. The data presented within provide new information regarding vaccination-induced antibody responses to key tick and mammalian phase antigens by both subunit and bacterin LD canine vaccine formulations.


Assuntos
Antígenos de Bactérias/imunologia , Antígenos de Superfície/imunologia , Proteínas da Membrana Bacteriana Externa/imunologia , Vacinas Bacterianas/imunologia , Lipoproteínas/imunologia , Vacinas contra Doença de Lyme/imunologia , Animais , Anticorpos Antibacterianos/imunologia , Formação de Anticorpos , Borrelia burgdorferi/imunologia , Doenças do Cão/imunologia , Doenças do Cão/prevenção & controle , Cães , Feminino , Doença de Lyme/prevenção & controle , Doença de Lyme/veterinária , Masculino , Vacinação/veterinária
15.
Sci Rep ; 11(1): 13213, 2021 06 24.
Artigo em Inglês | MEDLINE | ID: mdl-34168196

RESUMO

Acinetobacter baumannii (A. baumannii), an opportunistic, gram-negative pathogen, has evoked the interest of the medical community throughout the world because of its ability to cause nosocomial infections, majorly infecting those in intensive care units. It has also drawn the attention of researchers due to its evolving immune evasion strategies and increased drug resistance. The emergence of multi-drug-resistant-strains has urged the need to explore novel therapeutic options as an alternative to antibiotics. Due to the upsurge in antibiotic resistance mechanisms exhibited by A. baumannii, the current therapeutic strategies are rendered less effective. The aim of this study is to explore novel therapeutic alternatives against A. baumannii to control the ailed infection. In this study, a computational framework is employed involving, pan genomics, subtractive proteomics and reverse vaccinology strategies to identify core promiscuous vaccine candidates. Two chimeric vaccine constructs having B-cell derived T-cell epitopes from prioritized vaccine candidates; APN, AdeK and AdeI have been designed and checked for their possible interactions with host BCR, TLRs and HLA Class I and II Superfamily alleles. These vaccine candidates can be experimentally validated and thus contribute to vaccine development against A. baumannii infections.


Assuntos
Acinetobacter baumannii/imunologia , Vacinas Bacterianas/imunologia , Infecções por Acinetobacter/imunologia , Sequência de Aminoácidos , Antibacterianos/imunologia , Biologia Computacional/métodos , Infecção Hospitalar/imunologia , Epitopos/imunologia , Genoma Bacteriano/imunologia , Genômica/métodos , Proteômica/métodos , Vacinologia/métodos
16.
J Fish Dis ; 44(10): 1647-1655, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34133777

RESUMO

The orange-spotted grouper (Epinephelus coioides) is an important marine farmed fish in China. It is affected by the bacterial pathogen Vibrio alginolyticus, which causes high mortality and substantial economic losses. We studied the transcriptional changes of the IgZ gene in E. coioides following V. alginolyticus stimulation and investigated the distribution of IgZ in different tissues. The highest expression level of IgZ occurred in the head kidney. When fish were stimulated with live and inactivated V. alginolyticus, the expression levels of IgZ in the head kidney, spleen, intestine, gills and blood cells were significantly upregulated. In an in situ hybridization study, IgZ mRNA-positive cells were detected in the head kidney, spleen and gill, but positive signals were not detected in the liver and intestine. IgZ-labelled cells increased in the head kidney, spleen and gills post-infection with V. alginolyticus for 21 days. The present study provides additional evidence that IgZ is involved in mucosal immune responses and helps explain the role of IgZ in E. coioides defence against V. alginolyticus infection.


Assuntos
Bass , Doenças dos Peixes/imunologia , Proteínas de Peixes/genética , Perfilação da Expressão Gênica/veterinária , Vacinação/veterinária , Vibrioses/veterinária , Vibrio alginolyticus/fisiologia , Animais , Vacinas Bacterianas/administração & dosagem , Vacinas Bacterianas/imunologia , Doenças dos Peixes/microbiologia , Proteínas de Peixes/metabolismo , Cadeias Pesadas de Imunoglobulinas/genética , Cadeias Pesadas de Imunoglobulinas/metabolismo , Distribuição Aleatória , Vibrioses/imunologia , Vibrioses/microbiologia
17.
mBio ; 12(3): e0122721, 2021 06 29.
Artigo em Inglês | MEDLINE | ID: mdl-34182777

