Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 404
Filtrar
1.
Int J Mol Sci ; 20(17)2019 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-31466400

RESUMO

Streptococcus pneumoniae remains the most common bacterial pathogen causing lower respiratory tract infections and is a leading cause of morbidity and mortality worldwide, especially in children and the elderly. Another important aspect related to pneumococcal infections is the persistent rate of penicillin and macrolide resistance. Therefore, animal models have been developed to better understand the pathogenesis of pneumococcal disease and test new therapeutic agents and vaccines. This narrative review will focus on the characteristics of the different animal pneumococcal pneumonia models. The assessment of the different animal models will include considerations regarding pneumococcal strains, microbiology properties, procedures used for bacterial inoculation, pathogenesis, clinical characteristics, diagnosis, treatment, and preventive approaches.


Assuntos
Modelos Animais de Doenças , Pneumonia Pneumocócica/etiologia , Animais , Antibacterianos/uso terapêutico , Farmacorresistência Bacteriana , Pneumonia Pneumocócica/tratamento farmacológico , Pneumonia Pneumocócica/imunologia , Vacinas Estreptocócicas/imunologia
2.
PLoS Negl Trop Dis ; 13(7): e0007511, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31269021

RESUMO

The prevalence of rheumatic heart disease (RHD) in the Aboriginal population of the Australian Northern Territory is high, and Streptococcus pyogenes skin infections likely contribute to this. A promising candidate S. pyogenes "30mer" vaccine is composed of 30 pharyngitis associated type-specific antigens from the S. pyogenes M protein. Cross opsonisation experiments suggest that 30mer vaccine protection may extend to non-cognate emm types. A new "emm cluster" scheme for classifying M protein is based on the full-length coding sequence, and correlates with functional and immunological properties, and anatomical tropism. Twenty-seven years of research in the Northern Territory has yielded 1810 S. pyogenes isolates with clinical and emm type data. The primary aim was to analyse these data with reference to the emm cluster scheme and cross opsonisation information, to inform estimation of 30mer vaccine efficacy in the Northern Territory. The isolates encompass 101 emm types. Variants of cluster A-C were enriched in throat isolates, and variants of emm cluster D enriched in skin isolates. Throat isolates were enriched for 30mer vaccine cognate emm types in comparison with skin isolates of which only 25% were vaccine emm types. While cross opsonisation data indicates potential for enhancing 30mer vaccine coverage, more than one third of skin isolates were within 38 emm types untested for cross opsonisation. Emm cluster D variants, in particular emm cluster D4, were not only all non-cognate with the vaccine, but were abundant and diverse, and less likely to be cross-opsonisation positive than other emm clusters. Long term persistence of many emm types in the study area was revealed. It was concluded that the 30mer vaccine efficacy in the Northern Territory will likely require both cross protection, and additional measures to elicit immunity against variants of emm cluster D.


Assuntos
Antígenos de Bactérias/imunologia , Proteínas da Membrana Bacteriana Externa/imunologia , Proteínas de Transporte/imunologia , Cardiopatia Reumática/microbiologia , Infecções Estreptocócicas/prevenção & controle , Vacinas Estreptocócicas/uso terapêutico , Streptococcus pyogenes , Humanos , Northern Territory/epidemiologia , Faringite/epidemiologia , Faringite/microbiologia , Prevalência , Cardiopatia Reumática/epidemiologia , Cardiopatia Reumática/prevenção & controle , Pele/microbiologia , Infecções Estreptocócicas/complicações , Infecções Estreptocócicas/epidemiologia , Vacinas Estreptocócicas/imunologia
3.
J Med Microbiol ; 68(7): 1059-1071, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31192782

RESUMO

PURPOSE: Unlike western countries the knowledge of group A streptococcus (GAS) epidemiology in India remains patchy and incomplete. Typing is crucial for surveillance as well as in predicting the efficacy of multivalent M protein vaccine. The present study aimed to explore the emm types of 206 invasive and non-invasive GAS isolates from South India as well as reviewing all the published literature on GAS molecular epidemiology from India thereby generating a pan-Indian data to predict the conjectural coverage of the 30-valent M-protein vaccine in this population. METHODOLOGY: emm typing and superantigen (SAg) profiling of GAS along with reviewing literatures on GAS molecular epidemiology from India. RESULTS: This study revealed a high diversity of emm types with emm 63, 82, 183, 85, 92, 169, 42, 44, 106, 74, 12 being frequently encountered, belonging to twenty emm clusters. The pan-Indian data on prevalent emm types further supports our study findings with 135 emm different types. Six clusters dominated accounting for 80 % of the GAS isolates: E3(26 %), E6(20 %), E2(11 %), E4(10 %), D4(7 %), E1(6 %). No significant association was noted between emm types and the nature of infection (P≥0.05) while a few SAg profiles were significantly associated with certain emm types. Pan Indian data revealed that only 16 % of the emm types encountered were included in proposed 30-valent M protein based vaccine. CONCLUSION: The coverage among the South Indian GAS isolates was 28.2 % which increased to only 46.6 % with the cross-opsonic effect, thus highlighting the importance of developing a specific multivalent vaccine including the prevalent emm types in India or considering the use of conserved C-repeat vaccines and non-M protein based vaccines.


