Virulence capsular polysaccharide (Vi antigen) and Salmonella`s Pathogenicity Island type 1 and 2 TTSS (SPI-1 and SPI-2 TTSS) are important membrane virulence factors of human restricted pathogen S. Typhi. The Vi antigen modulates different proinflammatory signaling pathways in infected macrophages, microfold epithelial and dendritic cells. SPI-2 TTSS and its effectors are required for promoting bacterial intracellular survival, replication and apoptosis while SPI-1 and its effectors are associated with invasion of microfold epithelial cells. The purified Vi-antigen has been used as a vaccine against disease. It is a T cell independent antigen that induces moderate efficacy ( ̴ 55%) in adults and no efficacy in children bellow two years of age. Carrier protein conjugation of the Vi antigen has been successfully used to confer T cell dependency and to develop Vi conjugate vaccines with high efficacy, around 89% in three years, in all age groups. So far, the attenuated live vaccine with constitutive expression of Vi antigen and the SPI-2 TTSS mutant vaccine, progressed to phase 3 clinical tests. Particularly, the live attenuated vaccine with constitutive expression of Vi antigen might be also used to optimize the efficacies of other vaccines. The current preclinical studies consider also development of novel T cell independent vaccines from recombinant proteins and generalized modules for membrane antigens. An approach for future antivirulence therapy against disease might also consider the bioactive compounds with ability to inhibit TTSS secretions. It is concluded that combined approaches my successfully reduce S. Typhi infection in this new globalized era.
- MeSH
- antibakteriální látky farmakologie MeSH
- bakteriální polysacharidy antagonisté a inhibitory imunologie MeSH
- lidé MeSH
- Salmonella typhi účinky léků imunologie MeSH
- vakcíny farmakologie MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
The structures of polysaccharides (PS) isolated from Lactobacillus rhamnosus LOCK 0900 and results from stimulation of mouse bone marrow-derived dendritic cells (BM-DC) and human embryonal kidney (HEK293) cells stably transfected with Toll-like receptors (TLR) upon exposure to these antigens were studied. L. rhamnosus LOCK 0900 produces PS that differ greatly in their structure. The polymer L900/2, with a high average molecular mass of 830 kDa, is a branched heteropolysaccharide with a unique repeating unit consisting of seven sugar residues and pyruvic acid, whereas L900/3 has a low average molecular mass of 18 kDa and contains a pentasaccharide repeating unit and phosphorus. Furthermore, we found that both described PS neither induce cytokine production and maturation of mouse BM-DC nor induce signaling through TLR2/TLR4 receptors. However, they differ profoundly in their abilities to modulate the BM-DC immune response to the well-characterized human isolate Lactobacillus plantarum WCFS1. Exposure to L900/2 enhanced interleukin-10 (IL-10) production induced by L. plantarum WCFS1, while in contrast, L900/3 enhanced the production of IL-12p70. We conclude that PS, probably due to their chemical features, are able to modulate the immune responses to third-party antigens. The ability to induce regulatory IL-10 by L900/2 opens up the possibility to use this PS in therapy of inflammatory conditions, such as inflammatory bowel disease, whereas L900/3 might be useful in reverting the antigen-dependent Th2-skewed immune responses in allergies.
- MeSH
- bakteriální polysacharidy chemie imunologie farmakologie MeSH
- buňky kostní dřeně cytologie MeSH
- cytokiny metabolismus MeSH
- dendritické buňky účinky léků imunologie metabolismus MeSH
- HEK293 buňky účinky léků imunologie MeSH
- imunologické faktory imunologie farmakologie MeSH
- konformace sacharidů MeSH
- Lacticaseibacillus rhamnosus chemie imunologie MeSH
- lidé MeSH
- magnetická rezonanční spektroskopie MeSH
- molekulová hmotnost MeSH
- monosacharidy analýza MeSH
- myši inbrední BALB C MeSH
- probiotika MeSH
- toll-like receptor 2 metabolismus MeSH
- toll-like receptor 4 metabolismus MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Following primary and booster vaccination with an 11-valent pneumococcall protein D conjugate vaccine there was a 42.8% (95% CI: -16.7 to 71.9, ns) reduction in the carriage of Streptococcus pneumoniae vaccine serotypes and a 42.6% (95% CI: 1.3-66.6) reduction in the carriage of Haemophilus influenzae identified by standard microbiological techniques. When PCR and immunoblot assays were used to further improve specificity of non-typeable H. influenzae strain identification, carriage of H. influenzae was still reduced with 38.6% (95% CI: -6.3 to 64.6, ns). Reduction of acute otitis media (AOM) episodes preceded the impact on carriage. These data provide further support of the functional role of the protein D immunity.