RESUMO

Burkholderia pseudomallei is the causative agent of melioidosis, a fatal disease with a high mortality rate. The intrinsic resistance to commonly used antibiotics combined with the complex bacterial life cycle has hampered the development of preventive and therapeutic interventions and vaccines. Furthermore, the need of humoral and cell-mediated immunity in protection against B. pseudomallei has complicated the development of effective vaccines. Antigen delivery vaccine platforms that promote humoral and cellular responses while maintaining a safe profile are a roadblock to developing subunit vaccines against intracellular pathogens. Gold nanoparticles (AuNPs) were used for the delivery of multicomponent antigens with the goal of inducing vaccine-mediated immunity, promoting protection against melioidosis disease. Different nanoglycoconjugates using predicted immunogenic protein candidates, Hcp1, FlgL, OpcP, OpcP1, OmpW, and hemagglutinin, were covalently coupled to AuNPs, together with the lipopolysaccharide (LPS) from Burkholderia thailandensis, which acted as an additional antigen. Animals immunized with individually coupled (AuNP-protein-LPS) formulations containing OpcP or OpcP1, together with CpG as an adjuvant, showed a significant increase in protection, whereas a nanovaccine combination (AuNP-Combo2-LPS) showed significant and complete protection against a lethal intranasal B. pseudomallei challenge. Animals immunized with AuNP-Combo2-LPS showed robust humoral antigen-specific (IgG and IgA) responses with higher IgG2c titer, indicating a TH1-skewed response and promotion of macrophage uptake. In addition, immunization with the nanovaccine combination resulted in a mixed antigen-specific TH1-TH17 cytokine profile after immunization. This study provides the basis for an elegant and refined multicomponent glycoconjugate vaccine formulation capable of eliciting both humoral and cell-mediated responses against lethal B. pseudomallei challenge. IMPORTANCE Melioidosis is a complex human disease associated with a wide range of complications caused by the Gram-negative bacillus Burkholderia pseudomallei. The global burden of melioidosis is estimated to have 165,000 cases per year and 89,000 fatal outcomes. The endemicity of B. pseudomallei includes a wide range of tropical regions in Asia, Africa, Latin America, and Australia. Therefore, a viable alternative to prevent human infections is the development of an effective vaccine; however, no approved vaccine for human use is available. This study provides a vaccine strategy against B. pseudomallei and an immune-stimulatory platform to induce strong humoral and T-cell-mediated immunity.


Assuntos
Vacinas Bacterianas/imunologia , Burkholderia pseudomallei/imunologia , Ouro , Imunidade Humoral , Melioidose/prevenção & controle , Células Th1/imunologia , Células Th17/imunologia , Adjuvantes Imunológicos , Animais , Anticorpos Antibacterianos/sangue , Vacinas Bacterianas/administração & dosagem , Burkholderia/imunologia , Feminino , Glicoconjugados/química , Imunidade Celular , Melioidose/imunologia , Nanopartículas Metálicas/administração & dosagem , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Vacinação
18.
Front Immunol ; 12: 675735, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34149711

RESUMO

Introduction: Conventional or biologic disease-modifying anti-rheumatic drugs (DMARDs) are the mainstay of treatment for systemic autoimmune disease (SAD). Infectious complications are a major concern in their use. Objective: To evaluate the clinical benefit of sublingual mucosal polybacterial vaccines (MV130 and MV140), used to prevent recurrent respiratory and urinary tract infections, in patients with SAD and secondary recurrent infections following conventional or biologic DMARDs. Methods: An observational study in SAD patients with recurrent respiratory tract infections (RRTI) and/or recurrent urinary tract infections (RUTI) was carried out. All patients underwent mucosal (sublingual) vaccination with MV130 for RRTI or with MV140 for RUTI daily for 3 months. Clinical evaluation was assessed during 12 months of follow-up after the first dose, i.e., 3 months under treatment and 9 months once discontinued, and compared with the previous year. Results: Forty-one out of 55 patients completed 1-year follow-up. All patients were on either conventional or biologic DMARDs. A significant decrease in the frequency of RUTI (p<0.001), lower respiratory tract infections (LRTI) (p=0.009) and upper respiratory tract infections (URTI) (p=0.006) at 12-mo with respect to the previous year was observed. Antibiotic prescriptions and unscheduled medical visits decreased significantly (p<0.020) in all groups. Hospitalization rate also declined in patients with RRTI (p=0.019). The clinical benefit demonstrated was concomitant to a significant increase in both anti-S. pneumoniae IgA and IgG antibodies following MV130 vaccination. Conclusions: Sublingual polybacterial vaccines prevent recurrent infections in patients with SAD under treatment with immunosuppressant therapies, supporting a broad non-specific anti-infectious effect in these patients.