Assuntos
Epidemiologia Molecular , Infecções Estreptocócicas/epidemiologia , Infecções Estreptocócicas/microbiologia , Streptococcus pyogenes/genética , Adolescente , Adulto , Proteínas de Bactérias/genética , Criança , Feminino , Regulação Bacteriana da Expressão Gênica , Humanos , Índia/epidemiologia , Masculino , Pessoa de Meia-Idade , Infecções Estreptocócicas/prevenção & controle , Vacinas Estreptocócicas/imunologia , Adulto Jovem
4.
PLoS One ; 14(6): e0218544, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31237893

RESUMO

Although many influenza-related deaths are attributable to secondary bacterial infection with S. pneumoniae, vaccines that simultaneously protect against influenza and pneumococcal infection are currently not developed. The aim of our study was to evaluate the possibility to prevent post-influenza pneumococcal infection using an associated vaccine based on live influenza vaccine (LAIV) combined with recombinant polypeptides derived from superficial factors of Group B streptococcus (GBS) determining pathogenicity. We demonstrated in a model of post-influenza pneumococcal pneumonia that intranasal pneumococcal super-infection seriously complicated the course of A/Shanghai/2/2013(H7N9) CDC-RG virus infection in mice. Associated immunization using LAIV and GBS vaccine (GBSV) prevented post-influenza pneumococcal pneumonia better than mono-LAIV or GBSV immunization. At the same time, parenteral pneumococcal post-influenza infection of immune mice was more severe in the groups immunized using recombinant GBS peptides which can be explained by antibody-dependent enhancement of infection. In this case, the introduction of blockers of histamine receptors type 1 and 2 reduced the burden of secondary pneumococcal infection.


Assuntos
Coinfecção/prevenção & controle , Vacinas contra Influenza/imunologia , Influenza Humana/prevenção & controle , Pneumonia Pneumocócica/prevenção & controle , Vacinas Estreptocócicas/imunologia , Vacinas Conjugadas/imunologia , Animais , Antígenos de Bactérias/imunologia , Coinfecção/imunologia , Feminino , Humanos , Imunização/métodos , Subtipo H7N9 do Vírus da Influenza A/imunologia , Vacinas contra Influenza/genética , Vacinas contra Influenza/uso terapêutico , Influenza Humana/complicações , Influenza Humana/imunologia , Camundongos , Camundongos Endogâmicos DBA , Pneumonia Pneumocócica/etiologia , Pneumonia Pneumocócica/imunologia , Vacinas Estreptocócicas/genética , Vacinas Estreptocócicas/uso terapêutico , Vacinas Conjugadas/genética , Vacinas Conjugadas/uso terapêutico
5.
mBio ; 10(2)2019 04 30.
Artigo em Inglês | MEDLINE | ID: mdl-31040243

RESUMO

Group A Streptococcus (GAS) infections account for an estimated 500,000 deaths every year. This bacterial pathogen is responsible for a variety of mild and life-threatening infections and the triggering of chronic autoimmune sequelae. Pharyngitis caused by group A Streptococcus (GAS), but not asymptomatic GAS carriage, is a prerequisite for acute rheumatic fever (ARF). Repeated bouts of ARF may trigger rheumatic heart disease (RHD), a major cause of heart failure and stroke accounting for 275,000 deaths annually. A vaccine that prevents pharyngitis would markedly reduce morbidity and mortality from ARF and RHD. Nonhuman primates (NHPs) have been utilized to model GAS diseases, and experimentally infected rhesus macaques develop pharyngitis. Here we use an NHP model of GAS pharyngitis to evaluate the efficacy of an experimental vaccine, Combo5 (arginine deiminase [ADI], C5a peptidase [SCPA], streptolysin O [SLO], interleukin-8 [IL-8] protease [SpyCEP], and trigger factor [TF]), specifically designed to exclude GAS components potentially linked to autoimmune complications. Antibody responses against all Combo5 antigens were detected in NHP serum, and immunized NHPs showed a reduction in pharyngitis and tonsillitis compared to controls. Our work establishes the NHP model as a gold standard for the assessment of GAS vaccines.IMPORTANCE GAS-related diseases disproportionally affect disadvantaged populations (e.g., indigenous populations), and development of a vaccine has been neglected. A recent strong advocacy campaign driven by the World Health Organization and the International Vaccine Institute has highlighted the urgent need for a GAS vaccine. One significant obstacle in GAS vaccine development is the lack of a widely used animal model to assess vaccine efficacy. Researchers in the field use a wide range of murine models of infection and in vitro assays, sometimes yielding conflicting results. Here we present the nonhuman primate pharyngeal infection model as a tool to assess vaccine-induced protection against colonization and clinical symptoms of pharyngitis and tonsillitis. We have tested the efficacy of an experimental vaccine candidate with promising results. We believe that the utilization of this valuable tool by the GAS vaccine research community could significantly accelerate the realization of a safe and effective GAS vaccine for humans.