- MeSH
- bakteriální polysacharidy imunologie MeSH
- bakteriální proteiny imunologie MeSH
- DNA bakterií izolace a purifikace MeSH
- dvojitá slepá metoda MeSH
- hemofilové infekce imunologie prevence a kontrola MeSH
- imunoglobulin D imunologie MeSH
- kojenec MeSH
- lidé MeSH
- lipoproteiny imunologie MeSH
- nazofarynx mikrobiologie MeSH
- otitis media mikrobiologie prevence a kontrola MeSH
- pneumokokové infekce imunologie prevence a kontrola MeSH
- pneumokokové vakcíny imunologie MeSH
- předškolní dítě MeSH
- přenašečství imunologie prevence a kontrola MeSH
- prospektivní studie MeSH
- transportní proteiny imunologie MeSH
- vakcíny konjugované imunologie MeSH
- Check Tag
- kojenec MeSH
- lidé MeSH
- mužské pohlaví MeSH
- předškolní dítě MeSH
- ženské pohlaví MeSH
- Publikační typ
- práce podpořená grantem MeSH
- randomizované kontrolované studie MeSH
BACKGROUND: Combined diphtheria-tetanus-whole-cell pertussis (DTPw) vaccines remain the cornerstone of many childhood vaccination programs. Larger DTPw-based combination vaccines facilitate high coverage and protection against other childhood pathogens, such as hepatitis B (HBV) and Haemophilus influenzae type b (Hib). Such vaccines have been available since the mid-1990s (Tritanrix-HBV and Tritanrix-HBV/Hib; GlaxoSmithKline [GSK] Biologicals), demonstrating excellent immunogenicity in various schedules. In order to address growing demand for DTPw-based vaccines, GSK Biologicals have developed the Zilbrix range using a new DTPw antigen source and containing reduced quantities of polyribosylribitol phosphate [PRP]. OBJECTIVE: This article presents clinical trial results for both DTPw-based vaccines. METHODS: GSK Biologicals provided a comprehensive data package, which was supplemented with a Medline literature search. CONCLUSION: New antigen sources and reduced PRP will ensure the continued supply of DTPw-based combination vaccines for vital global mass vaccination campaigns
- MeSH
- bakteriální polysacharidy aplikace a dávkování imunologie škodlivé účinky MeSH
- bakteriální pouzdra MeSH
- dítě MeSH
- hemofilové vakcíny aplikace a dávkování imunologie škodlivé účinky MeSH
- hepatitida B - protilátky imunologie krev MeSH
- hromadná vakcinace MeSH
- klinické zkoušky jako téma MeSH
- kojenec MeSH
- lidé MeSH
- novorozenec MeSH
- očkovací schéma MeSH
- polysacharidy imunologie MeSH
- předškolní dítě MeSH
- protilátky bakteriální imunologie krev MeSH
- sekundární imunizace MeSH
- vakcína proti diftérii, tetanu a pertusi aplikace a dávkování imunologie škodlivé účinky MeSH
- vakcína proti hepatitidě B aplikace a dávkování imunologie škodlivé účinky MeSH
- Check Tag
- dítě MeSH
- kojenec MeSH
- lidé MeSH
- novorozenec MeSH
- předškolní dítě MeSH
- Publikační typ
- přehledy MeSH
BACKGROUND: Acute otitis media is one of the most commonly-diagnosed childhood infections. This study assessed the efficacy of a novel vaccine that contained polysaccharides from 11 different Streptococcus pneumoniae serotypes each conjugated to Haemophilus influenzae-derived protein D in prevention of acute otitis media. METHODS: 4968 infants were randomly assigned to receive either pneumococcal protein D conjugate or hepatitis A vaccine at the ages of 3, 4, 5, and 12-15 months and were followed-up until the end of the second year of life. Middle-ear fluid was obtained for bacteriological culture and serotyping in children who presented with abnormal tympanic membrane or presence of middle-ear effusion, plus two predefined clinical symptoms. The primary endpoint was protective efficacy against the first episode of acute otitis media caused by vaccine pneumococcal serotypes. Analysis was per protocol. FINDINGS: From 2 weeks after the third dose to 24-27 months of age, 333 clinical episodes of acute otitis media were recorded in the protein D conjugate group (n=2455) and 499 in the control group (n=2452), giving a significant (33.6% [95% CI 20.8-44.3]) reduction in the overall incidence of acute otitis media. Vaccine efficacy was shown for episodes of acute otitis media caused by pneumococcal vaccine serotypes (52.6% [35.0-65.5] for the first episode and 57.6% [41.4-69.3] for any episode). Efficacy was also shown against episodes of acute otitis media caused by non-typable H influenzae (35.3% [1.8-57.4]). The vaccine reduced frequency of infection from vaccine-related cross-reactive pneumococcal serotypes by 65.5%, but did not significantly change the number of episodes caused by other non-vaccine serotypes. INTERPRETATION: These results confirm that using the H influenzae-derived protein D as a carrier protein for pneumococcal polysaccharides not only allowed protection against pneumococcal otitis, but also against acute otitis media due to non-typable H influenzae. Whether this approach would also allow improved protection against lower respiratory tract infections warrants further investigation.