Assuntos
Doenças Autoimunes/tratamento farmacológico , Vacinas Bacterianas/imunologia , Imunossupressores/uso terapêutico , Reinfecção/prevenção & controle , Infecções Respiratórias/prevenção & controle , Infecções Urinárias/prevenção & controle , Vacinação , Adulto , Idoso , Doenças Autoimunes/imunologia , Vacinas Bacterianas/administração & dosagem , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem
19.
Res Vet Sci ; 137: 138-143, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33975192

RESUMO

Pasteurella multocida (P. multocida) infects the swine respiratory tract and mainly causes atrophic rhinitis (AR). Recently, many commercially inactivated and subunit vaccines have been used as preventive strategies. However, the best antigenic protein portion has not been selected, and the aluminum gel was used as the adjuvant, which may not induce full protection. P. multocida toxin (PMT) is the major virulence factor responsible for AR. PMT is a monomeric 146 kDa protein (approximately 1285 amino acids) encoded by the tox A gene. In this study, we expressed different fragments of recombinant PMT proteins, combined them with a water-in-oil-in-water adjuvant, and evaluated mice's immune response. The results indicated that the rPMT-C-immunized group showed significantly higher levels (p < 0.05) of IgG, IgG2a antibody and interferon-γ, IL-12 cytokine expression than other groups. Furthermore, vaccination with rPMT-C recombinant protein can provide homologous and heterologous protection against P. multocida challenge. In conclusion, our approach may be feasible for developing an effective subunit vaccine against atrophic rhinitis with a cost-down simple ingredient.


Assuntos
Proteínas de Bactérias/imunologia , Toxinas Bacterianas/imunologia , Vacinas Bacterianas/imunologia , Infecções por Pasteurella/veterinária , Pasteurella multocida , Rinite Atrófica/prevenção & controle , Adjuvantes Imunológicos , Animais , Imunização , Camundongos , Camundongos Endogâmicos ICR , Infecções por Pasteurella/imunologia , Infecções por Pasteurella/prevenção & controle , Rinite Atrófica/imunologia , Vacinas Sintéticas/uso terapêutico
20.
Fish Shellfish Immunol ; 114: 171-183, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33940174

RESUMO

Adjuvants are the helper substances that increase vaccine efficacy by enhancing the potency and longevity of specific immune responses to antigens. Most existing fish vaccines are presented in the form of oil-based emulsions delivered by intraperitoneal injection. The characterization of their mode of action is a valuable aid to future vaccine development, particularly for the potential identification and stimulation of specific immunological pathways related to the desired protective response. This study characterized the expression of selected immune-related genes in the peritoneal cavity, head kidney and spleen following the administration of two adjuvanted-bacterial vaccines thought to induce humoral (Montanide™ ISA 763A VG) or humoral and cell mediated (Montanide™ ISA 761 VG) immune responses, to determine if differences in responsiveness are readily apparent. The most informative site was the spleen, where Montanide™ ISA 763A VG + bacterin gave rise to upregulation of genes driving T-cell/lymphoid responses, namely IL-2, IL-15 and IL-21. This combined with upregulation of IFNγ1 and IFNγ2, IL-4/13B2, p35A1 and p40 (B1 and C) indicated that the induction of Th1 and possibly Th2 immunity was occurring in fish vaccinated with this adjuvant. Perhaps the most intriguing finding was the lack of a detectable Th1 response in fish given Montanide™ ISA 761 VG + bacterin, suggesting some other arm of the immune system is activated to give protection. Whatever the reason for the different responses detected, it is clear from the present study that the adjuvant used has a major impact on the responses elicited. Since these differences are readily detectable it allows, in principle, their use to help select the most appropriate adjuvants for inclusion into fish vaccines, where the type of response elicited may need to be tailored to a particular pathogen to confer protection.


Assuntos
Adjuvantes Imunológicos/farmacologia , Aeromonas salmonicida , Vacinas Bacterianas/imunologia , Doenças dos Peixes/prevenção & controle , Infecções por Bactérias Gram-Negativas/veterinária , Manitol/análogos & derivados , Oncorhynchus mykiss/imunologia , Animais , Citocinas/genética , Citocinas/metabolismo , Regulação da Expressão Gênica/imunologia , Infecções por Bactérias Gram-Negativas/prevenção & controle , Rim Cefálico/metabolismo , Macrófagos Peritoneais , Manitol/farmacologia , Oncorhynchus mykiss/microbiologia
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