Assuntos
Faringite/prevenção & controle , Infecções Estreptocócicas/prevenção & controle , Vacinas Estreptocócicas/imunologia , Streptococcus pyogenes/imunologia , Tonsilite/prevenção & controle , Animais , Anticorpos Antibacterianos/sangue , Modelos Animais de Doenças , Feminino , Macaca mulatta , Masculino , Vacinas Estreptocócicas/administração & dosagem , Resultado do Tratamento
6.
Microbiol Spectr ; 7(3)2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-31111819

RESUMO

Streptococcal pharyngitis (or strep throat) is a common childhood disease affecting millions of children each year, but it is one of the only childhood diseases for which a vaccine does not exist. While for decades the development of a vaccine has been the center of attention in many laboratories worldwide, with some successes, no corporate development has yet to be initiated. The reason for this probably lies in our inability to conclusively identify the streptococcal molecule or molecules responsible for the heart cross-reactive antibodies observed in the serum of rheumatic fever patients. Without this specific knowledge, any streptococcal vaccine antigen is suspect and thus not the target for a billion-dollar investment, despite the fact that the exact role of cross-reactive antibodies in rheumatic fever is still questionable. This article will describe the development of several approaches to protect against Streptococcus pyogenes infections over the past several decades.


Assuntos
Faringite/imunologia , Faringite/prevenção & controle , Infecções Estreptocócicas/imunologia , Infecções Estreptocócicas/prevenção & controle , Vacinas Estreptocócicas/imunologia , Streptococcus pyogenes/imunologia , Animais , Anticorpos Antibacterianos/sangue , Antígenos de Bactérias/imunologia , Proteínas da Membrana Bacteriana Externa/imunologia , Proteínas de Transporte/imunologia , Criança , Reações Cruzadas/imunologia , Bactérias Gram-Positivas/imunologia , Humanos , Imunidade nas Mucosas , Febre Reumática/imunologia , Vacinação , Vírus Vaccinia
7.
Nat Genet ; 51(6): 1035-1043, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-31133745

RESUMO

Group A Streptococcus (GAS; Streptococcus pyogenes) is a bacterial pathogen for which a commercial vaccine for humans is not available. Employing the advantages of high-throughput DNA sequencing technology to vaccine design, we have analyzed 2,083 globally sampled GAS genomes. The global GAS population structure reveals extensive genomic heterogeneity driven by homologous recombination and overlaid with high levels of accessory gene plasticity. We identified the existence of more than 290 clinically associated genomic phylogroups across 22 countries, highlighting challenges in designing vaccines of global utility. To determine vaccine candidate coverage, we investigated all of the previously described GAS candidate antigens for gene carriage and gene sequence heterogeneity. Only 15 of 28 vaccine antigen candidates were found to have both low naturally occurring sequence variation and high (>99%) coverage across this diverse GAS population. This technological platform for vaccine coverage determination is equally applicable to prospective GAS vaccine antigens identified in future studies.


Assuntos
Genômica , Vacinas Estreptocócicas/genética , Vacinas Estreptocócicas/imunologia , Streptococcus pyogenes/genética , Streptococcus pyogenes/imunologia , Antígenos de Bactérias/genética , Antígenos de Bactérias/imunologia , Genoma Bacteriano , Estudo de Associação Genômica Ampla , Genômica/métodos , Humanos , Filogenia , Recombinação Genética , Infecções Estreptocócicas/prevenção & controle , Streptococcus pyogenes/classificação
8.
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
9.
Infect Immun ; 87(6)2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30936156

RESUMO

Group A Streptococcus (GAS) (Streptococcus pyogenes) is an important human pathogen associated with significant global morbidity and mortality for which there is no safe and efficacious vaccine. The T antigen, a protein that polymerizes to form the backbone of the GAS pilus structure, is a potential vaccine candidate. Previous surveys of the tee gene, which encodes the T antigen, have identified 21 different tee types and subtypes such that any T antigen-based vaccine must be multivalent and carefully designed to provide broad strain coverage. In this study, the crystal structures of three two-domain T antigens (T3.2, T13, and T18.1) were determined and found to have remarkable structural similarity to the previously reported T1 antigen, despite moderate overall sequence similarity. This has enabled reliable modeling of all major two-domain T antigens to reveal that T antigen sequence variation is distributed along the full length of the protein and shields a highly conserved core. Immunoassays performed with sera from immunized animals and commercial T-typing sera identified a significant cross-reactive antibody response between T18.1, T18.2, T3.2, and T13. The existence of shared epitopes between T antigens, combined with the remarkably conserved structure and high level of surface sequence divergence, has important implications for the design of multivalent T antigen-based vaccines.