- MeSH
- akutní nemoc MeSH
- bakteriální polysacharidy imunologie MeSH
- bakteriální proteiny imunologie MeSH
- dvojitá slepá metoda MeSH
- financování organizované MeSH
- Haemophilus influenzae izolace a purifikace klasifikace patogenita MeSH
- imunoglobulin D MeSH
- kojenec MeSH
- lidé MeSH
- lipoproteiny imunologie MeSH
- otitis media s výpotkem mikrobiologie MeSH
- otitis media imunologie mikrobiologie prevence a kontrola MeSH
- pneumokokové vakcíny imunologie terapeutické užití MeSH
- sérotypizace MeSH
- Streptococcus pneumoniae izolace a purifikace klasifikace patogenita MeSH
- transportní proteiny imunologie MeSH
- vakcína proti hepatitidě A MeSH
- Check Tag
- kojenec MeSH
- lidé MeSH
- Publikační typ
- randomizované kontrolované studie MeSH
- MeSH
- bakteriální polysacharidy imunologie MeSH
- Cryptococcus neoformans izolace a purifikace klasifikace MeSH
- kryptokoková meningitida krev mikrobiologie MeSH
- lidé MeSH
- Check Tag
- lidé MeSH
- Geografické názvy
- Egypt MeSH
- MeSH
- bakteriální polysacharidy aplikace a dávkování imunologie škodlivé účinky MeSH
- hepatitida - protilátky krev MeSH
- hepatitida A aplikace a dávkování imunologie škodlivé účinky MeSH
- inaktivované vakcíny aplikace a dávkování imunologie škodlivé účinky MeSH
- kombinované vakcíny aplikace a dávkování imunologie škodlivé účinky MeSH
- lidé MeSH
- vakcíny proti tyfu a paratyfu aplikace a dávkování imunologie škodlivé účinky MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
Cíl: Stanovit koncentraci typových pneumokokových protilátek v séru pro neprimou diagnostiku pneumokokových onemocnění a k potvrzení úspěšností imunizace typově specifickou pneumokokovou vakcínou. Metodika: Pneumokokové typové protilátky tridy IgG byly kvantitativně stanoveny metodou ELISA ve vlastní modifikaci. Výsledky: V sérech 37 jedinců, u nichž nebyla prokázána kolonizace pneumokoky ani pneumokokové onemocnění, byla zj zjištěštěna velká variabilita hladiny typových protilátek (0 až 73 μg/ml). Typové protilátky byly rovněž stanoveny v sérech 91 pacientů s diagnózou pneumonic. Podle množství protilátek v sérech (nejméně dvojnásobný vzestup protilátek v párových sérech nebo jejich vysoká hladina >90 μg/ml v jednotlivém séru) bylo možné nepřímo stanovit pneumokokovou etilologii onemocnění (23 %). V sérech převážně starších 75 jedinců a 23 díalyzovaných pacientů očkovaných pneumokokovou vakcínou Pneumo 23 byly stanoveny typové protilátky vždy před a zhruba za 4 týdny po vakcinaci. Imunizací došlo u 90,3 % zdravých jedinců ke 2- až 59násobnému vzestupu protilátek v sérech, zatímco u 52,2 % díalyzovaných pacientů ke 2- až ISnásobněmu zvýšení. U imunodeficitních pacientů se koncentrace protilátek imunizací nezvýšila anebo zvýšila nedostatečně (<2krát). Závěr: Z uvedených výsledků vyplývá, že stanovení typových protilátek je vhodnou metodou pro klinickou praxi. Několikanásobné zvýšení těchto protilátek je důkazem dobré imunologické odpovědi očkovaných jedinců.
Objective: Determination of pneumococcal type-specific antibody concentrations in serum for indirect diagnostics of pneumococcal diseases and confiirmation of the efficacy of immunization with a type specific pneumococcal vaccine. Methods: Pneumococcal type-specific IgG-antibodies were determined by the ELISA technique in our modification. Results: In sera of 37 subjects, who had no evidence of pneumococcal colonization or disease, there was a great variability in the quantity of typespecific antibodies (0 - 73 μg/ml). Type-specific antibodies were also determined in sera of 91 patients with a diagnosis of pneumonia. According to the quantitiy of antibodies in sera (at least a two-fold increase of antibodies in paired sera, or their high level >90 μg/ml in a single serum) pneumococcal etiology of disease could be established indirectly (25 %, 21.4 % and 14.3 %). In sera of 75 predominantly elderly subjects and of 23 dialyzed patients immunized with a pneumococcal vaccine „Pneumo 23" type-specific antibodies were determined before and approx. 4 weeks after vaccination. Immunization in healthy subjects (90.3 %) led to a 2- to 59-fold increase in the concentration of antibodies in sera, while in dialyzed patients (52.2 %) to a 2- to 15-fold increase. In immunodeftcient patients the concentration of antibodies after immunization did not increase, or increased insufficiently (<2-fold). Conclusion: The results show that the determination of type-specific antibodies is a suitable method in clinical practice. A manifold increase of the level of these antibodies is proof of a favorable immunological response of the vaccinee.
- MeSH
- bakteriální polysacharidy imunologie MeSH
- imunizace normy MeSH
- imunoglobulin G krev MeSH
- lidé MeSH
- pneumokokové infekce imunologie krev terapie MeSH
- protilátky bakteriální krev MeSH
- specificita protilátek MeSH
- Streptococcus pneumoniae imunologie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- srovnávací studie MeSH