Assuntos
Antígenos de Bactérias/imunologia , Infecções Estreptocócicas/imunologia , Vacinas Estreptocócicas/imunologia , Streptococcus pyogenes/imunologia , Animais , Anticorpos Antibacterianos/imunologia , Antígenos de Bactérias/química , Antígenos de Bactérias/genética , Reações Cruzadas , Humanos , Coelhos , Infecções Estreptocócicas/genética , Infecções Estreptocócicas/microbiologia , Infecções Estreptocócicas/prevenção & controle , Vacinas Estreptocócicas/química , Vacinas Estreptocócicas/genética , Streptococcus pyogenes/química , Streptococcus pyogenes/genética
10.
Fish Shellfish Immunol ; 90: 235-243, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31009810

RESUMO

Streptococcus agalactiae species have been recognized as the main pathogen causing high mortality in fish leading to significant worldwide economical losses to the aquaculture industries. Vaccine development has become a priority in combating multidrug resistance in bacteria; however, there is a lack of commercial live attenuated vaccine (LAV) against S. agalactiae in Malaysia. The aim of this study is to compare two methods using attenuated bacteria as live vaccine and to evaluate the efficacy of selected LAV on the immune responses and resistance of Oreochromis niloticus (tilapia) against S. agalactiae. The LAV derived from S. agalactiae had been weakened using the chemical agent Acriflavine dye (LAV1), whereas the second vaccine was weakened using serial passages of bacteria on broth media (LAV2). Initial immunization was carried out only on day one, given twice-in the morning and evening, for the 42 day period. Serum samples were collected to determine the systemic antibody (IgM) responses and lysozymal (LSZ) activity using ELISA. On day 43 after immunization, the fish were injected intraperitoneally (i.p) with 0.1 mL of S. agalactiae at LD50 = 1.5 × 105 (CFU)/fish. Fish were monitored daily for 10 days. Clinical signs, mortality and the relative percent of survival (RPS) were recorded. Trial 1 results showed a significant increased (P < 0.05) in serum IgM titers and LSZ activity as compared to LAV2 and the control group (unvaccinated fish). The efficacy of LAV1 was proven effective as determined by the RPS values, LAV1 at 81.58% as compared to LAV2 at 65.79%. Trial 2 of LAV1 and control group were further determined by administering primary and booster doses revealed a RPS value for LAV1 of 82.05%, with the significant enhancement on the immune responses of tilapia as compared to control group. In conclusion, LAV revealed to elevate antibody IgM levels, LSZ activity and provide long-term protection when added to feed. LAV is a low-cost vaccine shown to rapidly increase the immune response of fish and increase survival rates of fish against S. agalactiae infection.


Assuntos
Ciclídeos/microbiologia , Doenças dos Peixes/imunologia , Vacinas Estreptocócicas/imunologia , Streptococcus agalactiae/imunologia , Vacinação/veterinária , Animais , Ciclídeos/imunologia , Doenças dos Peixes/prevenção & controle , Infecções Estreptocócicas/imunologia , Infecções Estreptocócicas/prevenção & controle , Infecções Estreptocócicas/veterinária , Vacinação/métodos , Vacinas Atenuadas/imunologia
11.
Fish Shellfish Immunol ; 89: 71-75, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30917926

RESUMO

Streptococcus iniae is an important aquaculture pathogen that is associated with disease outbreaks in wild and cultured fish species. Streptolysin S has been identified as an important virulence factor of S. iniae. With an aim to develop effective vaccines against S. iniae for Japanese flounder (Paralichthys olivaceus), in this study, we constructed a DNA vaccine based on the sagH gene, which belongs to the streptolysin S-associated gene cluster. In fish vaccinated with pSagH, the transcription of sagH was detected in tissues and SagH protein was also detected in the muscles of pSagH-vaccinated fish by immunohistochemistry. The immunoprotective effect of SagH showed that fish vaccinated with pSagH at one and two months exhibited a high relative percent survival (RPS) of 92.62% and 90.58% against S. iniae serotype I, respectively. In addition, SagH conferred strong cross protection against S. iniae serotype II and resulted in an RPS of 83.01% and 80.65% at one and two months, respectively. Compared to the control group, fish vaccinated with pSagH were able to induce much stronger respiratory burst activity, and higher titer of specific antibodies. The results of quantitative real-time PCR demonstrated that pSagH upregulated the expression of several immune genes that are possibly involved in both innate and adaptive immune responses. These results indicate that pSagH is a candidate DNA vaccine candidate against S. iniae serotype I and II infection in Japanese flounder in aquaculture.


Assuntos
Proteínas de Bactérias/imunologia , Linguados/imunologia , Vacinas Estreptocócicas/imunologia , Streptococcus iniae/imunologia , Estreptolisinas/imunologia , Animais , Proteção Cruzada , Família Multigênica/imunologia , Infecções Estreptocócicas/imunologia , Infecções Estreptocócicas/veterinária , Vacinas de DNA/imunologia
12.
Microbiol Spectr ; 7(2)2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30873933

RESUMO

The surface of the Gram-positive opportunistic pathogen Streptococcus agalactiae, or group B Streptococcus (GBS), harbors several carbohydrate and protein antigens with the potential to be effective vaccines. Capsular polysaccharides of all clinically-relevant GBS serotypes coupled to immunogenic proteins of both GBS and non-GBS origin have undergone extensive testing in animals that led to advanced clinical trials in healthy adult women. In addition, GBS proteins either alone or in combination have been tested in animals; a fusion protein construct has recently advanced to human clinical studies. Given our current understanding of the antigenicity and immunogenicity of the wide array of GBS surface antigens, formulations now exist for the generation of viable vaccines against diseases caused by GBS.


Assuntos
Antígenos de Bactérias/imunologia , Antígenos de Superfície/imunologia , Cápsulas Bacterianas/imunologia , Infecções Estreptocócicas/prevenção & controle , Vacinas Estreptocócicas/imunologia , Streptococcus agalactiae/imunologia , Animais , Cápsulas Bacterianas/classificação , Cápsulas Bacterianas/genética , Feminino , Humanos , Imunogenicidade da Vacina , Polissacarídeos Bacterianos/imunologia , Infecções Estreptocócicas/imunologia , Streptococcus agalactiae/genética , Streptococcus agalactiae/patogenicidade , Vacinas Conjugadas , Fatores de Virulência/imunologia
13.
J Infect Dis ; 220(1): 105-115, 2019 06 05.
Artigo em Inglês | MEDLINE | ID: mdl-30778554

RESUMO

BACKGROUND: Group B streptococcus (GBS) causes serious diseases in newborn infants, often resulting in lifelong neurologic impairments or death. Prophylactic vaccination of pregnant women prior to delivery could provide comprehensive protection, as early onset and late-onset disease and maternal complications potentially could be addressed. METHODS: Capsular polysaccharide conjugate vaccine GBS6 was designed using surveillance data yielded by whole-genome sequencing of a global collection of recently recovered GBS isolates responsible for invasive neonatal GBS disease. Capsular polysaccharides were isolated, oxidized using sodium periodate, and conjugated to CRM197 by reductive amination in dimethyl sulfoxide. Immune responses in mice and rhesus macaques were measured in a multiplex Luminex immunoglobulin G (IgG) assay and opsonophagocytic activity assays. RESULTS: The optimized conjugates were immunogenic, alone and in combination, in mice and rhesus macaques, inducing IgG antibodies that mediated opsonophagocytic killing. Active immunization of murine dams with GBS6 prior to mating resulted in serotype-specific protection of pups from a lethal challenge with GBS. Protection following passive administration of serotype-specific IgG monoclonal antibodies to dams demonstrated conclusively that anticapsular polysaccharide IgG alone is sufficient for protection. CONCLUSIONS: The findings support the ongoing clinical evaluation of maternal GBS6 vaccination as a potential alternative method to prevent GBS disease in infants.


Assuntos
Animais Recém-Nascidos/imunologia , Imunidade Materno-Adquirida/imunologia , Polissacarídeos Bacterianos/imunologia , Infecções Estreptocócicas/imunologia , Vacinas Estreptocócicas/imunologia , Streptococcus/imunologia , Vacinas Conjugadas/imunologia , Animais , Animais Recém-Nascidos/microbiologia , Anticorpos Antibacterianos/imunologia , Feminino , Imunização/métodos , Imunoglobulina G/imunologia , Macaca mulatta/imunologia , Macaca mulatta/microbiologia , Camundongos , Sorogrupo , Infecções Estreptocócicas/microbiologia , Vacinação/métodos
14.
Fish Shellfish Immunol ; 87: 155-165, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30630049

RESUMO

Channel catfish is one of the most extensively cultured species worldwide, which is widely used as a classical model for comparative immunology. Interleukin-1ß (IL1ß) is an immunoregulatory cytokine with the potential to enhance the immune response induced by vaccines in many animals. To characterize the molecular characterization and identify the immunoadjuvant role of channel catfish IL1ß, molecular cloning, phylogenetic analysis, and expression of two IL1ß genes were performed, the bioactivity of their recombinant proteins (rIL1ß1 and rIL1ß2) were detected in vitro and their adjuvant effects on a subunit vaccine encoding C5a peptidase (pSCPI) of Streptococcus iniae were evaluated. The results indicated that two IL1ßs remained highly conserved possessing five conserved motifs compared with other fish IL1ßs, although there were 28 nucleotide differences and 16 amino acid differences between channel catfish IL1ß1 and IL1ß2. Analysis of the ratios of nonsynonymous (dN) and synonymous (dS) substitutions revealed that fish IL1ß genes were subjected to negative/purifying selection with global dN/dS ratios value 0.425. The results of adjuvant effect showed that compared with injection of pSCPI alone, co-injecting pSCPI with both rIL1ß1 and rIL1ß2 significantly enhanced antibody levels, serum bactericidal activity, lysozyme activity, alternative complement hemolytic activity, and the expression of endogenous IL1ß and TNF-α in head kidney and spleen. Although vaccination with rIL1ß1 or rIL1ß2 failed to offer immunoprotection against S. iniae infection, the RPS (relative percent survival) of pSCPI+rIL1ß1 and pSCPI+rIL1ß2 groups were both higher than pSCPI alone (RPS, 50%), with 64.26% and 60.71%, respectively. Moreover, pSCPI+rIL1ß1+rIL1ß2 offered significantly higher (P < 0.05) immunoprotection (RPS, 75%) against S. iniae infection than pSCPI alone. Our present results not only enrich the molecular structure study of fish IL1ßs but also signify that two recombinant channel catfish IL1ßs can be used as potential adjuvants in a subunit vaccine model against bacterial infection, which are of profound importance to prevent and control bacterial disease in channel catfish.


Assuntos
Doenças dos Peixes/imunologia , Ictaluridae/imunologia , Interleucina-1beta/genética , Infecções Estreptocócicas/veterinária , Vacinas Estreptocócicas/imunologia , Streptococcus iniae/imunologia , Adesinas Bacterianas , Adjuvantes Imunológicos/farmacologia , Animais , Endopeptidases , Doenças dos Peixes/microbiologia , Doenças dos Peixes/prevenção & controle , Ictaluridae/genética , Interleucina-1beta/imunologia , Interleucina-1beta/metabolismo , Análise de Sequência de Proteína , Infecções Estreptocócicas/imunologia , Infecções Estreptocócicas/microbiologia , Infecções Estreptocócicas/prevenção & controle , Vacinas de Subunidades/imunologia
15.
J Infect Dis ; 219(3): 448-458, 2019 01 09.
Artigo em Inglês | MEDLINE | ID: mdl-30165645

RESUMO

Background: Streptococcus suis is an encapsulated zoonotic pathogen. Increasing antimicrobial resistance invokes the need for effective vaccines. Despite many attempts to develop an effective vaccine, none is currently available. Methods: A capsular polysaccharide (CPS)-expressing attenuated mutant 2015033 was constructed by deleting 5 virulence-associated factors (sly, scpA, ssnA, fhb, and ssads) in an infective S. suis strain SC19. The safety and immune effect of 2015033 were determined both in vitro and in vivo. Results: Deletion of 5 genes did not impact the growth ability and CPS generation of 2015033, and the mutant exhibited no cytotoxicity in different cell models. 2015033 was more easily eliminated by innate immunity both in vitro and in vivo. In addition, 2015033 showed a diminished invasive ability in different mouse organs (brain, lung, and liver) and avirulent properties in mice associated with weak inflammation-inducing ability. Immunization with 2015033 triggered T cell-dependent immunity, suppressed streptococcal toxic shock-like syndrome, and conferred sequence type-independent protection to mice during infection. Conclusions: This study presents the feasibility of the strategy of multigene deletion for the development of promising live vaccines against invasive encapsulated pathogens.


Assuntos
Choque Séptico/prevenção & controle , Infecções Estreptocócicas/prevenção & controle , Vacinas Estreptocócicas/imunologia , Streptococcus suis/imunologia , Vacinas Atenuadas/imunologia , Animais , Cápsulas Bacterianas/genética , Cápsulas Bacterianas/imunologia , Encéfalo/patologia , Células CACO-2 , Proteção Cruzada/imunologia , Modelos Animais de Doenças , Feminino , Deleção de Genes , Genes Bacterianos/genética , Humanos , Imunidade Inata , Imunização , Fígado/patologia , Pulmão/patologia , Camundongos , Camundongos Endogâmicos BALB C , Choque Séptico/imunologia , Infecções Estreptocócicas/imunologia , Infecções Estreptocócicas/patologia , Streptococcus suis/genética , Linfócitos T/imunologia , Vacinação , Virulência/genética , Fatores de Virulência/genética
16.
Fish Shellfish Immunol ; 86: 999-1008, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30590166

RESUMO

Streptococcus agalactiae infections are becoming an increasing problem in aquaculture because of significant morbidity and mortality, which restricts the healthy development of tilapia aquaculture. To seek safe and effective prevention measures, a Bacillus subtilis GC5 surface displayed vaccine was prepared and applied orally in tilapia. The study first showed that recombinant spores can engraft in the tilapia intestine. Then, the effect of protection and the immune responses were evaluated. The results of ELISA showed that Sip-specific antibody in the sera of GC5-Sip-immunized fish can be detected after the first oral administration when compared to the phosphate buffer saline (PBS) control group, and the levels of specific IgM gradually strengthened with boosting, so does the specific antibody against bacteria, proving that humoral immunity was induced. Quantitative real-time PCR (qRT-PCR) results showed that the immune-related gene expression of the gut and spleen exhibited a different rising trend in the GC5-Sip group, revealing that innate immune response and local as well as systemic cellular immunity were induced. The outcome of fish immunized with GC5-Sip spores provided a relative percent survival (RPS) of 41.7% against S. agalactiae and GC5 group had an RPS of 24.2%, indicating that GC5-Sip was safe and effective in protecting tilapia against bacterial infection. Our study demonstrated that the oral administration of B. subtilis spores expressing Sip could cause an effective immune response and offer good resistance to bacterial infection. Our work may lead to the development of new ideas for immunoprophylaxis against S. agalactiae infection.


Assuntos
Doenças dos Peixes/prevenção & controle , Vacinas Estreptocócicas/imunologia , Streptococcus agalactiae/imunologia , Tilápia , Administração Oral , Animais , Bacillus subtilis/metabolismo , Proteínas de Bactérias/imunologia , Doenças dos Peixes/microbiologia , Esporos Bacterianos , Infecções Estreptocócicas/prevenção & controle , Vacinas Estreptocócicas/administração & dosagem , Vacinação
17.
Microbiol Immunol ; 62(11): 711-719, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30357922

RESUMO

Protein subunit vaccines are often preferred because of their protective efficacy and safety. Lactic acid bacteria expressing heterologous antigens constitute a promising approach to vaccine development. However, their safety in terms of toxicity and bacterial clearance must be evaluated. Anti-Streptococcus pyogenes (S. pyogenes) vaccines face additional safety concerns because they may elicit autoimmune responses. The assessment of toxicity, clearance and autoimmunity of an anti-streptococcal vaccine based on Lactococcus lactis (L. lactis) expressing 10 different M protein fragments from S. pyogenes (L. lactis-Mx10) is here reported. Clearance of L. lactis from the oropharynges of immunocompetent mice and mice devoid of T/B lymphocytes mice was achieved without using antibiotics. The absence of autoimmune responses against human tissues was demonstrated with human brain, heart and kidney. Assessment of toxicity showed that leucocyte counts and selected serum biochemical factors were not affected in L. lactis-Mx10-immunized mice. In contrast, mice immunized with L. lactis wild type vector (L. lactis-WT) showed increased neutrophil and monocyte counts and altered histopathology of lymph nodes, lungs and nasal epithelium. Two days after immunization, L. lactis-Mx10-immunized and L. lactis-WT-immunized mice weighed significantly less than unimmunized mice. However, both groups of immunized mice recovered their body weights by Day 6. Our results demonstrate that L. lactis-WT, but not the vaccine L. lactis-Mx10, induces alterations in certain hematologic and histopathological variables. We consider these data a major contribution to data on L. lactis as a bacterial vector for vaccine delivery.


Assuntos
Administração Intranasal/métodos , Antígenos de Bactérias/imunologia , Lactococcus lactis/imunologia , Infecções Estreptocócicas/prevenção & controle , Vacinas Estreptocócicas/imunologia , Streptococcus pyogenes/imunologia , Vacinação/métodos , Vacinas Atenuadas/imunologia , Animais , Anticorpos Antibacterianos/sangue , Antígenos de Bactérias/genética , Autoimunidade/imunologia , Proteínas da Membrana Bacteriana Externa/genética , Proteínas da Membrana Bacteriana Externa/imunologia , Encéfalo/imunologia , Proteínas de Transporte/genética , Proteínas de Transporte/imunologia , Modelos Animais de Doenças , Feminino , Humanos , Imunização , Rim/imunologia , Lactococcus lactis/genética , Pulmão/microbiologia , Pulmão/patologia , Linfonodos/patologia , Camundongos , Camundongos Endogâmicos BALB C , Miocárdio/imunologia , Mucosa Nasal/patologia , Infecções Estreptocócicas/imunologia , Vacinas Estreptocócicas/administração & dosagem , Vacinas Estreptocócicas/genética , Vacinas Estreptocócicas/toxicidade , Streptococcus pyogenes/genética , Vacinas Atenuadas/administração & dosagem , Vacinas Atenuadas/genética
18.
Vaccine ; 36(46): 7033-7042, 2018 11 12.
Artigo em Inglês | MEDLINE | ID: mdl-30293765

RESUMO

BACKGROUND: There is a considerable global burden of invasive group B streptococcal (GBS) disease. Vaccines are being developed for use in pregnant women to offer protection to neonates. OBJECTIVE: To estimate the potential impact and cost-effectiveness of maternal immunisation against neonatal and maternal invasive GBS disease in the UK. METHODS: We developed a decision-tree model encompassing GBS-related events in infants and mothers, following a birth cohort with a time horizon equivalent to average life expectancy (81 years). We parameterised the model using contemporary data from disease surveillance and outcomes in GBS survivors. Costs were taken from NHS sources and research studies. Maternal immunisation in combination with risk-based intrapartum antibiotic prophylaxis (IAP) was compared to the current standard practice of risk-based IAP alone from an NHS and Personal Social Services (health-provider) perspective. We estimated the cases averted and cost per QALY gained through vaccination. One-way sensitivity analysis, scenario analysis and probabilistic sensitivity analysis were performed. RESULTS: An effective maternal immunisation programme could substantially reduce the burden of GBS disease. The deterministic analysis estimated the threshold cost-effective price for a GBS vaccine to be £54 per dose at £20,000/QALY (£71 per dose at £30,000/QALY). Results were most sensitive to assumptions on disease incidence, sequelae rate and vaccine efficacy. Probabilistic analysis showed 90.66% of iterations fell under the £30,000 threshold at a vaccine price of £55. Inclusion of modest prevention of stillbirths and/or, preterm births, carer health impacts, maternal GBS deaths and 1.5% discounting improved cost-effectiveness compared to the base case. Lowering vaccine strain coverage made the vaccine less cost-effective. A key limitation is that the properties of the final GBS vaccine are unknown. CONCLUSIONS: Maternal GBS immunisation is expected to be cost-effective, even at a relatively high vaccine price.


Assuntos
Sepse Neonatal/economia , Sepse Neonatal/prevenção & controle , Infecções Estreptocócicas/economia , Infecções Estreptocócicas/prevenção & controle , Vacinas Estreptocócicas/economia , Vacinas Estreptocócicas/imunologia , Streptococcus agalactiae/imunologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Análise Custo-Benefício , Feminino , Humanos , Incidência , Lactente , Recém-Nascido , Pessoa de Meia-Idade , Modelos Estatísticos , Sepse Neonatal/epidemiologia , Gravidez , Infecções Estreptocócicas/epidemiologia , Vacinas Estreptocócicas/administração & dosagem , Reino Unido/epidemiologia , Adulto Jovem
19.
Fish Shellfish Immunol ; 82: 522-530, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30118846

RESUMO

To effectively increase production and improve economic returns, the co-culture of Nile tilapia (Oreochromis niloticus) and marine shrimp has been adopted in many countries, including China. Although O. niloticus is an euryhaline fish that can tolerate elevated salinities and even full-strength seawater, fluctuations in salinity levels can undoubtedly induce stress and affect the immune response of this fish. Therefore, this study assessed the impact of salinity on vaccine efficacy in Nile tilapia, which used serum antibody level as a surrogate marker to detect vaccine efficacy. Nile tilapia were acclimatized to 0, 10, 20, or 30 ppt salinity, and then immunized with a formalin-inactivated Streptococcus agalactiae vaccine. Significantly lower levels of antibody in vaccinated fish were found at 20 and 30 ppt salinity compared to 0 and 10 ppt salinity. White blood cell counts, absolute blood lymphocyte counts, and serum bactericidal activity levels were all significantly lower in vaccinated fish at 20 and 30 ppt salinity. Elevated cortisol levels were detected in all of the fish exposure to salinity. Concentrations of serum electrolytes (Na+ and Cl-) were significantly higher in fish at 30 ppt salinity, as compared to fish at lower salinities. Furthermore, the mRNA transcription levels of three of the immune-related genes analyzed (IgM, IL-1ß, and IFN-γ, but not Hsp70) were significantly inhibited in the vaccinated fish at 20 and 30 ppt salinity. A suppressed immune response and decreased vaccine efficacy were also indicated by the lower survival rate of vaccinated fish at 20 ppt salinity when challenged with S. agalactiae. Therefore, salinities ≥20 ppt negatively affected antibody production in Nile tilapia, ultimately affecting vaccine efficacy.


Assuntos
Anticorpos Antibacterianos/sangue , Ciclídeos/imunologia , Doenças dos Peixes/prevenção & controle , Salinidade , Infecções Estreptocócicas/veterinária , Vacinas Estreptocócicas/uso terapêutico , Streptococcus agalactiae/imunologia , Animais , Doenças dos Peixes/imunologia , Doenças dos Peixes/microbiologia , Masculino , Infecções Estreptocócicas/imunologia , Infecções Estreptocócicas/microbiologia , Infecções Estreptocócicas/prevenção & controle , Vacinas Estreptocócicas/imunologia , Vacinação/veterinária
20.
Fish Shellfish Immunol ; 81: 49-56, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-29969706

RESUMO

Streptococcus agalactiae (S. agalactiae) is a gram-positive pathogen that causes a wide range of infections in fish and other animals including humans. Bacterial ghosts (BGs) are nonliving, empty cell envelopes and are well represented as novel vaccine candidates. In this study, we examined the immunogenicity and protective efficacy of S. agalactiae ghosts (SAG) against a virulent challenge in tilapia. Nonliving SAG was generated by a culture with Penicillin and Streptolysin, and then treated with the MIC of sodium hydroxide. The formation of a transmembrane lysis tunnel structure in SAG was visualized by electron microscopy. To investigate the SAG as a vaccine candidate, fish were divided into three groups, A (SAG immunized), B [Formalin-inactivated S. agalactiae (FSA) immunized] and C (phosphate-buffered saline, PBS-immunized control). The IgM antibody responses were significantly stronger in the SAG-immunized group than in FSA-immunized group, which was higher than in the non-immunized control group (P < 0.05). Moreover, phagocytic activity (percent phagocytes, PP) was significantly higher (p < 0.05) in the SAG-immunized group than in FSA-immunized group, which was higher than in the non-immunized control group (P < 0.05). In addition, non-specific immune immunity, such as lysozyme and superoxide dismutase activities, in the SAG-immunized fish showed significantly higher activities than FSA-immunized fish and the control group fish (P < 0.05). Also, fish immunized with SAG and FSA showed significantly higher (p < 0.05) gene expression of IL-1ß, TNF-α, IFN-γ and TGF-ß in the head kidney and spleen than fish treated with PBS during the whole observed period. In addition, fish immunized with SAG showed significantly higher gene expression of L-1ß, TNF-α, and TGF-ß in the spleen than in the FSA-immunized fish. Although there was no significant (P > 0.05) difference of survival rate (SR) or relative percent survival (RPS) between SAG and FSA immunized groups, they were all significantly more protected against the S. agalactiae challenge (SR: 86.67%, RPS: 76.395) and (SR: 80.00%, RPS: 67.50%) respectively, compared to the PBS-treated group (SR: 33.33%). These results suggest that immunization with SAG induces immune responses and provides protection against a virulent S. agalactiae challenge.


Assuntos
Doenças dos Peixes/prevenção & controle , Infecções Estreptocócicas/veterinária , Vacinas Estreptocócicas/imunologia , Streptococcus agalactiae/imunologia , Tilápia/imunologia , Animais , Antibacterianos/farmacologia , Anticorpos Antibacterianos , Membrana Celular , Doenças dos Peixes/imunologia , Imunidade Celular , Imunidade Humoral , Imunogenicidade da Vacina , Penicilinas/farmacologia , Infecções Estreptocócicas/imunologia , Infecções Estreptocócicas/prevenção & controle , Estreptolisinas/farmacologia
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA