Adjuvant Activity of Sargassum pallidum Polysaccharides against Combined Newcastle Disease, Infectious Bronchitis and Avian Influenza Inactivated Vaccines

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Li-Jie Li

2012-11-01

Full Text Available This study evaluates the effects of Sargassum pallidum polysaccharides (SPP on the immune responses in a chicken model. The adjuvanticity of Sargassum pallidum polysaccharides in Newcastle disease (ND, infectious bronchitis (IB and avian influenza (AI was investigated by examining the antibody titers and lymphocyte proliferation following immunization in chickens. The chickens were administrated combined ND, IB and AI inactivated vaccines containing SPP at 10, 30 and 50 mg/mL, using an oil adjuvant vaccine as a control. The ND, IB and AI antibody titers and the lymphocyte proliferation were enhanced at 30 mg/mL SPP. In conclusion, an appropriate dose of SPP may be a safe and efficacious immune stimulator candidate that is suitable for vaccines to produce early and persistent prophylaxis.

Transport of Streptococcus pneumoniae capsular polysaccharide in MHC Class II tubules.

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Tom Li Stephen

2007-03-01

Full Text Available Bacterial capsular polysaccharides are virulence factors and are considered T cell-independent antigens. However, the capsular polysaccharide Sp1 from Streptococcus pneumoniae serotype 1 has been shown to activate CD4(+ T cells in a major histocompatibility complex (MHC class II-dependent manner. The mechanism of carbohydrate presentation to CD4(+ T cells is unknown. We show in live murine dendritic cells (DCs that Sp1 translocates from lysosomal compartments to the plasma membrane in MHCII-positive tubules. Sp1 cell surface presentation results in reduction of self-peptide presentation without alteration of the MHCII self peptide repertoire. In DM-deficient mice, retrograde transport of Sp1/MHCII complexes resulting in T cell-dependent immune responses to the polysaccharide in vitro and in vivo is significantly reduced. The results demonstrate the capacity of a bacterial capsular polysaccharide antigen to use DC tubules as a vehicle for its transport as an MHCII/saccharide complex to the cell surface for the induction of T cell activation. Furthermore, retrograde transport requires the functional role of DM in self peptide-carbohydrate exchange. These observations open new opportunities for the design of vaccines against microbial encapsulated pathogens.

Determination of saccharide content in pneumococcal polysaccharides and conjugate vaccines by GC-MSD.

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Kim, John S; Laskowich, Erin R; Arumugham, Rasappa G; Kaiser, Raymond E; MacMichael, Gregory J

2005-12-15

A simple and sensitive gas chromatographic method was designed for quantitative analysis of Streptococcus pneumoniae capsular polysaccharides, activated polysaccharides, and polysaccharide conjugates. Pneumococcal serotypes 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, and 23F polysaccharide or conjugate were subjected to methanolysis in 3N hydrochloric acid in methanol followed by re-N-acetylation and trimethylsilylation. Derivatized samples were chromatographed and detected using gas chromatography with mass selective detector. Gas chromatographic results were compared with colorimetric values with agreement of 92 to 123% over the range of all samples tested. Monosaccharides released during methanolysis included hexoses, uronic acids, 6-deoxy-hexoses, amino sugars, and alditols. Quantitative recovery of monosaccharides was achieved for all serotypes by the use of a single methanolysis, derivatization, and chromatography procedure. Response factors generated from authentic monosaccharide standards were used for quantitation of pneumococcal polysaccharides and conjugates with confirmation of peak assignments by retention time and mass spectral analysis. This method allows saccharide quantitation in multivalent pneumococcal vaccine intermediates and final drug products with low-level detection (10 pg) and peak purity.

Production of bacterial polysaccharides

Energy Technology Data Exchange (ETDEWEB)

Ellwood, D C; Evans, C G.T.; Yeo, R G

1978-06-01

A process for the biochemical synthesis of polysaccharides comprises growing polysaccharide-producing bacteria of the genus Xanthomonas in a single stage continuous culture in a chemically-defined medium. The term chemically-defined medium denotes a culture medium wherein nutrients other than carbon are provided as inorganic salts or single organic compounds of known molecular structure rather than as complex naturally-derived mixtures. Normally the only organic component of the chemically-defined medium will be a conventional carbon source such as a carbohydrate, especially glucose, or glycerol. Preferably the medium should contain only one nitrogen source, since the use of multiple nitrogen sources, as present in complex media, appears to promote changes in the nature of the culture resulting in loss of polysaccharide production. 22 claims.

Flocculation of colloidal clay by bacterial polysaccharides: effect of macromolecule charge and structure.

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Labille, J; Thomas, F; Milas, M; Vanhaverbeke, C

2005-04-01

The molecular mechanism of montmorillonite flocculation by bacterial polysaccharides was investigated, with special emphasis on the effect of carboxylic charges in the macromolecules on the mechanisms of interaction with the clay surface. An indirect way to quantify the energy of interaction was used, by comparing the flocculation ability of variously acidic polysaccharides. Data on tensile strength of aggregates in diluted suspension were collected by timed size measurements in the domain 0.1-600 microm, using laser diffraction. The flow behavior of settled aggregates was studied by rheology measurements. Flocculation of colloidal clay suspension by polysaccharides requires cancelling of the electrostatic repulsions by salts, which allows approach of clay surfaces close enough to be bridged by adsorbing macromolecules. The amount of acidic charges of the polysaccharides, and especially their location in the molecular structure, governs the bridging mechanism and the resulting tensile strength of the aggregates. The exposure of carboxylate groups located on side chains strongly promotes flocculation. In turn, charges located on the backbone of the polysaccharide are less accessible to interaction, and the flocculation ability of such polysaccharides is lowered. Measurements at different pH indicate that adsorption of acidic polysaccharides occurs via electrostatic interactions on the amphoteric edge surface of clay platelets, whereas neutral polysaccharides rather adsorb via weak interactions. Increased tensile strength in diluted aggregates due to strong surface interactions results in proportionally increased viscosity of the concentrated aggregates.

Outer membrane protein complex of Meningococcus enhances the antipolysaccharide antibody response to pneumococcal polysaccharide-CRM₁₉₇ conjugate vaccine.

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Lai, Zengzu; Schreiber, John R

2011-05-01

Bacterial polysaccharides (PS) are T cell-independent antigens that do not induce immunologic memory and are poor immunogens in infants. Conjugate vaccines in which the PS is covalently linked to a carrier protein have enhanced immunogenicity that resembles that of T cell-dependent antigens. The Haemophilus influenzae type b (Hib) conjugate vaccine, which uses the outer membrane protein complex (OMPC) from meningococcus as a carrier protein, elicits protective levels of anti-capsular PS antibody (Ab) after a single dose, in contrast to other conjugate vaccines, which require multiple doses. We have previously shown that OMPC robustly engages Toll-like receptor 2 (TLR2) and enhances the early anti-Hib PS Ab titer associated with an increase in TLR2-mediated induction of cytokines. We now show that the addition of OMPC to the 7-valent pneumococcal PS-CRM₁₉₇ conjugate vaccine during immunization significantly increases the anti-PS IgG and IgM responses to most serotypes of pneumococcus contained in the vaccine. The addition of OMPC also increased the likelihood of anti-PS IgG3 production against serotypes 4, 6B, 9V, 18C, 19F, and 23F. Splenocytes from mice who had received OMPC with the pneumococcal conjugate vaccine produced significantly more interleukin-2 (IL-2), IL-4, IL-6, IL-10, tumor necrosis factor alpha (TNF-α), and gamma interferon (IFN-γ) than splenocytes from mice who received phosphate-buffered saline (PBS) plus the conjugate vaccine. We conclude that OMPC enhances the anti-PS Ab response to pneumococcal PS-CRM₁₉₇ conjugate vaccine, an effect associated with a distinct change in cytokine profile. It may be possible to reduce the number of conjugate vaccine doses required to achieve protective Ab levels by priming with adjuvants that are TLR2 ligands.

Polysaccharides from Dioscorea (山藥 Shān Yào and Other Phytochemicals Enhance Antitumor Effects Induced by DNA Vaccine Against Melanoma

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Wen-Chi Wei

2014-01-01

Full Text Available Adjuvants can be used to enhance the immunogenicity of antigens and improve the efficacy of vaccines. Potent adjuvant action is known to often correlate with the activation of the transcription factor, nuclear factor-κB (NF-κB. Specific plant polysaccharides and a variety of phytochemicals from foods and traditional medicinal herbs have been shown to modulate NF-κB activation. In the present study, selected plant polysaccharides and phytochemicals were evaluated for use as a DNA vaccine adjuvant in a murine melanoma model. We observed that a specific ethanol extract fraction (DsCE-I from the tuber of a key Traditional Chinese Medicine plant, Dioscorea (山藥 Shān Yào, enhanced the protection against melanoma after immunization with a gene-based vaccine. A number of anti-inflammatory phytochemicals tested were able to partially diminish the inflammation-associated tumorigenesis elicited by LPS. Among the several phytochemical combinations investigated, the use of an adjuvant containing LPS in combination with emodin resulted in smaller tumors and higher survival rate in test mice than the use of other adjuvant treatments and the control sets in this DNA cancer vaccine model. A Dioscorea polysaccharide fraction (DsCE-I and several specific phytochemicals warrant further exploration as useful adjuvants for anticancer vaccines.

Bacterial glycobiology: rhamnose-containing cell wall polysaccharides in Gram-positive bacteria.

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Mistou, Michel-Yves; Sutcliffe, Iain C; van Sorge, Nina M

2016-07-01

The composition of the Gram-positive cell wall is typically described as containing peptidoglycan, proteins and essential secondary cell wall structures called teichoic acids, which comprise approximately half of the cell wall mass. The cell walls of many species within the genera Streptococcus, Enterococcus and Lactococcus contain large amounts of the sugar rhamnose, which is incorporated in cell wall-anchored polysaccharides (CWP) that possibly function as homologues of well-studied wall teichoic acids (WTA). The presence and chemical structure of many rhamnose-containing cell wall polysaccharides (RhaCWP) has sometimes been known for decades. In contrast to WTA, insight into the biosynthesis and functional role of RhaCWP has been lacking. Recent studies in human streptococcal and enterococcal pathogens have highlighted critical roles for these complex polysaccharides in bacterial cell wall architecture and pathogenesis. In this review, we provide an overview of the RhaCWP with regards to their biosynthesis, genetics and biological function in species most relevant to human health. We also briefly discuss how increased knowledge in this field can provide interesting leads for new therapeutic compounds and improve biotechnological applications. © FEMS 2016.

Neonatal and Infantile Immune Responses to Encapsulated Bacteria and Conjugate Vaccines

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Peter Klein Klouwenberg

2008-01-01

Full Text Available Encapsulated bacteria are responsible for the majority of mortality among neonates and infants. The major components on the surface of these bacteria are polysaccharides which are important virulence factors. Immunity against these components protects against disease. However, most of the polysaccharides are thymus-independent (TI-2 antigens which induce an inadequate immune response in neonates and infants. The mechanisms that are thought to play a role in the unresponsiveness of this age group to TI-2 stimuli will be discussed. The lack of immune response may be overcome by conjugating the polysaccharides to a carrier protein. This transforms bacterial polysaccharides from a TI-2 antigen into a thymus-dependent (TD antigen, thereby inducing an immune response and immunological memory in neonates and infants. Such conjugated vaccines have been shown to be effective against the most common causes of invasive disease caused by encapsulated bacteria in neonates and children. These and several other approaches in current vaccine development will be discussed.

[Health economic evaluation of a 23 value pneumococcal polysaccharide vaccination pilot programme among elderly chronic obstructive pulmonary disease patients in China].

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Qiu, Y P; Zhao, K; Li, X; Shi, L W; Guo, W D; Qi, X R; Sui, B Y; Zhou, R M

2016-12-06

Objective: From the perspective of health economics, to evaluate 23 pneumococcal polysaccharide vaccination programme among chronic obstructive pulmonary disease (COPD) patient. Methods: In the pilot counties of the project of integrated care pathway for COPD patient (Hanbin district of Hanzhong city in Shanxi Province, Qianjian district of Qingqing city, Huandao district of Qindao city in Shangdong Province, Wen county of Jiaozuo city in Henan Province), information of insurance participants of New Rural Cooperative Medical System (NRCS) was collected by local NRCM information system, which included general information as well as records of medical care and medical fee. Nonprobability sampling method was applied to select a total of 860 objects, who were over 60 years old with local household registration, hospitalized within one recent year due to COPD acute exacerbation, and without vaccination of 23 voluntary pneumococcal polysaccharide vaccine within 3 years. A quasi-experimental design without control group was adopted. Objects were vaccinated with 23-valent pneumococcal polysaccharide vaccine from January to December in 2013, then were followed up from January in 2014 for one year. Data of effectiveness and medical cost was collected by self-designed questionnaire and (Chinese version). Paired rank sum test applied to test the difference of quality of life, number and direct medical cost of treatment (including outpatient treatment and hospitalization) due to COPD acute exacerbation, one year before and after intervention. The incremental cost-effectiveness ratio (ICER) and cost-benefit ratio (CBR) of the programme were calculated. Results: By January 2014, eight hundred sixty objects were vaccinated. By January 2015, seven hundred eighty eight objects were followed up, with 72 cases withdrawed (8.4%). On average, COPD patients reduced 1.12±2.51 treatments due to acute exacerbation, including 0.28±2.09 outpatient treatments and 0.85±1.15 hospitalizations

Immunosuppressive drugs impairs antibody response of the polysaccharide and conjugated pneumococcal vaccines in patients with Crohn's disease

DEFF Research Database (Denmark)

Kantsø, Bjørn; Halkjær, Sofie Ingdam; Thomsen, Ole Østergaard

2015-01-01

BACKGROUND: Patients with Crohn's disease (CD) have a higher risk of infectious diseases including pneumococcal infections, and the risk increases with immunotherapy. The primary endpoint of this study was to investigate the specific antibody response to two pneumococcal vaccines in CD patients...... with and without immunosuppressive treatment four weeks post vaccination. METHODS: In a randomized trial of the 23-valent pneumococcal polysaccharide vaccine (PPV23) and the 13-valent pneumococcal conjugated vaccine (PCV13), a group of CD patients treated with immunosuppressive drugs (IS) alone or in combination...... with TNF-α antagonists were compared to a group of CD patients not treated with any of these drugs (untreated). Specific pneumococcal antibody concentrations were measured against 12 serotypes common to the two vaccines before and 4 week after vaccination. RESULTS: PCV13 induced a significantly higher...

Nuclear Magnetic Resonance: new applications in the quantification and assessment of polysaccharide-based vaccine intermediates

International Nuclear Information System (INIS)

Garrido, Raine; Velez, Herman; Verez, Vicente

2013-01-01

Nuclear Magnetic Resonance has become the choice for structural studies, identity assays and simultaneous quantification of active pharmaceutical ingredient of different polysaccharide-based vaccine. In the last two decades, the application of quantitative Nuclear Magnetic Resonance had an increasing impact to support several quantification necessities. The technique involves experiments with several modified parameters in order to obtain spectra with quantifiable signals. The present review is supported by some recent relevant reports and it discusses several applications of NMR in carbohydrate-based vaccines. Moreover, it emphasizes and describes several parameters and applications of quantitative Nuclear Magnetic Resonance

An in vitro assessment of titanium functionalized with polysaccharides conjugated with vascular endothelial growth factor for enhanced osseointegration and inhibition of bacterial adhesion.

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Hu, Xuefeng; Neoh, Koon-Gee; Shi, Zhilong; Kang, En-Tang; Poh, Chyekhoon; Wang, Wilson

2010-12-01

The long-term success of orthopedic implants may be compromised by defective osseointegration and bacterial infection. An effective approach to minimize implant failure would be to modify the surface of the implant to make it habitable for bone-forming cells and anti-infective at the same time. In this in vitro study, the surfaces of titanium (Ti) substrates were functionalized by first covalently grafting either dopamine followed by carboxymethyl chitosan (CMCS) or hyaluronic acid-catechol (HAC). Vascular endothelial growth factor (VEGF) was then conjugated to the polysaccharide-grafted surface. Antibacterial assay with Staphylococcus aureus (S. aureus) showed that the polysaccharide-modified substrates significantly decrease bacterial adhesion. The CMCS-functionalized Ti demonstrated better antibacterial property than the HAC-functionalized Ti since CMCS is bactericidal while HA only inhibits the adhesion of bacteria without killing them. Osteoblast attachment, as well as alkaline phosphatase (ALP) activity and calcium deposition were enhanced by the immobilized VEGF on the polysaccharide-grafted Ti. Thus, Ti substrates modified with polysaccharides conjugated with VEGF can promote osteoblast functions and concurrently reduce bacterial adhesion. Since VEGF is also known to enhance angiogenesis, the VEGF-polysaccharide functionalized substrates will have promising applications in the orthopedic field. Copyright © 2010 Elsevier Ltd. All rights reserved.

Co-administration of the polysaccharide of Lycium barbarum with DNA vaccine of Chlamydophila abortus augments protection.

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Ling, Yong; Li, Shaowen; Yang, Junjing; Yuan, Jilei; He, Cheng

2011-01-01

Lycium barbarum polysaccharides (LBP) can stimulate moderate immune responses therefore could potentially be used as a substitute for oil adjuvants in veterinary vaccines. In the present study, it was shown that the isolated active component of LBP3a, combined with a DNA vaccine encoding the major outer membrane protein (MOMP) of Chlamydophila abortus, induced protection in mice against challenge. Sixty BALB/c mice were randomly assigned to 5 groups. Sub-fractions of polysaccharide LBP3a, at 12.5, 25 and 50 mg/kg concentrations, respectively, were mixed with a pCI-neo::MOMP (pMOMP) vaccine. Mice administrated with pCI-neo + LBP3a were served as a control. All mice were inoculated at day 0, 14, and 28, and challenged on day 44. The effects of LBp3a on serum antibody levels, in vitro lymphocyte proliferation, the activity of interleaukin-2 (IL-2), interferon-γ (IFN-γ), tumor necrosis factor α(TNF-α)and chlamydia clearance were determined. A combination of DNA vaccine and LBP3a induced significantly higher antibody levels in mice, higher T cell proliferation and higher levels of IFN-γ and IL-2. Mice immunized with DNA and LBP3a also showed significantly higher levels of chlamydia clearance in mice spleens and a greater Th1 immune response. The immunoenhancement induced by 25 mg/kg LBP3a is more effective than that induced by a 12.5 and 50 mg/kg. This implies that LBP3a at 25 mg/kg has a high potential to be used as an effective adjuvant with a DNA vaccine against swine Chlamydophila abortus.

Intracellular Bacterial Infections: A Challenge for Developing Cellular Mediated Immunity Vaccines for Farmed Fish

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Hetron Mweemba Munang’andu

2018-04-01

Full Text Available Aquaculture is one of the most rapidly expanding farming systems in the world. Its rapid expansion has brought with it several pathogens infecting different fish species. As a result, there has been a corresponding expansion in vaccine development to cope with the increasing number of infectious diseases in aquaculture. The success of vaccine development for bacterial diseases in aquaculture is largely attributed to empirical vaccine designs based on inactivation of whole cell (WCI bacteria vaccines. However, an upcoming challenge in vaccine design is the increase of intracellular bacterial pathogens that are not responsive to WCI vaccines. Intracellular bacterial vaccines evoke cellular mediated immune (CMI responses that “kill” and eliminate infected cells, unlike WCI vaccines that induce humoral immune responses whose protective mechanism is neutralization of extracellular replicating pathogens by antibodies. In this synopsis, I provide an overview of the intracellular bacterial pathogens infecting different fish species in aquaculture, outlining their mechanisms of invasion, replication, and survival intracellularly based on existing data. I also bring into perspective the current state of CMI understanding in fish together with its potential application in vaccine development. Further, I highlight the immunological pitfalls that have derailed our ability to produce protective vaccines against intracellular pathogens for finfish. Overall, the synopsis put forth herein advocates for a shift in vaccine design to include CMI-based vaccines against intracellular pathogens currently adversely affecting the aquaculture industry.

Meningococcal Disease (Bacterial Meningitis) Vaccine and Pregnancy

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Meningococcal Disease (Bacterial Meningitis) Vaccine In every pregnancy, a woman starts out with a 3-5% chance of having a baby with a ... advice from your health care provider. What is meningitis? Meningitis is an infection of the lining around ...

The Pneumococcal Serotype 15C Capsule Is Partially O-Acetylated and Allows for Limited Evasion of 23-Valent Pneumococcal Polysaccharide Vaccine-Elicited Anti-Serotype 15B Antibodies

OpenAIRE

Spencer, Brady L.; Shenoy, Anukul T.; Orihuela, Carlos J.; Nahm, Moon H.

2017-01-01

As a species, Streptococcus pneumoniae (the pneumococcus) utilizes a diverse array of capsular polysaccharides to evade the host. In contrast to large variations in sugar composition and linkage formation, O-acetylation is a subtle capsular modification that nonetheless has a large impact on capsular shielding and recognition of the capsule by vaccine-elicited antibodies. Serotype 15B, which is included in the 23-valent pneumococcal polysaccharide vaccine (PPV23), carries the putative O-acety...

Pneumococcal polysaccharide vaccination elicits IgG anti-AB blood group antibodies in healthy individuals and patients with Type I diabetes mellitus

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Wendelin Wolfram

2016-11-01

Full Text Available Hypothesis: Blood group antibodies are natural antibodies that develop early in life in response to cross-reactive environmental antigens in the absence of antigen encounter. Even later in life structural similarities in saccharide composition between environmental antigens such as bacterial polysaccharides and blood group A/B antigens could lead to changes in serum levels, IgM/IgG isotype and affinity maturation of blood group anti-A/B antibodies. We adressed the question whether immunization with pneumococcal polysaccharide (PnP vaccine (PPV Pneumovax®23 could have such an effect in patients with with type I diabetes mellitus (DM I, an autoimmune disease where an aberrant immune response to microbial antigens likely plays a role.Methods: Anti-PnP IgM and IgG responses were determined by ELISA and the Diamed-ID Micro Typing System was used to screen anti-A/B antibody titer before and after Pneumovax®23 immunization in 28 healthy individuals and 16 patients with DM I. In addition, surface plasmon resonance (SPR technology using the Biacore® device and a synthetic blood group A/B trisaccharide as the antigen was applied to investigate IgM and IgG anti-A/B antibodies and to measure antibody binding dynamics. Results: All healthy individuals and DM I patients responded with anti-PnP IgM and IgG antibody production four to six weeks after Pneumovax®23 (Pn23 immunization, while no increase in blood group anti-A/B antibody titer was observed when measured by the Diamed-ID Micro Typing System. Interestingly, isotype-specific testing by SPR-technology revealed an increase in blood group anti-A/B IgG, but not IgM, following Pn23 immunization in both patients and controls. No change in binding characteristics of blood group anti-A/B antibodies could be detected following Pn23 vaccination, supporting the assumption of an increase in IgG antibody titer with no or very little affinity maturation.Conclusion: The study provides evidence for epitope sharing

Immunogenicity of a 23-valent pneumococcal polysaccharide vaccine in elderly residents of a long-term care facility

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M. Teresa Valenzuela B.

Full Text Available S. pneumoniae is a significant cause of community-acquired pneumonia in the elderly, and accounts for the majority of the pneumonia deaths among the elderly. We conducted this randomized double-blind study to evaluate the immune response to a 23-valent pneumococcal polysaccharide vaccine and the persistence of antibodies two years after the vaccination in an elderly population in Santiago, Chile. A total of 118 elderly nursing home residents received either the pneumococcal or a tetanus control vaccine. Serum samples were taken at enrolment, at two months, and at two years post-vaccination. Pre-vaccination anti-pneumococcal antibody geometric mean concentrations (GMC were similar in both study groups, with increased levels of antibodies found only against serotype 14. The pneumococcal vaccine was highly immunogenic at 2 months, and titers remained high two years after the vaccination for the 10 serotypes studied in this elderly population. The results thus support the benefits of this pneumococcal vaccine in this elderly population who are at increased risk of invasive pneumococcal disease.

Immunogenicity and Safety of the 13-Valent Pneumococcal Conjugate Vaccine versus the 23-Valent Polysaccharide Vaccine in Unvaccinated HIV-Infected Adults: A Pilot, Prospective Controlled Study.

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Francesca Lombardi

Full Text Available Definition of the optimal pneumococcal vaccine strategy in HIV-infected adults is still under evaluation. We aimed to compare immunogenicity and safety of the 13-valent pneumococcal conjugate vaccine (PCV13 versus the 23-valent polysaccharide vaccine (PPSV23 in HIV-infected adults.We performed a pilot, prospective controlled study enrolling HIV-infected pneumococcal vaccine-naïve outpatients, aged 18-65 years with CD4 counts ≥200 cells/μL. Eligible subjects were recruited into two parallel groups: group 1 (n = 50 received two doses of PCV13 eight weeks apart, and group 2 (n = 50 received one dose of PPSV23, as part of their standard of care. Anti-pneumococcal capsular polysaccharide immunoglobulin G concentrations were quantified by ELISA at baseline, 8, 24 and 48 weeks. Clinical and viro-immunological follow-up was performed at the same time points. Unvaccinated, age-matched HIV-negative adults (n = 100 were also enrolled as baseline controls.Pre-vaccination specific IgG titers for each pneumococcal antigen did not differ between study groups but they were constantly lower than those from the HIV-negative controls. After immunization, significant increases in IgG titers were observed in both study groups at each time point compared to baseline, but response to serotype 3 was blunted in group 1. Antibody titers for each antigen did not differ between study groups at week 48. Overall, the proportion of subjects achieving seroprotection and seroconversion to all serotypes was comparable between groups. A marked decrease in IgG levels over time was observed with both vaccines. No relevant adverse reactions were reported in either group.In this population with favorable immune profile, no relevant differences were observed in immunogenicity between PCV13 and PPSV23. Both vaccines were safe and well tolerated.ClinicalTrials.gov NCT02123433.

Immunization and chemical conjugation of Bm95 obtained from Pichia pastoris enhances the immune response against vaccinal protein and Neisseria meningitidis capsular polysaccharide

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Rodriguez-Valle M

2014-03-01

Full Text Available Manuel Rodriguez-Valle,1 Leonardo Canan-Hadden,2 Olivia Niebla2 1Animal Biotechnology Division, 2Analytical Division, Centre for Genetic Engineering and Biotechnology, Havana, Cuba Abstract: The ectoparasite Rhipicephalus (Boophilus microplus causes severe economic losses to the cattle industry in tropical and subtropical regions, and transmits endoparasites, such as Babesia bovis. The glycoprotein Bm95 is homologous to Bm86, a surface membrane protein of gut epithelial cells in R. microplus, and has been shown to efficiently control this ectoparasite in regions of the Americas. The immunostimulant properties of Bm86 have already been demonstrated after its coinjection with hepatitis B surface antigen (HBsAg and the infectious bovine rhinotracheitis virus. This study evaluated the carrier and immunostimulant properties of Bm95 using low immunogenic Neisseria meningitidis capsular C polysaccharide (Men CpS and HBsAg. We produced two polysaccharide-Bm95 conjugates by carbodiimide (MenCpSBm-c and reductive amination (MenCpSBm-ra methods. These conjugates were characterized and evaluated in mice. Antibody titers against Men CpS were significantly higher in mice immunized with MenCpSBm-ra (2,350±250, P<0.01 than in those immunized with MenCpSBm-c (250±75 or Men CpS (570±104. The study data indicate effective immunological memory after booster inoculation in mice immunized with MenCpSBm-ra. Additionally, significant humoral immunity against HBsAg was documented in mice coimmunized via the intranasal route with recombinant Bm95 (11,400±345 and HBsAg (128,000±250 compared with mice immunized only with HBsAg (400±40 or Bm95 (5,461±150, P<0.01. In conclusion, the immunostimulatory properties of recombinant Bm95 make it a useful element for developing safer conjugated vaccines against bacterial pathogens and for evaluation against ticks and tick-borne diseases in the context of a polyvalent veterinary vaccine. Keywords: glycoconjugate, Bm86

Quantitative determination of pneumococcal capsular polysaccharide serotype 14 using a modification of phenol-sulfuric acid method.

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Cuesta, Gabriela; Suarez, Norma; Bessio, Maria I; Ferreira, Fernando; Massaldi, Hugo

2003-01-01

The capsular polysaccharide of Streptococcus pneumoniae, serotype 14, is part of every pneumococcal vaccine presently in the market or under development. A strategy for the quantitative determination of this polysaccharide by the phenol-sulfuric acid method is described. The modality of acid addition is shown to be the critical step for obtaining reproducible test results between different technicians. Raising the incubation temperature above 80 degrees C increased the consistency of the method by more than 60% regardless of the acid addition modality, but at the expense of some loss of sensitivity. Incubation at 110 degrees C was found necessary to obtain reproducible results within 3% for this technique, which was used to follow the enrichment of the polysaccharide during the last steps of purification. A model mixture of the component polysaccharide sugars provided an adequate and economic standard to construct the calibration curve for this assay, with absorbance reading either in the reaction tubes or in a microplate. A similar procedure may be applied to the determination of other bacterial polysaccharides as well.

A medically relevant capsular polysaccharide in Acinetobacter baumannii is a potential vaccine candidate.

Science.gov (United States)

Yang, Feng-Ling; Lou, Tze-Chi; Kuo, Shu-Chen; Wu, Wan-Ling; Chern, Jeffy; Lee, Yi-Tzu; Chen, Shui-Tsung; Zou, Wei; Lin, Nien-Tsung; Wu, Shih-Hsiung

2017-03-07

Concerns of Acinetobacter baumannii infection have increased due to the emergence of multi-drug resistance. In the present study, we determined the capsular polysaccharide (CPS) structure of A. baumannii SK44, a clinical isolate from Taiwan, to consist of pentasaccharide repeats. We found that CPS-induced antibody provided 55% protection against challenge in an animal model. The CPS-specific antibody reacted with the surface components of about 62% clinical isolates (342/554 strains) from cross-sectional and longitudinal studies by dot-immunoassay. Pulsed-field gel electrophoresis of positive strains showed the antibody covered different clonalites of A. baumannii clinical isolates. Meanwhile, using the CPS antibody as a probe, we found a number of outer membrane proteins bound to the antibody, including OmpA/motB, TonB-dependent receptor, and Omp38, indicating their association with CPS. These results might lead to the use of the capsular polysaccharide as a vaccine to prevent A. baumannii infection. Copyright © 2017 Elsevier Ltd. All rights reserved.

The effects of vaccination and immunity on bacterial infection dynamics in vivo.

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Chris Coward

2014-09-01

Full Text Available Salmonella enterica infections are a significant global health issue, and development of vaccines against these bacteria requires an improved understanding of how vaccination affects the growth and spread of the bacteria within the host. We have combined in vivo tracking of molecularly tagged bacterial subpopulations with mathematical modelling to gain a novel insight into how different classes of vaccines and branches of the immune response protect against secondary Salmonella enterica infections of the mouse. We have found that a live Salmonella vaccine significantly reduced bacteraemia during a secondary challenge and restrained inter-organ spread of the bacteria in the systemic organs. Further, fitting mechanistic models to the data indicated that live vaccine immunisation enhanced both the bacterial killing in the very early stages of the infection and bacteriostatic control over the first day post-challenge. T-cell immunity induced by this vaccine is not necessary for the enhanced bacteriostasis but is required for subsequent bactericidal clearance of Salmonella in the blood and tissues. Conversely, a non-living vaccine while able to enhance initial blood clearance and killing of virulent secondary challenge bacteria, was unable to alter the subsequent bacterial growth rate in the systemic organs, did not prevent the resurgence of extensive bacteraemia and failed to control the spread of the bacteria in the body.

Protein carriers of conjugate vaccines

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Pichichero, Michael E

2013-01-01

The immunogenicity of polysaccharides as human vaccines was enhanced by coupling to protein carriers. Conjugation transformed the T cell-independent polysaccharide vaccines of the past to T cell-dependent antigenic vaccines that were much more immunogenic and launched a renaissance in vaccinology. This review discusses the conjugate vaccines for prevention of infections caused by Hemophilus influenzae type b, Streptococcus pneumoniae, and Neisseria meningitidis. Specifically, the characteristics of the proteins used in the construction of the vaccines including CRM, tetanus toxoid, diphtheria toxoid, Neisseria meningitidis outer membrane complex, and Hemophilus influenzae protein D are discussed. The studies that established differences among and key features of conjugate vaccines including immunologic memory induction, reduction of nasopharyngeal colonization and herd immunity, and antibody avidity and avidity maturation are presented. Studies of dose, schedule, response to boosters, of single protein carriers with single and multiple polysaccharides, of multiple protein carriers with multiple polysaccharides and conjugate vaccines administered concurrently with other vaccines are discussed along with undesirable consequences of conjugate vaccines. The clear benefits of conjugate vaccines in improving the protective responses of the immature immune systems of young infants and the senescent immune systems of the elderly have been made clear and opened the way to development of additional vaccines using this technology for future vaccine products. PMID:23955057

Vaccines in historic evolution and perspective: a narrative of vaccine discoveries.

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Hilleman, M R

2000-01-01

The sciences of vaccinology and immunology were created only two centuries ago by Jenner's scientific studies of prevention of smallpox through inoculation with cowpox virus. This rudimentary beginning was expanded greatly by the giants of late 19th- and early 20th-century biomedical sciences. The period from 1930 to 1950 was a transitional era, with the introduction of chick embryos and minced tissues for propagating viruses and rickettsiae in vitro for vaccines. Modern vaccinology began about 1950 as a continuum following notable advances made during the 1940s and World War II. Its pursuit has been based largely on breakthroughs in cell culture, bacterial polysaccharide chemistry, molecular biology, and immunology which have yielded many live and killed viral and bacterial vaccines plus the recombinant-expressed hepatitis B vaccine. The present paper was presented as a lecture given at a Meeting of the Institute of Human Virology entitled A Symposium on HIV-AIDS and Cancer Biology, Baltimore, Maryland, on August 30, 1999 and recounts, by invitation, more than 55 years of vaccine research from the venue of personal experience and attainment by the author. The paper is intentionally brief and truncated with focus only on highlights and limited referencing. Detailed recounting and referencing are given elsewhere in text references 1 and 2. This narration will have achieved its purpose if it provides a background of understanding and guidelines that will assist others who seek to engage in creation of new vaccines.

History of meningococcal vaccines and their serological correlates of protection.

Science.gov (United States)

Vipond, Caroline; Care, Rory; Feavers, Ian M

2012-05-30

For over a hundred years Neisseria meningitidis has been known to be one of the major causes of bacterial meningitis. However, effective vaccines were not developed until the latter part of the 20th century. The first of these were based on purified high molecular weight capsular polysaccharides and more recently the development of glycoconjugate vaccines has made paediatric immunisation programmes possible. The prevention of group B meningococcal disease has remained a challenge throughout this period. This review charts the history of the development of meningococcal vaccines and the importance of serological correlates of protection in their evaluation. Copyright © 2012 Elsevier Ltd. All rights reserved.

Stimulation of protective antibodies against type Ia and Ib group B streptococci by a type Ia polysaccharide-tetanus toxoid conjugate vaccine.

OpenAIRE

Wessels, M R; Paoletti, L C; Rodewald, A K; Michon, F; DiFabio, J; Jennings, H J; Kasper, D L

1993-01-01

Antisera elicited by type Ia group B streptococci (GBS) contain antibodies that react with both type Ia and type Ib strains. Previous studies suggested that antibodies elicited by type Ia organisms recognized a carbohydrate antigen or epitope common to Ia and Ib strains. We now report the synthesis and immunogenicity testing of a type Ia polysaccharide-tetanus toxoid (Ia-TT) conjugate vaccine. Ia-TT elicited type Ia polysaccharide-specific immunoglobulin G antibodies in all three of the rabbi...

New recombinant vaccines for the prevention of meningococcal B disease

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Taha MK

2012-06-01

Full Text Available Muhamed-Kheir Taha, Ala-Eddine DeghmaneInstitut Pasteur, Unit of Invasive Bacterial Infections and National Reference Center for Meningococci, Paris, FranceAbstract: Meningococcal disease is a life-threatening invasive infection (mainly septicemia and meningitis that occurs as epidemic or sporadic cases. The causative agent, Neisseria meningitidis or meningococcus, is a capsulated Gram-negative bacterium. Current vaccines are prepared from the capsular polysaccharides (that also determine serogroups and are available against strains of serogroups A, C, Y, and W-135 that show variable distribution worldwide. Plain polysaccharide vaccines were first used and subsequently conjugate vaccines with enhanced immunogenicity were introduced. The capsular polysaccharide of meningococcal serogroup B is poorly immunogenic due to similarity to the human neural cells adhesion molecule. Tailor-made, strain-specific vaccines have been developed to control localized and clonal outbreaks due to meningococci of serogroup B but no “universal” vaccine is yet available. This unmet medical need was recently overcome using several subcapsular proteins to allow broad range coverage of strains and to reduce the risk of escape variants due to genetic diversity of the meningococcus. Several vaccines are under development that target major or minor surface proteins. One vaccine (Bexsero®; Novartis, under registration, is a multicomponent recombinant vaccine that showed an acceptable safety profile and covers around 80% of the currently circulating serogroup B isolates. However, its reactogenicity in infants seems to be high and the long term persistence of the immune response needs to be determined. Its activity on carriage, and therefore transmission, is under evaluation. Indirect protection is expected through restricting strain circulation and acquisition. This vaccine covers the circulating strains according to the presence of the targeted antigens in the

Visualization of bacterial polysaccharides by scanning transmission electron microscopy.

Science.gov (United States)

Wolanski, B S; McAleer, W J; Hilleman, M R

1983-04-01

Highly purified capsular polysaccharides of Neisseria meningitidis groups A, B, and C have been visualized by high resolution Scanning Transmission Electron Microscopy (STEM). Spheroidal macromolecules approximately 200 A in diameter are characteristic of the Meningococcus A and C polysaccharides whereas filaments that are 400-600 A in length are found in Meningococcus B polysaccharide preparations. Filaments are occasionally found associated with the spheroidal Meningococcus A and C polysaccharides and it is proposed that these structures are composed of a long (1-4 microns) filament or filaments that are arranged in spheroidal molecules or micelles of high molecular weight. The Meningococcus B polysaccharide, by contrast, is a short flexuous filament or strand of relatively low molecular weight. A relationship between morphology and antigenicity is proposed.

Directed antigen delivery as a vaccine strategy for an intracellular bacterial pathogen

Science.gov (United States)

Bouwer, H. G. Archie; Alberti-Segui, Christine; Montfort, Megan J.; Berkowitz, Nathan D.; Higgins, Darren E.

2006-03-01

We have developed a vaccine strategy for generating an attenuated strain of an intracellular bacterial pathogen that, after uptake by professional antigen-presenting cells, does not replicate intracellularly and is readily killed. However, after degradation of the vaccine strain within the phagolysosome, target antigens are released into the cytosol for endogenous processing and presentation for stimulation of CD8+ effector T cells. Applying this strategy to the model intracellular pathogen Listeria monocytogenes, we show that an intracellular replication-deficient vaccine strain is cleared rapidly in normal and immunocompromised animals, yet antigen-specific CD8+ effector T cells are stimulated after immunization. Furthermore, animals immunized with the intracellular replication-deficient vaccine strain are resistant to lethal challenge with a virulent WT strain of L. monocytogenes. These studies suggest a general strategy for developing safe and effective, attenuated intracellular replication-deficient vaccine strains for stimulation of protective immune responses against intracellular bacterial pathogens. CD8+ T cell | replication-deficient | Listeria monocytogenes

An improved haemolytic plaque assay for the detection of cells secreting antibody to bacterial antigens

DEFF Research Database (Denmark)

Barington, T; Heilmann, C

1992-01-01

Recent advances in the development of conjugate polysaccharide vaccines for human use have stimulated interest in the use of assays detecting antibody-secreting cells (AbSC) with specificity for bacterial antigens. Here we present improved haemolytic plaque-forming cell (PFC) assays detecting Ab......SC with specificity for tetanus and diphtheria toxoid as well as for Haemophilus influenzae type b and pneumococcal capsular polysaccharides. These assays were found to be less time consuming, more economical and yielded 1.9-3.4-fold higher plaque numbers than traditional Jerne-type PFC assays. In the case of anti......-polysaccharide antibodies aggregation of secreted monomeric antibody (IgG) is critical for plaque formation and increases the avidity of binding to target cells....

Bacterially produced recombinant influenza vaccines based on virus-like particles.

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Andrea Jegerlehner

Full Text Available Although current influenza vaccines are effective in general, there is an urgent need for the development of new technologies to improve vaccine production timelines, capacities and immunogenicity. Herein, we describe the development of an influenza vaccine technology which enables recombinant production of highly efficient influenza vaccines in bacterial expression systems. The globular head domain of influenza hemagglutinin, comprising most of the protein's neutralizing epitopes, was expressed in E. coli and covalently conjugated to bacteriophage-derived virus-like particles produced independently in E.coli. Conjugate influenza vaccines produced this way were used to immunize mice and found to elicit immune sera with high antibody titers specific for the native influenza hemagglutinin protein and high hemagglutination-inhibition titers. Moreover vaccination with these vaccines induced full protection against lethal challenges with homologous and highly drifted influenza strains.

Capsular Polysaccharide Expression in Commensal Streptococcus Species

DEFF Research Database (Denmark)

Skov Sørensen, Uffe B; Yao, Kaihu; Yang, Yonghong

2016-01-01

Expression of a capsular polysaccharide is considered a hallmark of most invasive species of bacteria, including Streptococcus pneumoniae, in which the capsule is among the principal virulence factors and is the basis for successful vaccines. Consequently, it was previously assumed that capsule....... pneumoniae evolved by import of cps fragments from commensal Streptococcus species, resulting in a mosaic of genes of different origins. The demonstrated antigenic identity of at least eight of the numerous capsular polysaccharide structures expressed by commensal streptococci with recognized serotypes of S...... of Streptococcus pneumoniae and is the basis for successful vaccines against infections caused by this important pathogen. Contrasting with previous assumptions, this study showed that expression of capsular polysaccharides by the same genetic mechanisms is a general property of closely related species...

Serotype-specific immunoglobulin G antibody responses to pneumococcal polysaccharide vaccine in children with sickle cell anemia : Effects of continued penicillin prophylaxis

NARCIS (Netherlands)

Bjornson, AB; Falletta, JM; Verter, JI; Buchanan, GR; Miller, ST; Pegelow, CH; Iyer, RV; Johnstone, HS; DeBaun, MR; Wethers, DL; Woods, GM; Holbrook, CT; Becton, DL; Kinney, TR; Reaman, GH; Kalinyak, K; Grossman, NJ; Vichinsky, E; Reid, CD

1996-01-01

Objectives: (1) To determine serotype-specific IgG antibody responses to reimmunization with pneumococcal polysaccharide vaccine at age 5 years ski children with sickle cell anemia and (2) to determine whether continued penicillin prophylaxis had any adverse effects on these responses. Study design:

Improved coupling of bacterial polysaccharides to macromolecules and solid supports

DEFF Research Database (Denmark)

2013-01-01

The invention relates to a method of producing a polysaccharide-carrier conjugate comprising coupling a polysaccharide to a carrier, said polysaccharide comprising at least one monosaccharide unit comprising a keto-carboxy group according to the formula -C(=O)COOR, where R is either hydrogen or C1......-alkoxyamine group of the carrier with a keto-carboxy group of said polysaccharide to form a covalent amide bond between the carrier and the polysaccharide. Another aspect of the present invention relates to a compound or solid surface obtained when performing the method of the present invention. A third aspect...

Vaccination for the control of childhood bacterial pneumonia - Haemophilus influenzae type b and pneumococcal vaccines

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Diana C Otczyk

2013-01-01

Full Text Available Pneumonia in childhood is endemic in large parts of the world and in particular, in developing countries, as well as in many indigenous communities within developed nations. Haemophilus influenzae type b and Streptococcus pneumoniae conjugate vaccines are currently available against the leading bacterial causes of pneumonia.  The use of the vaccines in both industrialised and developing countries have shown a dramatic reduction in the burden of pneumonia and invasive disease in children.  However, the greatest threat facing pneumococcal conjugate vaccine effectiveness is serotype replacement.  The current vaccines provide serotype-specific, antibody–mediated protection against only a few of the 90+ capsule serotypes.  Therefore, there has been a focus in recent years to rapidly advance technologies that will result in broader disease coverage and more affordable vaccines that can be used in developing countries.  The next generation of pneumococcal vaccines have advanced to clinical trials.

Live bacterial delivery systems for development of mucosal vaccines

NARCIS (Netherlands)

Thole, J.E.R.; Dalen, P.J. van; Havenith, C.E.G.; Pouwels, P.H.; Seegers, J.F.M.L.; Tielen, F.D.; Zee, M.D. van der; Zegers, N.D.; Shaw, M.

2000-01-01

By expression of foreign antigens in attenuated strains derived from bacterial pathogens and in non-pathogenic commensal bacteria, recombinant vaccines are being developed that aim to stimulate mucosal immunity. Recent advances in the pathogenesis and molecular biology of these bacteria have allowed

The adjuvanticity of ophiopogon polysaccharide liposome against an inactivated porcine parvovirus vaccine in mice.

Science.gov (United States)

Fan, Yunpeng; Ma, Xia; Hou, Weifeng; Guo, Chao; Zhang, Jing; Zhang, Weimin; Ma, Lin; Song, Xiaoping

2016-01-01

In this study, the adjuvant activity of ophiopogon polysaccharide liposome (OPL) was investigated. The effects of OPL on the splenic lymphocyte proliferation of mice were measured in vitro. The results showed that OPL could significantly promote lymphocyte proliferation singly or synergistically with PHA and LPS and that the effect was better than ophiopogon polysaccharide (OP) at most of concentrations. The adjuvant activities of OPL, OP and mineral oil were compared in BALB/c mice inoculated with inactivated PPV in vivo. The results showed that OPL could significantly enhance lymphocyte proliferation, increase the proportion of CD4(+) and CD8(+) T cells, improve the HI antibody titre and specific IgG response, and promote the production of cytokines, and the efficacy of OPL was significantly better than that of OP. In addition, OPL significantly improved the cellular immune response compared with oil adjuvant. These results suggested that OPL possess superior adjuvanticity and that a medium dose had the best efficacy. Therefore, OPL can be used as an effective immune adjuvant for an inactivated PPV vaccine. Copyright © 2015. Published by Elsevier B.V.

Genome-wide identification of Streptococcus pneumoniae genes essential for bacterial replication during experimental meningitis

DEFF Research Database (Denmark)

Molzen, T E; Burghout, P; Bootsma, H J

2010-01-01

Meningitis is the most serious of invasive infections caused by the Gram-positive bacterium Streptococcus pneumoniae. Vaccines protect only against a limited number of serotypes, and evolving bacterial resistance to antimicrobials impedes treatment. Further insight into the molecular pathogenesis...... as targets for future therapy and prevention of pneumococcal meningitis, since their mutants were attenuated in both models of infection as well as in competitive growth in human cerebrospinal fluid in vitro.......Meningitis is the most serious of invasive infections caused by the Gram-positive bacterium Streptococcus pneumoniae. Vaccines protect only against a limited number of serotypes, and evolving bacterial resistance to antimicrobials impedes treatment. Further insight into the molecular pathogenesis...... genes mutants of which had become attenuated or enriched, respectively, during infection. The results point to essential roles for capsular polysaccharides, nutrient uptake, and amino acid biosynthesis in bacterial replication during experimental meningitis. The GAF phenotype of a subset of identified...

Effectiveness of 23-valent pneumococcal polysaccharide vaccine and seasonal influenza vaccine for pneumonia among the elderly - Selection of controls in a case-control study.

Science.gov (United States)

Kondo, Kyoko; Suzuki, Kanzo; Washio, Masakazu; Ohfuji, Satoko; Fukushima, Wakaba; Maeda, Akiko; Hirota, Yoshio

2017-08-24

We conducted a case-control study to elucidate associations between pneumonia in elderly individuals and 23-valent pneumococcal polysaccharide vaccine (PPSV23) and seasonal influenza vaccine (influenza vaccine). Here, we examined selection of controls in our study using an analytic epidemiology approach. The study period was from October 1, 2009 through September 30, 2014. Cases comprised ≥65-year-old patients newly diagnosed with pneumonia. For every case with pneumonia, two patients with other diseases (one respiratory medicine, one non-respiratory medicine) who were sex-, age-, visit date- and visit hospital-matched were selected as controls. Odds ratios (ORs) and 95% confidence intervals (CIs) of vaccination for pneumonia were calculated using conditional logistic regression model. Similar analyses were also conducted based on the clinical department of controls. Analysis was conducted in 234 cases and 438 controls. Effectiveness of pneumococcal vaccination or influenza vaccination against pneumonia was not detected. Proportions of either vaccination in controls were greater among respiratory medicine (pneumococcal vaccine, 38%; influenza vaccine, 55%) than among non-respiratory medicine (23%; 48%). Analysis using controls restricted to respiratory medicine showed marginally significant effectiveness of pneumococcal vaccination (OR, 0.59; 95%CI, 0.34-1.03; P=0.064) and influenza vaccination (0.64; 0.40-1.04; 0.072). However, this effectiveness might have been overestimated by selection bias of controls, as pneumonia cases are not necessarily respiratory medicine patients. In the analysis using controls restricted to non-respiratory medicine, OR of pneumococcal vaccination for pneumonia was close to 1, presumably because the proportion of pneumococcal vaccination was higher in cases than in controls. Because pneumococcal vaccine was not routinely administered during the study period, differences in recommendations of vaccination by physician in different

Development of a vaccine for bacterial kidney disease in salmon

International Nuclear Information System (INIS)

Kaatari, S.; Turaga, P.; Wiens, G.

1989-08-01

This document is the executive summary and background review for the final report of ''Development of a Vaccine for Bacterial Kidney Disease in Salmon''. A description of the disease is provided, with microbiological characterization of the infective agent. A brief discussion of attempts to eradicate the disease is included. Recent progress in vaccine development and attempts to control the disease through pharmacological means are described, along with potential ways to break the cycle of infection. 80 refs

Quantitative high throughput analytics to support polysaccharide production process development.

Science.gov (United States)

Noyes, Aaron; Godavarti, Ranga; Titchener-Hooker, Nigel; Coffman, Jonathan; Mukhopadhyay, Tarit

2014-05-19

The rapid development of purification processes for polysaccharide vaccines is constrained by a lack of analytical tools current technologies for the measurement of polysaccharide recovery and process-related impurity clearance are complex, time-consuming, and generally not amenable to high throughput process development (HTPD). HTPD is envisioned to be central to the improvement of existing polysaccharide manufacturing processes through the identification of critical process parameters that potentially impact the quality attributes of the vaccine and to the development of de novo processes for clinical candidates, across the spectrum of downstream processing. The availability of a fast and automated analytics platform will expand the scope, robustness, and evolution of Design of Experiment (DOE) studies. This paper details recent advances in improving the speed, throughput, and success of in-process analytics at the micro-scale. Two methods, based on modifications of existing procedures, are described for the rapid measurement of polysaccharide titre in microplates without the need for heating steps. A simplification of a commercial endotoxin assay is also described that features a single measurement at room temperature. These assays, along with existing assays for protein and nucleic acids are qualified for deployment in the high throughput screening of polysaccharide feedstreams. Assay accuracy, precision, robustness, interference, and ease of use are assessed and described. In combination, these assays are capable of measuring the product concentration and impurity profile of a microplate of 96 samples in less than one day. This body of work relies on the evaluation of a combination of commercially available and clinically relevant polysaccharides to ensure maximum versatility and reactivity of the final assay suite. Together, these advancements reduce overall process time by up to 30-fold and significantly reduce sample volume over current practices. The

Development of capsular polysaccharide-based glycoconjugates for immunization against melioidosis and glanders

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Mary N Burtnick

2012-08-01

Full Text Available Burkholderia pseudomallei and Burkholderia mallei, the etiologic agents of melioidosis and glanders respectively, cause severe disease in humans and animals and are considered potential agents of biological warfare and terrorism. Diagnosis and treatment of infections caused by these pathogens can be challenging and, in the absence of chemotherapeutic intervention, acute disease is frequently fatal. At present, there are no human or veterinary vaccines available for immunization against these emerging/re-emerging infectious diseases. One of the long term objectives of our research, therefore, is to identify and characterize protective antigens expressed by B. pseudomallei and B. mallei and use them to develop efficacious vaccine candidates. Previous studies have demonstrated that the 6-deoxy-heptan capsular polysaccharide (CPS expressed by these bacterial pathogens is both a virulence determinant and a protective antigen. Consequently, this carbohydrate moiety has become an important component of the various subunit vaccines that we are currently developing in our laboratory. In the present study, we describe a reliable method for isolating CPS antigens from O-polysaccharide deficient strains of B. pseudomallei; including a derivative of the select agent excluded strain Bp82. Utilizing these purified CPS samples, we also describe a simple procedure for covalently linking these T-cell independent antigens to carrier proteins. In addition, we demonstrate that high titer IgG responses can be raised against the CPS component of such constructs. Collectively, these approaches provide a tangible starting point for the development of novel CPS-based glycoconjugates for immunization against melioidosis and glanders.

Bacterial Artificial Chromosome Clones of Viruses Comprising the Towne Cytomegalovirus Vaccine

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Xiaohong Cui

2012-01-01

Full Text Available Bacterial artificial chromosome (BAC clones have proven invaluable for genetic manipulation of herpesvirus genomes. BAC cloning can also be useful for capturing representative genomes that comprise a viral stock or mixture. The Towne live attenuated cytomegalovirus vaccine was developed in the 1970s by serial passage in cultured fibroblasts. Although its safety, immunogenicity, and efficacy have been evaluated in nearly a thousand human subjects, the vaccine itself has been little studied. Instead, genetic composition and in vitro growth properties have been inferred from studies of laboratory stocks that may not always accurately represent the viruses that comprise the vaccine. Here we describe the use of BAC cloning to define the genotypic and phenotypic properties of viruses from the Towne vaccine. Given the extensive safety history of the Towne vaccine, these BACs provide a logical starting point for the development of next-generation rationally engineered cytomegalovirus vaccines.

Bacterial artificial chromosome clones of viruses comprising the towne cytomegalovirus vaccine.

Science.gov (United States)

Cui, Xiaohong; Adler, Stuart P; Davison, Andrew J; Smith, Larry; Habib, El-Sayed E; McVoy, Michael A

2012-01-01

Bacterial artificial chromosome (BAC) clones have proven invaluable for genetic manipulation of herpesvirus genomes. BAC cloning can also be useful for capturing representative genomes that comprise a viral stock or mixture. The Towne live attenuated cytomegalovirus vaccine was developed in the 1970s by serial passage in cultured fibroblasts. Although its safety, immunogenicity, and efficacy have been evaluated in nearly a thousand human subjects, the vaccine itself has been little studied. Instead, genetic composition and in vitro growth properties have been inferred from studies of laboratory stocks that may not always accurately represent the viruses that comprise the vaccine. Here we describe the use of BAC cloning to define the genotypic and phenotypic properties of viruses from the Towne vaccine. Given the extensive safety history of the Towne vaccine, these BACs provide a logical starting point for the development of next-generation rationally engineered cytomegalovirus vaccines.

Two dimensional NMR studies of polysaccharides

International Nuclear Information System (INIS)

Byrd, R.A.; Egan, W.; Summers, M.F.

1987-01-01

Polysaccharides are very important components in the immune response system. Capsular polysaccharides and lipopolysaccharides occupy cell surface sites of bacteria, play key roles in recognition and some have been used to develop vaccines. Consequently, the ability to determine chemical structures of these systems is vital to an understanding of their immunogenic action. The authors have been utilizing recently developed two-dimensional homonuclear and heteronuclear correlation spectroscopy for unambiguous assignment and structure determination of a number of polysaccharides. In particular, the 1 H-detected heteronuclear correlation experiments are essential to the rapid and sensitive determination of these structures. Linkage sites are determined by independent polarization transfer experiments and multiple quantum correlation experiments. These methods permit the complete structure determination on very small amounts of the polysaccharides. They present the results of a number of structural determinations and discuss the limits of these experiments in terms of their applications to polysaccharides

Protein carriers of conjugate vaccines: characteristics, development, and clinical trials.

Science.gov (United States)

Pichichero, Michael E

2013-12-01

The immunogenicity of polysaccharides as human vaccines was enhanced by coupling to protein carriers. Conjugation transformed the T cell-independent polysaccharide vaccines of the past to T cell-dependent antigenic vaccines that were much more immunogenic and launched a renaissance in vaccinology. This review discusses the conjugate vaccines for prevention of infections caused by Hemophilus influenzae type b, Streptococcus pneumoniae, and Neisseria meningitidis. Specifically, the characteristics of the proteins used in the construction of the vaccines including CRM, tetanus toxoid, diphtheria toxoid, Neisseria meningitidis outer membrane complex, and Hemophilus influenzae protein D are discussed. The studies that established differences among and key features of conjugate vaccines including immunologic memory induction, reduction of nasopharyngeal colonization and herd immunity, and antibody avidity and avidity maturation are presented. Studies of dose, schedule, response to boosters, of single protein carriers with single and multiple polysaccharides, of multiple protein carriers with multiple polysaccharides and conjugate vaccines administered concurrently with other vaccines are discussed along with undesirable consequences of conjugate vaccines. The clear benefits of conjugate vaccines in improving the protective responses of the immature immune systems of young infants and the senescent immune systems of the elderly have been made clear and opened the way to development of additional vaccines using this technology for future vaccine products.

Effect of pH values on the extracellular polysaccharide secreted by Acidithiobacillus ferrooxidans during chalcopyrite bioleaching

Science.gov (United States)

Yu, Run-lan; Liu, Jing; Tan, Jian-xi; Zeng, Wei-min; Shi, Li-juan; Gu, Guo-hua; Qin, Wen-qing; Qiu, Guan-zhou

2014-04-01

The pH value plays an important role in the bioleaching of sulphide minerals. The effect of pH values on the extracellular polysaccharide secreted by Acidithiobacillus ferrooxidans was investigated in different phases of bacterial growth during chalcopyrite bioleaching. It is found that extracellular polysaccharide secretion from the cells attached to chalcopyrite is more efficiently than that of the free cells in the bioleaching solution. Three factors, pH values, the concentration of soluble metal ions, and the bacterial growth and metabolism, affect extracellular polysaccharide secretion in the free cells, and are related to the bacterial growth phase. Extracellular polysaccharide secretion from the attached cells is mainly dependent on the pH value of the bacterial culture.

No long-term evidence of hyporesponsiveness after use of pneumococcal conjugate vaccine in children previously immunized with pneumococcal polysaccharide vaccine.

Science.gov (United States)

Licciardi, Paul V; Toh, Zheng Quan; Clutterbuck, Elizabeth A; Balloch, Anne; Marimla, Rachel A; Tikkanen, Leena; Lamb, Karen E; Bright, Kathryn J; Rabuatoka, Uraia; Tikoduadua, Lisi; Boelsen, Laura K; Dunne, Eileen M; Satzke, Catherine; Cheung, Yin Bun; Pollard, Andrew J; Russell, Fiona M; Mulholland, Edward K

2016-06-01

A randomized controlled trial in Fiji examined the immunogenicity and effect on nasopharyngeal carriage after 0, 1, 2, or 3 doses of 7-valent pneumococcal conjugate vaccine (PCV7; Prevnar) in infancy followed by 23-valent pneumococcal polysaccharide vaccine (23vPPV; Pneumovax) at 12 months of age. At 18 months of age, children given 23vPPV exhibited immune hyporesponsiveness to a micro-23vPPV (20%) challenge dose in terms of serotype-specific IgG and opsonophagocytosis, while 23vPPV had no effect on vaccine-type carriage. This follow-up study examined the long-term effect of the 12-month 23vPPV dose by evaluating the immune response to 13-valent pneumococcal conjugate vaccine (PCV13) administration 4 to 5 years later. Blood samples from 194 children (now 5-7 years old) were taken before and 28 days after PCV13 booster immunization. Nasopharyngeal swabs were taken before PCV13 immunization. We measured levels of serotype-specific IgG to all 13 vaccine serotypes, opsonophagocytosis for 8 vaccine serotypes, and memory B-cell responses for 18 serotypes before and after PCV13 immunization. Paired samples were obtained from 185 children. There were no significant differences in the serotype-specific IgG, opsonophagocytosis, or memory B-cell response at either time point between children who did or did not receive 23vPPV at 12 months of age. Nasopharyngeal carriage of PCV7 and 23vPPV serotypes was similar among the groups. Priming with 1, 2, or 3 PCV7 doses during infancy did not affect serotype-specific immunity or carriage. Immune hyporesponsiveness induced by 23vPPV in toddlers does not appear to be sustained among preschool children in this context and does not affect the pneumococcal carriage rate in this age group. Copyright © 2016 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Effectiveness of the 23-valent polysaccharide pneumococcal vaccine against invasive pneumococcal disease in people 60 years or older

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Salsench Elisabet

2010-03-01

Full Text Available Abstract Background The 23-valent polysaccharide pneumococcal vaccine (PPV is currently recommended in elderly and high-risk adults. However, its efficacy in preventing pneumococcal infections remains controversial. This study assessed the clinical effectiveness of vaccination against invasive pneumococcal disease (IPD among people over 60 years. Methods Population-based case-control study that included 88 case patients over 60 years-old with a laboratory-confirmed IPD (bacteraemic pneumonia, meningitis or sepsis and 176 outpatient control subjects who were matched by primary care centre, age, sex and risk stratum. Adjusted odds ratios (ORs for vaccination were calculated using conditional logistic regression, controlling for underlying conditions. Vaccine effectiveness was estimated as (1 - OR ×100. Results Pneumococcal vaccination rate was significantly lower in cases than in control subjects (38.6% vs 59.1%; p = 0.002. The adjusted vaccine effectiveness was 72% (OR: 0.28; 95% CI: 0.15-0.54 against all IPD and 77% (OR: 0.23; 95% CI: 0.08-0.60 against vaccine-type IPD. Vaccination was significantly effective against all IPD in both age groups: 60-79 years-old (OR 0.32; 95% CI: 0.14-0.74 and people 80 years or older (OR: 0.29; 95% CI: 0.09-0.91. Vaccination appears significantly effective as for high-risk immunocompetent subjects (OR: 0.29; 95% CI: 0.11-0.79 as well as for immunocompromised subjects (OR: 0.12; 95% CI: 0.03-0.53. Conclusion These findings confirm the effectiveness of the 23-valent PPV against IPD, and they also support the benefit of vaccination in preventing invasive infections among high-risk and older people.

Trend of bacterial meningitis in Bahrain from 1990 to 2013 and effect of introduction of new vaccines.

Science.gov (United States)

Saeed, N; AlAnsari, H; AlKhawaja, S; Jawad, J S; Nasser, K; AlYousef, E

2016-06-15

Meningitis is among the 10 commonest infectious causes of death worldwide. This retrospective analysis of reported cases of meningitis in Bahrain aimed to assess the trend in the incidence of bacterial meningitis from 1990 to 2013, before and after the introduction of new vaccines. Of 1455 reported cases of meningitis during the study period 73.1% were viral and 26.9% were bacterial etiology (tuberculous meningitis 8.3%; Streptococcus pneumoniae 4.9%, Haemophilus influenzae 3.6% and Neisseria meningitidis 1.7%). There was a peak of meningitis cases in 1995-1996. The incidence of meningitis due to H. influenzae and N. meningitidis showed a marked reduction after the introduction of the corresponding vaccines in 1998 and 2001 respectively, and S. pneumoniae became the predominant organism after Mycobacterium tuberculosis. The changing trend in the etiology of bacterial meningitis points to the need to study vaccination programme modifications, such as pneumococcal vaccine for the adult population, especially high-risk groups.

Evaluation of a Group A Streptococcus synthetic oligosaccharide as vaccine candidate.

Science.gov (United States)

Kabanova, Anna; Margarit, Immaculada; Berti, Francesco; Romano, Maria R; Grandi, Guido; Bensi, Giuliano; Chiarot, Emiliano; Proietti, Daniela; Swennen, Erwin; Cappelletti, Emilia; Fontani, Paola; Casini, Daniele; Adamo, Roberto; Pinto, Vittoria; Skibinski, David; Capo, Sabrina; Buffi, Giada; Gallotta, Marilena; Christ, William J; Campbell, A Stewart; Pena, John; Seeberger, Peter H; Rappuoli, Rino; Costantino, Paolo

2010-12-10

Bacterial infections caused by Group A Streptococcus (GAS) are a serious health care concern that currently cannot be prevented by vaccination. The GAS cell-wall polysaccharide (GAS-PS) is an attractive vaccine candidate due to its constant expression pattern on different bacterial strains and protective properties of anti-GAS-PS antibodies. Here we report for the first time the immunoprotective efficacy of glycoconjugates with synthetic GAS oligosaccharides as compared to those containing the native GAS-PS. A series of hexa- and dodecasaccharides based on the GAS-PS structure were prepared by chemical synthesis and conjugated to CRM(197). When tested in mice, the conjugates containing the synthetic oligosaccharides conferred levels of immunoprotection comparable to those elicited by the native conjugate. Antisera from immunized rabbits promoted phagocytosis of encapsulated GAS strains. Furthermore we discuss variables that might correlate with glycoconjugate immunogenicity and demonstrate the potential of the synthetic approach that benefits from increased antigen purity and facilitated manufacturing. Copyright © 2010 Elsevier Ltd. All rights reserved.

A mass vaccination campaign targeting adults and children to prevent typhoid fever in Hechi; Expanding the use of Vi polysaccharide vaccine in Southeast China: A cluster-randomized trial

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Yang Hong-hui

2005-05-01

Full Text Available Abstract Background One of the goals of this study was to learn the coverage, safety and logistics of a mass vaccination campaign against typhoid fever in children and adults using locally produced typhoid Vi polysaccharide (PS and group A meningococcal PS vaccines in southern China. Methods The vaccination campaign targeted 118,588 persons in Hechi, Guangxi Province, aged between 5 to 60 years, in 2003. The study area was divided into 107 geographic clusters, which were randomly allocated to receive one of the single-dose parenteral vaccines. All aspects regarding vaccination logistics, feasibility and safety were documented and systematically recorded. Results of the logistics, feasibility and safety are reported. Results The campaign lasted 5 weeks and the overall vaccination coverage was 78%. On average, the 30 vaccine teams gave immunizations on 23 days. Vaccine rates were higher in those aged ≤ 15 years (90% than in adolescents and young adults (70%. Planned mop-up activities increased the coverage by 17%. The overall vaccine wastage was 11%. The cold chain was maintained and documented. 66 individuals reported of adverse events out of all vaccinees, where fever (21%, malaise (19% and local redness (19% were the major symptoms; no life-threatening event occurred. Three needle-sharp events were reported. Conclusion The mass immunization proved feasible and safe, and vaccine coverage was high. Emphasis should be placed on: injection safety measures, community involvement and incorporation of mop-up strategies into any vaccination campaign. School-based and all-age Vi mass immunizations programs are potentially important public health strategies for prevention of typhoid fever in high-risk populations in southern China.

Immunogenicity of fractional doses of tetravalent a/c/y/w135 meningococcal polysaccharide vaccine: results from a randomized non-inferiority controlled trial in Uganda.

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Philippe J Guerin

Full Text Available Neisseria meningitidis serogroup A is the main causative pathogen of meningitis epidemics in sub-Saharan Africa. In recent years, serogroup W135 has also been the cause of epidemics. Mass vaccination campaigns with polysaccharide vaccines are key elements in controlling these epidemics. Facing global vaccine shortage, we explored the use of fractional doses of a licensed A/C/Y/W135 polysaccharide meningococcal vaccine.We conducted a randomized, non-inferiority trial in 750 healthy volunteers 2-19 years old in Mbarara, Uganda, to compare the immune response of the full dose of the vaccine versus fractional doses (1/5 or 1/10. Safety and tolerability data were collected for all subjects during the 4 weeks following the injection. Pre- and post-vaccination sera were analyzed by measuring serum bactericidal activity (SBA with baby rabbit complement. A responder was defined as a subject with a > or =4-fold increase in SBA against a target strain from each serogroup and SBA titer > or =128. For serogroup W135, 94% and 97% of the vaccinees in the 1/5- and 1/10-dose arms, respectively, were responders, versus 94% in the full-dose arm; for serogroup A, 92% and 88% were responders, respectively, versus 95%. Non-inferiority was demonstrated between the full dose and both fractional doses in SBA seroresponse against serogroups W135 and Y, in total population analysis. Non-inferiority was shown between the full and 1/5 doses for serogroup A in the population non-immune prior to vaccination. Non-inferiority was not shown for any of the fractionate doses for serogroup C. Safety and tolerability data were favourable, as observed in other studies.While the advent of conjugate A vaccine is anticipated to largely contribute to control serogroup A outbreaks in Africa, the scale-up of its production will not cover the entire "Meningitis Belt" target population for at least the next 3 to 5 years. In view of the current shortage of meningococcal vaccines for Africa

Bacterial surface adaptation

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Utada, Andrew

2014-03-01

Biofilms are structured multi-cellular communities that are fundamental to the biology and ecology of bacteria. Parasitic bacterial biofilms can cause lethal infections and biofouling, but commensal bacterial biofilms, such as those found in the gut, can break down otherwise indigestible plant polysaccharides and allow us to enjoy vegetables. The first step in biofilm formation, adaptation to life on a surface, requires a working knowledge of low Reynolds number fluid physics, and the coordination of biochemical signaling, polysaccharide production, and molecular motility motors. These crucial early stages of biofilm formation are at present poorly understood. By adapting methods from soft matter physics, we dissect bacterial social behavior at the single cell level for several prototypical bacterial species, including Pseudomonas aeruginosa and Vibrio cholerae.

Effect of the Infectious Bursal Disease Vaccine on the Aero-Anaerobic Enteric Bacterial Flora of Chickens

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F. A. Kembi

2001-03-01

Full Text Available The enteric bacterial flora of birds was examined after vaccination with the infectious bursal disease (IBD vaccine via the ocular and oral routes. Throughout the test period, the bacterial loads were higher in the test groups than in the control (p < 0.05. However, significant differences between the two test groups only occurred in the first three weeks postvaccination. The bacteria isolates included Salmonella sp., Edwardsiella sp., Escherichia sp. and Klebsiella sp. in the test and control groups.

Protection from Staphylococcus aureus mastitis associated with poly-N-acetyl β-1,6 glucosamine specific antibody production using biofilm-embedded bacteria

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Pérez, M. M.; Prenafeta, A.; Valle, J.; Penadés, J.; Rota, C.; Solano, C.; Marco, J.; Grilló, M.J.; Lasa, I.; Irache, J.M.; Maira-Litran, T.; Jiménez-Barbero, J.; Costa, L.; Pier, G.B.; de Andrés, D.; Amorena, B.

2010-01-01

Staphylococcus aureus vaccines based on bacterins surrounded by slime, surface polysaccharides coupled to protein carriers and polysaccharides embedded in liposomes administered together with non-biofilm bacterins confer protection against mastitis. However, it remains unknown whether protective antibodies are directed to slime-associated known exopolysaccharides and could be produced in the absence of bacterin immunizations. Here, a sheep mastitis vaccination study was carried out using bacterins, crude bacterial extracts or a purified exopolysaccharide from biofilm bacteria delivered in different vehicles. This polysaccharide reacted specifically with antibodies to poly-N-acetyl-β-1,6-glucosamine (PNAG) and not with antibodies to other capsular antigens or bacterial components. Following intra-mammary challenge with biofilm-producing bacteria, antibody production against the polysaccharide, milk bacterial counts and mastitis lesions were determined. Bacterins from strong biofilm-producing bacteria triggered the highest production of antibodies to PNAG and conferred the highest protection against infection and mastitis, compared with weak biofilm-producing bacteria and non-cellular inocula. Thus, bacterins from strong biofilm bacteria, rather than purified polysaccharide, are proposed as a cost-efficient vaccination against S. aureus ruminant mastitis. PMID:19428854

Evaluation of components of X-ray irradiated 7-valent pneumococcal conjugate vaccine and pneumococcal vaccine polyvalent and X-ray and gamma-ray irradiated acellular pertussis component of DTaP vaccine products

International Nuclear Information System (INIS)

May, J.C.; Rey, L.; Lee, C.-J.; Arciniega, Juan

2004-01-01

Samples of pneumococcal vaccine polyvalent, 7-valent pneumococcal conjugate vaccine, and two different diphtheria and tetanus toxoids and acellular pertussis vaccines adsorbed were irradiated with X-rays and/or gamma-rays (Co-60). Mouse IgG and IgM antibody responses (ELISA) for types 9V, 14, 18C, and 19F pneumococcal polysaccharides and conjugates indicated that the polysaccharides were more tolerant of the radiation than the conjugates. The mouse antibody response for the detoxified pertussis toxin (PT) antigen, filamentous hemagglutinin antigen (FHA), pertactin (PRN), and fimbriae types 2 and 3 (FIM) antigens for the appropriate vaccine type indicated that the antibody response was not significantly changed in the 25 kGy X-ray irradiated vaccines frozen in liquid nitrogen compared to the control vaccine

Evaluation of components of X-ray irradiated 7-valent pneumococcal conjugate vaccine and pneumococcal vaccine polyvalent and X-ray and gamma-ray irradiated acellular pertussis component of DTaP vaccine products

Energy Technology Data Exchange (ETDEWEB)

May, J.C. E-mail: may@cber.fda.gov; Rey, L. E-mail: louis.rey@bluewin.ch; Lee, C.-J.; Arciniega, Juan

2004-10-01

Samples of pneumococcal vaccine polyvalent, 7-valent pneumococcal conjugate vaccine, and two different diphtheria and tetanus toxoids and acellular pertussis vaccines adsorbed were irradiated with X-rays and/or gamma-rays (Co-60). Mouse IgG and IgM antibody responses (ELISA) for types 9V, 14, 18C, and 19F pneumococcal polysaccharides and conjugates indicated that the polysaccharides were more tolerant of the radiation than the conjugates. The mouse antibody response for the detoxified pertussis toxin (PT) antigen, filamentous hemagglutinin antigen (FHA), pertactin (PRN), and fimbriae types 2 and 3 (FIM) antigens for the appropriate vaccine type indicated that the antibody response was not significantly changed in the 25 kGy X-ray irradiated vaccines frozen in liquid nitrogen compared to the control vaccine.

Binding of Hg by bacterial extracellular polysaccharide: a possible role in Hg tolerance.

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Cruz, Kimberly; Guézennec, Jean; Barkay, Tamar

2017-07-01

Bacteria employ adaptive mechanisms of mercury (Hg) tolerance to survive in environments containing elevated Hg concentrations. The potential of extracellular polysaccharides (EPS) production by bacteria as a mechanism of Hg tolerance has not been previously investigated. The objectives of this study were to determine if bacterial EPS sorb Hg, and if so does sorption provide protection against Hg toxicity. Purified EPS with different chemical compositions produced by bacterial isolates from microbial mats in French Polynesian atolls and deep-sea hydrothermal vents were assessed for Hg sorption. The data showed that EPS sorbed up to 82% of Hg from solution, that this sorption was dependent on EPS composition, and that sorption was a saturable mechanism. Hg uptake capacities ranged from 0.005 to 0.454 mmol Hg/g for the different EPS. To determine if EPS production could alter bacterial Hg tolerance, Escherichia coli K-12 strains and their EPS defective mutants were tested by the disc inhibition assay. Mercury inhibited growth in a dose-dependent manner with wild-type strains having smaller (~1 mm), but statistically significant, zones of inhibition than various mutants and this difference was related to a 2-fold decline in the amount of EPS produced by the mutants relative to cell biomass. These experiments identified colanic acid and hexosamine as Hg-binding moieties in EPS. Together these data indicate that binding of Hg to EPS affords a low level of resistance to the producing bacteria.

The Capricious Nature of Bacterial Pathogens: Phasevarions and Vaccine Development

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Aimee Tan

2016-12-01

Full Text Available Infectious diseases are a leading cause of morbidity and mortality worldwide, and vaccines are one of the most successful and cost-effective tools for disease prevention. One of the key considerations for rational vaccine development is the selection of appropriate antigens. Antigens must induce a protective immune response, and this response should be directed to stably expressed antigens so the target microbe can always be recognized by the immune system. Antigens with variable expression, due to environmental signals or phase variation (i.e., high frequency, random switching of expression, are not ideal vaccine candidates because variable expression could lead to immune evasion. Phase variation is often mediated by the presence of highly mutagenic simple tandem DNA repeats, and genes containing such sequences can be easily identified, and their use discounted as vaccine antigens reconsidered. Recent research has identified phase variably expressed DNA methyltransferases that act as global epigenetic regulators. These phase variable regulons, known as phasevarions, are associated with altered virulence phenotypes and/or expression of vaccine candidates. As such, genes encoding candidate vaccine antigens that have no obvious mechanism of phase variation may be subject to indirect, epigenetic control as part of a phasevarion. Bioinformatic and experimental studies are required to elucidate the distribution and mechanism of action of these DNA methyltransferases, and most importantly, whether they mediate epigenetic regulation of potential and current vaccine candidates. This process is essential to define the stably expressed antigen target profile of bacterial pathogens and thereby facilitate efficient, rational selection of vaccine antigens.

The effect of prophylaxis with chloroquine and proguanil on delayed-type hypersensitivity and antibody production following vaccination with diphtheria, tetanus, polio, and pneumococcal vaccines

DEFF Research Database (Denmark)

Gyhrs, A; Pedersen, B K; Bygbjerg, I

1991-01-01

(1,000 mg/week), or 4) proguanil hydrochloride (200 mg/day) for six weeks. Skin testing was performed on days 0 and 28. Vaccinations with diphtheria, tetanus, polio, and pneumococcal polysaccharide antigen vaccines were performed on day 28, and the presence of specific antibodies was determined...... dosages, does not induce any detectable suppression of delayed-type hypersensitivity or vaccination responses to diphtheria, tetanus, polio, or pneumococcal polysaccharide antigens....

Antibiofilm activity of Actinobacillus pleuropneumoniae serotype 5 capsular polysaccharide.

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Michael T Karwacki

Full Text Available Cell-free extracts isolated from colony biofilms of Actinobacillus pleuropneumoniae serotype 5 were found to inhibit biofilm formation by Staphylococcus aureus, S. epidermidis and Aggregatibacter actinomycetemcomitans, but not by A. pleuropneumoniae serotype 5 itself, in a 96-well microtiter plate assay. Physical and chemical analyses indicated that the antibiofilm activity in the extract was due to high-molecular-weight polysaccharide. Extracts isolated from a mutant strain deficient in the production of serotype 5 capsular polysaccharide did not exhibit antibiofilm activity. A plasmid harboring the serotype 5 capsule genes restored the antibiofilm activity in the mutant extract. Purified serotype 5 capsular polysaccharide also exhibited antibiofilm activity against S. aureus. A. pleuropneumoniae wild-type extracts did not inhibit S. aureus growth, but did inhibit S. aureus intercellular adhesion and binding of S. aureus cells to stainless steel surfaces. Furthermore, polystyrene surfaces coated with A. pleuropneumoniae wild-type extracts, but not with capsule-mutant extracts, resisted S. aureus biofilm formation. Our findings suggest that the A. pleuropneumoniae serotype 5 capsule inhibits cell-to-cell and cell-to-surface interactions of other bacteria. A. pleuropneumoniae serotype 5 capsular polysaccharide is one of a growing number of bacterial polysaccharides that exhibit broad-spectrum, nonbiocidal antibiofilm activity. Future studies on these antibiofilm polysaccharides may uncover novel functions for bacterial polysaccharides in nature, and may lead to the development of new classes of antibiofilm agents for industrial and clinical applications.

Generalized herd effects and vaccine evaluation: impact of live influenza vaccine on off-target bacterial colonisation.

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Mina, Michael J

2017-06-01

Interactions between pathogens and commensal microbes are major contributors to health and disease. Infectious diseases however are most often considered independent, viewed within a one-host one-pathogen paradigm and, by extension, the interventions used to treat and prevent them are measured and evaluated within this same paradigm. Vaccines, especially live vaccines, by stimulating immune responses or directly interacting with other microbes can alter the environment in which they act, with effects that span across pathogen species. Live attenuated infl uenza vaccines for example, while safe, increase upper respiratory tract bacterial carriage density of important human commensal pathogens like Streptococcus pneumoniae and Staphylococcus aureus. Further, by altering the ecological niche and dynamics of phylogenetically distinct microbes within the host, vaccines may unintentionally affect transmission of non-vaccine targeted pathogens. Thus, vaccine effects may span across species and across scales, from the individual to the population level. In keeping with traditional vaccine herd-effects that indirectly protect even unvaccinated individuals by reducing population prevalence of vaccine-targeted pathogens, we call these cross-species cross-scale effects "generalized herd-effects". As opposed to traditional herd-effects, "generalized" relaxes the assumption that the effect occurs at the level of the vaccine-target pathogen and "herd effect" implies, as usual, that the effects indirectly impact the population at large, including unvaccinated bystanders. Unlike traditional herd-effects that decrease population prevalence of the vaccine-target, generalized herd-effects may decrease or increase prevalence and disease by the off-target pathogen. LAIV, for example, by increasing pneumococcal density in the upper respiratory tract of vaccine recipients, especially children, may increase pneumococcal transmission and prevalence, leading to excess pneumococcal invasive

O-polysaccharide is important for Salmonella Pullorum survival in egg albumen, and virulence and colonization in chicken embryos.

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Guo, Rongxian; Li, Zhuoyang; Jiao, Yang; Geng, Shizhong; Pan, Zhiming; Chen, Xiang; Li, Qiuchun; Jiao, Xinan

2017-10-01

The pathogen Salmonella Pullorum is the causative agent of persistent systemic infection of poultry, leading to economic losses in developing countries due to morbidity, mortality and reduction in egg production. These infections may result in vertical transmission to eggs or progeny. Limited information is available regarding the mechanisms involved in the survival of Salmonella Pullorum in egg albumen and developing chicken embryos. Hence, we investigated the role of O-polysaccharide in the contamination of eggs and the colonization of chicken embryos. Compared with the wild-type strain, the isogenic waaL mutant exhibited an O-antigen-deficient rough phenotype, and increased sensitivity to egg albumen and chicken serum, as well as reduced adherence to DF-1 cells. Infection with Salmonella Pullorum lacking O-polysaccharide resulted in significantly reduced embryo lethality and bacterial colonization. These results suggest that O-polysaccharide is essential for Salmonella Pullorum colonization in eggs, both post-lay and developing embryos. The chicken embryo infection model could be used to characterize the interaction between Salmonella Pullorum and developing embryos, and it will also contribute to the development of more rational vaccines to protect laying hens and embryos.

Structural modification of polysaccharides: A biochemical-genetic approach

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Kern, Roger G.; Petersen, Gene R.

1991-01-01

Polysaccharides have a wide range of industrial and biomedical applications. An industry trend is underway towards the increased use of bacteria to produce polysaccharides. Long term goals of this work are the adaptation and enhancement of saccharide properties for electronic and optic applications. In this report we illustrate the application of enzyme-bearing bacteriophage on strains of the enteric bacterium Klebsiella pneumoniae, which produces a polysaccharide with the relatively rare rheological property of drag-reduction. This has resulted in the production of new polysaccharides with enhanced rheological properties. Our laboratory is developing techniques for processing and structurally modifying bacterial polysaccharides and oligosaccharides which comprise their basic polymeric repeat units. Our research has focused on bacteriophage which produce specific polysaccharide degrading enzymes. This has lead to the development of enzymes generated by bacteriophage as tools for polysaccharide modification and purification. These enzymes were used to efficiently convert the native material to uniform-sized high molecular weight polymers, or alternatively into high-purity oligosaccharides. Enzyme-bearing bacteriophage also serve as genetic selection tools for bacteria that produce new families of polysaccharides with modified structures.

A target oriented expeditious approach towards synthesis of certain bacterial rare sugar derivatives.

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Chaudhury, Aritra; Ghosh, Rina

2017-02-07

Bacterial rare amino deoxy sugars are found in the cell surface polysaccharides of multiple pathogenic bacterial strains, but are absent in the human metabolism. This helps in the differentiation between pathogens and host cells which can be exploited for target specific drug discovery and carbohydrate based vaccine development. The principal bacterial atypical sugar derivatives include 2-acetamido-4-amino-2,4,6-trideoxy-d-galactose (AAT), 2,4-diacetamido-2,4,6-trideoxy-d-galactose (DATDG) and N-acetylfucosamine (FucNAc). Herein, a highly streamlined protocol leading to the aforesaid derivatives is presented. The highlights of the method lie in radical mediated 6-deoxygenation along with a one-pot like protection profile manipulation on suitably derivatised d-glucosamine or d-mannose motifs to obtain a vital quinovosaminoside or rhamnoside from which rare sugar derivatives were synthesized in a diversity oriented manner.

Campylobacter jejuni cocultured with epithelial cells reduces surface capsular polysaccharide expression.

LENUS (Irish Health Repository)

Corcionivoschi, N

2012-02-01

The host cell environment can alter bacterial pathogenicity. We employed a combination of cellular and molecular techniques to study the expression of Campylobacter jejuni polysaccharides cocultured with HCT-8 epithelial cells. After two passages, the amount of membrane-bound high-molecular-weight polysaccharide was considerably reduced. Microarray profiling confirmed significant downregulation of capsular polysaccharide (CPS) locus genes. Experiments using conditioned media showed that sugar depletion occurred only when the bacterial and epithelial cells were cocultured. CPS depletion occurred when C. jejuni organisms were exposed to conditioned media from a different C. jejuni strain but not when exposed to conditioned media from other bacterial species. Proteinase K or heat treatment of conditioned media under coculture conditions abrogated the effect on the sugars, as did formaldehyde fixation and cycloheximide treatment of host cells or chloramphenicol treatment of the bacteria. However, sugar depletion was not affected in flagellar export (fliQ) and quorum-sensing (luxS) gene mutants. Passaged C. jejuni showed reduced invasiveness and increased serum sensitivity in vitro. C. jejuni alters its surface polysaccharides when cocultured with epithelial cells, suggesting the existence of a cross talk mechanism that modulates CPS expression during infection.

Polysaccharide microarray technology for the detection of Burkholderia pseudomallei and Burkholderia mallei antibodies.

Science.gov (United States)

Parthasarathy, Narayanan; DeShazer, David; England, Marilyn; Waag, David M

2006-11-01

A polysaccharide microarray platform was prepared by immobilizing Burkholderia pseudomallei and Burkholderia mallei polysaccharides. This polysaccharide array was tested with success for detecting B. pseudomallei and B. mallei serum (human and animal) antibodies. The advantages of this microarray technology over the current serodiagnosis of the above bacterial infections were discussed.

Bacterial Meningitis in Brazil: Baseline Epidemiologic Assessment of the Decade Prior to the Introduction of Pneumococcal and Meningococcal Vaccines.

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Luciano Cesar Pontes Azevedo

Full Text Available Bacterial meningitis is associated with significant burden in Brazil. In 2010, both 10-valent pneumococcal conjugate vaccine and meningococcal capsular group C conjugate vaccine were introduced into the routine vaccination schedule. Haemophilus influenzae type b vaccine was previously introduced in 1999. This study presents trends in demographics, microbiological characteristics and seasonality patterns of bacterial meningitis cases in Brazil from 2000 to 2010.All meningitis cases confirmed by clinical and/or laboratory criteria notified to the national information system for notifiable diseases between 2000 and 2010 were analyzed. Proportions of bacterial meningitis cases by demographic characteristics, criteria used for confirmation and etiology were calculated. We estimated disease rates per 100,000 population and trends for the study period, with emphasis on H. influenzae, N. meningitidis and S. pneumoniae cases. In the decade, 341,805 cases of meningitis were notified in Brazil. Of the 251,853 cases with defined etiology, 110,264 (43.8% were due to bacterial meningitis (excluding tuberculosis. Of these, 34,997 (31.7% were due to meningococcal disease. The incidence of bacterial meningitis significantly decreased from 3.1/100,000 population in 2000-2002 to 2.14/100,000 in 2009-2010 (p<0.01. Among cases of meningococcal disease, the proportion of those associated with group C increased from 41% in 2007 to 61.7% in 2010, while the proportion of group B disease progressively declined. Throughout the study period, an increased number of cases occurred during winter.Despite the reduction in bacterial meningitis incidence during the last decade, it remains a significant healthcare issue in Brazil. Meningococcal disease is responsible for the majority of the cases with group C the most common capsular type. Our study demonstrates the appropriateness of introduction of meningococcal vaccination in Brazil. Furthermore, this study provides a baseline

Otitis-Prone Children Produce Functional Antibodies to Pneumolysin and Pneumococcal Polysaccharides.

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Kirkham, Lea-Ann S; Wiertsema, Selma P; Corscadden, Karli J; Mateus, Tulia; Mullaney, Gemma L; Zhang, Guicheng; Richmond, Peter C; Thornton, Ruth B

2017-03-01

The pneumococcus is a major otitis media (OM) pathogen, but data are conflicting regarding whether otitis-prone children have impaired humoral immunity to pneumococcal antigens. We and others have shown that otitis-prone and healthy children have similar antibody titers to pneumococcal proteins and polysaccharides (vaccine and nonvaccine types); however, the quality of antibodies from otitis-prone children has not been investigated. Antibody function, rather than titer, is considered to be a better correlate of protection from pneumococcal disease. Therefore, we compared the capacities of antibodies from otitis-prone (cases) and healthy (controls) children to neutralize pneumolysin, the pneumococcal toxin currently in development as a vaccine antigen, and to opsonize pneumococcal vaccine and nonvaccine serotypes. A pneumolysin neutralization assay was conducted on cholesterol-depleted complement-inactivated sera from 165 cases and 61 controls. A multiplex opsonophagocytosis assay (MOPA) was conducted on sera from 20 cases and 20 controls. Neutralizing and opsonizing titers were calculated with antigen-specific IgG titers to determine antibody potency for pneumolysin, pneumococcal conjugate vaccine (PCV) polysaccharides, and non-PCV polysaccharides. There was no significant difference in antibody potencies between cases and controls for the antigens tested. Antipneumolysin neutralizing titers increased with the number of episodes of acute OM, but antibody potency did not. Pneumolysin antibody potency was lower in children colonized with pneumococci than in noncarriers, and this was significant for the otitis-prone group ( P otitis-prone children demonstrates that they respond to the current PCV and are likely to respond to pneumolysin-based vaccines as effectively as healthy children. Copyright © 2017 Kirkham et al.

Cross-protection in Neisseria meningitidis serogroups Y and W polysaccharides: A comparative conformational analysis.

Science.gov (United States)

Kuttel, Michelle M; Timol, Zaheer; Ravenscroft, Neil

2017-06-29

The capsular polysaccharide is the main virulence factor in meningococcus. The capsular polysaccharides for meningococcal serogroups Y and W are almost identical polymers of hexose-sialic acid, suggesting the possibility of cross-protection between group Y and W vaccines. However, early studies indicated that they elicit different levels of cross-protection. Here we explore the conformations of the meningococcal Y and W polysaccharides with molecular dynamics simulations of three repeating unit oligosaccharide strands. We find differences in Y and W antigen conformation: the Y polysaccharide has a single dominant conformation, whereas W exhibits a family of conformations including the Y conformation. This result is supported by our NMR NOESY analysis, which indicates key close contacts for W that are not present in Y. These conformational differences provide an explanation for the different levels of cross-protection measured for the Y and W monovalent vaccines and the high group W responses observed in HibMenCY-TT vaccinees. Copyright © 2017 Elsevier Ltd. All rights reserved.

IMMUNOGENICITY AND SAFETY OF 23-VALENT POLYSACCHARIDE PNEUMOCOCCAL VACCINE IN PATIENTS WITH RHEUMATOID ARTHRITIS: RESULTS OF A TWO-YEAR FOLLOW-UP STUDY

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M. S. Naumtseva

2016-01-01

Full Text Available Objective: to investigate the immunogenicity, safety, and clinical efficacy of 23-valent polysaccharide pneumococcal vaccine in patients with rheumatoid arthritis (RA during a two-year follow-up study.Subjects and methods. The prospective open-label comparative study enrolled 110 people, of them there were 81 (73.6% women and 29 (26.4% men at the age of 23 to 76 years, including 79 patients with RA, as well as 31 subjects without systemic inflammatory rheumatic diseases (RD (a control group. The group of RA patients exhibited a predominance of middle-aged women who had > 3 years’ disease duration and a moderate inflammatory activity (the mean value of DAS28, 4.32. 52 patients received methotrexate (MTX, 14 had Leflunomide (LEF, and 13 were treated with tumor necrosis factor-α (TNF-α inhibitors + MTX.The 23-valent polysaccharide pneumococcal vaccine Pneumo-23 (Sanofi Pasteur, France was administered in a single dose of 0.5 ml subcutaneously during continuous MTX or LEF therapy for the underlying disease or 3–4 weeks before the use of TNF-α inhibitors. Clinical examinations of the patient and conventional clinical and laboratory studies were performed during control visits (1, 3, 12, and 24 months after vaccination. Clinical effectiveness and safety were evaluated in all the patients included in the study. The serum levels of anti-pneumococcal capsular polysaccharide antibodies (Ab were measured in 72 patients with RA and in 30 individuals in the control group during a 12-month follow-up study, including in 25 patients with RA for a 24-month follow-up study by enzyme immunoassay using commercial VaccZymeTM Anti-PCP IgG Enzyme Immunoassay kits (The Binding Site Group Ltd, Birmingham, United Kingdom. Along with this, the post-immunization response coefficient was calculated for each patient as the ratio of postvaccination Ab levels during Visits 2, 3, 4, and 5 to the baseline Ab level. Results and discussion. No clinical and

Structural studies of the O-specific polysaccharide(s) from the lipopolysaccharide of Azospirillum brasilense type strain Sp7.

Science.gov (United States)

Sigida, Elena N; Fedonenko, Yuliya P; Shashkov, Alexander S; Zdorovenko, Evelina L; Konnova, Svetlana A; Ignatov, Vladimir V; Knirel, Yuriy A

2013-10-18

Lipopolysaccharide was obtained by phenol-water extraction from dried bacterial cells of Azospirillum brasilense type strain Sp7. Mild acid hydrolysis of the lipopolysaccharide followed by GPC on Sephadex G-50 resulted in a polysaccharide mixture, which was studied by composition and methylation analyses, Smith degradation and (1)H and (13)C NMR spectroscopy. The following polysaccharide structures were established, where italics indicate a non-stoichiometric (∼40%) 2-O-methylation of l-rhamnose. Copyright © 2013 Elsevier Ltd. All rights reserved.

Exploiting the Campylobacter jejuni protein glycosylation system for glycoengineering vaccines and diagnostic tools directed against brucellosis

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Iwashkiw Jeremy A

2012-01-01

Full Text Available Abstract Background Immune responses directed towards surface polysaccharides conjugated to proteins are effective in preventing colonization and infection of bacterial pathogens. Presently, the production of these conjugate vaccines requires intricate synthetic chemistry for obtaining, activating, and attaching the polysaccharides to protein carriers. Glycoproteins generated by engineering bacterial glycosylation machineries have been proposed to be a viable alternative to traditional conjugation methods. Results In this work we expressed the C. jejuni oligosaccharyltansferase (OTase PglB, responsible for N-linked protein glycosylation together with a suitable acceptor protein (AcrA in Yersinia enterocolitica O9 cells. MS analysis of the acceptor protein demonstrated the transfer of a polymer of N-formylperosamine to AcrA in vivo. Because Y. enterocolitica O9 and Brucella abortus share an identical O polysaccharide structure, we explored the application of the resulting glycoprotein in vaccinology and diagnostics of brucellosis, one of the most common zoonotic diseases with over half a million new cases annually. Injection of the glycoprotein into mice generated an IgG response that recognized the O antigen of Brucella, although this response was not protective against a challenge with a virulent B. abortus strain. The recombinant glycoprotein coated onto magnetic beads was efficient in differentiating between naïve and infected bovine sera. Conclusion Bacterial engineered glycoproteins show promising applications for the development on an array of diagnostics and immunoprotective opportunities in the future.

Streptococcus iniae cpsG alters capsular carbohydrate composition and is a cause of serotype switching in vaccinated fish.

Science.gov (United States)

Heath, Candice; Gillen, Christine M; Chrysanthopoulos, Panagiotis; Walker, Mark J; Barnes, Andrew C

2016-09-25

Streptococcus iniae causes septicaemia and meningitis in marine and freshwater fish wherever they are farmed in warm-temperate and tropical regions. Although serotype specific, vaccination with bacterins (killed bacterial cultures) is largely successful and vaccine failure occurs only occasionally through emergence of new capsular serotypes. Previously we showed that mutations in vaccine escapes are restricted to a limited repertoire of genes within the 20-gene capsular polysaccharide (cps) operon. cpsG, a putative UDP-galactose 4-epimerase, has three sequence types based on the insertion or deletion of the three amino acids leucine, serine and lysine in the substrate binding site of the protein. To elucidate the role of cpsG in capsular polysaccharide (CPS) biosynthesis and capsular composition, we first prepared isogenic knockout and complemented mutants of cpsG by allelic exchange mutagenesis. Deletion of cpsG resulted in changes to colony morphology and cell buoyant density, and also significantly decreased galactose content relative to glucose in the capsular polysaccharide as determined by GC-MS, consistent with epimerase activity of CpsG. There was also a metabolic penalty of cpsG knockout revealed by slower growth in complex media, and reduced proliferation in whole fish blood. Moreover, whilst antibodies raised in fish against the wild type cross-reacted in whole cell and cps ELISA, they did not cross-opsonise the mutant in a peripheral blood neutrophil opsonisation assay, consistent with reported vaccine escape. We have shown here that mutation in cpsG results in altered CPS composition and this in turn results in poor cross-opsonisation that explains some of the historic vaccination failure on fish farms in Australia. Crown Copyright © 2016. Published by Elsevier B.V. All rights reserved.

Factors contributing to the immunogenicity of meningococcal conjugate vaccines

Science.gov (United States)

Bröker, Michael; Berti, Francesco; Costantino, Paolo

2016-01-01

ABSTRACT Various glycoprotein conjugate vaccines have been developed for the prevention of invasive meningococcal disease, having significant advantages over pure polysaccharide vaccines. One of the most important features of the conjugate vaccines is the induction of a T-cell dependent immune response, which enables both the induction of immune memory and a booster response after repeated immunization. The nature of the carrier protein to which the polysaccharides are chemically linked, is often regarded as the main component of the vaccine in determining its immunogenicity. However, other factors can have a significant impact on the vaccine's profile. In this review, we explore the physico-chemical properties of meningococcal conjugate vaccines, which can significantly contribute to the vaccine's immunogenicity. We demonstrate that the carrier is not the sole determining factor of the vaccine's profile, but, moreover, that the conjugate vaccine's immunogenicity is the result of multiple physico-chemical structures and characteristics. PMID:26934310

Thermostable cross-protective subunit vaccine against Brucella species.

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Cherwonogrodzky, John W; Barabé, Nicole D; Grigat, Michelle L; Lee, William E; Poirier, Robert T; Jager, Scott J; Berger, Bradley J

2014-12-01

A subunit vaccine candidate was produced from Brucella suis 145 (biovar 4; expressing both the A antigen of Brucella abortus and the M antigen of Brucella melitensis). The preparation consisted mostly of polysaccharide (PS; >90% [wt/wt]; both cell-associated PS and exo-PS were combined) and a small amount of protein (1 to 3%) with no apparent nucleic acids. Vaccinated mice were protected (these had a statistically significant reduction in bacterial colonization compared to that of unvaccinated controls) when challenged with representative strains of three Brucella species most pathogenic for humans, i.e., B. abortus, B. melitensis, and B. suis. As little as 1 ng of the vaccine, without added adjuvant, protected mice against B. suis 145 infection (5 × 10(5) CFU), and a single injection of 1 μg of this subunit vaccine protected mice from B. suis 145 challenge for at least 14 months. A single immunization induced a serum IgG response to Brucella antigens that remained elevated for up to 9 weeks. The use of heat (i.e., boiling-water bath, autoclaving) in the vaccine preparation showed that it was thermostable. This method also ensured safety and security. The vaccine produced was immunogenic and highly protective against multiple strains of Brucella and represents a promising candidate for further evaluation. Copyright © 2014, American Society for Microbiology. All Rights Reserved.

Is 13-Valent Pneumococcal Conjugate Vaccine (PCV13 Combined With 23-Valent Pneumococcal Polysaccharide Vaccine (PPSV23 Superior to PPSV23 Alone for Reducing Incidence or Severity of Pneumonia in Older Adults? A Clin-IQ

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Starla Hayward

2016-04-01

Full Text Available Pneumonia infection is a significant cause of morbidity and mortality worldwide. In addition to the public health concerns, pneumonia also accounts for a significant cost to the health care system. Currently there are two leading vaccines targeted against Streptococcus pneumoniae: 23-valent pneumococcal polysaccharide vaccine (PPSV23 and 13-valent pneumococcal conjugate vaccine (PCV13. Until recently, the recommendation for adult pneumonia vaccination has been a single dose of PPSV23 for all adults aged 65 years or older. However, concerns were raised regarding the vaccine’s efficacy due to the persistent burden of pneumococcal disease in the elderly population. This paper focuses on two trials that evaluated the safety and efficacy of PCV13 in the adult population. The first study reveals improved immune response with the addition of PCV13 to PPSV23, while the second shows PCV13 was effective in the prevention of vaccine-type community-acquired pneumonia. Both studies observed adequate safety profiles for PCV13 in series with PPSV23 and with PCV13 compared to placebo.

The role of economic evaluation in vaccine decision making : Focus on meningococcal group C conjugate vaccine

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Welte, R.; Trotter, C.L.; Edmunds, W.J.; Postma, Maarten; Beutels, P.H.

2005-01-01

In recent years, several countries have experienced increases in the incidence of serogroup C meningococcal disease. It can be controlled with older polysaccharide vaccines and particularly the recently developed conjugate vaccines. For 21 developed countries, we investigated the role that economic

Vaccines for viral and bacterial pathogens causing acute gastroenteritis: Part II: Vaccines for Shigella, Salmonella, enterotoxigenic E. coli (ETEC) enterohemorragic E. coli (EHEC) and Campylobacter jejuni

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O’Ryan, Miguel; Vidal, Roberto; del Canto, Felipe; Carlos Salazar, Juan; Montero, David

2015-01-01

In Part II we discuss the following bacterial pathogens: Shigella, Salmonella (non-typhoidal), diarrheogenic E. coli (enterotoxigenic and enterohemorragic) and Campylobacter jejuni. In contrast to the enteric viruses and Vibrio cholerae discussed in Part I of this series, for the bacterial pathogens described here there is only one licensed vaccine, developed primarily for Vibrio cholerae and which provides moderate protection against enterotoxigenic E. coli (ETEC) (Dukoral®), as well as a few additional candidates in advanced stages of development for ETEC and one candidate for Shigella spp. Numerous vaccine candidates in earlier stages of development are discussed. PMID:25715096

A novel multi-stage subunit vaccine against paratuberculosis induces significant immunity and reduces bacterial burden in tissues (P4304)

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Thakur, Aneesh; Aagaard, Claus; Riber, Ulla

2013-01-01

Effective control of paratuberculosis is hindered by lack of a vaccine preventing infection, transmission and without diagnostic interference with tuberculosis. We have developed a novel multi-stage recombinant subunit vaccine in which a fusion of four early expressed MAP antigens is combined...... characterized by a significant containment of bacterial burden in gut tissues compared to non-vaccinated animals. There was no cross-reaction with bovine tuberculosis in vaccinated animals. This novel multi-stage vaccine has the potential to become a marker vaccine for paratuberculosis....

Immunogenicity and Immunological Memory Induced by the 13-Valent Pneumococcal Conjugate Followed by the 23-Valent Polysaccharide Vaccine in HIV-Infected Adults.

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Farmaki, Paraskevi F; Chini, Maria C; Mangafas, Nikolaos M; Tzanoudaki, Marianna T; Piperi, Christina P; Lazanas, Marios Z; Spoulou, Vana S

2018-05-02

Vaccine-induced memory B-cell (MBC) subsets have distinct roles in the establishment of protective immunity; MBCs expressing nonswitched immunoglobulin M (IgM+ MBCs) replenish the MBC pool, whereas MBCs expressing isotype-switched immunoglobulin (sIg+ MBCs) differentiate into plasma cells upon antigen reencounter. We investigated immunogenicity and MBCs induced by combined 13-valent pneumococcal conjugate vaccine (PCV13) and 23-valent pneumococcal polysaccharide vaccine (PPV23) in human immunodeficiency virus (HIV)-infected adults. Forty HIV-seropositive adults receiving ART with undetectable viral loads were enrolled. Seventeen had a CD4+ T-cell count of ≥400 cells/μL (group A), and 23 had a CD4+ T-cell count of 200-399 cells/μL (group B). All adults received PCV13 and, 1 year later, PPV23. Levels of IgM+ MBCs (defined as polysaccharide [PS]-specific CD19+CD10-CD27+CD21++IgM+ MBCs) and sIg+ MBCs (defined as PS-specific CD19+CD10-CD27+CD21++IgM- MBCs) and antibodies against PS14 and PS3 were measured prior and 1 month after each vaccination. Immunization caused a significant increase in PS antibodies, compared with levels at baseline (P < .001). Group B achieved significantly lower titers than group A (P < .05 for both PS14 and PS3). After receipt of PCV13, levels of IgM+ MBCs were unchanged, whereas levels of sIg+ MBCs increased significantly (P < .05 for PS14 and P < .001 for PS3). In contrast, following PPV23 receipt, levels of IgM+ MBCs were significantly reduced, and levels of sIg+ MBCs remained stable. A positive correlation was observed between baseline IgM+ and sIg+ MBC counts 1 month after PCV13 receipt but not after PPV23 receipt. PPV23 receipt 12 months after PCV13 receipt improved PCV13 immunogenicity. The reduction in the IgM+ MBC count observed after PPV23 receipt suggests that PPV23 has a depleting effect on PCV13-associated immunological memory. NCT03041051.

Emerging clinical experience with vaccines against group B meningococcal disease.

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Wilkins, A L; Snape, M D

2017-08-01

The prevention of paediatric bacterial meningitis and septicaemia has recently entered a new era with the availability of two vaccines against capsular group B meningococcus (MenB). Both of these vaccines are based on sub-capsular proteins of the meningococcus, an approach that overcomes the challenges set by the poorly immunogenic MenB polysaccharide capsule but adds complexity to predicting and measuring the impact of their use. This review describes the development and use of MenB vaccines to date, from the use of outer membrane vesicle (OMV) vaccines in MenB outbreaks around the world, to emerging evidence on the effectiveness of the newly available vaccines. While recent data from the United Kingdom supports the potential for protein-based vaccines to provide direct protection against MenB disease in immunised children, further research is required to understand the breadth and duration of this protection. A more detailed understanding of the impact of immunisation with these vaccines on nasopharyngeal carriage of the meningococcus is also required, to inform both their potential to induce herd immunity and to preferentially select for carriage of strains not susceptible to vaccine-induced antibodies. Although a full understanding of the potential impact of these vaccines will only be possible with this additional information, the availability of new tools to prevent the devastating effect of invasive MenB disease is a significant breakthrough in the fight against childhood sepsis and meningitis. Copyright © 2017 Elsevier Ltd. All rights reserved.

Vaccination promotes TH1-like inflammation and survival in chronic Pseudomonas aeruginosa pneumonia. A new prophylactic principle

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Johansen, H K; Cryz, S J; Hougen, H P

1997-01-01

The ongoing lung tissue damage in chronically Pseudomonas aeruginosa infected cystic fibrosis (CF) patients has been shown to be caused by elastase liberated from polymorphonuclear leukocytes (PMN), which dominate the chronic inflammation in these patients. Most CF patients, however, contract...... the chronic lung infection with P. aeruginosa after a one-year period (median) of intermittent colonization. Therefore, prevention of the onset of the chronic infection or prevention of the dominance of the inflammation by PMNs would be important goals for a vaccine strategy against P. aeruginosa in CF....... In a rat model of acute P. aeruginosa pneumonia we studied whether it was possible to improve the initial bacterial clearance and diminish the inflammatory response by vaccination prior to challenge with free, live P. aeruginosa. The vaccines studied were PAO 579 sonicate, O-polysaccharide toxin A (TA...

Emerging pneumococcal carriage serotypes in a high-risk population receiving universal 7-valent pneumococcal conjugate vaccine and 23-valent polysaccharide vaccine since 2001

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Stubbs Liz

2009-08-01

Full Text Available Abstract Background In Australia in June 2001, a unique pneumococcal vaccine schedule commenced for Indigenous infants; seven-valent pneumococcal conjugate vaccine (7PCV given at 2, 4, and 6 months of age and 23-valent pneumococcal polysaccharide vaccine (23PPV at 18 months of age. This study presents carriage serotypes following this schedule. Methods We conducted cross sectional surveys of pneumococcal carriage in Aboriginal children 0 to 6 years of age living in remote Aboriginal communities (RACs in 2003 and 2005. Nasal secretions were collected and processed according to published methods. Results 902 children (mean age 25 months living in 29 communities in 2003 and 818 children (mean age 35 months in 17 communities in 2005 were enrolled. 87% children in 2003 and 96% in 2005 had received two or more doses of 7PCV. From 2003 to 2005, pneumococcal carriage was reduced from 82% to 76% and reductions were apparent in all age groups; 7PCV-type carriage was reduced from 11% to 8%, and 23PPV-non-7PCV-type carriage from 31% to 25% respectively. Thus non-23PPV-type carriage increased from 57% to 67%. All these changes were statistically significant, as were changes for some specific serotypes. Shifts could not be attributed to vaccination alone. The top 10 of 40 serotypes identified were (in descending order 16F, 19A, 11A, 6C, 23B, 19F, 6A, 35B, 6B, 10A and 35B. Carriage of penicillin non-susceptible (MIC > = 0.12 μg/mL strains (15% overall was detected in serotypes (descending order 19A, 19F, 6B, 16F, 11A, 9V, 23B, and in 4 additional serotypes. Carriage of azithromycin resistant (MIC > = 2 μg/mL strains (5% overall, was detected in serotypes (descending order 23B, 17F, 9N, 6B, 6A, 11A, 23F, and in 10 additional serotypes including 6C. Conclusion Pneumococcal carriage remains high (~80% in this vaccinated population. Uptake of both pneumococcal vaccines increased, and carriage was reduced between 2003 and 2005. Predominant serotypes in combined

Optimization of Molecular Approaches to Genogroup Neisseria meningitidis Carriage Isolates and Implications for Monitoring the Impact of New Serogroup B Vaccines.

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Eduardo Rojas

Full Text Available The reservoir for Neisseria meningitidis (Nm is the human oropharynx. Implementation of Nm serogroup C (NmC glycoconjugate vaccines directly reduced NmC carriage. Prophylactic vaccines are now available to prevent disease caused by the five major Nm disease causing serogroups (ABCWY. Nm serogroup B (NmB vaccines are composed of antigens that are conserved across Nm serogroups and therefore have the potential to impact all Nm carriage. To assess the effect of these vaccines on carriage, standardized approaches to identify and group Nm are required. Real-time PCR (rt-PCR capsule grouping assays that were internally controlled to confirm Nm species were developed for eight serogroups associated with carriage (A, B, C, E, W, X, Y and Z. The grouping scheme was validated using diverse bacterial species associated with carriage and then used to evaluate a collection of diverse Nm carriage isolates (n=234. A scheme that also included porA and ctrA probes was able to speciate the isolates, while ctrA also provided insights on the integrity of the polysaccharide loci. Isolates were typed for the Nm vaccine antigen factor H binding protein (fHbp, and were found to represent the known diversity of this antigen. The porA rt-PCR yielded positive results with all 234 of the Nm carriage isolates. Genogrouping assays classified 76.5% (179/234 of these isolates to a group, categorized 53 as nongenogroupable (NGG and two as mixed results. Thirty seven NGG isolates evidenced a disrupted capsular polysaccharide operon judged by a ctrA negative result. Only 28.6% (67/234 of the isolates were serogrouped by slide agglutination (SASG, highlighting the reduced capability of carriage strains to express capsular polysaccharide. These rt-PCR assays provide a comprehensive means to identify and genogroup N. meningitidis in carriage studies used to guide vaccination strategies and to assess the impact of novel fHbp containing vaccines on meningococcal carriage.

Development of a multicomponent Staphylococcus aureus vaccine designed to counter multiple bacterial virulence factors

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Anderson, Annaliesa S.; Miller, Alita A.; Donald, Robert G.K.; Scully, Ingrid L.; Nanra, Jasdeep S.; Cooper, David; Jansen, Kathrin U.

2012-01-01

Staphylococcus aureus is a major cause of healthcare-associated infections and is responsible for a substantial burden of disease in hospitalized patients. Despite increasingly rigorous infection control guidelines, the prevalence and corresponding negative impact of S. aureus infections remain considerable. Difficulties in controlling S. aureus infections as well as the associated treatment costs are exacerbated by increasing rates of resistance to available antibiotics. Despite ongoing efforts over the past 20 years, no licensed S. aureus vaccine is currently available. However, learnings from past clinical failures of vaccine candidates and a better understanding of the immunopathology of S. aureus colonization and infection have aided in the design of new vaccine candidates based on multiple important bacterial pathogenesis mechanisms. This review outlines important considerations in designing a vaccine for the prevention of S. aureus disease in healthcare settings. PMID:22922765

The Meningitis Vaccine Project.

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LaForce, F Marc; Konde, Kader; Viviani, Simonetta; Préziosi, Marie-Pierre

2007-09-03

Epidemic meningococcal meningitis is an important public health problem in sub-Saharan Africa. Current control measures rely on reactive immunizations with polysaccharide (PS) vaccines that do not induce herd immunity and are of limited effectiveness in those under 2 years of age. Conversely, polysaccharide conjugate vaccines are effective in infants and have consistently shown an important effect on decreasing carriage, two characteristics that facilitate disease control. In 2001 the Meningitis Vaccine Project (MVP) was created as a partnership between PATH and the World Health Organization (WHO) with the goal of eliminating meningococcal epidemics in Africa through the development, licensure, introduction, and widespread use of conjugate meningococcal vaccines. Since group A Neisseria meningitidis (N. meningitidis) is the dominant pathogen causing epidemic meningitis in Africa MVP is developing an affordable (US$ 0.40 per dose) meningococcal A (Men A) conjugate vaccine through an innovative international partnership that saw transfer of a conjugation and fermentation technology to a developing country vaccine manufacturer. A Phase 1 study of the vaccine in India has shown that the product is safe and immunogenic. Phase 2 studies have begun in Africa, and a large demonstration study of the conjugate vaccine is envisioned for 2008-2009. After extensive consultations with African public health officials a vaccine introduction plan has been developed that includes introduction of the Men A conjugate vaccine into standard Expanded Programme on Immunization (EPI) schedules but also emphasizes mass vaccination of 1-29 years old to induce herd immunity, a strategy that has been shown to be highly effective when the meningococcal C (Men C) conjugate vaccine was introduced in several European countries. The MVP model is a clear example of the usefulness of a "push mechanism" to finance the development of a needed vaccine for the developing world.

Mexico introduces pentavalent vaccine.

Science.gov (United States)

1999-08-01

Combination vaccines have been introduced in Mexico. The national immunization program has incorporated the measles-mumps-rubella (MMR) vaccines in 1998, and the pentavalent vaccine in 1999. The two categories of antigen composition in combination vaccines are: 1) multiple different antigenic types of a single pathogen, such as the 23 valent pneumococcal polysaccharide vaccine, and 2) antigens from different pathogens causing different diseases, such as the DPT and MMR vaccines. Pentavalent vaccines are included in the second category. The vaccine protects against diphtheria, tetanus, pertussis, hepatitis B, and other diseases produced by Haemophilus influenzae type b (Hib). Combined diphtheria, tetanus, pertussis, hepatitis B, and Haemophilus influenza type b (DTP-HB/Hib) vaccine has been distributed to 87% of Mexican children under 1 year of age. Over 800,000 doses of pentavalent vaccine have been administered.

The diversity of Klebsiella pneumoniae surface polysaccharides.

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Follador, Rainer; Heinz, Eva; Wyres, Kelly L; Ellington, Matthew J; Kowarik, Michael; Holt, Kathryn E; Thomson, Nicholas R

2016-08-01

Klebsiella pneumoniae is considered an urgent health concern due to the emergence of multi-drug-resistant strains for which vaccination offers a potential remedy. Vaccines based on surface polysaccharides are highly promising but need to address the high diversity of surface-exposed polysaccharides, synthesized as O-antigens (lipopolysaccharide, LPS) and K-antigens (capsule polysaccharide, CPS), present in K. pneumoniae . We present a comprehensive and clinically relevant study of the diversity of O- and K-antigen biosynthesis gene clusters across a global collection of over 500 K. pneumoniae whole-genome sequences and the seroepidemiology of human isolates from different infection types. Our study defines the genetic diversity of O- and K-antigen biosynthesis cluster sequences across this collection, identifying sequences for known serotypes as well as identifying novel LPS and CPS gene clusters found in circulating contemporary isolates. Serotypes O1, O2 and O3 were most prevalent in our sample set, accounting for approximately 80 % of all infections. In contrast, K serotypes showed an order of magnitude higher diversity and differ among infection types. In addition we investigated a potential association of O or K serotypes with phylogenetic lineage, infection type and the presence of known virulence genes. K1 and K2 serotypes, which are associated with hypervirulent K. pneumoniae , were associated with a higher abundance of virulence genes and more diverse O serotypes compared to other common K serotypes.

Trivalent pneumococcal protein recombinant vaccine protects against lethal Streptococcus pneumoniae pneumonia and correlates with phagocytosis by neutrophils during early pathogenesis.

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Xu, Qingfu; Surendran, Naveen; Verhoeven, David; Klapa, Jessica; Ochs, Martina; Pichichero, Michael E

2015-02-18

Due to the fact that current polysaccharide-based pneumococcal vaccines have limited serotype coverage, protein-based vaccine candidates have been sought for over a decade to replace or complement current vaccines. We previously reported that a trivalent Pneumococcal Protein recombinant Vaccine (PPrV), showed protection against pneumonia and sepsis in an infant murine model. Here we investigated immunological correlates of protection of PPrV in the same model. C57BL/6J infant mice were intramuscularly vaccinated at age 1-3 weeks with 3 doses of PPrV, containing pneumococcal histidine triad protein D (PhtD), pneumococcal choline binding protein A (PcpA), and detoxified pneumolysin mutant PlyD1. 3-4 weeks after last vaccination, serum and lung antibody levels to PPrV components were measured, and mice were intranasally challenged with a lethal dose of Streptococcus pneumoniae (Spn) serotype 6A. Lung Spn bacterial burden, number of neutrophils and alveolar macrophages, phagocytosed Spn by granulocytes, and levels of cytokines and chemokines were determined at 6, 12, 24, and 48h after challenge. PPrV vaccination conferred 83% protection against Spn challenge. Vaccinated mice had significantly elevated serum and lung antibody levels to three PPrV components. In the first stage of pathogenesis of Spn induced pneumonia (6-24h after challenge), vaccinated mice had lower Spn bacterial lung burdens and more phagocytosed Spn in the granulocytes. PPrV vaccination led to lower levels of pro-inflammatory cytokines IL-6, IL-1β, and TFN-α, and other cytokines and chemokines (IL-12, IL-17, IFN-γ, MIP-1b, MIP-2 and KC, and G-CSF), presumably due to a lower lung bacterial burden. Trivalent PPrV vaccination results in increased serum and lung antibody levels to the vaccine components, a reduction in Spn induced lethality, enhanced early clearance of Spn in lungs due to more rapid and thorough phagocytosis of Spn by neutrophils, and correspondingly a reduction in lung inflammation

Live-Attenuated Bacterial Vectors: Tools for Vaccine and Therapeutic Agent Delivery

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Ivan Y. C. Lin

2015-11-01

Full Text Available Genetically attenuated microorganisms, including pathogenic and commensal bacteria, can be engineered to carry and deliver heterologous antigens to elicit host immunity against both the vector as well as the pathogen from which the donor gene is derived. These live attenuated bacterial vectors have been given much attention due to their capacity to induce a broad range of immune responses including localized mucosal, as well as systemic humoral and/or cell-mediated immunity. In addition, the unique tumor-homing characteristics of these bacterial vectors has also been exploited for alternative anti-tumor vaccines and therapies. In such approach, tumor-associated antigen, immunostimulatory molecules, anti-tumor drugs, or nucleotides (DNA or RNA are delivered. Different potential vectors are appropriate for specific applications, depending on their pathogenic routes. In this review, we survey and summarize the main features of the different types of live bacterial vectors and discussed the clinical applications in the field of vaccinology. In addition, different approaches for using live attenuated bacterial vectors for anti-cancer therapy is discussed, and some promising pre-clinical and clinical studies in this field are outlined.

Pneumococcal Vaccination Recommendations for Children and Adults by Age and/or Risk Factor

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Pneumococcal Vaccination Recommendations for Children 1 and Adults by Age and/or Risk Factor Routine Recommendations for Pneumococcal Conjugate Vaccine (PCV13) and Pneumococcal Polysaccharide Vaccine (PPSV23) For children Administer PCV13 ...

In vivo production of a novel glycoconjugate vaccine against Shigella flexneri 2a in recombinant Escherichia coli: identification of stimulating factors for in vivo glycosylation.

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Kämpf, Michael M; Braun, Martin; Sirena, Dominique; Ihssen, Julian; Thöny-Meyer, Linda; Ren, Qun

2015-01-23

Glycoconjugated vaccines composed of polysaccharide antigens covalently linked to immunogenic carrier proteins have proved to belong to the most effective and safest vaccines for combating bacterial pathogens. The functional transfer of the N-glycosylation machinery from Campylobacter jejuni to the standard prokaryotic host Escherichia coli established a novel bioconjugation methodology termed bacterial glycoengineering. In this study, we report on the production of a new recombinant glycoconjugate vaccine against Shigella flexneri 2a representing the major serotype for global outbreaks of shigellosis. We demonstrate that S. flexneri 2a O-polysaccharides can be transferred to a detoxified variant of Pseudomonas aeruginosa carrier protein exotoxin A (EPA) by the C. jejuni oligosaccharyltransferase PglB, resulting in glycosylated EPA-2a. Moreover, we optimized the in vivo production of this novel vaccine by identification and quantitative analysis of critical process parameters for glycoprotein synthesis. It was found that sequential induction of oligosaccharyltransferase PglB and carrier protein EPA increased the specific productivity of EPA-2a by a factor of 1.6. Furthermore, by the addition of 10 g/L of the monosaccharide N-acetylglucosamine during induction, glycoconjugate vaccine yield was boosted up to 3.1-fold. The optimum concentration of Mg2+ ions for N-glycan transfer was determined to be 10 mM. Finally, optimized parameters were transferred to high cell density cultures with a 46-fold increase of overall yield of glycoconjugate compared to the one in initial shake flask production. The present study is the first attempt to identify stimulating parameters for improved productivity of S. flexneri 2a bioconjugates. Optimization of glycosylation efficiency will ultimately foster the transfer of lab-scale expression to a cost-effective in vivo production process for a glycoconjugate vaccine against S. flexneri 2a in E. coli. This study is an important step

Impact of 4 Lactobacillus plantarum capsular polysaccharide clusters on surface glycan composition and host cell signaling

NARCIS (Netherlands)

Remus, D.M.; Kranenburg, van R.; Swam, van I.I.; Taverne, N.; Bongers, R.S.; Wels, M.; Wells, J.; Bron, P.A.; Kleerebezem, M.

2012-01-01

Background - Bacterial cell surface-associated polysaccharides are involved in the interactions of bacteria with their environment and play an important role in the communication between pathogenic bacteria and their host organisms. Cell surface polysaccharides of probiotic species are far less well

A Semi-Synthetic Glycoconjugate Vaccine Candidate for Carbapenem-Resistant Klebsiella pneumoniae.

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Seeberger, Peter H; Pereira, Claney L; Khan, Naeem; Xiao, Guozhi; Diago-Navarro, Elizabeth; Reppe, Katrin; Opitz, Bastian; Fries, Bettina C; Witzenrath, Martin

2017-11-06

Hospital-acquired infections are an increasingly serious health concern. Infections caused by carpabenem-resistant Klebsiella pneumoniae (CR-Kp) are especially problematic, with a 50 % average survival rate. CR-Kp are isolated from patients with ever greater frequency, 7 % within the EU but 62 % in Greece. At a time when antibiotics are becoming less effective, no vaccines to protect from this severe bacterial infection exist. Herein, we describe the convergent [3+3] synthesis of the hexasaccharide repeating unit from its capsular polysaccharide and related sequences. Immunization with the synthetic hexasaccharide 1 glycoconjugate resulted in high titers of cross-reactive antibodies against CR-Kp CPS in mice and rabbits. Whole-cell ELISA was used to establish the surface staining of CR-Kp strains. The antibodies raised were found to promote phagocytosis. Thus, this semi-synthetic glycoconjugate is a lead for the development of a vaccine against a rapidly progressing, deadly bacterium. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Immunogenicity of simultaneous versus sequential administration of a 23-valent pneumococcal polysaccharide vaccine and a quadrivalent influenza vaccine in older individuals: A randomized, open-label, non-inferiority trial.

Science.gov (United States)

Nakashima, Kei; Aoshima, Masahiro; Ohfuji, Satoko; Yamawaki, Satoshi; Nemoto, Masahiro; Hasegawa, Shinya; Noma, Satoshi; Misawa, Masafumi; Hosokawa, Naoto; Yaegashi, Makito; Otsuka, Yoshihito

2018-03-21

It is unclear whether simultaneous administration of a 23-valent pneumococcal polysaccharide vaccine (PPSV23) and a quadrivalent influenza vaccine (QIV) produces immunogenicity in older individuals. This study tested the hypothesis that the pneumococcal antibody response elicited by simultaneous administration of PPSV23 and QIV in older individuals is not inferior to that elicited by sequential administration of PPSV23 and QIV. We performed a single-center, randomized, open-label, non-inferiority trial comprising 162 adults aged ≥65 years randomly assigned to either the simultaneous (simultaneous injections of PPSV23 and QIV) or sequential (control; PPSV23 injected 2 weeks after QIV vaccination) groups. Pneumococcal immunoglobulin G (IgG) titers of serotypes 23F, 3, 4, 6B, 14, and 19A were assessed. The primary endpoint was the serotype 23F response rate (a ≥2-fold increase in IgG concentrations 4-6 weeks after PPSV23 vaccination). With the non-inferiority margin set at 20% fewer patients, the response rate of serotype 23F in the simultaneous group (77.8%) was not inferior to that of the sequential group (77.6%; difference, 0.1%; 90% confidence interval, -10.8% to 11.1%). None of the pneumococcal IgG serotype titers were significantly different between the groups 4-6 weeks after vaccination. Simultaneous administration did not show a significant decrease in seroprotection odds ratios for H1N1, H3N2, or B/Phuket influenza strains other than B/Texas. Additionally, simultaneous administration did not increase adverse reactions. Hence, simultaneous administration of PPSV23 and QIV shows an acceptable immunogenicity that is comparable to sequential administration without an increase in adverse reactions. (This study was registered with ClinicalTrials.gov [NCT02592486]).

Structural studies of some bacterial capsular polysaccharides from the family enterobacteriaceae: Klebsiella serotypes K79 and K35 and Escherichia coli serotype K44

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Lim, A.V.S.

1986-01-01

The techniques of sugar analysis, methylation, chromic acid oxidation, deamination, base-catalyzed uronic acid degradation, Smith degradation and partial hydrolysis were used in the structural elucidation of bacterial capsular polysaccharides. Methods such as gas-liquid chromatography, gas chromatography-mass spectrometry, gel permeation, ion-exchange and paper-chromatography were used to isolate and characterize oligosaccharides obtained from degradative procedures. N.m.r. spectroscopy (/sup 1/H and /sup 13/C) was widely used in the characterization of the polysaccharides and of derived poly- and oligo-saccharides. In a few instances, n.m.r. spectroscopy and mass spectrometry were used to delineate the sequence of the sugars in the structure of the poly- and oligo-saccharides. The bacteriophage-induced depolymerizations of the capsular polysaccharides of Klebsiella K79 and E. coli K44 are also reported in this thesis. The sum of these experiments demonstrated that the endoglycanase associated with Klebsiella Phi 79 had ..beta..-galactosidase activity. The endoglycanase from E. coli Phi 44 exhibited ..beta..-N-acetyl-galactosaminidase activity which is novel, in that it is the first reported action of this nature in the bacteriophages isolated for the species E. coli.

Meningitis registry of hospitalized cases in children: epidemiological patterns of acute bacterial meningitis throughout a 32-year period

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Syriopoulou Vassiliki P

2007-08-01

Full Text Available Abstract Background Bacterial meningitis remains a source of substantial morbidity and mortality in childhood. During the last decades gradual changes have been observed in the epidemiology of bacterial meningitis, related to the introduction of new polysaccharide and conjugate vaccines. The study presents an overview of the epidemiological patterns of acute bacterial meningitis in a tertiary children 's hospital during a 32-year period, using information from a disease registry. Moreover, it discusses the contribution of communicable disease registries in the study of acute infectious diseases. Methods In the early 1970s a Meningitis Registry (MR was created for patients admitted with meningitis in Aghia Sofia Children's Hospital in Athens. The MR includes demographic, clinical and laboratory data as well as treatment, complications and outcome of the patients. In 2000 a database was created and the collected data were entered, analyzed and presented in three chronological periods: A (1974–1984, B (1985–1994 and C (1995–2005. Results Of the 2,477 cases of bacterial meningitis registered in total, 1,146 cases (46.3% were classified as "probable" and 1,331 (53.7% as "confirmed" bacterial meningitis. The estimated mean annual Incidence Rate (IR was 16.9/100,000 for bacterial meningitis, 8.9/100,000 for Neisseria meningitidis, 1.3/100,000 for Streptococcus pneumoniae, 2.5/100,000 for Haemophilus influenzae type b (Hib before vaccination and 0.4/100,000 for Hib after vaccination. Neisseria meningitis constituted the leading cause of childhood bacterial meningitis for all periods and in all age groups. Hib was the second most common cause of bacterial meningitis before the introduction of Hib conjugate vaccine, in periods A and B. The incidence of bacterial meningitis due to Streptococcus pneumoniae was stable. The long-term epidemiological pattern of Neisseria meningitidis appears in cycles of approximately 10 years, confirmed by a significant

Bacterial infec tions in travellers

African Journals Online (AJOL)

namely bacterial causes of travellers' diarrhoea and skin infections, as well as .... Vaccination: protective efficacy against typhoid may be overcome by ingesting a high bacterial load. Vaccine ..... preparation such as cream sauce. Only after ...

9 CFR 113.65 - Brucella Abortus Vaccine.

Science.gov (United States)

2010-01-01

... 9 Animals and Animal Products 1 2010-01-01 2010-01-01 false Brucella Abortus Vaccine. 113.65... Bacterial Vaccines § 113.65 Brucella Abortus Vaccine. Brucella Abortus Vaccine shall be prepared as a desiccated live culture bacterial vaccine from smooth colonial forms of the Brucella abortus organism...

New technology for regiospecific covalent coupling of polysaccharide antigens in ELISA for serological detection

DEFF Research Database (Denmark)

Jauho, E.S.; Boas, Ulrik; Wiuff, Camilla

2000-01-01

In this study we demonstrate a new UV irradiation technique for covalent coupling of bacterial polysaccharides derived from lipopolysaccharides to microtiter plates and the use of such plates in an enzyme linked immunosorbent assay (ELISA). Lipopolysaccharides were cleaved by mild acid hydrolysis...... describe the use of this technique for the immobilization of Lipopolysaccharide derived polysaccharides from Salmonella Typhimurium and Salmonella Choleraesuis lipopolysaccharides, representing the O-antigens 1, 4, 5, 6, 7, and 12, The functional polysaccharide surface gave similar ELISA results to plates...

Challenges and opportunities of using liquid chromatography and mass spectrometry methods to develop complex vaccine antigens as pharmaceutical dosage forms.

Science.gov (United States)

Hickey, John M; Sahni, Neha; Toth, Ronald T; Kumru, Ozan S; Joshi, Sangeeta B; Middaugh, C Russell; Volkin, David B

2016-10-01

Liquid chromatographic methods, combined with mass spectrometry, offer exciting and important opportunities to better characterize complex vaccine antigens including recombinant proteins, virus-like particles, inactivated viruses, polysaccharides, and protein-polysaccharide conjugates. The current abilities and limitations of these physicochemical methods to complement traditional in vitro and in vivo vaccine potency assays are explored in this review through the use of illustrative case studies. Various applications of these state-of-the art techniques are illustrated that include the analysis of influenza vaccines (inactivated whole virus and recombinant hemagglutinin), virus-like particle vaccines (human papillomavirus and hepatitis B), and polysaccharide linked to protein carrier vaccines (pneumococcal). Examples of utilizing these analytical methods to characterize vaccine antigens in the presence of adjuvants, which are often included to boost immune responses as part of the final vaccine dosage form, are also presented. Some of the challenges of using chromatographic and LC-MS as physicochemical assays to routinely test complex vaccine antigens are also discussed. Copyright © 2016 Elsevier B.V. All rights reserved.

Immune response to pneumococcal polysaccharides 4 and 14 in elderly and young adults. I Antibody concentrations, avidity and functional activity

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Carlone George M

2005-06-01

Full Text Available Abstract Streptococcus pneumoniae is a serious worldwide pathogen and the focus of numerous vaccine development projects. Currently the most widely accepted surrogate marker for evaluating the efficacy of a given vaccine is to utilize ELISA. Measurement of antibody concentration by ELISA without reduction in cross-reactive antibodies causes an overestimation of antibody concentration and therefore protection, this is most notable in the aged, an at risk group for this infection. We compared the immune response to the pneumococcal polysaccharides (PPS 4 and 14 of 20 young to 20 elderly adults. Pre-and post-vaccination IgG antibody concentrations and antibody avidity against PPS4 and PPS14 were measured using two different enzyme-linked immunosorbant assay (ELISA absorption protocols. All sera were pre-absorbed with either cell-wall polysaccharide (CPS, or CPS and serotype 22F polysaccharide. Pre- and post-vaccination IgG antibody concentrations for serotype 4, but not 14, were significantly lowered with the additional absorption with serotype 22F polysaccharide in both age groups. Young and elderly demonstrated a significant increase from pre- to post-immunization antibody concentration, using either absorption method; and opsonophagocytic antibody titers in response to both PPS4 and PPS14. The correlation coefficients between ELISA and opsonophagocytic assays were improved by additional absorption with serotype 22F in response to serotype 4, but not serotype 14 in all age groups. Opsonophagocytic antibody titers in a sub-group of elderly (>77 years of age were significantly lower than the opsonophagocytic antibody concentrations in young adults. These results suggest the importance of eliminating cross-reactive antibodies from ELISA measurements by absorption of serum and an age-related impairment in the antibody response to pneumococcal polysaccharides.

A Cholera Conjugate Vaccine Containing O-specific Polysaccharide (OSP of V. cholerae O1 Inaba and Recombinant Fragment of Tetanus Toxin Heavy Chain (OSP:rTTHc Induces Serum, Memory and Lamina Proprial Responses against OSP and Is Protective in Mice.

Directory of Open Access Journals (Sweden)

Md Abu Sayeed

Full Text Available Vibrio cholerae is the cause of cholera, a severe watery diarrhea. Protection against cholera is serogroup specific. Serogroup specificity is defined by the O-specific polysaccharide (OSP component of lipopolysaccharide (LPS.Here we describe a conjugate vaccine for cholera prepared via squaric acid chemistry from the OSP of V. cholerae O1 Inaba strain PIC018 and a recombinant heavy chain fragment of tetanus toxin (OSP:rTTHc. We assessed a range of vaccine doses based on the OSP content of the vaccine (10-50 μg, vaccine compositions varying by molar loading ratio of OSP to rTTHc (3:1, 5:1, 10:1, effect of an adjuvant, and route of immunization.Immunized mice developed prominent anti-OSP and anti-TT serum IgG responses, as well as vibriocidal antibody and memory B cell responses following intramuscular or intradermal vaccination. Mice did not develop anti-squarate responses. Intestinal lamina proprial IgA responses targeting OSP occurred following intradermal vaccination. In general, we found comparable immune responses in mice immunized with these variations, although memory B cell and vibriocidal responses were blunted in mice receiving the highest dose of vaccine (50 μg. We found no appreciable change in immune responses when the conjugate vaccine was administered in the presence or absence of immunoadjuvant alum. Administration of OSP:rTTHc resulted in 55% protective efficacy in a mouse survival cholera challenge model.We report development of an Inaba OSP:rTTHc conjugate vaccine that induces memory responses and protection against cholera in mice. Development of an effective cholera conjugate vaccine that induces high level and long-term immune responses against OSP would be beneficial, especially in young children who respond poorly to polysaccharide antigens.

Development of canine herpesvirus based antifertility vaccines for foxes using bacterial artificial chromosomes.

Science.gov (United States)

Strive, Tanja; Hardy, Christopher M; French, Nigel; Wright, John D; Nagaraja, Nitin; Reubel, Gerhard H

2006-02-13

Using bacterial artificial chromosome (BAC) technology, a canine herpesvirus (CHV)-based recombinant vaccine vector was produced for the development of an antifertility vaccine for foxes. Infectious viruses were recovered following transfection of canid cells with a BAC plasmid carrying the complete CHV genome. In vitro growth characteristics of BAC-derived viruses were similar to that of wildtype (wt)-CHV. Two recombinant antigens, fox zona pellucida protein subunit 3 (fZPC) and enhanced green fluorescent protein (EGFP) as control antigen, were inserted into thymidine kinase (TK) locus of the CHV genome and shown to be efficiently expressed in vitro. Inoculation of foxes with transgenic CHVs induced CHV specific antibodies, but was innocuous and failed to elicit transgene-specific antibody responses. Infectious virus or viral DNA was not detected in mucosal secretions or tissues of vaccinated foxes. The CHV-BAC system proved to be a quick and reliable method to manipulate the CHV genome. It will help to readily apply changes in the vector design in order to improve virus replication in vivo.

Development of a new trend conjugate vaccine for the prevention of Klebsiella pneumoniae

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Tarek A. Ahmad

2012-07-01

Full Text Available Klebsiella pneumoniae is a major cause of nosocomial pneumonia, septicemia and urinary tract infections, especially in newborns, blood cancer patients, and other immunocompromised candidates. The control of K. pneumoniae is a complicated issue due to its tight pathogenesis. Immuno-prophylactic preparations, especially those directed toward the bacterium O-antigen, showed to be the most successful way to prevent the infection incidence. However, all previously proposed preparations were either of limited spectrum or non-maternal, and hence not targeting the main Klebsiella patients. Moreover, all preparations were directed only to prevent the respiratory diseases due to that pathogen. This article addresses the development of a method originally used to purify the non-capsular bacterial- endotoxins, as a new and easy method for vaccine production against K. pneumoniae. The application of this method was preceded by a biotechnological control of capsular polysaccharide production in K. pneumoniae. The new produced natural conjugate between the bacterial O-antigen and its outer membrane proteins was evaluated by physicochemical and immunological methods to investigate its purity, integrity, safety and immunogenicity. It showed to be pure, stable, safe for use, and able to elicit a protective immunoglobulin titer against different Klebsiella infections. This immune-response proved to be transferable to the offspring of the vaccinated experimental rabbits via placenta.

Effect of exo-polysaccharides producing bacterial inoculation on growth of roots of wheat(Triticum aestivum L. ) plants grown in a salt-affected soil

International Nuclear Information System (INIS)

Ashraf, M.; Hasnain, S.; Berge, O.

2006-01-01

Effect of soil salinity on physico-chemical and biological properties renders the salt-affected soils unsuitable for soil microbial processes and growth of the crop plants. Soil aggregation around roots of the plants is a function of the bacterial exo-polysaccharides, however, such a role of the EPS-producing bacteria in the saline environments has rarely been investigated. Pot experiments were conducted to observe the effects of inoculating six strains of exo-polysaccharides-producing bacteria on growth of primary (seminal) roots and its relationship with saccharides, cations (Ca 2+, Na +, K +) contents and mass of rhizosheath soils of roots of the wheat plants grown in a salt-affected soil. A strong positive relationship of RS with different root growth parameters indicated that an integrated influence of various biotic and abiotic RS factors would have controlled and promoted growth of roots of the inoculated wheat plants. The increase in root growth in turn could help inoculated wheat plants to withstand the negative effects of soil salinity through an enhanced soil water uptake, a restricted Na +i nflux in the plants and the accelerated soil microbial process involved in cycling and availability of the soil nutrients to the plants. It was concluded that inoculation of the exo- polysaccharides producing would be a valuable tool for amelioration and increasing crop productivity of the salt-affected soils

Vaccines for preventing typhoid fever.

Science.gov (United States)

Milligan, Rachael; Paul, Mical; Richardson, Marty; Neuberger, Ami

2018-05-31

Typhoid fever and paratyphoid fever continue to be important causes of illness and death, particularly among children and adolescents in south-central and southeast Asia. Two typhoid vaccines are widely available, Ty21a (oral) and Vi polysaccharide (parenteral). Newer typhoid conjugate vaccines are at varying stages of development and use. The World Health Organization has recently recommended a Vi tetanus toxoid (Vi-TT) conjugate vaccine, Typbar-TCV, as the preferred vaccine for all ages. To assess the effects of vaccines for preventing typhoid fever. In February 2018, we searched the Cochrane Infectious Diseases Group Specialized Register, CENTRAL, MEDLINE, Embase, LILACS, and mRCT. We also searched the reference lists of all included trials. Randomized and quasi-randomized controlled trials (RCTs) comparing typhoid fever vaccines with other typhoid fever vaccines or with an inactive agent (placebo or vaccine for a different disease) in adults and children. Human challenge studies were not eligible. Two review authors independently applied inclusion criteria and extracted data, and assessed the certainty of the evidence using the GRADE approach. We computed vaccine efficacy per year of follow-up and cumulative three-year efficacy, stratifying for vaccine type and dose. The outcome addressed was typhoid fever, defined as isolation of Salmonella enterica serovar Typhi in blood. We calculated risk ratios (RRs) and efficacy (1 - RR as a percentage) with 95% confidence intervals (CIs). In total, 18 RCTs contributed to the quantitative analysis in this review: 13 evaluated efficacy (Ty21a: 5 trials; Vi polysaccharide: 6 trials; Vi-rEPA: 1 trial; Vi-TT: 1 trial), and 9 reported on adverse events. All trials but one took place in typhoid-endemic countries. There was no information on vaccination in adults aged over 55 years of age, pregnant women, or travellers. Only one trial included data on children under two years of age.Ty21a vaccine (oral vaccine, three doses

Competitive adsorption of Reactive Orange 16 and Reactive Brilliant Blue R on polyaniline/bacterial extracellular polysaccharides composite-A novel eco-friendly polymer

Energy Technology Data Exchange (ETDEWEB)

Janaki, V. [Department of Chemistry, Periyar University, Salem 636011, Tamil Nadu (India); Vijayaraghavan, K. [Singapore-Delft Water Alliance, National University of Singapore, 117577 (Singapore); Ramasamy, A.K. [Department of Chemistry, Periyar University, Salem 636011, Tamil Nadu (India); Lee, Kui-Jae [Division of Biotechnology, Advanced Institute of Environment and Bioscience, College of Environmental and Bioresource Sciences, Chonbuk National University, Iksan 570752 (Korea, Republic of); Oh, Byung-Taek, E-mail: btoh@jbnu.ac.kr [Division of Biotechnology, Advanced Institute of Environment and Bioscience, College of Environmental and Bioresource Sciences, Chonbuk National University, Iksan 570752 (Korea, Republic of); Kamala-Kannan, Seralathan, E-mail: kannan@jbnu.ac.kr [Division of Biotechnology, Advanced Institute of Environment and Bioscience, College of Environmental and Bioresource Sciences, Chonbuk National University, Iksan 570752 (Korea, Republic of)

2012-11-30

Highlights: Black-Right-Pointing-Pointer Competitive adsorption of reactive dyes onto polyaniline/bacterial extracellular polysaccharides composite. Black-Right-Pointing-Pointer The composite have functional groups of both polyaniline and bacterial extracellular polysaccharides. Black-Right-Pointing-Pointer The presence of Reactive Brilliant Blue R diminished the uptake of Reactive Orange 16. Black-Right-Pointing-Pointer Electrostatic interaction was identified as a major mechanism in adsorption process. Black-Right-Pointing-Pointer Reactive Brilliant Blue R and Reactive Orange 16 adsorption was endothermic process. - Abstract: The performance of polyaniline/extracellular polymeric substances (Pn/EPS) composite as an adsorbent to remove the anionic reactive dyes, Reactive Brilliant Blue R (RBBR) and Reactive Orange 16 (RO), was investigated in single and binary systems. The pH{sub pzc} of Pn/EPS composite was calculated as 3.7 through potentiometric mass titration method. Electrostatic interaction between the dye anion and the nitrogen present in the polymer was identified as a major mechanism in adsorption process. Single component isotherms followed the Langmuir model with the maximum adsorption capacity of 0.5775 mmol g{sup -1} for RBBR and 0.4748 mmol g{sup -1} for RO. In binary system, both the reactive dye anions compete with each other and resulted in lower uptake. Binary adsorption data were interpreted well by the Sheindorf-Rehbun-Sheintuch equation as compared to extended Langmuir model with constant interaction factor. Kinetic analysis of single solute followed pseudo-first order model. Thermodynamic studies computed that RBBR and RO adsorption was endothermic, spontaneous, and feasible process.

Entirely Carbohydrate-Based Vaccines: An Emerging Field for Specific and Selective Immune Responses

Directory of Open Access Journals (Sweden)

Sharmeen Nishat

2016-05-01

Full Text Available Carbohydrates are regarded as promising targets for vaccine development against infectious disease because cell surface glycans on many infectious agents are attributed to playing an important role in pathogenesis. In addition, oncogenic transformation of normal cells, in many cases, is associated with aberrant glycosylation of the cell surface glycan generating tumor associated carbohydrate antigens (TACAs. Technological advances in glycobiology have added a new dimension to immunotherapy when considering carbohydrates as key targets in developing safe and effective vaccines to combat cancer, bacterial infections, viral infections, etc. Many consider effective vaccines induce T-cell dependent immunity with satisfactory levels of immunological memory that preclude recurrence. Unfortunately, carbohydrates alone are poorly immunogenic as they do not bind strongly to the MHCII complex and thus fail to elicit T-cell immunity. To increase immunogenicity, carbohydrates have been conjugated to carrier proteins, which sometimes can impede carbohydrate specific immunity as peptide-based immune responses can negate antibodies directed at the targeted carbohydrate antigens. To overcome many challenges in using carbohydrate-based vaccine design and development approaches targeting cancer and other diseases, zwitterionic polysaccharides (ZPSs, isolated from the capsule of commensal anaerobic bacteria, will be discussed as promising carriers of carbohydrate antigens to achieve desired immunological responses.

Structure of the polysaccharides from the lipopolysaccharide of Azospirillum brasilense Jm125A2.

Science.gov (United States)

Sigida, Elena N; Fedonenko, Yuliya P; Shashkov, Alexander S; Zdorovenko, Evelina L; Konnova, Svetlana A; Ignatov, Vladimir V; Knirel, Yuriy A

2015-10-30

Two polysaccharides were obtained by mild acid degradation of the lipopolysaccharide of associative nitrogen-fixing bacteria Azospirillum brasilense Jm125A2 isolated from the rhizosphere of a pearl millet. The following structures of the polysaccharides were established by sugar and methylation analyses, Smith degradation, and (1)H and (13)C NMR spectroscopy: [Formula: see text] Structure 1 has been reported earlier for a polysaccharide from A. brasilense S17 (Fedonenko YP, Konnova ON, Zdorovenko EL, Konnova SA, Zatonsky GV, Shaskov AS, Ignatov VV, Knirel YA. Carbohydr Res 2008;343:810-6), whereas to our knowledge structure 2 has not been hitherto found in bacterial polysaccharides. Copyright © 2015 Elsevier Ltd. All rights reserved.

Immunity induced shortly after DNA vaccination of rainbow trout against rhabdoviruses protects against heterologous virus but not against bacterial pathogens

DEFF Research Database (Denmark)

Lorenzen, Niels; Lorenzen, Ellen; Einer-Jensen, Katja

2002-01-01

whereas no increased survival was found upon challenge with bacterial pathogens. Within two months after vaccination, the cross-protection disappeared while the specific immunity to homologous virus remained high. The early immunity induced by the DNA vaccines thus appeared to involve short-lived non......It was recently reported that DNA vaccination of rainbow trout fingerlings against viral hemorrhagic septicaemia virus (VHSV) induced protection within 8 days after intramuscular injection of plasmid DNA. In order to analyse the specificity of this early immunity, fish were vaccinated with plasmid...... DNA encoding the VHSV or the infectious haematopoietic necrosis virus (IHNV) glycoprotein genes and later challenged with homologous or heterologous pathogens. Challenge experiments revealed that immunity established shortly after vaccination was cross-protective between the two viral pathogens...

Effectiveness, immunogenicity and safety of 23-valent pneumococcal polysaccharide vaccine revaccinations in the elderly: a systematic review

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Cornelius Remschmidt

2016-11-01

Full Text Available Abstract Background In many industrialized countries routine vaccination with the 23-valent pneumococcal polysaccharide vaccine (PPSV-23 is recommended to prevent pneumococcal disease in the elderly. However, vaccine-induced immunity wanes after a few years, and there are controversies around revaccination with PPSV-23. Here, we systematically assessed the effectiveness and safety of PPSV-23 revaccination. Method We conducted a systematic literature review in MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials from inception to June 2015. We included all study types that compared effectiveness, immunogenicity and/or safety of PPSV-23 as a primary vs. a revaccination dose in persons aged 50 years and older. With respect to immunogenicity, we calculated the ratio of geometric mean antibody concentrations and opsonophagocytic indexes at identical time-points after primary and revaccination. Additionally, we compared rates and severity of adverse events (AEs after primary and revaccination. Results We included 14 observational studies. 10 studies had a prospective design and analysed data on (i the same individuals after a first and a second dose of PPSV-23 given 1 to 10 years later (n = 5 or (ii two groups consisting of participants receiving PPSV-23 who were either vaccine-naïve or had received a first PPSV-23 dose 3 to 13 years earlier (n = 5. Three studies used electronic data bases to compare AEs after primary vs. revaccination doses of PPSV-23 after 1 to 10 years and one study had a cross-sectional design. Number of participants in the non-register-based and register-based studies ranged from 29 to 1414 and 360 to 316,000, respectively. 11 out of 14 included studies were at high risk of bias, three studies had an unclear risk of bias. None of the studies reported data on clinical effectiveness. Immunogenicity studies revealed that during the first two months antibody levels tended to be lower after revaccination as compared to

[Bacterial etiology of acute otitis media in Spain in the post-pneumococcal conjugate vaccine era].

Science.gov (United States)

Pumarola, Felix; Salamanca de la Cueva, Ignacio; Sistiaga-Hernando, Alessandra; García-Corbeira, Pilar; Moraga-Llop, Fernando A; Cardelús, Sara; McCoig, Cynthia; Gómez Martínez, Justo Ramón; Rosell Ferrer, Rosa; Iniesta Turpin, Jesús; Devadiga, Raghavendra

2016-11-01

Acute otitis media (AOM) is common in children aged <3 years. A pneumococcal conjugate vaccine (PCV) (PCV7; Prevenar, Pfizer/Wyeth, USA) has been available in Spain since 2001, which has a coverage rate of 50-60% in children aged <5 years. Children aged ≥3 to 36 months with AOM confirmed by an ear-nose-throat specialist were enrolled at seven centers in Spain (February 2009-May 2012) (GSK study identifier: 111425). Middle-ear-fluid samples were collected by tympanocentesis or spontaneous otorrhea and cultured for bacterial identification. Culture-negative samples were further analyzed using polymerase chain reaction (PCR). Of 125 confirmed AOM episodes in 124 children, 117 were analyzed (median age: 17 months (range: 3-35); eight AOM episodes were excluded from analyses. Overall, 69% (81/117) episodes were combined culture- and PCR-positive for ≥1 bacterial pathogen; 44% (52/117) and 39% (46/117) were positive for Haemophilus influenzae (Hi) and Streptococcus pneumoniae (Spn), respectively. 77 of 117 episodes were cultured for ≥1 bacteria, of which 63 were culture-positive; most commonly Spn (24/77; 31%) and Hi (32/77; 42%). PCR on culture-negative episodes identified 48% Hi- and 55% Spn-positive episodes. The most common Spn serotype was 19F (4/24; 17%) followed by 19A (3/24; 13%); all Hi-positive episodes were non-typeable (NTHi). 81/117 AOM episodes (69%) occurred in children who had received ≥1 pneumococcal vaccine dose. NTHi and Spn were the main etiological agents for AOM in Spain. Impact of pneumococcal vaccination on AOM requires further evaluation in Spain, after higher vaccination coverage rate is reached. Copyright © 2015 Asociación Española de Pediatría. Publicado por Elsevier España, S.L.U. All rights reserved.

Structure and genetics of the O-specific polysaccharide of Escherichia coli O27.

Science.gov (United States)

Perepelov, Andrei V; Chen, Tingting; Senchenkova, Sofya N; Filatov, Andrei V; Song, Jingjie; Shashkov, Alexander S; Liu, Bin; Knirel, Yuriy A

2018-02-01

The O-specific polysaccharide (O-antigen) is a part of the lipopolysaccharide on the cell surface of Gram-negative bacteria. The O-polysaccharide was obtained by mild acid hydrolysis of the lipopolysaccharide of Escherichia coli O27 and studied by sugar analysis and Smith degradation along with 1 H and 13 C NMR spectroscopy. The following structure of the branched hexasaccharide repeating unit was established, which is unique among known structures of bacterial polysaccharides:where GlcA is non-stoichiometrically O-acetylated at position 3 (∼22%) or 4 (∼37%). Functions of genes in the O-antigen gene cluster of E. coli O27 were tentatively assigned by comparison with sequences in the available databases and found to be consistent with the O-polysaccharide structure. Copyright © 2017 Elsevier Ltd. All rights reserved.

Vaccines against invasive Salmonella disease

Science.gov (United States)

MacLennan, Calman A; Martin, Laura B; Micoli, Francesca

2014-01-01

Though primarily enteric pathogens, Salmonellae are responsible for a considerable yet under-appreciated global burden of invasive disease. In South and South-East Asia, this manifests as enteric fever caused by serovars Typhi and Paratyphi A. In sub-Saharan Africa, a similar disease burden results from invasive nontyphoidal Salmonellae, principally serovars Typhimurium and Enteritidis. The existing Ty21a live-attenuated and Vi capsular polysaccharide vaccines target S. Typhi and are not effective in young children where the burden of invasive Salmonella disease is highest. After years of lack of investment in new Salmonella vaccines, recent times have seen increased interest in the area led by emerging-market manufacturers, global health vaccine institutes and academic partners. New glycoconjugate vaccines against S. Typhi are becoming available with similar vaccines against other invasive serovars in development. With other new vaccines under investigation, including live-attenuated, protein-based and GMMA vaccines, now is an exciting time for the Salmonella vaccine field. PMID:24804797

Effect of different adjuvant formulations on the immunogenicity and protective effect of a live Mycoplasma hyopneumoniae vaccine after intramuscular inoculation.

Science.gov (United States)

Xiong, Qiyan; Wei, Yanna; Xie, Haidong; Feng, Zhixin; Gan, Yuan; Wang, Chunlai; Liu, Maojun; Bai, Fangfang; Xie, Fang; Shao, Guoqing

2014-06-05

Mycoplasma hyopneumoniae (M. hyopneumoniae) vaccine strain 168 is an intrapulmonically injected attenuated live vaccine that is available in the Chinese market. The aim of this study was to develop suitable adjuvants for this live vaccine to provide effective protection after intramuscular inoculation. Several adjuvant components were screened to assess their toxicity for the live vaccine, and various adjuvant formulations were then designed and prepared. Vaccines supplemented with these adjuvants were used to immunize mice intramuscularly to assess the capacity of the adjuvants to induce a specific immune response. The screened formulations were then evaluated in pigs. Seven of the eight adjuvant components did not affect the viability of the live vaccine, and seven different adjuvant formulations were then designed. In mice, the ISCOM-matrix adjuvant and the levamisole-chitosan mixture adjuvant significantly enhanced serum IgG responses against M. hyopneumoniae, while lymphocyte proliferation was enhanced by the ISCOM-matrix adjuvant, the carbomer-astragalus polysaccharide mixture adjuvant and an oil-in-water emulsion adjuvant. These four adjuvants were evaluated in pigs. Enhancement of specific lymphocyte proliferation responses was observed in the groups vaccinated with the ISCOM-matrix adjuvant and the carbomer-astragalus polysaccharide mixture adjuvant. Significant enhancement of serum IgG antibody production was observed before challenge in pigs vaccinated with the carbomer-astragalus polysaccharide mixture adjuvant and the levamisole-chitosan mixture adjuvant, while after challenge, all of the animals that received vaccines containing adjuvants had higher antibody concentrations against M. hyopneumoniae than unvaccinated animals. Animals inoculated with a vaccine containing the ISCOM-matrix adjuvant (median score 3.57) or the carbomer-astragalus polysaccharide mixture adjuvant (median score 5.28) had reduced lesion scores compared to unvaccinated animals

Unliganded and substrate bound structures of the cellooligosaccharide active lytic polysaccharide monooxygenase LsAA9A at low pH

DEFF Research Database (Denmark)

Frandsen, Kristian Erik Høpfner; Poulsen, Jens-Christian Navarro; Tandrup, Tobias

2017-01-01

Lytic polysaccharide monooxygenases (LPMOs) have been found to be key components in microbial (bacterial and fungal) degradation of biomass. They are copper metalloenzymes that degrade polysaccharides oxidatively and act in synergy with glycoside hydrolases. Recently crystallographic studies...

Genetic analysis of the capsular biosynthetic locus from all 90 pneumococcal serotypes.

Directory of Open Access Journals (Sweden)

Stephen D Bentley

2006-03-01

Full Text Available Several major invasive bacterial pathogens are encapsulated. Expression of a polysaccharide capsule is essential for survival in the blood, and thus for virulence, but also is a target for host antibodies and the basis for effective vaccines. Encapsulated species typically exhibit antigenic variation and express one of a number of immunochemically distinct capsular polysaccharides that define serotypes. We provide the sequences of the capsular biosynthetic genes of all 90 serotypes of Streptococcus pneumoniae and relate these to the known polysaccharide structures and patterns of immunological reactivity of typing sera, thereby providing the most complete understanding of the genetics and origins of bacterial polysaccharide diversity, laying the foundations for molecular serotyping. This is the first time, to our knowledge, that a complete repertoire of capsular biosynthetic genes has been available, enabling a holistic analysis of a bacterial polysaccharide biosynthesis system. Remarkably, the total size of alternative coding DNA at this one locus exceeds 1.8 Mbp, almost equivalent to the entire S. pneumoniae chromosomal complement.

Recurrent Invasive Pneumococcal Disease Serotype 12F in a Vaccinated Splenectomized Patient

DEFF Research Database (Denmark)

Blaabjerg, Anne Katrine; Schumacher, Anna Holst; Kantsø, Bjørn

2016-01-01

This is the first case report of recurrent invasive pneumococcal disease (IPD), specifically, due to serotype 12F. The patient described here was vaccinated with the 23-valent pneumococcal polysaccharide vaccine (PPV23) due to previous splenectomy, and an anti-pneumococcal IgG test concluded...

Towards biocompatible vaccine delivery systems: interactions of colloidal PECs based on polysaccharides with HIV-1 p24 antigen.

Science.gov (United States)

Drogoz, Alexandre; Munier, Séverine; Verrier, Bernard; David, Laurent; Domard, Alain; Delair, Thierry

2008-02-01

This work reports on the interactions of a model protein (p24, the capside protein of HIV-1 virus) with colloids obtained from polyelectrolyte complexes (PECs) involving two polysaccharides: chitosan and dextran sulfate (DS). The PECs were elaborated by a one-shot addition of default amounts of one counterpart to the polymer in excess. Depending on the nature of the excess polyelectrolyte, the submicrometric colloid was either positively or negatively charged. HIV-1 capsid p24 protein was chosen as antigen, the ultrapure form, lipopolysaccharide-free (endotoxin-, vaccine grade) was used in most experiments, as the level of purity of the protein had a great impact on the immobilization process. p24 sorption kinetics, isotherms, and loading capacities were investigated for positively and negatively charged particles of chitosans and dextran sulfates differing in degrees of polymerization (DP) or acetylation (DA). Compared with the positive particles, negatively charged colloids had higher binding capacities, faster kinetics, and a better stability of the adsorbed p24. Capacities up to 600 mg x g(-1) (protein-colloid) were obtained, suggesting that the protein interacted within the shell of the particles. Small-angle X-rays scattering experiments confirmed this hypothesis. Finally, the immunogenicity of the p24-covered particles was assessed for vaccine purposes in mice. The antibody titers obtained with immobilized p24 was dose dependent and in the same range as for Freund's adjuvant, a gold standard for humoral responses.

Synthesis and immunological evaluation of protein conjugates of Neisseria meningitidis X capsular polysaccharide fragments

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Laura Morelli

2014-10-01

Full Text Available A vaccine to prevent infections from the emerging Neisseria meningitidis X (MenX is becoming an urgent issue. Recently MenX capsular polysaccharide (CPS fragments conjugated to CRM197 as carrier protein have been confirmed at preclinical stage as promising candidates for vaccine development. However, more insights about the minimal epitope required for the immunological activity of MenX CPS are needed. We report herein the chemical conjugation of fully synthetic MenX CPS oligomers (monomer, dimer, and trimer to CRM197. Moreover, improvements in some crucial steps leading to the synthesis of MenX CPS fragments are described. Following immunization with the obtained neoglycoconjugates, the conjugated trimer was demonstrated as the minimal fragment possessing immunogenic activity, even though significantly lower than a pentadecamer obtained from the native polymer and conjugated to the same protein. This finding suggests that oligomers longer than three repeating units are possibly needed to mimic the activity of the native polysaccharide.

Meningococcal polysaccharide A O-acetylation levels do not impact the immunogenicity of the quadrivalent meningococcal tetanus toxoid conjugate vaccine: results from a randomized, controlled phase III study of healthy adults aged 18 to 25 years.

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Lupisan, Socorro; Limkittikul, Kriengsak; Sosa, Nestor; Chanthavanich, Pornthep; Bianco, Véronique; Baine, Yaela; Van der Wielen, Marie; Miller, Jacqueline M

2013-10-01

In this study, we compared the immunogenicities of two lots of meningococcal ACWY-tetanus toxoid conjugate vaccine (MenACWY-TT) that differed in serogroup A polysaccharide (PS) O-acetylation levels and evaluated their immunogenicities and safety in comparison to a licensed ACWY polysaccharide vaccine (Men-PS). In this phase III, partially blinded, controlled study, 1,170 healthy subjects aged 18 to 25 years were randomized (1:1:1) to receive one dose of MenACWY-TT lot A (ACWY-A) (68% O-acetylation), MenACWY-TT lot B (ACWY-B) (92% O-acetylation), or Men-PS (82% O-acetylation). Immunogenicity was evaluated in terms of serum bactericidal activity using rabbit complement (i.e., rabbit serum bactericidal activity [rSBA]). Solicited symptoms, unsolicited adverse events (AEs), and serious AEs (SAEs) were recorded. The immunogenicities, in terms of rSBA geometric mean titers, were comparable for both lots of MenACWY-TT. The vaccine response rates across the serogroups were 79.1 to 97.0% in the two ACWY groups and 73.7 to 94.1% in the Men-PS group. All subjects achieved rSBA titers of ≥1:8 for all serogroups. All subjects in the two ACWY groups and 99.5 to 100% in the Men-PS group achieved rSBA titers of ≥1:128. Pain was the most common solicited local symptom and was reported more frequently in the ACWY group (53.9 to 54.7%) than in the Men-PS group (36.8%). The most common solicited general symptoms were fatigue and headache, which were reported by 28.6 to 30.3% and 26.9 to 31.0% of subjects, respectively. Two subjects reported SAEs; one SAE was considered to be related to vaccination (blighted ovum; ACWY-B group). The level of serogroup A PS O-acetylation did not affect vaccine immunogenicity. MenACWY-TT (lot A) was not inferior to Men-PS in terms of vaccine response and was well tolerated.

Vaccine development: From concept to early clinical testing.

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Cunningham, Anthony L; Garçon, Nathalie; Leo, Oberdan; Friedland, Leonard R; Strugnell, Richard; Laupèze, Béatrice; Doherty, Mark; Stern, Peter

2016-12-20

In the 21st century, an array of microbiological and molecular allow antigens for new vaccines to be specifically identified, designed, produced and delivered with the aim of optimising the induction of a protective immune response against a well-defined immunogen. New knowledge about the functioning of the immune system and host pathogen interactions has stimulated the rational design of vaccines. The design toolbox includes vaccines made from whole pathogens, protein subunits, polysaccharides, pathogen-like particles, use of viral/bacterial vectors, plus adjuvants and conjugation technology to increase and broaden the immune response. Processes such as recombinant DNA technology can simplify the complexity of manufacturing and facilitate consistent production of large quantities of antigen. Any new vaccine development is greatly enhanced by, and requires integration of information concerning: 1. Pathogen life-cycle & epidemiology. Knowledge of pathogen structure, route of entry, interaction with cellular receptors, subsequent replication sites and disease-causing mechanisms are all important to identify antigens suitable for disease prevention. The demographics of infection, specific risk groups and age-specific infection rates determine which population to immunise, and at what age. 2. Immune control & escape. Interactions between the host and pathogen are explored, with determination of the relative importance of antibodies, T-cells of different types and innate immunity, immune escape strategies during infection, and possible immune correlates of protection. This information guides identification and selection of antigen and the specific immune response required for protection. 3. Antigen selection & vaccine formulation. The selected antigen is formulated to remain suitably immunogenic and stable over time, induce an immune response that is likely to be protective, plus be amenable to eventual scale-up to commercial production. 4. Vaccine preclinical

Plasma and memory B-cell kinetics in infants following a primary schedule of CRM 197-conjugated serogroup C meningococcal polysaccharide vaccine.

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Kelly, Dominic F; Snape, Matthew D; Perrett, Kirsten P; Clutterbuck, Elizabeth A; Lewis, Susan; Blanchard Rohner, Geraldine; Jones, Meryl; Yu, Ly-Mee; Pollard, Andrew J

2009-05-01

The induction of persistent protective levels of pathogen-specific antibody is an important goal of immunization against childhood infections. However, antibody persistence is poor after immunization in infancy versus later in life. Serogroup C meningococci (MenC) are an important cause of bacteraemia and meningitis in children. The use of protein-polysaccharide conjugate vaccines against MenC has been associated with a significant decline in the incidence of invasive disease. However, vaccine effectiveness is negligible by more than 1 year after a three-dose priming series in infancy and corresponds to a rapid decline in antibody following an initial immune response. The cellular mechanisms underlying the generation of persistent antibody in this age group are unclear. An essential prelude to larger studies of peripheral blood B cells is an understanding of B-cell kinetics following immunization. We measured MenC- and diphtheria-specific plasma and memory B-cell kinetics in infants receiving a CRM(197) (cross-reactive material; mutant diphtheria toxoid)-conjugated MenC vaccine at 2, 3 and 4 months of age. Plasma cell responses were more delayed after the first dose when compared with the rapid appearance of plasma cells after the third dose. Memory B cells were detectable at all time-points following the third dose as opposed to the low frequency seen following a first dose. This study provides data on B-cell kinetics following a primary schedule of immunization in young infants upon which to base further studies of the underlying cellular mechanism of humoral immunity.

Effects of selenylation modification on immune-enhancing activity of garlic polysaccharide.

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Shulei Qiu

Full Text Available The garlic polysaccharide was modified by HNO3-Na2SeO3 method according to orthogonal design L9(3(4 to obtain nine selenizing garlic polysaccharides, sGPS1-sGPS9. Their effects on chicken peripheral lymphocytes proliferation in vitro were compared by MTT assay. The results showed that sGPSs could significantly promote lymphocytes proliferation, sGPS3, sGPS5 and sGPS6 presented stronger efficacy. In vivo experiment, 14-day-old chickens were injected respectively with sGPS3, sGPS5 and sGPS6 when they were vaccinated with ND vaccine taking unmodified GPS as control. The results showed that three sGPSs could significantly promote lymphocyte proliferation, enhance serum antibody titer, IFN-γ and IL-2 contents. These results indicated that selenylation modification could significantly enhance the immune-enhancing activity of GPS, sGPS6 possessed the best efficacy and could be as a candidate drug of immunoenhancer. Its optimal modification conditions were 400 mg of sodium selenite for 500 mg of GPS, reaction temperature of 70°C and reaction time of 6 h.

Structural studies of the polysaccharides from the lipopolysaccharides of Azospirillum brasilense Sp246 and SpBr14.

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Sigida, Elena N; Fedonenko, Yuliya P; Shashkov, Alexander S; Grinev, Vyacheslav S; Zdorovenko, Evelina L; Konnova, Svetlana A; Ignatov, Vladimir V; Knirel, Yuriy A

2014-10-29

Lipopolysaccharides from closely related Azospirillum brasilense strains, Sp246 and SpBr14, were obtained by phenol-water extraction. Mild acid hydrolysis of the lipopolysaccharides followed by GPC on Sephadex G-50 resulted in polysaccharide mixtures. On the basis of sugar and methylation analyses, Smith degradation and (1)H and (13)C NMR spectroscopy data, it was concluded that both bacteria possess the same two distinct polysaccharides having structures 1 and 2: [structure: see text]. Structure 1 has been reported earlier for a polysaccharide of A. brasilense 54 [Fedonenko et al., 2011] whereas to our knowledge structure 2 has not been hitherto found in bacterial polysaccharides. Copyright © 2014 Elsevier Ltd. All rights reserved.

Construction of a full-length infectious bacterial artificial chromosome clone of duck enteritis virus vaccine strain

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2013-01-01

Background Duck enteritis virus (DEV) is the causative agent of duck viral enteritis, which causes an acute, contagious and lethal disease of many species of waterfowl within the order Anseriformes. In recent years, two laboratories have reported on the successful construction of DEV infectious clones in viral vectors to express exogenous genes. The clones obtained were either created with deletion of viral genes and based on highly virulent strains or were constructed using a traditional overlapping fosmid DNA system. Here, we report the construction of a full-length infectious clone of DEV vaccine strain that was cloned into a bacterial artificial chromosome (BAC). Methods A mini-F vector as a BAC that allows the maintenance of large circular DNA in E. coli was introduced into the intergenic region between UL15B and UL18 of a DEV vaccine strain by homologous recombination in chicken embryoblasts (CEFs). Then, the full-length DEV clone pDEV-vac was obtained by electroporating circular viral replication intermediates containing the mini-F sequence into E. coli DH10B and identified by enzyme digestion and sequencing. The infectivity of the pDEV-vac was validated by DEV reconstitution from CEFs transfected with pDEV-vac. The reconstructed virus without mini-F vector sequence was also rescued by co-transfecting the Cre recombinase expression plasmid pCAGGS-NLS/Cre and pDEV-vac into CEF cultures. Finally, the in vitro growth properties and immunoprotection capacity in ducks of the reconstructed viruses were also determined and compared with the parental virus. Results The full genome of the DEV vaccine strain was successfully cloned into the BAC, and this BAC clone was infectious. The in vitro growth properties of these reconstructions were very similar to parental DEV, and ducks immunized with these viruses acquired protection against virulent DEV challenge. Conclusions DEV vaccine virus was cloned as an infectious bacterial artificial chromosome maintaining full

Non-epitope-specific suppression of the antibody response to Haemophilus influenzae type b conjugate vaccines by preimmunization with vaccine components

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Barington, T; Skettrup, M; Juul, L

1993-01-01

children and adults. Despite its potential importance, the possible influence of preexisting immunity to the components of such conjugates on the vaccination response in humans has been addressed by few studies. To study this issue, we randomized 82 healthy adult volunteers into six groups and vaccinated......Recently, conjugate vaccines containing Haemophilus influenzae type b capsular polysaccharide (HibCP) coupled to protein carriers were introduced for use in infants and certain adult risk groups. Similar conjugate vaccines against other capsulated bacteria are currently under development for both......CP-TT, P = 0.00002; HibCP-TT and then HibCP-DT, P = 0.06) as well as to HibCP itself. Possible mechanisms behind this non-epitope-specific suppression and its relevance for vaccine development are discussed....

Epstein-Barr virus but not cytomegalovirus is associated with reduced vaccine antibody responses in Gambian infants.

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Beth Holder

2010-11-01

Full Text Available Epstein-Barr virus (EBV and cytomegalovirus (CMV are persistent herpesviruses that have various immunomodulatory effects on their hosts. Both viruses are usually acquired in infancy in Sub-Saharan Africa, a region where childhood vaccines are less effective than in high income settings. To establish whether there is an association between these two observations, we tested the hypothesis that infection with one or both viruses modulate antibody responses to the T-cell independent meningococcal polysaccharide vaccine and the T-cell dependent measles vaccines.Infection with EBV and CMV was diagnosed by the presence of virus-specific IgM in the peripheral blood or by the presence of IgG at higher levels than that found in umbilical cord blood. Anti-meningococcus IgG and IgM were quantified by ELISA. Anti-measles antibody responses were quantified by haemagglutinin antibody inhibition assay. Infants infected with EBV had reduced IgG and IgM antibody responses to meningococcal polysaccharides and to measles vaccine. Infection with CMV alone predicted no changes in the response to meningococcal polysaccharide. While CMV alone had no discernable effect on the antibody response to measles, the response of infants infected with both CMV and EBV was similar to that of infants infected with neither, suggesting that the effects of CMV infection countered the effects of EBV on measles antibody responses.The results of this exploratory study indicate that infection with EBV is associated with reduced antibody responses to polysaccharides and to measles vaccine, but suggest that the response to T-cell dependent antigens such as measles haemagglutinin may be restored by infection with CMV.

Vaccine manufacturing and technology: from biotechnological platforms to syntethic epitopes, current viepoint.

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Ignateva, G A

2016-01-01

The Purposes: the review take into account short history of vaccination practice and development of vaccine technology. In the review we include data from several monographs about manufacturing of vaccines published by authors from such companies as Merck & Co; Sanofi Pasteur; Dynavax Europe/Rhein Biotech GmbH; Latham Biopharm Group; Aridis Pharmaceuticals LLC; Genentech; Amgen; Shamir Biologics LLC; Biopharm Services US; Novartis Pharma AG, аnd several research centers: Laboratory of Bacterial Polysaccharides, Center for Biologics Evaluation and Research; Purdue University, West Lafayette, IN, US; Department of Pharmaceutical Chemistry, Univ. Of Kansas; Max Planck Institute for dynamics of Complex Technical Systems; Fraunhofer USA Center for Molecular Biotechnology; US Dep. of Agriculture Animal and Plant Health Inspection Service, etc. In historic literature there are data about inoculation practices in antique China, Persia, India, Byzantium, native Americans, some African population. In modern immunology since the end of XIX century the vaccines were produced at the in vivo platforms - in animals (rabbits, mice, cows). Since 1931 due to E. Goodpasture' elaboration most virus vaccines were and are produced at the in ovo platform. In 1949 J.F. Enders elaborated large-scale polio virus production in the primary culture of monkey kidney cells in vitro. Up to day primary culture of chiken embrio fibroblasts are used to large-scale production of vaccine viruses of measles, mumps, rabies. Since 2000-th in Western countries most part of virus vaccines were began to produced via a cultivation in continuous tumor cell lines. The last technology is the most low cost for large-scale production of vaccines. We review several new biotechnological platforms for the production of the recombinant protein or virus-like particles as subunit vaccines: plant system, algae, mushrooms, insect cells, etc. Beside of good purpose of vaccination - prophylactic of several infectious

Advax™, a novel microcrystalline polysaccharide particle engineered from delta inulin, provides robust adjuvant potency together with tolerability and safety.

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Petrovsky, Nikolai; Cooper, Peter D

2015-11-04

There is an ongoing need for new adjuvants to facilitate development of vaccines against HIV, tuberculosis, malaria and cancer, amongst many others. Unfortunately, the most potent adjuvants are often associated with toxicity and safety issues. Inulin, a plant-derived polysaccharide, has no immunological activity in its native soluble form but when crystallized into a stable microcrystalline particulate from (delta inulin) acquires potent adjuvant activity. Delta inulin has been shown to enhance humoral and cellular immune responses against a broad range of co-administered viral, bacterial, parasitic and toxin antigens. Inulin normally crystallizes as large heterogeneous particles with a broad size distribution and variable solubility temperatures. To ensure reproducible delta inulin particles with a consistent size distribution and temperature of solubility, a current Good Manufacturing Practice (cGMP) process was designed to produce Advax™ adjuvant. In its cCMP form, Advax™ adjuvant has proved successful in human trials of vaccines against seasonal and pandemic influenza, hepatitis B and insect sting anaphylaxis, enhancing antibody and T-cell responses while being safe and well tolerated. Advax™ adjuvant represents a novel human adjuvant that enhances both humoral and cellular immunity. This review describes the discovery and development of Advax™ adjuvant and research into its unique mechanism of action. Copyright © 2015 Elsevier Ltd. All rights reserved.

Safety and immunogenicity of meningococcal ACWY CRM197-conjugate vaccine in children, adolescents and adults in Russia.

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Ilyina, Natalia; Kharit, Susanna; Namazova-Baranova, Leila; Asatryan, Asmik; Benashvili, Mayya; Tkhostova, Elmira; Bhusal, Chiranjiwi; Arora, Ashwani Kumar

2014-01-01

Neisseria meningitidis is the leading cause of bacterial invasive infections in people aged safety of the quadrivalent meningococcal CRM197-conjugate vaccine MenACWY when administered to healthy Russian subjects aged 2 years and above. A total of 197 subjects were immunized with a single dose of the vaccine, and serogroup-specific serum bactericidal activity was measured pre and 1-month post-vaccination with human complement (hSBA) serum titers. Regardless of baseline serostatus, 1 month after a single dose of MenACWY-CRM197 85% (95%CI, 79-90%) of subjects showed serologic response against serogroup A, 74% (67-80%) against serogroup C, 60% (53-67%) against serogroup W, and 83% (77-88%) against serogroup Y. The percentage of subjects with hSBA titers ≥ 1:8 1 month after vaccination was 89% (83-93%) against serogroup A, 84% (78-89%) against serogroup C, 97% (93-99%) against serogroup W, and 88% (82-92%) against serogroup Y. Comparable results were obtained across all subjects: children (2 to 10 years), adolescents (11 to 17 years), and adults (≥18 years). The MenACWY-CRM197 vaccine showed an acceptable safety profile and was well tolerated across all age groups, with no serious adverse events or deaths reported during the study. In conclusion, a single dose of meningococcal MenACWY-CRM197 vaccine is immunogenic and has an acceptable safety profile, provides a broad protection against the most frequent epidemic serogroups, and is a suitable alternative to currently available unconjugated monovalent or bivalent polysaccharide vaccines in Russia.

CLINICAL AND IMMUNOLOGICAL EFFECT OF PNEUMOCOCCAL CONJUGATED VACCINES IN IMMUNOCOMPROMISED PATIENTS

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A.A. Tarasova

2010-01-01

Full Text Available Invasive pneumococcal infection is the most frequent cause of death in patients with immunodeficiences. The antibiotics used previously for prevention purposes are not efficient enough due to the developing antibiotic resistance. Polysaccharide pneumococcal vaccines create short-lived immunity. The overview summarizes the experience of applying conjugated pneumococcal vaccines in patients with primary immunodeficiences, HIV infection, oncological and rheumatic diseases. Key words: pneumococcal infection, pneumococcal conjugated vaccines, children, immunosuppression. (Pediatric Pharmacology. – 2010; 7(5:18-23

Antibody response to Haemophilus influenzae type b capsular polysaccharide conjugated to tetanus toxoid in preterm infants

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Kristensen, Kim; Gyhrs, A; Lausen, B

1996-01-01

OBJECTIVE: To evaluate the antibody response to a Haemophilus influenzae type b capsular polysaccharide (HibCP) tetanus toxoid (TT) conjugate vaccine (HibCP-TT) in preterm infants. SUBJECTS: Thirty-five healthy preterm infants with gestational ages (GA) from 27 to 36 weeks and birth weights from...

Bacterial Protein Characterization of Streptococcus agalactiae by SDS-page Method for Subclinical Mastitis Irradiated Vaccine Materials in Dairy Cattle

International Nuclear Information System (INIS)

Tuasikal, B.J.; Wibawan, I.W.T.; Pasaribu, F.H; Estuningsih, S.

2012-01-01

A study have been conducted to isolate and characterize bacterial protein S. agalactiae, which is antigenic and can be used to test immunogenicity of vaccine in order to manufacture irradiated mastitis (inflammation of the udder) vaccine in ruminant. The study aims to determine the Molecular Weight (MW) bacterial protein S. agalactiae irradiation, which can be used to test the nature of its antigenic caharacteristic. The character of S. agalactiae antigenic stimulates antibody induction of the immune system, in which case is the body's defense system against mastitis disease in cattle. In this study, irradiation of gamma ray is used to attenuate the pathogenicity of bacteria by reducing S. agalactiae antigenic characteristic. Previous research, in irradiation dose orientation before antigenic protein isolation of S. agalactiae, indicated that irradiation lethal dose to 50% (LD 50 ) is 17 Gy. The characterization of S. agalactiae bacteria isolate using SDS-page method results in no significance different between irradiated and non-irradiated group, which indicated by MW range 75 - 100 kDa base on marker standard which used, or 99 kDa by the linier equation of Y = 11,60 - 0.05X (where Y = bands distance; X = MW standard protein); r 2 = 0.99. In conclusion, 17 Gy irradiation dose does not impair antigenic property of S. agalactiae and therefore, can be applied to produce base material of irradiated vaccine for mastitis. (author)

Structural determination of Streptococcus pneumoniae repeat units in serotype 41A and 41F capsular polysaccharides to probe gene functions in the corresponding capsular biosynthetic loci

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Petersen, Bent O.; Skovsted, Ian C.; Paulsen, Berit Smestad

2014-01-01

(1) by anambitionto help close the remaining gaps in S. pneumoniaecapsular polysaccharide structures, and (2)by the attempt to derive functional annotationsof carbohydrate active enzymes in the biosynthesis of bacterial polysaccharides from the determined structures. Anactivitypresent in 41F...

Safety, immunogenicity and dose ranging of a new Vi-CRM₁₉₇ conjugate vaccine against typhoid fever: randomized clinical testing in healthy adults.

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van Damme, Pierre; Kafeja, Froukje; Anemona, Alessandra; Basile, Venere; Hilbert, Anne Katrin; De Coster, Ilse; Rondini, Simona; Micoli, Francesca; Qasim Khan, Rana M; Marchetti, Elisa; Di Cioccio, Vito; Saul, Allan; Martin, Laura B; Podda, Audino

2011-01-01

Typhoid fever causes more than 21 million cases of disease and 200,000 deaths yearly worldwide, with more than 90% of the disease burden being reported from Asia. Epidemiological data show high disease incidence in young children and suggest that immunization programs should target children below two years of age: this is not possible with available vaccines. The Novartis Vaccines Institute for Global Health developed a conjugate vaccine (Vi-CRM₁₉₇) for infant vaccination concomitantly with EPI vaccines, either starting at 6 weeks with DTP or at 9 months with measles vaccine. We report the results from a Phase 1 and a Phase 2 dose ranging trial with Vi-CRM₁₉₇ in European adults. Following randomized blinded comparison of single vaccination with either Vi-CRM₁₉₇ or licensed polysaccharide vaccines (both containing 25·0 µg of Vi antigen), a randomised observer blinded dose ranging trial was performed in the same center to compare three concentrations of Vi-CRM₁₉₇ (1·25 µg, 5·0 µg and 12·5 µg of Vi antigen) with the polysaccharide vaccine. All vaccines were well tolerated. Compared to the polysaccharide vaccine, Vi-CRM₁₉₇ induced a higher incidence of mild to moderate short lasting local pain. All Vi-CRM₁₉₇ formulations induced higher Vi antibody levels compared to licensed control, with clear dose response relationship. Vi-CRM₁₉₇ did not elicit safety concerns, was highly immunogenic and is therefore suitable for further clinical testing in endemic populations of South Asia. ClinicalTrials.gov NCT01123941 NCT01193907.

Fabrication of a new polysaccharide-based adsorbent for water purification.

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Qi, Xiaoliang; Wei, Wei; Su, Ting; Zhang, Jianfa; Dong, Wei

2018-09-01

Expanding the application of polysaccharide material has attracted tremendous attention in the fields of wastewater treatment, agriculture and biomedical engineering, on account of its tunable and unique properties. Herein, we employ a water-soluble, sustainable and low cost bacterial polysaccharide, salecan as a matrix, poly(acrylamide-co-itaconic acid) (PAI) as a synthetic component to synthesize salecan-g-PAI hydrogels through a simple chemical crosslinking method. Their physicochemical properties were fully characterized by various methods including Fourier transformed infrared spectroscopy, X-ray diffraction, thermogravimetry, scanning electron microscope and rheometry. We found that salecan not only acted as the interaction sites to regulate the water content of the developing hydrogels, but also endowed them with tailorable morphology. The designed salecan-g-PAI hydrogels exhibited excellent adsorption properties toward methylene blue (MB) dye, and the adsorption process could be well described by the pseudo-second-order kinetic and Freundlich isotherm models. Altogether, this study broadens the application of salecan polysaccharides and provides a new device for dye decontamination. Copyright © 2018 Elsevier Ltd. All rights reserved.

The Type of Growth Medium Affects the Presence of a Mycobacterial Capsule and Is Associated With Differences in Protective Efficacy of BCG Vaccination Against Mycobacterium tuberculosis.

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Prados-Rosales, Rafael; Carreño, Leandro J; Weinrick, Brian; Batista-Gonzalez, Ana; Glatman-Freedman, Aarona; Xu, Jiayong; Chan, John; Jacobs, William R; Porcelli, Steven A; Casadevall, Arturo

2016-08-01

Bacillus Calmette-Guerin (BCG) vaccine is widely used for the prevention of tuberculosis, despite limited efficacy. Most immunological studies of BCG or Mycobacterium tuberculosis strains grow bacteria in the presence of detergent, which also strips the mycobacterial capsule. The impact of the capsule on vaccine efficacy has not been explored. We tested the influence of detergent in cultures of BCG and M. tuberculosis strains on the outcome of vaccination experiments on mice and transcriptional responses on M. tuberculosis  Vaccination of mice with encapsulated BCG promoted a more potent immune response relative to vaccination with unencapsulated BCG, including higher polysaccharide-specific capsule antibody titers, higher interferon γ and interleukin 17 splenic responses, and more multifunctional CD4(+) T cells. These differences correlated with variability in the bacterial burden in lung and spleen of mice infected with encapsulated or unencapsulated M. tuberculosis The combination of vaccination and challenge with encapsulated strains resulted in the greatest protection efficacy. The transcriptome of encapsulated M. tuberculosis was similar to that of starvation, hypoxia, stationary phase, or nonreplicating persistence. The presence of detergent in growth media and a capsule on BCG were associated with differences in the outcome of vaccination, implying that these are important variables in immunological studies. © The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.

Bacteriële meningitis

NARCIS (Netherlands)

Brouwer, M. C.; van de Beek, D.

2012-01-01

Bacterial meningitis is a severe disease which affects 35.000 Europeans each year and has a mortality rate of about 20%. During the past 25 years the epidemiology of bacterial meningitis has changed significantly due to the implementation of vaccination against Haemophilus influenzae, Neisseria

Typhoid fever vaccination strategies.

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Date, Kashmira A; Bentsi-Enchill, Adwoa; Marks, Florian; Fox, Kimberley

2015-06-19

Typhoid vaccination is an important component of typhoid fever prevention and control, and is recommended for public health programmatic use in both endemic and outbreak settings. We reviewed experiences with various vaccination strategies using the currently available typhoid vaccines (injectable Vi polysaccharide vaccine [ViPS], oral Ty21a vaccine, and injectable typhoid conjugate vaccine [TCV]). We assessed the rationale, acceptability, effectiveness, impact and implementation lessons of these strategies to inform effective typhoid vaccination strategies for the future. Vaccination strategies were categorized by vaccine disease control strategy (preemptive use for endemic disease or to prevent an outbreak, and reactive use for outbreak control) and vaccine delivery strategy (community-based routine, community-based campaign and school-based). Almost all public health typhoid vaccination programs used ViPS vaccine and have been in countries of Asia, with one example in the Pacific and one experience using the Ty21a vaccine in South America. All vaccination strategies were found to be acceptable, feasible and effective in the settings evaluated; evidence of impact, where available, was strongest in endemic settings and in the short- to medium-term. Vaccination was cost-effective in high-incidence but not low-incidence settings. Experience in disaster and outbreak settings remains limited. TCVs have recently become available and none are WHO-prequalified yet; no program experience with TCVs was found in published literature. Despite the demonstrated success of several typhoid vaccination strategies, typhoid vaccines remain underused. Implementation lessons should be applied to design optimal vaccination strategies using TCVs which have several anticipated advantages, such as potential for use in infant immunization programs and longer duration of protection, over the ViPS and Ty21a vaccines for typhoid prevention and control. Copyright © 2015. Published by

Human Infant Memory B Cell and CD4+ T Cell Responses to HibMenCY-TT Glyco-Conjugate Vaccine.

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Angela Fuery

Full Text Available Carrier-specific T cell and polysaccharide-specific B cell memory responses are not well characterised in infants following glyco-conjugate vaccination. We aimed to determine if the number of Meningococcal (Men C- and Y- specific memory B cells and; number and quality of Tetanus Toxoid (TT carrier-specific memory CD4+ T cells are associated with polysaccharide-specific IgG post HibMenCY-TT vaccination. Healthy infants received HibMenCY-TT vaccine at 2, 4 and 6 months with a booster at 12 months. Peripheral blood mononuclear cells were isolated and polysaccharide-specific memory B cells enumerated using ELISpot. TT-specific memory CD4+ T cells were detected and phenotyped based on CD154 expression and intracellular TNF-α, IL-2 and IFN-γ expression following stimulation. Functional polysaccharide-specific IgG titres were measured using the serum bactericidal activity (SBA assay. Polysaccharide-specific Men C- but not Men Y- specific memory B cell frequencies pre-boost (12 months were significantly associated with post-boost (13 months SBA titres. Regression analysis showed no association between memory B cell frequencies post-priming (at 6 or 7 months and SBA at 12 months or 13 months. TT-specific CD4+ T cells were detected at frequencies between 0.001 and 0.112 as a percentage of CD3+ T cells, but their numbers were not associated with SBA titres. There were significant negative associations between SBA titres at M13 and cytokine expression at M7 and M12.Induction of persistent polysaccharide-specific memory B cells prior to boosting is an important determinant of secondary IgG responses in infants. However, polysaccharide-specific functional IgG responses appear to be independent of the number and quality of circulating carrier-specific CD4+ T cells after priming.

Development of a Vaccine for Bacterial Kidney Disease in Salmon, 1987 Annual Report.

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Kaattari, Stephen

1988-06-01

Bacterial kidney disease (BKD) has been and remains a chronic contributory problem limiting the productivity of salmon in the Columbia River Basin. Control of this disease will not come easily, but it would lead to a tremendous increase in the health and numbers of salmon populations. Vaccination of salmon to Renibacterium salmoninarum (KDB) is a potentially successful method of controlling this disease. To date, however, no successful vaccine has been developed for general use. A possible solution to this problem, and thus the goal of this research, is to isolate the antigenic components of KDB and enhance their ability to activate the host defenses. This will be accomplished by the chemical modification of these antigens with potent immunomodulatory substances. These modified antigens will then be tested for their effectiveness in inducing immunity to BKD and thereby preventing the disease. The goal of the project's fourth year was to test the immunogenicity and prophylactic value in coho salmon (Oncorhynchus kisutch) of various--chemical conjugates of Renibacterium salmoninarum cell and major antigens. This was accomplished by assessing the serum antibody response, the cellular immune response (chemiluminescence), and the kinetics of mortality after lethal injections of the bacteria. The studies completed this year have: (1) identified immunization procedures which enhance the induction of high levels of antibody; (2) identified functionally distinct serum antibodies which may possess different abilities to protect salmon against BKD; (3) begun the isolation and characterization of anti-R. salmoninarum antibodies which may correlate with varying degrees of protection; (4) identified chemiluminescence as a potential method for assessing cellular immunity to bacterial kidney disease; and (5) characterized two monoclonal antibodies to R. salmoninarum which will be of benefit in the diagnosis of this disease.

The Pneumococcal Serotype 15C Capsule Is Partially O-Acetylated and Allows for Limited Evasion of 23-Valent Pneumococcal Polysaccharide Vaccine-Elicited Anti-Serotype 15B Antibodies.

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Spencer, Brady L; Shenoy, Anukul T; Orihuela, Carlos J; Nahm, Moon H

2017-08-01

As a species, Streptococcus pneumoniae (the pneumococcus) utilizes a diverse array of capsular polysaccharides to evade the host. In contrast to large variations in sugar composition and linkage formation, O-acetylation is a subtle capsular modification that nonetheless has a large impact on capsular shielding and recognition of the capsule by vaccine-elicited antibodies. Serotype 15B, which is included in the 23-valent pneumococcal polysaccharide vaccine (PPV23), carries the putative O-acetyltransferase gene wciZ The coding sequence of wciZ contains eight consecutive TA repeats [(TA) 8 ]. Replication slippage is thought to result in the addition or loss of TA repeats, subsequently causing frameshift and truncation of WciZ to yield a nonacetylated serotype, 15C. Using sensitive serological tools, we show that serotype 15C isolates whose wciZ contains seven or nine TA repeats retain partial O-acetylation, while serotype 15C isolates whose wciZ contains six TA repeats have barely detectable O-acetylation. We confirmed by inhibition enzyme-linked immunosorbent assay that (TA) 7 serotype 15C is ∼0.1% as acetylated as serotype 15B, while serotype 15X is nonacetylated. To eliminate the impact of genetic background, we created isogenic serotype 15B, (TA) 7 serotype 15C, and 15BΔ wciZ (15X) strains and found that reduction or absence of WciZ-mediated O-acetylation did not affect capsular shielding from phagocytes, biofilm formation, adhesion to nasopharyngeal cells, desiccation tolerance, or murine colonization. Sera from PPV23-immunized persons opsonized serotype 15B significantly but only slightly better than serotypes 15C and 15X; thus, PPV23 may not result in expansion of serotype 15C. Copyright © 2017 American Society for Microbiology.

Safety, immunogenicity and dose ranging of a new Vi-CRM₁₉₇ conjugate vaccine against typhoid fever: randomized clinical testing in healthy adults.

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Pierre van Damme

Full Text Available Typhoid fever causes more than 21 million cases of disease and 200,000 deaths yearly worldwide, with more than 90% of the disease burden being reported from Asia. Epidemiological data show high disease incidence in young children and suggest that immunization programs should target children below two years of age: this is not possible with available vaccines. The Novartis Vaccines Institute for Global Health developed a conjugate vaccine (Vi-CRM₁₉₇ for infant vaccination concomitantly with EPI vaccines, either starting at 6 weeks with DTP or at 9 months with measles vaccine. We report the results from a Phase 1 and a Phase 2 dose ranging trial with Vi-CRM₁₉₇ in European adults.Following randomized blinded comparison of single vaccination with either Vi-CRM₁₉₇ or licensed polysaccharide vaccines (both containing 25·0 µg of Vi antigen, a randomised observer blinded dose ranging trial was performed in the same center to compare three concentrations of Vi-CRM₁₉₇ (1·25 µg, 5·0 µg and 12·5 µg of Vi antigen with the polysaccharide vaccine.All vaccines were well tolerated. Compared to the polysaccharide vaccine, Vi-CRM₁₉₇ induced a higher incidence of mild to moderate short lasting local pain. All Vi-CRM₁₉₇ formulations induced higher Vi antibody levels compared to licensed control, with clear dose response relationship.Vi-CRM₁₉₇ did not elicit safety concerns, was highly immunogenic and is therefore suitable for further clinical testing in endemic populations of South Asia.ClinicalTrials.gov NCT01123941 NCT01193907.

Development of novel O-polysaccharide based glycoconjugates for immunization against glanders

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Mary N Burtnick

2012-11-01

Full Text Available Burkholderia mallei, the etiologic agent of glanders, causes severe disease in humans and animals and is a potential agent of biological warfare and terrorism. Diagnosis and treatment of glanders can be challenging, and in the absence of chemotherapeutic intervention, acute human disease is invariably fatal. At present, there are no human or veterinary vaccines available for immunization against disease. One of the goals of our research, therefore, is to identify and characterize protective antigens expressed by B. mallei and use them to develop efficacious glanders vaccine candidates. Previous studies have demonstrated that the O-polysaccharide (OPS expressed by B. mallei is both a virulence factor and a protective antigen. Recently, we demonstrated that Burkholderia thailandensis, a closely related but non-pathogenic species, can be genetically manipulated to express OPS antigens that are recognized by B. mallei OPS-specific monoclonal antibodies. As a result, these antigens have become important components of the various OPS-based subunit vaccines that we are currently developing in our laboratory. In this study, we describe a method for isolating B. mallei-like OPS antigens from B. thailandensis oacA mutants. Utilizing these purified OPS antigens, we also describe a simple procedure for coupling the polysaccharides to protein carriers such as cationized bovine serum albumin, diphtheria toxin mutant CRM197 and cholera toxin B subunit. Additionally, we demonstrate that high titer IgG responses against purified B. mallei LPS can be generated by immunizing mice with the resulting constructs. Collectively, these approaches provide a rational starting point for the development of novel OPS-based glycoconjugates for immunization against glanders.

Development of a thermostable microneedle patch for influenza vaccination

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Mistilis, Matthew; Bommarius, Andreas S; Prausnitz, Mark R.

2017-01-01

The goal of this study is to develop thermostable microneedle patch formulations for influenza vaccine that can be partially or completely removed from the cold chain. During vaccine drying associated with microneedle patch manufacturing, ammonium acetate and HEPES buffer salts stabilized influenza vaccine, surfactants had little effect during drying, drying temperature had weak effects on vaccine stability, and drying on polydimethylsiloxane led to increased stability compared to drying on stainless steel. A number of excipients, mostly polysaccharides and some amino acids, further stabilized the influenza vaccine during drying. Over longer time scales of storage, combinations of stabilizers preserved the most vaccine activity. Finally, dissolving microneedle patches formulated with arginine and calcium heptagluconate had no significant activity loss for all three strains of seasonal influenza vaccine during storage at room temperature for six months. We conclude that appropriately formulated microneedle patches can exhibit remarkable thermostability that could enable storage and distribution of influenza vaccine outside the cold chain. PMID:25448542

Enzymatic modification of bacterial exopolysaccharides : xanthan lyase as a tool for structural and functional modification of xanthan

NARCIS (Netherlands)

Ruijssenaars, H.J.

2001-01-01

Bacterial extracellular polysaccharides (EPSs) can be applied, e.g., in foods, as a thickener or stabilizer. The functional properties that make a polysaccharide suitable for such applications are largely determined by the primary structure, i.e., the sugar composition, the linkage types

Meningococcal X polysaccharide quantification by high-performance anion-exchange chromatography using synthetic N-acetylglucosamine-4-phosphate as standard.

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Micoli, F; Adamo, R; Proietti, D; Gavini, M; Romano, M R; MacLennan, C A; Costantino, P; Berti, F

2013-11-15

A method for meningococcal X (MenX) polysaccharide quantification by high-performance anion-exchange chromatography with pulsed amperometric detection (HPAEC-PAD) is described. The polysaccharide is hydrolyzed by strong acidic treatment, and the peak of glucosamine-4-phosphate (4P-GlcN) is detected and measured after chromatography. In the selected conditions of hydrolysis, 4P-GlcN is the prevalent species formed, with GlcN detected for less than 5% in moles. As standard for the analysis, the monomeric unit of MenX polysaccharide, N-acetylglucosamine-4-phosphate (4P-GlcNAc), was used. This method for MenX quantification is highly selective and sensitive, and it constitutes an important analytical tool for the development of a conjugate vaccine against MenX. Copyright © 2013 Elsevier Inc. All rights reserved.

Transcriptional Responses of Bacillus cereus towards Challenges with the Polysaccharide Chitosan : Direct Dating, Culture and Behavior

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Mellegard, Hilde; Kovacs, Akos T.; Lindback, Toril; Christensen, Bjorn E.; Kuipers, Oscar P.; Granum, Per E.

2011-01-01

The antibacterial activity of the polysaccharide chitosan towards different bacterial species has been extensively documented. The response mechanisms of bacteria exposed to this biopolymer and the exact molecular mechanism of action, however, have hardly been investigated. This paper reports the

Utilization of oligo- and polysaccharides at microgram-per-litre levels in freshwater by Flavobacterium johnsoniae

NARCIS (Netherlands)

Sack, E.L.W.; Wielen, van der P.W.J.J.; Kooij, van der D.

2010-01-01

Aims: To obtain a bacterial strain that can be used to quantify biodegradable polysaccharides at concentrations of a few micrograms per litre in freshwater. Methods and Results: Flavobacterium johnsoniae strain A3 was isolated from tap water supplemented with laminarin, pectin or amylopectin at 100

Vaccines and Immunization Practice.

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Hogue, Michael D; Meador, Anna E

2016-03-01

Vaccines are among most cost-effective public health strategies. Despite effective vaccines for many bacterial and viral illnesses, tens of thousands of adults and hundreds of children die each year in the United States from vaccine-preventable diseases. Underutilization of vaccines requires rethinking the approach to incorporating vaccines into practice. Arguably, immunizations could be a part all health care encounters. Shared responsibility is paramount if deaths are to be reduced. This article reviews the available vaccines in the US market, as well as practice recommendations of the Centers for Disease Control and Prevention's Advisory Committee on Immunization Practices. Copyright © 2016 Elsevier Inc. All rights reserved.

High field nuclear magnetic resonance application to polysaccharide chemistry

International Nuclear Information System (INIS)

Vincendon, Marc

1972-01-01

Nuclear magnetic resonance has been applied to polysaccharide chemistry using time averaging technique and high fields (100 and 250 MHz). The three methyl signals of methyl cellulose and cellulose triacetate are separated, and the C-6 substituent has been identified. Biosynthesis of bacterial cellulose has been performed using deuterium labelled D-glucose and Acetobacter xylinum. Per-acetylated derivative of bacterial cellulose has been studied by NMR; this study permitted us to determine the quantity of deuterium on each position of the anhydro-glucose unit in the polymer. NMR has also been used to see the anomeric end chain of cellulose and amylose derivatives and to show the fixation of bromine and t-butyl group on the free anomeric end chain of cellulose triacetate. (author) [fr

Bacterial Meningitis after Cochlear Implantation among Children without Polyvalent Conjugate Vaccine: A Brief Report of an Iranian Cohort Study on 371 Cases

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Shahla Afsharpaiman

2014-01-01

Full Text Available Background: Regarding risk of bacterial meningitis (BM after Cochlear implantation (CI, it was suggested to receive polyvalent conjugate vaccine. We aimed to estimate the prevalence of BM post CI in child recipients who do not receive polyvalent vaccine. Methods: We enrolled 371 children who had received cochlear implants from 2007 to 2010. None of them received pre or post implantation polyvalent conjugate vaccine for BM. We followed all of them for BM for 2 years after implantation. Results: We detected only one female case of BM (0.3% of patients with the age of 24 months. The mean age of noninfected children was 36.7 ± 23.2 months. The education level of parents was "college level or higher" in less than half of them, and about 65% of patients were products of consanguineous marriage. Conclusions: Our findings indicated that the incidence of BM was not higher in our cochlear implanted children who did not receive immunization than patients from countries in which routine vaccination is done. We suggest that although proper immunization is recommended before surgery, this procedure could be performed without vaccination, especially in developing countries that face financial problems for preparing vaccines.

Meningococcal groups C and Y and haemophilus B tetanus toxoid conjugate vaccine (HibMenCY-TT; MenHibrix(®)): a review.

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Perry, Caroline M

2013-05-01

The meningococcal groups C and Y and Haemophilus b (Hib) tetanus toxoid conjugate vaccine (HibMenCY-TT) contains Neisseria meningitidis serogroup C and Y capsular polysaccharide antigens, and Hib capsular polysaccharide [polyribosyl-ribitol-phosphate (PRP)]. The HibMenCY-TT vaccine is available in the USA for use as active immunization to prevent invasive disease caused by N. meningitidis serogroups C (MenC) and Y (MenY), and Hib in children 6 weeks-18 months of age. HibMenCY-TT is the first meningococcal vaccine available for use in the USA that can be administered to infants as young as 6 weeks of age. In a randomized, controlled, phase III clinical trial, the HibMenCY-TT vaccine, administered to infants at 2, 4, 6 and 12-15 months of age, was immunogenic against MenC and MenY, and met the prespecified criteria for immunogenicity. Anti-PRP antibodies, which have been shown to correlate with protection against Hib invasive disease, were also induced in the infants who received the HibMenCY-TT vaccine, with induced levels of this antibody noninferior to those occurring in the control group of infants who received a Hib tetanus toxoid conjugate vaccine at 2, 4, and 6 months and a single dose of Hib conjugated to N. meningitidis outer membrane protein at 12-15 months. In several randomized, controlled clinical trials, HibMenCY-TT was coadministered with vaccines that are routinely administered to infants and toddlers in the USA. These vaccines included: diphtheria and tetanus toxoids and acellular pertussis adsorbed, hepatitis B (recombinant) and inactivated poliovirus vaccine combined; 7-valent Streptococcus pneumoniae polysaccharide conjugate vaccine; measles, mumps and rubella vaccine; and varicella vaccine. Coadministration of these vaccines did not interfere with the immunogenicity of the HibMenCY-TT vaccine. Similarly, immune responses to the coadministered vaccines were not affected by the HibMenCY-TT vaccine. The tolerability profile of the Hib

Iron oxyhydroxide mineralization on microbial extracellular polysaccharides

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Chan, Clara S.; Fakra, Sirine C.; Edwards, David C.; Emerson, David; Banfield, Jillian F.

2010-06-22

Iron biominerals can form in neutral pH microaerophilic environments where microbes both catalyze iron oxidation and create polymers that localize mineral precipitation. In order to classify the microbial polymers that influence FeOOH mineralogy, we studied the organic and mineral components of biominerals using scanning transmission X-ray microscopy (STXM), micro X-ray fluorescence ({mu}XRF) microscopy, and high-resolution transmission electron microscopy (HRTEM). We focused on iron microbial mat samples from a creek and abandoned mine; these samples are dominated by iron oxyhydroxide-coated structures with sheath, stalk, and filament morphologies. In addition, we characterized the mineralized products of an iron-oxidizing, stalk-forming bacterial culture isolated from the mine. In both natural and cultured samples, microbial polymers were found to be acidic polysaccharides with carboxyl functional groups, strongly spatially correlated with iron oxyhydroxide distribution patterns. Organic fibrils collect FeOOH and control its recrystallization, in some cases resulting in oriented crystals with high aspect ratios. The impact of polymers is particularly pronounced as the materials age. Synthesis experiments designed to mimic the biomineralization processes show that the polysaccharide carboxyl groups bind dissolved iron strongly but release it as mineralization proceeds. Our results suggest that carboxyl groups of acidic polysaccharides are produced by different microorganisms to create a wide range of iron oxyhydroxide biomineral structures. The intimate and potentially long-term association controls the crystal growth, phase, and reactivity of iron oxyhydroxide nanoparticles in natural systems.

PolySac3DB: an annotated data base of 3 dimensional structures of polysaccharides

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Sarkar Anita

2012-11-01

Full Text Available Abstract Background Polysaccharides are ubiquitously present in the living world. Their structural versatility makes them important and interesting components in numerous biological and technological processes ranging from structural stabilization to a variety of immunologically important molecular recognition events. The knowledge of polysaccharide three-dimensional (3D structure is important in studying carbohydrate-mediated host-pathogen interactions, interactions with other bio-macromolecules, drug design and vaccine development as well as material science applications or production of bio-ethanol. Description PolySac3DB is an annotated database that contains the 3D structural information of 157 polysaccharide entries that have been collected from an extensive screening of scientific literature. They have been systematically organized using standard names in the field of carbohydrate research into 18 categories representing polysaccharide families. Structure-related information includes the saccharides making up the repeat unit(s and their glycosidic linkages, the expanded 3D representation of the repeat unit, unit cell dimensions and space group, helix type, diffraction diagram(s (when applicable, experimental and/or simulation methods used for structure description, link to the abstract of the publication, reference and the atomic coordinate files for visualization and download. The database is accompanied by a user-friendly graphical user interface (GUI. It features interactive displays of polysaccharide structures and customized search options for beginners and experts, respectively. The site also serves as an information portal for polysaccharide structure determination techniques. The web-interface also references external links where other carbohydrate-related resources are available. Conclusion PolySac3DB is established to maintain information on the detailed 3D structures of polysaccharides. All the data and features are available

Bacterial meningitis

NARCIS (Netherlands)

Heckenberg, Sebastiaan G. B.; Brouwer, Matthijs C.; van de Beek, Diederik

2014-01-01

Bacterial meningitis is a neurologic emergency. Vaccination against common pathogens has decreased the burden of disease. Early diagnosis and rapid initiation of empiric antimicrobial and adjunctive therapy are vital. Therapy should be initiated as soon as blood cultures have been obtained,

Live Attenuated Influenza Vaccine Enhances Colonization of Streptococcus pneumoniae and Staphylococcus aureus in Mice

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Mina, Michael J.; McCullers, Jonathan A.; Klugman, Keith P.

2014-01-01

ABSTRACT Community interactions at mucosal surfaces between viruses, like influenza virus, and respiratory bacterial pathogens are important contributors toward pathogenesis of bacterial disease. What has not been considered is the natural extension of these interactions to live attenuated immunizations, and in particular, live attenuated influenza vaccines (LAIVs). Using a mouse-adapted LAIV against influenza A (H3N2) virus carrying the same mutations as the human FluMist vaccine, we find that LAIV vaccination reverses normal bacterial clearance from the nasopharynx and significantly increases bacterial carriage densities of the clinically important bacterial pathogens Streptococcus pneumoniae (serotypes 19F and 7F) and Staphylococcus aureus (strains Newman and Wright) within the upper respiratory tract of mice. Vaccination with LAIV also resulted in 2- to 5-fold increases in mean durations of bacterial carriage. Furthermore, we show that the increases in carriage density and duration were nearly identical in all aspects to changes in bacterial colonizing dynamics following infection with wild-type (WT) influenza virus. Importantly, LAIV, unlike WT influenza viruses, had no effect on severe bacterial disease or mortality within the lower respiratory tract. Our findings are, to the best of our knowledge, the first to demonstrate that vaccination with a live attenuated viral vaccine can directly modulate colonizing dynamics of important and unrelated human bacterial pathogens, and does so in a manner highly analogous to that seen following wild-type virus infection. PMID:24549845

Mouse dendritic cells pulsed with capsular polysaccharide induce resistance to lethal pneumococcal challenge: roles of T cells and B cells.

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Noam Cohen

Full Text Available Mice are exceedingly sensitive to intra-peritoneal (IP challenge with some virulent pneumococci (LD50 = 1 bacterium. To investigate how peripheral contact with bacterial capsular polysaccharide (PS antigen can induce resistance, we pulsed bone marrow dendritic cells (BMDC of C57BL/6 mice with type 4 or type 3 PS, injected the BMDC intra-foot pad (IFP and challenged the mice IP with supra-lethal doses of pneumococci. We examined the responses of T cells and B cells in the draining popliteal lymph node and measured the effects on the bacteria in the peritoneum and blood. We now report that: 1 The PS co-localized with MHC molecules on the BMDC surface; 2 PS-specific T and B cell proliferation and IFNγ secretion was detected in the draining popliteal lymph nodes on day 4; 3 Type-specific resistance to lethal IP challenge was manifested only after day 5; 4 Type-specific IgM and IgG antibodies were detected in the sera of only some of the mice, but B cells were essential for resistance; 5 Control mice vaccinated with a single injection of soluble PS did not develop a response in the draining popliteal lymph node and were not protected; 6 Mice injected with unpulsed BMDC also did not resist challenge: In unprotected mice, pneumococci entered the blood shortly after IP inoculation and multiplied exponentially in both blood and peritoneum killing the mice within 20 hours. Mice vaccinated with PS-pulsed BMDC trapped the bacteria in the peritoneum. The trapped bacteria proliferated exponentially IP, but died suddenly at 18-20 hours. Thus, a single injection of PS antigen associated with intact BMDC is a more effective vaccine than the soluble PS alone. This model system provides a platform for studying novel aspects of PS-targeted vaccination.

Development of a Vaccine for Bacterial Kidney Disease in Salmon, 1988 Final Report.

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Kaattari, Stephen L.

1989-08-01

Bacterial kidney disease of salmonids is a very complex disease which appears to exploit a variety of pathogenic mechanisms. An understanding of these mechanisms is essential to the development of efficacious vaccines. It has become well established from the studies published .in this report and those of others that soluble antigens which are secreted by Renibacterium salmoninarum have toxigenic potential. If they are found to be responsible for mortality, the development of toxoid(s) could be paramount to the production of a vaccine. One must, however, be circumspect in producing a vaccine. A thorough knowledge, not only of the pathogen, but also of the immune system of the host is an absolute requirement. This becomes of particular importance when dealing with fish diseases, since the field of fish immunology is still within its infancy. This lack of knowledge is particularly felt when the induction of a prophylactic immune response concomitantly leads to pathological side effects which may be as destructive as the original infection. Indeed, it appears that some aspects of BKD may be due to the induction of hypersensitivity reactions. If such immunopathologies are expressed, it is prudent to thoroughly evaluate the nature of the immunoprophylaxis to insure that these harmful sequelae do not occur. Evaluation of a variety of antigens, adjuvants, immune responses, and survival data leads us to recommend that attempts at prophylaxis against BKD should center upon the elicitation of cellular immunity utilizing preparations of Mycobacterium chelonii. The choice of this species of mycobacteria was made because of its effectiveness, ease of maintenance and production, and the lack of need for its propagation within containment facilities. These assets are important to consider if large scale vaccine production is to be profitable. As can be seen from the data provided, M. chelonii alone is capable of producing prophylaxis to BKD, however, this is likely due to the

Pediatric bacterial meningitis in French Guiana.

Science.gov (United States)

Elenga, N; Sicard, S; Cuadro-Alvarez, E; Long, L; Njuieyon, F; Martin, E; Kom-Tchameni, R; Balcaen, J; Moreau, B; Boukhari, R

2015-01-01

Controlling vaccine-preventable infectious diseases is a public health priority in French Guiana but there is currently no epidemiological data on pediatric bacterial meningitis in this overseas department. Our aim was to describe data related to pediatric bacterial meningitis in French Guiana and compare it with that of metropolitan France. We conducted a multicenter retrospective study from 2000 to 2010 to describe the clinical picture, biological data, epidemiology, and outcome of pediatric bacterial meningitis case patients in French Guiana. The median age of bacterial meningitis patients was 6months [0-15] and the sex ratio 1.06. We observed a total of 60 bacterial meningitis case patients. Most presented with pneumococcal meningitis (24 patients; 40%); 11 with Haemophilus influenzae type b meningitis (23%), five with group B streptococcal meningitis (8.5%), and five others (8.5%) with staphylococcal meningitis (three patients presented with coagulase-negative staphylococci and two with Staphylococcus aureus). Only one patient presented with group B meningococcal meningitis, an 18-month-old infant. We recorded 14 deaths (overall case fatality: 23%); eight were due to Streptococcus pneumoniae (case fatality: 33%). The overall sequelae rate was 28%. It was 32% for patients presenting with pneumococcal meningitis. We observed that 38% of children who had never been vaccinated were infected by a vaccine-preventable bacterium. We observed many differences in the distribution of the bacteria and in the patients' prognosis when comparing the French Guiana data with that of metropolitan France. Improving vaccination coverage would decrease the incidence of H. influenzae meningitis. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

A potential disruptive technology in vaccine development: gene-based vaccines and their application to infectious diseases.

Science.gov (United States)

Kaslow, David C

2004-10-01

Vaccine development requires an amalgamation of disparate disciplines and has unique economic and regulatory drivers. Non-viral gene-based delivery systems, such as formulated plasmid DNA, are new and potentially disruptive technologies capable of providing 'cheaper, simpler, and more convenient-to-use' vaccines. Typically and somewhat ironically, disruptive technologies have poorer product performance, at least in the near-term, compared with the existing conventional technologies. Because successful product development requires that the product's performance must meet or exceed the efficacy threshold for a desired application, the appropriate selection of the initial product applications for a disruptive technology is critical for its successful evolution. In this regard, the near-term successes of gene-based vaccines will likely be for protection against bacterial toxins and acute viral and bacterial infections. Recent breakthroughs, however, herald increasing rather than languishing performance improvements in the efficacy of gene-based vaccines. Whether gene-based vaccines ultimately succeed in eliciting protective immunity in humans to persistent intracellular pathogens, such as HIV, malaria and tuberculosis, for which the conventional vaccine technologies have failed, remains to be determined. A success against any one of the persistent intracellular pathogens would be sufficient proof that gene-based vaccines represent a disruptive technology against which future vaccine technologies will be measured.

The impact of administration of conjugate vaccines containing cross reacting material on Haemophilus influenzae type b antibody responses in infants: A systematic review and meta-analysis of randomised controlled trials.

Science.gov (United States)

Voysey, Merryn; Sadarangani, Manish; Clutterbuck, Elizabeth; Bolgiano, Barbara; Pollard, Andrew J

2016-07-25

Protein-polysaccharide conjugate vaccines such as Haemophilus influenzae type b (Hib), meningococcal, and pneumococcal vaccine, induce immunological memory and longer lasting protection than plain polysaccharide vaccines. The most common proteins used as carriers are tetanus toxoid (TT) and cross reacting material-197 (CRM), a mutant form of diphtheria toxoid. CRM conjugate vaccines have been reported to suppress antibody responses to co-administered Hib-TT vaccine. We conducted a systematic review and meta-analysis of randomised controlled trials in which infants were randomised to receive meningococcal or pneumococcal conjugate vaccines along with Hib-TT. Trials of licensed vaccines with different carrier proteins were included for group C meningococcal (MenC), quadrivalent ACWY meningococcal (MenACWY), and pneumococcal vaccines. Twenty-three trials were included in the meta-analyses. Overall, administration of MenC-CRM in a 2 or 3 dose schedule resulted in a 45% reduction in Hib antibody concentrations (GMR 0.55, 95% CI 0.49-0.62). MenACWY-CRM boosted Hib antibody responses by 22% (GMR 1.22, 95% CI 1.06-1.41) whilst pneumococcal CRM conjugate vaccines had no impact on Hib antibody responses (GMR 0.91, 95% CI 0.68-1.22). The effect of CRM protein-polysaccharide conjugate vaccines on Hib antibody responses varies greatly between vaccines. Co-administration of a CRM conjugate vaccine can produce either positive or negative effects on Hib antibody responses. These inconsistencies suggest that CRM itself may not be the main driver of variability in Hib responses, and challenge current perspectives on this issue. Copyright © 2016 Elsevier Ltd. All rights reserved.

Antibodies to Staphylococcus aureus Serotype 8 Capsular Polysaccharide React with and Protect against Serotype 5 and 8 Isolates

OpenAIRE

Park, Saeyoung; Gerber, Sabina; Lee, Jean C.

2014-01-01

Most Staphylococcus aureus isolates produce either a serotype 5 (CP5) or 8 (CP8) capsular polysaccharide, and the CP antigens are targets for vaccine development. Since CP5 and CP8 have similar trisaccharide repeating units, it is important to identify an epitope shared by both CP5 and CP8. To characterize cross-reactivity between CP5 and CP8, the immunogenicity of CP5 and CP8 conjugate vaccines in mice and rabbits was evaluated by serological assays. Immune sera were also tested for function...

The dietary polysaccharide maltodextrin promotes Salmonella survival and mucosal colonization in mice.

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Kourtney P Nickerson

Full Text Available In the latter half of the 20th century, societal and technological changes led to a shift in the composition of the American diet to include a greater proportion of processed, pre-packaged foods high in fat and carbohydrates, and low in dietary fiber (a "Western diet". Over the same time period, there have been parallel increases in Salmonella gastroenteritis cases and a broad range of chronic inflammatory diseases associated with intestinal dysbiosis. Several polysaccharide food additives are linked to bacterially-driven intestinal inflammation and may contribute to the pathogenic effects of a Western diet. Therefore, we examined the effect of a ubiquitous polysaccharide food additive, maltodextrin (MDX, on clearance of the enteric pathogen Salmonella using both in vitro and in vivo infection models. When examined in vitro, murine bone marrow-derived macrophages exposed to MDX had altered vesicular trafficking, suppressed NAPDH oxidase expression, and reduced recruitment of NADPH oxidase to Salmonella-containing vesicles, which resulted in persistence of Salmonella in enlarged Rab7+ late endosomal vesicles. In vivo, mice consuming MDX-supplemented water had a breakdown of the anti-microbial mucous layer separating gut bacteria from the intestinal epithelium surface. Additionally, oral infection of these mice with Salmonella resulted in increased cecal bacterial loads and enrichment of lamina propria cells harboring large Rab7+ vesicles. These findings indicate that consumption of processed foods containing the polysaccharide MDX contributes to suppression of intestinal anti-microbial defense mechanisms and may be an environmental priming factor for the development of chronic inflammatory disease.

Dismantling the Taboo against Vaccines in Pregnancy

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Maurizio de Martino

2016-06-01

Full Text Available Vaccinating pregnant women in order to protect them, the fetus, and the child has become universal in no way at all. Prejudice in health professionals add to fears of women and their families. Both these feelings are not supported by even the smallest scientific data. Harmlessness for the mother and the child has been observed for seasonal, pandemic, or quadrivalent influenza, mono, combined polysaccharide or conjugated meningococcal or pneumococcal, tetanus toxoid, acellular pertussis, human papillomavirus, cholera, hepatitis A, Japanese encephalitis, rabies, anthrax, smallpox, yellow fever, mumps, measles and rubella combined, typhoid fever, inactivated or attenuated polio vaccines, and Bacillus Calmétte Guerin vaccines. Instead, the beneficial effects of influenza vaccine for the mother and the child as well as of pertussis vaccine for the child have been demonstrated. Obstetrician-gynecologists, general practitioners, and midwives must incorporate vaccination into their standard clinical care. Strong communication strategies effective at reducing parental vaccine hesitancy and approval of regulatory agencies for use of vaccines during pregnancy are needed. It must be clear that the lack of pre-licensure studies in pregnant women and, consequently, the lack of a statement about the use of the vaccine in pregnant women does not preclude its use in pregnancy.

Conjugating recombinant proteins to Pseudomonas aeruginosa ExoProtein A: a strategy for enhancing immunogenicity of malaria vaccine candidates

OpenAIRE

Qian, Feng; Wu, Yimin; Muratova, Olga; Zhou, Hong; Dobrescu, Gelu; Duggan, Peter; Lynn, Lambert; Song, Guanhong; Zhang, Yanling; Reiter, Karine; MacDonald, Nicholas; Narum, David L.; Long, Carole A.; Miller, Louis H.; Saul, Allan

2007-01-01

Conjugation of polysaccharides to carrier proteins has been a successful approach for producing safe and effective vaccines. In an attempt to increase the immunogenicity of two malarial vaccine candidate proteins of Plasmodium falciparum, apical membrane antigen 1 (AMA1) for blood stage vaccines and surface protein 25 (Pfs25) for mosquito stage vaccines, each was chemically conjugated to the mutant, nontoxic Pseudomonas aeruginosa ExoProtein A (rEPA). AMA1 is a large (66 kD) relatively good i...

The effect of prophylaxis with chloroquine and proguanil on delayed-type hypersensitivity and antibody production following vaccination with diphtheria, tetanus, polio, and pneumococcal vaccines.

Science.gov (United States)

Gyhrs, A; Pedersen, B K; Bygbjerg, I; Henrichsen, J; Heron, I; Petersen, I; Skinhoj, P

1991-11-01

In vitro studies have shown that anti-malarial drugs suppress immunity. In this study, the effects of chloroquine and proguanil (Paludrine) on the cellular and humoral immune system were measured by two in vivo methods: 1) cell-mediated immunity (delayed cutaneous hypersensitivity) i.e., skin tests with seven delayed-type common antigens (Multitest) and 2) humoral immunity by measurement of specific antibody response to vaccination. Sixty healthy young individuals were randomized into four groups and given 1) no treatment (controls), 2) chloroquine diphosphate (500 mg/week), 3) chloroquine diphosphate (1,000 mg/week), or 4) proguanil hydrochloride (200 mg/day) for six weeks. Skin testing was performed on days 0 and 28. Vaccinations with diphtheria, tetanus, polio, and pneumococcal polysaccharide antigen vaccines were performed on day 28, and the presence of specific antibodies was determined on days 0, 28, and 42. The skin tests induced a significant increase in skin reactive areas from day 0 to day 28 in all groups. Furthermore, the skin test induced an increase in the level of specific IgG for diphtheria and tetanus, but had no effect on antibodies to antigens not included in the skin test. The results showed that there were no significant differences among the four groups regarding skin test areas and increases in antibody titers following vaccination. Therefore, it is concluded that in healthy persons, six weeks intake of chloroquine, even in double doses, or proguanil in chemoprophylactic dosages, does not induce any detectable suppression of delayed-type hypersensitivity or vaccination responses to diphtheria, tetanus, polio, or pneumococcal polysaccharide antigens.

Gamma radiation effects on the cuban antimeningococcic BC vaccine

International Nuclear Information System (INIS)

Padron Soler, E.; Romay Penabad, Z.; Le Riveran Morales, E.; Campa Huergo, C.; Sierra Gonzalez, G.; Alfalla Valdes, L.; Prieto Miranda, E.

1994-01-01

The effects of gamma rays on the Cuban antimeningococcic BC vaccine properties were studied. These were performanced by simulation with different bio burden of microbial pollutants. The isolated spores of the pollutants of non- aseptic areas were used. Its D10 was determined as 2.045 Gy. On that basis, the sterilization dose setting was performed. The quality of the irradiated vaccine was performed according to the Cuban standards: sterility, protein and polysaccharide concentration, immunogenicity, per cent of protein adsorption, nonspecific innocuousness. There were observed non negative effects on the vaccine of the radiation process in the dose range of 0-25 Gy. It was also studied the preservation of the properties of the irradiated vaccine, by storing it during one year at four celsius grade. The results were satisfactory

Vaccination with Brucella abortus recombinant in vivo-induced antigens reduces bacterial load and promotes clearance in a mouse model for infection.

Directory of Open Access Journals (Sweden)

Jake E Lowry

Full Text Available Current vaccines used for the prevention of brucellosis are ineffective in inducing protective immunity in animals that are chronically infected with Brucella abortus, such as elk. Using a gene discovery approach, in vivo-induced antigen technology (IVIAT on B. abortus, we previously identified ten loci that encode products up-regulated during infection in elk and consequently may play a role in virulence. In our present study, five of the loci (D15, 0187, VirJ, Mdh, AfuA were selected for further characterization and compared with three additional antigens with virulence potential (Hia, PrpA, MltA. All eight genes were PCR-amplified from B. abortus and cloned into E. coli. The recombinant products were then expressed, purified, adjuvanted, and delivered subcutaneously to BALB/c mice. After primary immunization and two boosts, mice were challenged i.p. with 5 x 10⁴ CFU of B. abortus strain 19. Spleens from challenged animals were harvested and bacterial loads determined by colony count at various time points. While vaccination with four of the eight individual proteins appeared to have some effect on clearance kinetics, mice vaccinated with recombinant Mdh displayed the most significant reduction in bacterial colonization. Furthermore, mice immunized with Mdh maintained higher levels of IFN-γ in spleens compared to other treatment groups. Collectively, our in vivo data gathered from the S19 murine colonization model suggest that vaccination with at least three of the IVIAT antigens conferred an enhanced ability of the host to respond to infection, reinforcing the utility of this methodology for the identification of potential vaccine candidates against brucellosis. Mechanisms for immunity to one protein, Mdh, require further in vitro exploration and evaluation against wild-type B. abortus challenge in mice, as well as other hosts. Additional studies are being undertaken to clarify the role of Mdh and other IVI antigens in B. abortus virulence

Progress towards meningitis prevention in the conjugate vaccines era

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Cristina Aparecida Borges Laval

Full Text Available Acute bacterial meningitis is an important cause of morbidity and mortality among children less than five years old. Haemophilus influenzae, Streptococcus pneumoniae and Neisseria meningitidis are the most important agents of bacterial meningitis in developing countries. The development of the conjugate vaccines in the beginning of the 90's, especially type b H. influenzae (Hib, and more recently the heptavalent pneumococcal and the serogroup C meningococcal vaccines, have contributed directly to changes in the epidemiological profile of these invasive diseases (direct effect and of their carriage status (indirect effect. We review the impact of the Hib conjugate vaccine in Latin American countries, where this vaccine has been implemented, and the potential of pneumococcal and meningococcal conjugate vaccines for the reduction of meningitis worldwide. We also address constraints for the development and delivery of these vaccines and review new candidate state-of-the-art vaccines. The greatest challenge, undoubtedly, is to implement these vaccines worldwide, especially in the developing regions.

Photorhabdus adhesion modification protein (Pam) binds extracellular polysaccharide and alters bacterial attachment

LENUS (Irish Health Repository)

Jones, Robert T

2010-05-12

Abstract Background Photorhabdus are Gram-negative nematode-symbiotic and insect-pathogenic bacteria. The species Photorhabdus asymbiotica is able to infect humans as well as insects. We investigated the secreted proteome of a clinical isolate of P. asymbiotica at different temperatures in order to identify proteins relevant to the infection of the two different hosts. Results A comparison of the proteins secreted by a clinical isolate of P. asymbiotica at simulated insect (28°C) and human (37°C) temperatures led to the identification of a small and highly abundant protein, designated Pam, that is only secreted at the lower temperature. The pam gene is present in all Photorhabdus strains tested and shows a high level of conservation across the whole genus, suggesting it is both ancestral to the genus and probably important to the biology of the bacterium. The Pam protein shows limited sequence similarity to the 13.6 kDa component of a binary toxin of Bacillus thuringiensis. Nevertheless, injection or feeding of heterologously produced Pam showed no insecticidal activity to either Galleria mellonella or Manduca sexta larvae. In bacterial colonies, Pam is associated with an extracellular polysaccharide (EPS)-like matrix, and modifies the ability of wild-type cells to attach to an artificial surface. Interestingly, Surface Plasmon Resonance (SPR) binding studies revealed that the Pam protein itself has adhesive properties. Although Pam is produced throughout insect infection, genetic knockout does not affect either insect virulence or the ability of P. luminescens to form a symbiotic association with its host nematode, Heterorhabditis bacteriophora. Conclusions We studied a highly abundant protein, Pam, which is secreted in a temperature-dependent manner in P. asymbiotica. Our findings indicate that Pam plays an important role in enhancing surface attachment in insect blood. Its association with exopolysaccharide suggests it may exert its effect through mediation of

Photorhabdus adhesion modification protein (Pam) binds extracellular polysaccharide and alters bacterial attachment.

Science.gov (United States)

Jones, Robert T; Sanchez-Contreras, Maria; Vlisidou, Isabella; Amos, Matthew R; Yang, Guowei; Muñoz-Berbel, Xavier; Upadhyay, Abhishek; Potter, Ursula J; Joyce, Susan A; Ciche, Todd A; Jenkins, A Toby A; Bagby, Stefan; Ffrench-Constant, Richard H; Waterfield, Nicholas R

2010-05-12

Photorhabdus are Gram-negative nematode-symbiotic and insect-pathogenic bacteria. The species Photorhabdus asymbiotica is able to infect humans as well as insects. We investigated the secreted proteome of a clinical isolate of P. asymbiotica at different temperatures in order to identify proteins relevant to the infection of the two different hosts. A comparison of the proteins secreted by a clinical isolate of P. asymbiotica at simulated insect (28 degrees C) and human (37 degrees C) temperatures led to the identification of a small and highly abundant protein, designated Pam, that is only secreted at the lower temperature. The pam gene is present in all Photorhabdus strains tested and shows a high level of conservation across the whole genus, suggesting it is both ancestral to the genus and probably important to the biology of the bacterium. The Pam protein shows limited sequence similarity to the 13.6 kDa component of a binary toxin of Bacillus thuringiensis. Nevertheless, injection or feeding of heterologously produced Pam showed no insecticidal activity to either Galleria mellonella or Manduca sexta larvae. In bacterial colonies, Pam is associated with an extracellular polysaccharide (EPS)-like matrix, and modifies the ability of wild-type cells to attach to an artificial surface. Interestingly, Surface Plasmon Resonance (SPR) binding studies revealed that the Pam protein itself has adhesive properties. Although Pam is produced throughout insect infection, genetic knockout does not affect either insect virulence or the ability of P. luminescens to form a symbiotic association with its host nematode, Heterorhabditis bacteriophora. We studied a highly abundant protein, Pam, which is secreted in a temperature-dependent manner in P. asymbiotica. Our findings indicate that Pam plays an important role in enhancing surface attachment in insect blood. Its association with exopolysaccharide suggests it may exert its effect through mediation of EPS properties. Despite

Photorhabdus adhesion modification protein (Pam binds extracellular polysaccharide and alters bacterial attachment

Directory of Open Access Journals (Sweden)

Joyce Susan A

2010-05-01

Full Text Available Abstract Background Photorhabdus are Gram-negative nematode-symbiotic and insect-pathogenic bacteria. The species Photorhabdus asymbiotica is able to infect humans as well as insects. We investigated the secreted proteome of a clinical isolate of P. asymbiotica at different temperatures in order to identify proteins relevant to the infection of the two different hosts. Results A comparison of the proteins secreted by a clinical isolate of P. asymbiotica at simulated insect (28°C and human (37°C temperatures led to the identification of a small and highly abundant protein, designated Pam, that is only secreted at the lower temperature. The pam gene is present in all Photorhabdus strains tested and shows a high level of conservation across the whole genus, suggesting it is both ancestral to the genus and probably important to the biology of the bacterium. The Pam protein shows limited sequence similarity to the 13.6 kDa component of a binary toxin of Bacillus thuringiensis. Nevertheless, injection or feeding of heterologously produced Pam showed no insecticidal activity to either Galleria mellonella or Manduca sexta larvae. In bacterial colonies, Pam is associated with an extracellular polysaccharide (EPS-like matrix, and modifies the ability of wild-type cells to attach to an artificial surface. Interestingly, Surface Plasmon Resonance (SPR binding studies revealed that the Pam protein itself has adhesive properties. Although Pam is produced throughout insect infection, genetic knockout does not affect either insect virulence or the ability of P. luminescens to form a symbiotic association with its host nematode, Heterorhabditis bacteriophora. Conclusions We studied a highly abundant protein, Pam, which is secreted in a temperature-dependent manner in P. asymbiotica. Our findings indicate that Pam plays an important role in enhancing surface attachment in insect blood. Its association with exopolysaccharide suggests it may exert its effect

Antibiotic resistance of bacterial biofilms

DEFF Research Database (Denmark)

Hoiby, N.; Bjarnsholt, T.; Givskov, M.

2010-01-01

A biofilm is a structured consortium of bacteria embedded in a self-produced polymer matrix consisting of polysaccharide, protein and DNA. Bacterial biofilms cause chronic infections because they show increased tolerance to antibiotics and disinfectant chemicals as well as resisting phagocytosis...... and other components of the body's defence system. The persistence of, for example, staphylococcal infections related to foreign bodies is due to biofilm formation. Likewise, chronic Pseudomonas aeruginosa lung infection in cystic fibrosis patients is caused by biofilm-growing mucoid strains....... Characteristically, gradients of nutrients and oxygen exist from the top to the bottom of biofilms and these gradients are associated with decreased bacterial metabolic activity and increased doubling times of the bacterial cells; it is these more or less dormant cells that are responsible for some of the tolerance...

Activity of glycated chitosan and other adjuvants to PDT vaccines

Science.gov (United States)

Korbelik, Mladen; Banáth, Judit; Čiplys, Evaldas; Szulc, Zdzislaw; Bielawska, Alicja; Chen, Wei R.

2015-03-01

Glycated chitosan (GC), a water soluble galactose-conjugated natural polysaccharide, has proven to be an effective immunoadjuvant for treatment of tumors based on laser thermal therapy. It was also shown to act as adjuvant for tumor therapy with high-intensity ultrasound and in situ photodynamic therapy (PDT). In the present study, GC was examined as potential adjuvant to PDT-generated cancer vaccine. Two other agents, pure calreticulin protein and acid ceramidase inhibitor LCL521, were also tested as prospective adjuvants for use in conjunction with PDT vaccines. Single treatment with GC, included with PDT vaccine cells suspension, improved the therapeutic efficacy when compared to vaccine alone. This attractive prospect of GC application remains to be carefully optimized and mechanistically elucidated. Both calreticulin and LCL521 proved also effective adjuvants when combined with PDT vaccine tumor treatment.

Bacterial derived proteoliposome for allergy vaccines.

Science.gov (United States)

Lastre, Miriam; Pérez, Oliver; Labrada, Alexis; Bidot, Igor; Pérez, Jorge; Bracho, Gustavo; del Campo, Judith; Pérez, Dainerys; Facenda, Elisa; Zayas, Caridad; Rodríguez, Claudio; Sierra, Gustavo

2006-04-12

One current approach in developing anti allergic vaccines is the use of potent adjuvants, capable of inducing Th1 or T regulatory cells. Proteoliposomes (PL) could be a suitable adjuvant. Purified Dermatophagoides siboney (Ds) allergens were mixed with PL and adsorbed into Al(OH)3 and evaluated in mice. The Th1/Th2 responses were measured at classes, subclasses, cytokines, and DTH levels. Anti Ds response was deviated to a Thl pattern, with the production of IgG2a and gamma1FN. A positive DTH response and a dramatic decrease of specific IgE and IL5 were not detected. The low dose was more effective than high dose. These results clearly support the potential use of PL as possible adjuvants for anti-allergic vaccines.

Fully human monoclonal antibodies from antibody secreting cells after vaccination with Pneumovax®23 are serotype specific and facilitate opsonophagocytosis.

Science.gov (United States)

Smith, Kenneth; Muther, Jennifer J; Duke, Angie L; McKee, Emily; Zheng, Nai-Ying; Wilson, Patrick C; James, Judith A

2013-05-01

B lymphocyte memory generates antibody-secreting cells (ASCs) that represent a source of protective antibodies that may be exploited for therapeutics. Here we vaccinated four donors with Pneumovax®23 and produced human monoclonal antibodies (hmAbs) from ASCs. We have cloned 137 hmAbs and the specificities of these antibodies encompass 19 of the 23 serotypes in the vaccine, as well as cell wall polysaccharide (CWPS). Although the majority of the antibodies are serotype specific, 12% cross-react with two serotypes. The Pneumovax®23 ASC antibody sequences are highly mutated and clonal, indicating an anamnestic response, even though this was a primary vaccination. Hmabs from 64% of the clonal families facilitate opsonophagocytosis. Although 9% of the total antibodies bind to CWPS impurity in the vaccine, none of these clonal families showed opsonophagocytic activity. Overall, these studies have allowed us to address unanswered questions in the field of human immune responses to polysaccharide vaccines, including the cross-reactivity of individual antibodies between serotypes and the percentage of antibodies that are protective after vaccination with Pneumovax®23. Copyright © 2012 Elsevier GmbH. All rights reserved.

Polysaccharide-producing microalgae

Energy Technology Data Exchange (ETDEWEB)

Braud, J.P.; Chaumont, D.; Gudin, C.; Thepenier, C.; Chassin, P.; Lemaire, C.

1982-11-01

The production of extracellular polysaccharides is studied with Nostoc sp (cyanophycus), Porphiridium cruentum, Rhodosorus marinus, Rhodella maculata (rhodophyci) and Chlamydomonas mexicana (chlorophycus). The polysaccharides produced are separated by centrifugation of the culture then precipitation with alcohol. Their chemical structure was studied by infrared spectrometry and acid hydrolysis. By their rheological properties and especially their insensitivity to temperatrure and pH variations the polysaccharides produced by Porphryridium cruentum and Rhodella maculata appear as suitable candidates for industrial applications.

Global practices of meningococcal vaccine use and impact on invasive disease

Science.gov (United States)

Ali, Asad; Jafri, Rabab Zehra; Messonnier, Nancy; Tevi-Benissan, Carol; Durrheim, David; Eskola, Juhani; Fermon, Florence; Klugman, Keith P; Ramsay, Mary; Sow, Samba; Zhujun, Shao; Bhutta, Zulfiqar; Abramson, Jon

2014-01-01

A number of countries now include meningococcal vaccines in their routine immunization programs. This review focuses on different approaches to including meningococcal vaccines in country programs across the world and their effect on the burden of invasive meningococcal disease (IMD) as reflected by pre and post-vaccine incidence rates in the last 20 years. Mass campaigns using conjugated meningococcal vaccines have lead to control of serogroup C meningococcal disease in the UK, Canada, Australia, Spain, Belgium, Ireland, and Iceland. Serogroup B disease, predominant in New Zealand, has been dramatically decreased, partly due to the introduction of an outer membrane vesicle (OMV) vaccine. Polysaccharide vaccines were used in high risk people in Saudi Arabia and Syria and in routine immunization in China and Egypt. The highest incidence region of the meningitis belt initiated vaccination with the serogroup A conjugate vaccine in 2010 and catch-up vaccination is ongoing. Overall results of this vaccine introduction are encouraging especially in countries with a moderate to high level of endemic disease. Continued surveillance is required to monitor effectiveness in countries that recently implemented these programs. PMID:24548156

[Vaccinal strategies in response to new epidemiological challenges in 2010. Reasonable hope for a "B" meningococcal vaccine].

Science.gov (United States)

Nicolas, P

2010-08-01

In 2010, vaccines have achieved good effectiveness against invasive meningococcal infection. Development of monovalent and bivalent polysaccharide (PS) vaccines in the 70s and later of tetravalent PS vaccine (ACWY) was followed by development in 2003 of a trivalent ACW vaccine in response to the W135 or mixed A/W135 epidemics that appeared in Africa. More recently PS-conjugated vaccines have shown numerous advantages in comparison with PS vaccines. Mass vaccination campaigns with the C-conjugated vaccine have almost completely eradicated group C meningitis in the UK. It is hoped that introduction of the A-conjugated vaccine MenAfriVac in Africa at the end of year 2010 will end group A meningococcal epidemics in the meningitis belt. The problem of group B meningococcal meningitis has not been completely resolved. For the B strain that has been implicated in hyperendemic waves, a protein vaccine has been produced from outer membrane vesicles (OMV). Use of OMV vaccines achieved good results in Norway and recently in New Zealand. The Norwegian vaccine was also used in Normandy since the strain responsible for the Norman epidemic showed the same PorA as the Norwegian strain. In this regard, a major limitation for OMV vaccines is that they are effective only against the immuno-dominant porin A protein. Current efforts to develop a vaccine against group B meningococci causing sporadic cases are promising. Research is being focused on a blend of surface proteins targeting most of circulating isolates. Field tests will be carried out in the next years, but it is probable that the efficacy of these vaccines will be short-lived since meningococcal antigens vary over time.

Serum bactericidal assay for the evaluation of typhoid vaccine using a semi-automated colony-counting method.

Science.gov (United States)

Jang, Mi Seon; Sahastrabuddhe, Sushant; Yun, Cheol-Heui; Han, Seung Hyun; Yang, Jae Seung

2016-08-01

Typhoid fever, mainly caused by Salmonella enterica serovar Typhi (S. Typhi), is a life-threatening disease, mostly in developing countries. Enzyme-linked immunosorbent assay (ELISA) is widely used to quantify antibodies against S. Typhi in serum but does not provide information about functional antibody titers. Although the serum bactericidal assay (SBA) using an agar plate is often used to measure functional antibody titers against various bacterial pathogens in clinical specimens, it has rarely been used for typhoid vaccines because it is time-consuming and labor-intensive. In the present study, we established an improved SBA against S. Typhi using a semi-automated colony-counting system with a square agar plate harboring 24 samples. The semi-automated SBA efficiently measured bactericidal titers of sera from individuals immunized with S. Typhi Vi polysaccharide vaccines. The assay specifically responded to S. Typhi Ty2 but not to other irrelevant enteric bacteria including Vibrio cholerae and Shigella flexneri. Baby rabbit complement was more appropriate source for the SBA against S. Typhi than complements from adult rabbit, guinea pig, and human. We also examined the correlation between SBA and ELISA for measuring antibody responses against S. Typhi using pre- and post-vaccination sera from 18 human volunteers. The SBA titer showed a good correlation with anti-Vi IgG quantity in the serum as determined by Spearman correlation coefficient of 0.737 (P measure functional antibody titers against S. Typhi in sera from human subjects immunized with typhoid vaccines. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

Polysaccharides enriched in rare sugars: bacterial sources, production and applications

Directory of Open Access Journals (Sweden)

Christophe eRoca

2015-04-01

Full Text Available Microbial extracellular polysaccharides (EPS, produced by a wide range of bacteria, are high molecular weight biopolymers, presenting an extreme diversity in terms of chemical structure and composition. They may be used in many applications, depending on their chemical and physical properties. A rather unexplored aspect is the presence of rare sugars in the composition of some EPS. Rare sugars, such as rhamnose or fucose, may provide EPS with additional biological properties compared to those composed of more common sugar monomers.This review gives a brief overview of these specific EPS and their producing bacteria. Cultivation conditions are summarized, demonstrating their impact on the EPS composition, together with downstream processing. Finally, their use in different areas, including cosmetics, food products, pharmaceuticals and biomedical applications, are discussed.

Immunologic properties and therapeutic efficacy of a multivalent epitope-based vaccine against four Helicobacter pylori adhesins (urease, Lpp20, HpaA, and CagL) in Mongolian gerbils.

Science.gov (United States)

Guo, Le; Yin, Runting; Xu, Guangxian; Gong, Xiaojuan; Chang, Zisong; Hong, Dantong; Liu, Hongpeng; Ding, Shuqin; Han, Xuebo; Li, Yuan; Tang, Feng; Liu, Kunmei

2017-12-01

Therapeutic vaccination is a desirable alternative for controlling Helicobacter pylori (H. pylori) infection. Attachment to the gastric mucosa is the first step in establishing bacterial colonization, and adhesins, which are on the surface of H. pylori, play a pivotal role in binding to human gastric mucosa. In the present study, we constructed a multivalent epitope-based vaccine named CFAdE with seven carefully selected antigenic fragments from four H. pylori adhesins (urease, Lpp20, HpaA and CagL). The specificity, immunogenicity and ability to produce neutralizing antibodies of CFAdE were evaluated in BALB/c mice. After that, its therapeutic efficacy and protective immune mechanisms were explored in H. pylori-infected Mongolian gerbils. The results indicated that CFAdE could induce comparatively high levels of specific antibodies against urease, Lpp20, HpaA and CagL. Additionally, oral therapeutic immunization with CFAdE plus polysaccharide adjuvant (PA) significantly decreased H. pylori colonization compared with oral immunization with urease plus PA, and the protection was correlated with IgG and sIgA antibody and antigen-specific CD4 + T cells. This study indicated that the multivalent epitope-based vaccine, which targeted multiple adhesins in adherence of H. pylori to the gastric mucosa, is more effective than the univalent vaccine targeting urease only. This multivalent epitope-based vaccine may be a promising therapeutic candidate vaccine against H. pylori infection. © 2017 John Wiley & Sons Ltd.

Vaccine process technology.

Science.gov (United States)

Josefsberg, Jessica O; Buckland, Barry

2012-06-01

The evolution of vaccines (e.g., live attenuated, recombinant) and vaccine production methods (e.g., in ovo, cell culture) are intimately tied to each other. As vaccine technology has advanced, the methods to produce the vaccine have advanced and new vaccine opportunities have been created. These technologies will continue to evolve as we strive for safer and more immunogenic vaccines and as our understanding of biology improves. The evolution of vaccine process technology has occurred in parallel to the remarkable growth in the development of therapeutic proteins as products; therefore, recent vaccine innovations can leverage the progress made in the broader biotechnology industry. Numerous important legacy vaccines are still in use today despite their traditional manufacturing processes, with further development focusing on improving stability (e.g., novel excipients) and updating formulation (e.g., combination vaccines) and delivery methods (e.g., skin patches). Modern vaccine development is currently exploiting a wide array of novel technologies to create safer and more efficacious vaccines including: viral vectors produced in animal cells, virus-like particles produced in yeast or insect cells, polysaccharide conjugation to carrier proteins, DNA plasmids produced in E. coli, and therapeutic cancer vaccines created by in vitro activation of patient leukocytes. Purification advances (e.g., membrane adsorption, precipitation) are increasing efficiency, while innovative analytical methods (e.g., microsphere-based multiplex assays, RNA microarrays) are improving process understanding. Novel adjuvants such as monophosphoryl lipid A, which acts on antigen presenting cell toll-like receptors, are expanding the previously conservative list of widely accepted vaccine adjuvants. As in other areas of biotechnology, process characterization by sophisticated analysis is critical not only to improve yields, but also to determine the final product quality. From a regulatory

Epidemiology and outcomes of bacterial meningitis in Mexican children: 10-year experience (1993-2003).

Science.gov (United States)

Franco-Paredes, Carlos; Lammoglia, Lorena; Hernández, Isabel; Santos-Preciado, José Ignacio

2008-07-01

Acute bacterial meningitis remains an important cause of morbidity, neurologic sequelae, and mortality in children in Latin America. We retrospectively reviewed the hospital-based medical records of children diagnosed with acute bacterial meningitis, aged 1 month to 18 years, at a large inner city referral Hospital in Mexico City, for a 10-year period (1993-2003). To characterize the epidemiology, clinical features, and outcomes of acute bacterial meningitis, we subdivided our study into two time periods: the period prior to the routine use of Haemophilus influenzae type b (Hib) vaccine (1993-1998) and the period after the vaccine became available (1999-2003). A total of 218 cases of acute bacterial meningitis were identified during the study period. The most frequently affected age group was that of children aged between 1 and 6 months. Hib was the most commonly isolated pathogen, found in 50% of cases. However, its incidence declined significantly after the introduction of the combined diphtheria, tetanus, pertussis, hepatitis B, and conjugated Hib (DTP-HB/Hib) pentavalent vaccine into the universal vaccination schedule for children in 1998. Streptococcus pneumoniae followed as the second most commonly isolated bacterial pathogen. Neisseria meningitidis was isolated in only a few cases, confirming the historically low incidence of this pathogen in Mexico. Identified risk factors for death were found to include the presence of septic shock and intracranial hypertension, but were not attributable to any particular bacterial pathogen. In our hospital, acute bacterial meningitis remains a severe disease with important sequelae and mortality. The incidence of Hib meningitis cases has declined since the introduction of the Hib vaccine. However, S. pneumoniae persists as an important cause of bacterial meningitis, highlighting the need for the implementation of vaccination policies against this pathogen.

A DTAP–IPV//PRP~T VACCINE: A REVIEW OF 16 YEARS’ CLINICAL EXPERIENCE

Directory of Open Access Journals (Sweden)

Stanley A. Plotkin

2012-01-01

Full Text Available Owing to their low reactogenicity, confirmed efficacy and availability in combination vaccines, acellular pertussis (aP-inactivated poliovirus (IPV combined vaccines are now included in various national immunization programs worldwide. We provide an overview of 16 years of clinical experience with a diphtheria (D, tetanus (T, aP, IPV and Haemophilus influenzae type b (Hib polysaccharide conjugated to tetanus protein (PRP~T combined vaccine (DTaP–IPV//PRP~T — Pentaxim, Sanofi Pasteur, France. Good immunogenicity has been demonstrated after primary vaccination with Pentaxim, regardless of the population ethnicity and primary vaccination schedule. A booster vaccination in the second year of life also resulted in a high immune response for each antigen. Furthermore, 10 years of national surveillance in Sweden has demonstrated the effectiveness of Pentaxim in controlling pertussis. As is the case for other aP-containing combined vaccines, Pentaxim is well tolerated, with the safety profile being better than for whole-cell pertussiscontaining combination vaccines for primary and booster vaccinations.

Reduction of Coxiella burnetii prevalence by vaccination of goats and sheep, The Netherlands.

Science.gov (United States)

Hogerwerf, Lenny; van den Brom, René; Roest, Hendrik I J; Bouma, Annemarie; Vellema, Piet; Pieterse, Maarten; Dercksen, Daan; Nielen, Mirjam

2011-03-01

Recently, the number of human Q fever cases in the Netherlands increased dramatically. In response to this increase, dairy goats and dairy sheep were vaccinated against Coxiella burnetii. All pregnant dairy goats and dairy sheep in herds positive for Q fever were culled. We identified the effect of vaccination on bacterial shedding by small ruminants. On the day of culling, samples of uterine fluid, vaginal mucus, and milk were obtained from 957 pregnant animals in 13 herds. Prevalence and bacterial load were reduced in vaccinated animals compared with unvaccinated animals. These effects were most pronounced in animals during their first pregnancy. Results indicate that vaccination may reduce bacterial load in the environment and human exposure to C. burnetii.

A Perfect Storm: Increased Colonization and Failure of Vaccination Leads to Severe Secondary Bacterial Infection in Influenza Virus-Infected Obese Mice

Directory of Open Access Journals (Sweden)

Erik A. Karlsson

2017-09-01

Full Text Available Obesity is a risk factor for developing severe disease following influenza virus infection; however, the comorbidity of obesity and secondary bacterial infection, a serious complication of influenza virus infections, is unknown. To fill this gap in knowledge, lean and obese C57BL/6 mice were infected with a nonlethal dose of influenza virus followed by a nonlethal dose of Streptococcus pneumoniae. Strikingly, not only did significantly enhanced death occur in obese coinfected mice compared to lean controls, but also high mortality was seen irrespective of influenza virus strain, bacterial strain, or timing of coinfection. This result was unexpected, given that most influenza virus strains, especially seasonal human A and B viruses, are nonlethal in this model. Both viral and bacterial titers were increased in the upper respiratory tract and lungs of obese animals as early as days 1 and 2 post-bacterial infection, leading to a significant decrease in lung function. This increased bacterial load correlated with extensive cellular damage and upregulation of platelet-activating factor receptor, a host receptor central to pneumococcal invasion. Importantly, while vaccination of obese mice against either influenza virus or pneumococcus failed to confer protection, antibiotic treatment was able to resolve secondary bacterial infection-associated mortality. Overall, secondary bacterial pneumonia could be a widespread, unaddressed public health problem in an increasingly obese population.

Strain-Specific Features of Extracellular Polysaccharides and Their Impact on Lactobacillus plantarum-Host Interactions.

Science.gov (United States)

Lee, I-Chiao; Caggianiello, Graziano; van Swam, Iris I; Taverne, Nico; Meijerink, Marjolein; Bron, Peter A; Spano, Giuseppe; Kleerebezem, Michiel

2016-07-01

Lactobacilli are found in diverse environments and are widely applied as probiotic, health-promoting food supplements. Polysaccharides are ubiquitously present on the cell surface of lactobacilli and are considered to contribute to the species- and strain-specific probiotic effects that are typically observed. Two Lactobacillus plantarum strains, SF2A35B and Lp90, have an obvious ropy phenotype, implying high extracellular polysaccharide (EPS) production levels. In this work, we set out to identify the genes involved in EPS production in these L. plantarum strains and to demonstrate their role in EPS production by gene deletion analysis. A model L. plantarum strain, WCFS1, and its previously constructed derivative that produced reduced levels of EPS were included as reference strains. The constructed EPS-reduced derivatives were analyzed for the abundance and sugar compositions of their EPS, revealing cps2-like gene clusters in SF2A35B and Lp90 responsible for major EPS production. Moreover, these mutant strains were tested for phenotypic characteristics that are of relevance for their capacity to interact with the host epithelium in the intestinal tract, including bacterial surface properties as well as survival under the stress conditions encountered in the gastrointestinal tract (acid and bile stress). In addition, the Toll-like receptor 2 (TLR2) signaling and immunomodulatory capacities of the EPS-negative derivatives and their respective wild-type strains were compared, revealing strain-specific impacts of EPS on the immunomodulatory properties. Taken together, these experiments illustrate the importance of EPS in L. plantarum strains as a strain-specific determinant in host interaction. This study evaluates the role of extracellular polysaccharides that are produced by different strains of Lactobacillus plantarum in the determination of the cell surface properties of these bacteria and their capacity to interact with their environment, including their

Biochemical And Genetic Modification Of Polysaccharides

Science.gov (United States)

Kern, Roger G.; Petersen, Gene R.; Richards, Gil F.

1993-01-01

Bacteriophages producing endopolysaccharase-type enzymes used to produce, isolate, and purify high yields of modified polysaccharides from polysaccharides produced by, and incorporated into capsules of, certain bacteria. Bacteriophages used in conversion of native polysaccharide materials into polymers of nearly uniform high molecular weight or, alternatively, into highly pure oligosaccharides. Also used in genetic selection of families of polysaccharides structurally related to native polysaccharide materials, but having altered properties. Resulting new polysaccharides and oligosaccharides prove useful in variety of products, including pharmaceutical chemicals, coating materials, biologically active carbohydrates, and drag-reducing additives for fluids.

Genome-derived vaccines.

Science.gov (United States)

De Groot, Anne S; Rappuoli, Rino

2004-02-01

Vaccine research entered a new era when the complete genome of a pathogenic bacterium was published in 1995. Since then, more than 97 bacterial pathogens have been sequenced and at least 110 additional projects are now in progress. Genome sequencing has also dramatically accelerated: high-throughput facilities can draft the sequence of an entire microbe (two to four megabases) in 1 to 2 days. Vaccine developers are using microarrays, immunoinformatics, proteomics and high-throughput immunology assays to reduce the truly unmanageable volume of information available in genome databases to a manageable size. Vaccines composed by novel antigens discovered from genome mining are already in clinical trials. Within 5 years we can expect to see a novel class of vaccines composed by genome-predicted, assembled and engineered T- and Bcell epitopes. This article addresses the convergence of three forces--microbial genome sequencing, computational immunology and new vaccine technologies--that are shifting genome mining for vaccines onto the forefront of immunology research.

AEROMONAS SALMONICIDA INFECTION IN VACCINATED RAINBOW TROUT

DEFF Research Database (Denmark)

Chettri, Jiwan Kumar; Skov, Jakob; Mohammad, Rezkar Jaafar

In vivo testing of any candidate vaccine is influenced by the choice of challenge method and the external environmental conditions. In the present study, a comparative challenge study was performed to evaluate the efficacy of different vaccines against the bacterial pathogen Aeromonas salmonicida...

Polysaccharide charge density regulating protein adsorption to air/water interfaces by protein/polysaccharide complex formation

NARCIS (Netherlands)

Ganzevles, R.A.; Kosters, H.; Vliet, T. van; Stuart, M.A.C.; Jongh, H.H.J. de

2007-01-01

Because the formation of protein/polysaccharide complexes is dominated by electrostatic interaction, polysaccharide charge density is expected to play a major role in the adsorption behavior of the complexes. In this study, pullulan (a non-charged polysaccharide) carboxylated to four different

Surface-bound capsular polysaccharide of type Ia group B Streptococcus mediates C1 binding and activation of the classic complement pathway

International Nuclear Information System (INIS)

Levy, N.J.; Kasper, D.L.

1986-01-01

The role of surface-bound type Ia group B Streptococcus (GBS) capsular polysaccharide in anti-body-independent binding of C1 and activation of the classic component pathway was investigated. In a radiolabeled bacterial-polymorphonuclear leukocyte (PMN) association assay, a measure of bacterial opsonization, preincubation of 3 H-type Ia GBS with purified F(ab') 2 to the organism blocked the association of the bacteria with PMN', and the inhibitory effect was dose dependent. The specificity of F(ab') 2 blocking was shown after adsorption of F(ab') 2 with type Ia polysaccharide-sensitized erythrocytes. Polysaccharide-adsorbed F(ab') 2 had a 70% decrease in ability to block the association of bacteria with PMN. Neuraminidase digestion removed 80% of the terminal sialic acid residues from the native polysaccharide. These neuraminidase-digested organisms had a 72% decrease in binding and transfer of purified C1 compared with non-enzyme-treated organisms. Type Ia capsular polysaccharide bound to sheep erythrocytes promoted classic complement pathway-mediated hemolysis of the cells. The role of C1 inhibitor (INH) in modulation of C1 activation by the organisms was investigated. The possibility existed that the C1 INH could be bound by the bacteria, allowing C1 activation to occur in the fluid phase. The inhibitor was purified from human serum, and its activity was measured before and after incubation with type Ia GBS. The organisms had no effect on C1 INH activity. Thus surface-bound capsular polysacchardie of type Ia GBS mediates C1 binding and classic pathway activation, and this does not involve the C1 INH

Postviral Complications: Bacterial Pneumonia.

Science.gov (United States)

Prasso, Jason E; Deng, Jane C

2017-03-01

Secondary bacterial pneumonia after viral respiratory infection remains a significant source of morbidity and mortality. Susceptibility is mediated by a variety of viral and bacterial factors, and complex interactions with the host immune system. Prevention and treatment strategies are limited to influenza vaccination and antibiotics/antivirals respectively. Novel approaches to identifying the individuals with influenza who are at increased risk for secondary bacterial pneumonias are urgently needed. Given the threat of further pandemics and the heightened prevalence of these viruses, more research into the immunologic mechanisms of this disease is warranted with the hope of discovering new potential therapies. Published by Elsevier Inc.

A Direct Sulfation Process of a Marine Polysaccharide in Ionic Liquid

Directory of Open Access Journals (Sweden)

Nathalie Chopin

2015-01-01

Full Text Available GY785 is an exopolysaccharide produced by a mesophilic bacterial strain Alteromonas infernus discovered in the deep-sea hydrothermal vents. GY785 highly sulfated derivative (GY785 DRS was previously demonstrated to be a promising molecule driving the efficient mesenchymal stem cell chondrogenesis for cartilage repair. This glycosaminoglycan- (GAG- like compound was modified in a classical solvent (N,N′-dimethylformamide. However, the use of classical solvents limits the polysaccharide solubility and causes the backbone degradation. In the present study, a one-step efficient sulfation process devoid of side effects (e.g., polysaccharide depolymerization and/or degradation was developed to produce GAG-like derivatives. The sulfation of GY785 derivative (GY785 DR was carried out using ionic liquid as a reaction medium. The successful sulfation of this anionic and highly branched heteropolysaccharide performed in ionic liquid would facilitate the production of new molecules of high specificity for biological targets such as tissue engineering or regenerative medicine.

Vaccine preventable meningitis in Malaysia: epidemiology and management.

Science.gov (United States)

McNeil, Hannah C; Jefferies, Johanna M C; Clarke, Stuart C

2015-06-01

Worldwide bacterial meningitis accounts for more than one million cases and 135,000 deaths annually. Profound, lasting neurological complications occur in 9-25% of cases. This review confirms the greatest risk from bacterial meningitis is in early life in Malaysia. Much of the disease burden can be avoided by immunization, particularly against Haemophilus influenzae type b (Hib) and Streptococcus pneumoniae. Despite inclusion of the Hib vaccine in the National Immunisation Programme and the licensure of pneumococcal vaccines, these two species are the main contributors to bacterial meningitis in Malaysia, with Neisseria meningitidis and Mycobacterium tuberculosis, causing a smaller proportion of disease. The high Hib prevalence may partly be due to dated, small-scale studies limiting the understanding of the current epidemiological situation. This highlights the need for larger, better quality surveillance from Malaysia to evaluate the success of Hib immunization and to help guide immunization policy for vaccines against S. pneumoniae and N. meningitidis.

Computer simulation and experimental study of the polysaccharide-polysaccharide interaction in the bacteria Azospirillum brasilense Sp245

Science.gov (United States)

Arefeva, Oksana A.; Kuznetsov, Pavel E.; Tolmachev, Sergey A.; Kupadze, Machammad S.; Khlebtsov, Boris N.; Rogacheva, Svetlana M.

2003-09-01

We have studied the conformational properties and molecular dynamics of polysaccharides by using molecular modeling methods. Theoretical and experimental results of polysaccharide-polysaccharide interactions are described.

Bacterial Meningitis in Adults After Splenectomy and Hyposplenic States

NARCIS (Netherlands)

Adriani, Kirsten S.; Brouwer, Matthijs C.; van der Ende, Arie; van de Beek, Diederik

2013-01-01

Objective: To examine the occurrence, disease course, prognosis, and vaccination status of patients with community-acquired bacterial meningitis with a history of splenectomy or functional hyposplenia. Patients and Methods: Patients with bacterial meningitis proven by cerebrospinal fluid culture

Curdlan sulfate-O-linked quaternized chitosan nanoparticles: potential adjuvants to improve the immunogenicity of exogenous antigens via intranasal vaccination.

Science.gov (United States)

Zhang, Shu; Huang, Shengshi; Lu, Lu; Song, Xinlei; Li, Pingli; Wang, Fengshan

2018-01-01

The development of ideal vaccine adjuvants for intranasal vaccination can provide convenience for many vaccinations. As an ideal intranasal vaccine adjuvant, it should have the properties of assisting soluble antigens to pass the mucosal barrier and potentiating both systemic and mucosal immunity via nasal administration. By using the advantages of polysaccharides, which can promote both T-helper 1 and 2 responses, curdlan sulfate (CS)- O -(2-hydroxyl)propyl-3-trimethyl ammonium chitosan chloride ( O -HTCC) nanoparticles were prepared by interacting CS with O -HTCC, and the adjuvancy of the nanoparticles was investigated. The results showed that the polysaccharide-based nanoparticles induced the proliferation and activation of antigen-presenting cells. High protein-loading efficiency was obtained by testing with the model antigen ovalbumin (Ova), and the Ova adsorbed onto the cationic CS/ O -HTCC complexes was taken up easily by the epithelium. To evaluate the capacity of the Ova/CS/ O -HTCC nanoparticles for immune enhancement in vivo, we collected and analyzed immunocytes, serum, and mucosal lavage fluid from intranasally vaccinated mice. The results showed that Ova/CS/ O -HTCC nanoparticles induced activation and maturation of antigen-presenting cells and provoked the proliferation and differentiation of lymphocytes more significantly compared to the immunization of Ova mixed with aluminum hydroxide gel. Furthermore, CS/ O -HTCC evoked a significantly higher level of Ova-specific antibodies. Therefore, these results suggest that CS/ O -HTCC nanoparticles are ideal vaccine adjuvants for soluble antigens used in intranasal or mucosal vaccination.

Seaweed Polysaccharides and Derived Oligosaccharides Stimulate Defense Responses and Protection Against Pathogens in Plants

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Alejandra Moenne

2011-11-01

Full Text Available Plants interact with the environment by sensing “non-self” molecules called elicitors derived from pathogens or other sources. These molecules bind to specific receptors located in the plasma membrane and trigger defense responses leading to protection against pathogens. In particular, it has been shown that cell wall and storage polysaccharides from green, brown and red seaweeds (marine macroalgae corresponding to ulvans, alginates, fucans, laminarin and carrageenans can trigger defense responses in plants enhancing protection against pathogens. In addition, oligosaccharides obtained by depolymerization of seaweed polysaccharides also induce protection against viral, fungal and bacterial infections in plants. In particular, most seaweed polysaccharides and derived oligosaccharides trigger an initial oxidative burst at local level and the activation of salicylic (SA, jasmonic acid (JA and/or ethylene signaling pathways at systemic level. The activation of these signaling pathways leads to an increased expression of genes encoding: (i Pathogenesis-Related (PR proteins with antifungal and antibacterial activities; (ii defense enzymes such as pheylalanine ammonia lyase (PAL and lipoxygenase (LOX which determine accumulation of phenylpropanoid compounds (PPCs and oxylipins with antiviral, antifugal and antibacterial activities and iii enzymes involved in synthesis of terpenes, terpenoids and/or alkaloids having antimicrobial activities. Thus, seaweed polysaccharides and their derived oligosaccharides induced the accumulation of proteins and compounds with antimicrobial activities that determine, at least in part, the enhanced protection against pathogens in plants.

Pneumococcal and influenza vaccination status of hospitalized adults with community acquired pneumonia and the effects of vaccination on clinical presentation.

Science.gov (United States)

Demirdogen Cetinoglu, Ezgi; Uzaslan, Esra; Sayıner, Abdullah; Cilli, Aykut; Kılınc, Oguz; Sakar Coskun, Aysın; Hazar, Armağan; Kokturk, Nurdan; Filiz, Ayten; Polatli, Mehmet

2017-09-02

Previous reports have shown that vaccination rates of adult at-risk populations are low in Turkey. There are differing reports with regards to the effectiveness of the influenza and the pneumococcal polysaccharide vaccine (PPSV23) on the clinical outcomes of community acquired pneumonia (CAP). The purpose of this study was to analyze the influenza (FV) and pneumococcal vaccination (PV) status, the factors that influence the receipt of influenza/pneumococcal vaccine and the effects of prior vaccination on the clinical outcomes in adults hospitalized with CAP. Patients hospitalized with CAP between March 2009 and October 2013 and registered at the web-based Turkish Thoracic Society Pneumonia Database (TURCAP) were included in this multicentric, observational study. Of a total of 787 cases, data were analyzed for 466 patients for whom self-reported information on PV and FV was available. In this adult population with CAP, the vaccination rate with both the pneumococcal and influenza vaccines was found to be 6%. Prior FV was found to be the sole variable that was associated with the receipt of PV [OR 17.8, 95% CI (25-75:8.56-37.01), p pneumonia severity index (PSI) score ≥ 90, CURB-65 score ≥3 and multilobar involvement, but not the vaccination status, were identified as independent determinants of ICU admission. This study showed that, among patients hospitalized with CAP, the FV and/or PV rates are low. Prior vaccination does not appear to significantly affect the clinical outcomes.

Rationale and methods of a randomized controlled trial of immunogenicity, safety and impact on carriage of pneumococcal conjugate and polysaccharide vaccines in infants in Papua New Guinea.

Science.gov (United States)

Lehmann, Deborah; Kirarock, Wendy; van den Biggelaar, Anita H J; Passey, Megan; Jacoby, Peter; Saleu, Gerard; Masiria, Geraldine; Nivio, Birunu; Greenhill, Andrew; Orami, Tilda; Francis, Jacinta; Ford, Rebecca; Kirkham, Lea-Ann; Solomon, Vela; Richmond, Peter C; Pomat, William S

2017-01-01

Children in third-world settings including Papua New Guinea (PNG) experience early onset of carriage with a broad range of pneumococcal serotypes, resulting in a high incidence of severe pneumococcal disease and deaths in the first 2 years of life. Vaccination trials in high endemicity settings are needed to provide evidence and guidance on optimal strategies to protect children in these settings against pneumococcal infections. This report describes the rationale, objectives, methods, study population, follow-up and specimen collection for a vaccination trial conducted in an endemic and logistically challenging setting in PNG. The trial aimed to determine whether currently available pneumococcal conjugate vaccines (PCV) are suitable for use under PNG's accelerated immunization schedule, and that a schedule including pneumococcal polysaccharide vaccine (PPV) in later infancy is safe and immunogenic in this high-risk population. This open randomized-controlled trial was conducted between November 2011 and March 2016, enrolling 262 children aged 1 month between November 2011 and April 2014. The participants were randomly allocated (1:1) to receive 10-valent PCV (10vPCV) or 13-valent PCV (13vPCV) in a 1-2-3-month schedule, with further randomization to receive PPV or no PPV at age 9 months, followed by a 1/5 th PPV challenge at age 23 months. A total of 1229 blood samples were collected to measure humoral and cellular immune responses and 1238 nasopharyngeal swabs to assess upper respiratory tract colonization and carriage load. Serious adverse events were monitored throughout the study. Of the 262 children enrolled, 87% received 3 doses of PCV, 79% were randomized to receive PPV or no PPV at age 9 months, and 67% completed the study at 24 months of age with appropriate immunization and challenge. Laboratory testing of the many samples collected during this trial will determine the impact of the different vaccine schedules and formulations on nasopharyngeal

From Epidemic Meningitis Vaccines for Africa to the Meningitis Vaccine Project.

Science.gov (United States)

Aguado, M Teresa; Jodar, Luis; Granoff, Dan; Rabinovich, Regina; Ceccarini, Costante; Perkin, Gordon W

2015-11-15

Polysaccharide vaccines had been used to control African meningitis epidemics for >30 years but with little or modest success, largely because of logistical problems in the implementation of reactive vaccination campaigns that are begun after epidemics are under way. After the major group A meningococcal meningitis epidemics in 1996-1997 (250,000 cases and 25,000 deaths), African ministers of health declared the prevention of meningitis a high priority and asked the World Health Organization (WHO) for help in developing better immunization strategies to eliminate meningitis epidemics in Africa. WHO accepted the challenge and created a project called Epidemic Meningitis Vaccines for Africa (EVA) that served as an organizational framework for external consultants, PATH, the US Centers for Disease Control and Prevention (CDC), and the Bill & Melinda Gates Foundation (BMGF). Consultations were initiated with major vaccine manufacturers. EVA commissioned a costing study/business plan for the development of new group A or A/C conjugate vaccines and explored the feasibility of developing these products as a public-private partnership. Representatives from African countries were consulted. They confirmed that the development of conjugate vaccines was a priority and provided information on preferred product characteristics. In parallel, a strategy for successful introduction was also anticipated and discussed. The expert consultations recommended that a group A meningococcal conjugate vaccine be developed and introduced into the African meningitis belt. The results of the costing study indicated that the "cost of goods" to develop a group A - containing conjugate vaccine in the United States would be in the range of US$0.35-$1.35 per dose, depending on composition (A vs A/C), number of doses/vials, and presentation. Following an invitation from BMGF, a proposal was submitted in the spring of 2001. In June 2001, BMGF awarded a grant of US$70 million to create the Meningitis

Radiation processed polysaccharide products

International Nuclear Information System (INIS)

Nguyen, Quoc Hien

2007-01-01

Radiation crosslinking, degradation and grafting techniques for modification of polymeric materials including natural polysaccharides have been providing many unique products. In this communication, typical products from radiation processed polysaccharides particularly plant growth promoter from alginate, plant protector and elicitor from chitosan, super water absorbent containing starch, hydrogel sheet containing carrageenan/CM-chitosan as burn wound dressing, metal ion adsorbent from partially deacetylated chitin were described. The procedures for producing those above products were also outlined. Future development works on radiation processing of polysaccharides were briefly presented. (author)

Severe febrile systemic reaction to pneumococcal vaccine.

Science.gov (United States)

Hasan, Syed; Yousef, Mahmoud; Shridharani, Sachin

2005-02-01

Polyvalent pneumococcal polysaccharide vaccine (Pneumovax, PPV) has been shown to substantially reduce the risk of Streptococcus pneumoniae infections in susceptible individuals. Side effects, such as mild local erythema, induration, pain and fever, have been reported with various frequencies. Rarely, systemic symptoms, including high fever, headache, nausea and photophobia, have been reported in the literature. This case report describes a 38-year-old male who developed severe and prolonged local and systemic symptoms necessitating hospitalization following a dose of pneumovax.

Using polysaccharides against cancer

Directory of Open Access Journals (Sweden)

E. Azarnoosh

2017-11-01

Full Text Available Background and objectives: Nowadays cancer is one of the most important concerns of the society. The adverse effects of common therapeutics and resistance of some cancerous cells to treatment have brought the necessity of new approaches towards the issue. Polysaccharides are a group of carbohydrates found in natural sources. In the present article, our goal was to show the positive effects of carbohydrates (especially polysaccharides in cancer treatment, based on literature review. Methods: The literature review was carried out between 1990 and 2017 inclusive using the following search terms: cancer, carbohydrate and polysaccharide and was performed with use of Google scholar, Medline, Scopus, PubMed, Elsevier and other similar data banks, related to medicine and pharmaceutical fields. Results: Plants like Lyceum barbarum, Astragalus membrannceous, Panax ginseng, and Antrodia camphorate have been studied with promising effects in combating cancerous cells. The polysaccharides from these plants have benefits with numerous mechanisms such as apoptosis, inhibition of angiogenesis, anti-proliferation, immunomodulation, tumor suppression, and increase in macrophage activity. Other studies showed over 200 mushrooms with anticancer effects, especially basidiomycetes (e.g. Ganoderma lucidum. Sulfated polysaccharides found in sea and animals or even a few bacteria like E. coli showed to be useful in cancer. Conclusion: Scientists are realizing the importance of natural drugs and polysaccharide as good and available sources that could give a bright future for prevention, cure and palliative therapy in cancer.

Subcutaneous immunization with inactivated bacterial components and purified protein of Escherichia coli, Fusobacterium necrophorum and Trueperella pyogenes prevents puerperal metritis in Holstein dairy cows.

Science.gov (United States)

Machado, Vinícius Silva; Bicalho, Marcela Luccas de Souza; Meira Junior, Enoch Brandão de Souza; Rossi, Rodolfo; Ribeiro, Bruno Leonardo; Lima, Svetlana; Santos, Thiago; Kussler, Arieli; Foditsch, Carla; Ganda, Erika Korzune; Oikonomou, Georgios; Cheong, Soon Hon; Gilbert, Robert Owen; Bicalho, Rodrigo Carvalho

2014-01-01

In this study we evaluate the efficacy of five vaccine formulations containing different combinations of proteins (FimH; leukotoxin, LKT; and pyolysin, PLO) and/or inactivated whole cells (Escherichia coli, Fusobacterium necrophorum, and Trueperella pyogenes) in preventing postpartum uterine diseases. Inactivated whole cells were produced using two genetically distinct strains of each bacterial species (E. coli, F. necrophorum, and T. pyogenes). FimH and PLO subunits were produced using recombinant protein expression, and LKT was recovered from culturing a wild F. necrophorum strain. Three subcutaneous vaccines were formulated: Vaccine 1 was composed of inactivated bacterial whole cells and proteins; Vaccine 2 was composed of proteins only; and Vaccine 3 was composed of inactivated bacterial whole cells only. Two intravaginal vaccines were formulated: Vaccine 4 was composed of inactivated bacterial whole cells and proteins; and Vaccine 5 was composed of PLO and LKT. To evaluate vaccine efficacy, a randomized clinical trial was conducted at a commercial dairy farm; 371 spring heifers were allocated randomly into one of six different treatments groups: control, Vaccine 1, Vaccine 2, Vaccine 3, Vaccine 4 and Vaccine 5. Late pregnant heifers assigned to one of the vaccine groups were each vaccinated twice: at 230 and 260 days of pregnancy. When vaccines were evaluated grouped as subcutaneous and intravaginal, the subcutaneous ones were found to significantly reduce the incidence of puerperal metritis. Additionally, subcutaneous vaccination significantly reduced rectal temperature at 6±1 days in milk. Reproduction was improved for cows that received subcutaneous vaccines. In general, vaccination induced a significant increase in serum IgG titers against all antigens, with subcutaneous vaccination again being more effective. In conclusion, subcutaneous vaccination with inactivated bacterial components and/or protein subunits of E. coli, F. necrophorum and T. pyogenes

Antioxidant effects of polysaccharides from traditional Chinese medicines.

Science.gov (United States)

Liu, Yang; Huang, Gangliang

2017-12-07

Polysaccharides are a kind of biological macromolecules with immune regulation, anti-tumor, anti-radiation, anti-inflammation, anti-fatigue and anti-aging effects. These effects are related to their antioxidant properties. The action mechanisms of antioxidation and scavenging free radicals for polysaccharides were reviewed. The polysaccharides contain plant polysaccharides, animal polysaccharides and microbial polysaccharides. The recent research progresses and our work on antioxidant properties of polysaccharides and their derivatives were summarized. At last, the existing problems of antioxidant polysaccharides were analyzed, and the development prospects were also presented. It is important to study the antioxidant activities of polysaccharides and their derivatives for the development of natural antioxidants. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Human body temperature and new approaches to constructing temperature-sensitive bacterial vaccines.

Science.gov (United States)

White, Matthew D; Bosio, Catharine M; Duplantis, Barry N; Nano, Francis E

2011-09-01

Many of the live human and animal vaccines that are currently in use are attenuated by virtue of their temperature-sensitive (TS) replication. These vaccines are able to function because they can take advantage of sites in mammalian bodies that are cooler than the core temperature, where TS vaccines fail to replicate. In this article, we discuss the distribution of temperature in the human body, and relate how the temperature differential can be exploited for designing and using TS vaccines. We also examine how one of the coolest organs of the body, the skin, contains antigen-processing cells that can be targeted to provoke the desired immune response from a TS vaccine. We describe traditional approaches to making TS vaccines, and highlight new information and technologies that are being used to create a new generation of engineered TS vaccines. We pay particular attention to the recently described technology of substituting essential genes from Arctic bacteria for their homologues in mammalian pathogens as a way of creating TS vaccines.

Polysaccharide-Based Micelles for Drug Delivery

Directory of Open Access Journals (Sweden)

Nan Zhang

2013-05-01

Full Text Available Delivery of hydrophobic molecules and proteins has been an issue due to poor bioavailability following administration. Thus, micelle carrier systems are being investigated to improve drug solubility and stability. Due to problems with toxicity and immunogenicity, natural polysaccharides are being explored as substitutes for synthetic polymers in the development of new micelle systems. By grafting hydrophobic moieties to the polysaccharide backbone, self-assembled micelles can be readily formed in aqueous solution. Many polysaccharides also possess inherent bioactivity that can facilitate mucoadhesion, enhanced targeting of specific tissues, and a reduction in the inflammatory response. Furthermore, the hydrophilic nature of some polysaccharides can be exploited to enhance circulatory stability. This review will highlight the advantages of polysaccharide use in the development of drug delivery systems and will provide an overview of the polysaccharide-based micelles that have been developed to date.

EFFICACY AND SAFETY OF 23-VALENT PNEUMOCOCCAL POLYSACCHARIDE VACCINE IN PATIENTS WITH RHEUMATOID ARTHRITIS

Directory of Open Access Journals (Sweden)

M. S. Naumtseva

2015-01-01

Full Text Available Objective: to study the clinical efficacy, immunogenicity, and safety of a 23-valent pneumococcal vaccine in patients with rheumatoid arthritis (RA. Subjects and methods. The investigation enrolled 70 patients (55 women and 15 men aged 23–70 years, including 40 patients with RA and 30 people without systemic inflammatory rheumatic diseases (a control group who had a recent history of 2 and more cases of lower respiratory tract infections (bronchitis, pneumonia. When included, all the patients received anti-inflammatory therapy with methotrexate (MT (n = 24, leflunomide (LEF (n = 6, or MT + tumor necrosis factor-α (TNF-α inhibitors (n = 10. A single 0.5-ml dose of the 23-valent pneumococcal vaccine Pneumo-23 (Sanofi Pasteur was administered subcutaneously or intramuscularly during continuous MT or LEF therapy for the underlying disease or 3–4 weeks before the use of a TNF-α inhibitor. During control visits (1 and 3 months and 1 year after administration of the vaccine, the patients underwent physical examination and routine clinical and laboratory studies. Results. No clinical and radiological symptoms of pneumonia were recorded in any case during a 12-month follow-up. The RA and control groups showed a more than 2-fold increase in anti-pneumococcal antibody levels 1 year after vaccination. The vaccine was well tolerated by 50 patients. Sixteen patients were observed to have pain, cutaneous swelling and hyperemia and 4 had subfebrility. There were neither episodes of RA exacerbation nor new autoimmune disorders during the follow-up. Conclusion. The findings suggest that 23-valent pneumococcal vaccine shows a good clinical efficacy, adequate immunogenicity, and good tolerability in the patients with RA. 

Low Concentrations of Vitamin C Reduce the Synthesis of Extracellular Polymers and Destabilize Bacterial Biofilms

KAUST Repository

Pandit, Santosh

2017-12-26

Extracellular polymeric substances (EPS) produced by bacteria form a matrix supporting the complex three-dimensional architecture of biofilms. This EPS matrix is primarily composed of polysaccharides, proteins and extracellular DNA. In addition to supporting the community structure, the EPS matrix protects bacterial biofilms from the environment. Specifically, it shields the bacterial cells inside the biofilm, by preventing antimicrobial agents from getting in contact with them, thereby reducing their killing effect. New strategies for disrupting the formation of the EPS matrix can therefore lead to a more efficient use of existing antimicrobials. Here we examined the mechanism of the known effect of vitamin C (sodium ascorbate) on enhancing the activity of various antibacterial agents. Our quantitative proteomics analysis shows that non-lethal concentrations of vitamin C inhibit bacterial quorum sensing and other regulatory mechanisms underpinning biofilm development. As a result, the EPS biosynthesis in reduced, and especially the polysaccharide component of the matrix is depleted. Once the EPS content is reduced beyond a critical point, bacterial cells get fully exposed to the medium. At this stage, the cells are more susceptible to killing, either by vitamin C-induced oxidative stress as reported here, or by other antimicrobials or treatments.

Low Concentrations of Vitamin C Reduce the Synthesis of Extracellular Polymers and Destabilize Bacterial Biofilms

KAUST Repository

Pandit, Santosh; Ravikumar, Vaishnavi; Abdel-Haleem, Alyaa M.; Derouiche, Abderahmane; Mokkapati, V. R. S. S.; Sihlbom, Carina; Mineta, Katsuhiko; Gojobori, Takashi; Gao, Xin; Westerlund, Fredrik; Mijakovic, Ivan

2017-01-01

Extracellular polymeric substances (EPS) produced by bacteria form a matrix supporting the complex three-dimensional architecture of biofilms. This EPS matrix is primarily composed of polysaccharides, proteins and extracellular DNA. In addition to supporting the community structure, the EPS matrix protects bacterial biofilms from the environment. Specifically, it shields the bacterial cells inside the biofilm, by preventing antimicrobial agents from getting in contact with them, thereby reducing their killing effect. New strategies for disrupting the formation of the EPS matrix can therefore lead to a more efficient use of existing antimicrobials. Here we examined the mechanism of the known effect of vitamin C (sodium ascorbate) on enhancing the activity of various antibacterial agents. Our quantitative proteomics analysis shows that non-lethal concentrations of vitamin C inhibit bacterial quorum sensing and other regulatory mechanisms underpinning biofilm development. As a result, the EPS biosynthesis in reduced, and especially the polysaccharide component of the matrix is depleted. Once the EPS content is reduced beyond a critical point, bacterial cells get fully exposed to the medium. At this stage, the cells are more susceptible to killing, either by vitamin C-induced oxidative stress as reported here, or by other antimicrobials or treatments.

Characterization of the antibody response to a Haemophilus influenzae type b conjugate vaccine in children with recurrent lower respiratory tract infection

DEFF Research Database (Denmark)

Kristensen, K; Barington, T; Pressler, T

1995-01-01

single total IgG subclass, but total IgG measured as the sum of all four subclasses was significantly lower in the children with RLRI than in the controls (P = 0.036). Before vaccination, the children with RLRI had significantly less IgG antipolysaccharide Hib antibody than the controls (P = 0......M response to Hib conjugate vaccine in these children, since this isotype predominates in the primary immune response, i.e., in the absence of immunologic memory.(ABSTRACT TRUNCATED AT 250 WORDS)......Children with recurrent lower respiratory tract infection (RLRI) may respond poorly to polysaccharide antigens. To examine how such children respond to a polysaccharide coupled to a protein carrier, we immunized 15 children with RLRI aged 8-69 months and 15 carefully age-matched healthy controls...

Prophylactic effect of a therapeutic vaccine against TB based on fragments of Mycobacterium tuberculosis.

Science.gov (United States)

Vilaplana, Cristina; Gil, Olga; Cáceres, Neus; Pinto, Sergio; Díaz, Jorge; Cardona, Pere-Joan

2011-01-01

The prophylactic capacity of the RUTI® vaccine, based on fragmented cells of Mycobacterium tuberculosis, has been evaluated in respect to aerosol challenge with virulent bacilli. Subcutaneous vaccination significantly reduced viable bacterial counts in both lungs and spleens of C57Bl mice, when challenged 4 weeks after vaccination. RUTI® protected the spleen less than BCG. Following a 9 month vaccination-challenge interval, protection was observed for the lungs, but not for the spleen. Survival of infected guinea pigs was prolonged by vaccination given 5 weeks before challenge. Inoculations of RUTI® shortly after infection significantly reduced the viable bacterial counts in the lungs, when compared with infected control mice. Thus, vaccination by RUTI® has potential for both the prophylaxis and immunotherapy of tuberculosis.

Bacterial Polymertropism, the Response to Strain-Induced Alignment of Polymers

Science.gov (United States)

Lemon, David J.

In nature, bacteria often live in surface-associated communities known as biofilms. Biofilm-forming bacteria deposit a layer of polysaccharide on the surfaces they inhabit; hence, polysaccharide is their immediate environment on any surface. In this study, we examined how the physical characteristics of polysaccharide substrates influence the behavior of the biofilm-forming bacterium Myxococcus xanthus. M. xanthus colonies, and indeed those of the majority of biofilm-forming species tested, respond to the compression-induced deformation of polysaccharide substrates by preferentially spreading across the surface perpendicular to the axis of compression. This response is conserved across multiple distantly related phyla and is found in species with an array of distinct motility apparatuses.The birefringence and small angle X-ray scattering patterns of compressed polysaccharide substrates indicate that the directed surface movements of these bacteria consistently match the orientation of the long axes of aligned and tightly packed polysaccharide fibers in compressed substrates. Therefore, we refer to this behavior as polymertropism to denote that the directed movements are a response to the physical arrangement of the change in packing and alignment of the polymers in the substrate. In addition to altering the colony morphology we find the behavior of groups of cells, called flares, is also affected in several species resulting in increased flare speed, duration, and displacement on compressed gel substrates.We suggest that polymertropism, which requires a downward-facing motility apparatus in M. xanthus, may be responsible for the observed tendency of bacterial cells to follow trails of extruded and presumably aligned polysaccharides, which their neighbors secrete and deposit on the substrate as they move across it. Polymertropism may also play a role in the organization of bacteria in a biofilm, as the iterative process of polysaccharide trail deposition and

Critical appraisal of a quadrivalent CRM(197) conjugate vaccine against meningococcal serogroups A, C W-135 and Y (Menveo) in the context of treatment and prevention of invasive disease.

Science.gov (United States)

Bröker, Michael; Cooper, Brian; Detora, Lisa M; Stoddard, Jeffrey J

2011-01-01

Worldwide, invasive meningococcal disease affects about 500,000 people annually. Case fatality in developed countries averages 10%, and higher rates are reported in less prosperous regions. According to the World Health Organization, the most important pathogenic serogroups are A, B, C, W-135, X, and Y. Clinical features of invasive meningococcal disease make diagnosis and management difficult. Antibiotic measures are recommended for prophylaxis after exposure and for treatment of invasive meningococcal disease cases; however, resistant strains may be emerging. Vaccines are generally regarded as the best preventative measure for invasive meningococcal disease. Polysaccharide vaccines against serogroups A, C, W-135, and Y using protein conjugation technology have clear advantages over older plain polysaccharide formulations without a protein component. The first quadrivalent meningococcal conjugate vaccine (MenACWY-D) was licensed in the US in 2005. More recently, MenACWY-CRM (Menveo(®)) was licensed in Europe, the US, the Middle East, and Latin America. MenACWY-CRM uses cross-reactive material 197, a nontoxic mutant of diphtheria toxin, as the carrier protein. MenACWY-CRM offers robust immunogenicity in all age groups, with a tolerability profile similar to that of a plain polysaccharide vaccine. Given its potential for protecting persons from infancy to old age, MenACWY-CRM offers the opportunity to protect broad populations against invasive meningococcal disease. The most optimal strategy for use of the vaccine has to be assessed country by country on the basis of local epidemiology, individual health care systems, and need.

Reactogenicity, safety and immunogenicity of a protein-based pneumococcal vaccine in Gambian children aged 2-4 years: A phase II randomized study.

Science.gov (United States)

Odutola, A; Ota, M O; Ogundare, E O; Antonio, M; Owiafe, P; Worwui, A; Greenwood, B; Alderson, M; Traskine, M; Verlant, V; Dobbelaere, K; Borys, D

2016-01-01

Pneumococcal conjugate vaccines (PCVs) have been successful in preventing invasive pneumococcal disease but effectiveness has been challenged by replacement of vaccine serotypes with non-vaccine serotypes. Vaccines targeting common pneumococcal protein(s) found in most/all pneumococci may overcome this limitation. This phase II study assessed safety and immunogenicity of a new protein-based pneumococcal vaccine containing polysaccharide conjugates of 10 pneumococcal serotypes combined with pneumolysin toxoid(dPly) and pneumococcal histidine triad protein D(PhtD) (PHiD-CV/dPly/PhtD-30) in African children. 120 Gambian children (2-4 years, not previously vaccinated against Streptococcus pneumoniae) randomized (1:1) received a single dose of PHiD-CV/dPly/PhtD-30 or PCV13. Adverse events occurring over 4 d post-vaccination were reported, and blood samples obtained pre- and 1-month post-vaccination. Serious adverse events were reported for 6 months post-vaccination. Solicited local and systemic adverse events were reported at similar frequency in each group. One child (PHiD-CV/dPly/PhtD-30 group) reported a grade 3 local reaction to vaccination. Haematological and biochemical parameters seemed similar pre- and 1-month post-vaccination in each group. High pre-vaccination Ply and PhtD antibody concentrations were observed in each group, but only increased in PHiD-CV/dPly/PhtD-30 vaccinees one month post-vaccination. One month post-vaccination, for each vaccine serotype ≥96.2% of PHiD-CV/dPly/PhtD-30 vaccinees had serotype-specific polysaccharide antibody concentrations ≥0.20µg/mL except serotypes 6B (80.8%) and 23F (65.4%), and ≥94.1% had OPA titres of ≥8 except serotypes 1 (51.9%), 5 (38.5%) and 6B (78.0%), within ranges seen in PCV13-vaccinated children. A single dose of PHiD-CV/dPly/PhtD-30 vaccine, administered to Gambian children aged 2-4 y not previously vaccinated with a pneumococcal vaccine, was well-tolerated and immunogenic.

Rapid DNA vaccination against Burkholderia pseudomallei flagellin by tattoo or intranasal application.

Science.gov (United States)

Lankelma, Jacqueline M; Wagemakers, Alex; Birnie, Emma; Haak, Bastiaan W; Trentelman, Jos J A; Weehuizen, Tassili A F; Ersöz, Jasmin; Roelofs, Joris J T H; Hovius, Joppe W; Wiersinga, W Joost; Bins, Adriaan D

2017-11-17

Melioidosis is a severe infectious disease with a high mortality that is endemic in South-East Asia and Northern Australia. The causative pathogen, Burkholderia pseudomallei, is listed as potential bioterror weapon due to its high virulence and potential for easy dissemination. Currently, there is no licensed vaccine for prevention of melioidosis. Here, we explore the use of rapid plasmid DNA vaccination against B. pseudomallei flagellin for protection against respiratory challenge. We tested three flagellin DNA vaccines with different subcellular targeting designs. C57BL/6 mice were vaccinated via skin tattoo on day 0, 3 and 6 before intranasal challenge with B. pseudomallei on day 21. Next, the most effective construct was used as single vaccination on day 0 by tattoo or intranasal formulation. Mice were sacrificed 72 hours post-challenge to assess bacterial loads, cytokine responses, inflammation and microscopic lesions. A construct encoding a cellular secretion signal resulted in the most effective protection against melioidosis via tattooing, with a 10-fold reduction in bacterial loads in lungs and distant organs compared to the empty vector. Strikingly, a single intranasal administration of the same vaccine resulted in >1000-fold lower bacterial loads and increased survival. Pro-inflammatory cytokine responses were significantly diminished and strong reductions in markers for distant organ damage were observed. A rapid vaccination scheme using flagellin DNA tattoo provides significant protection against intranasal challenge with B. pseudomallei, markedly improved by a single administration via airway mucosa. Hence intranasal vaccination with flagellin-encoding DNA may be applicable when acute mass vaccination is indicated and warrants further testing.

Evaluation of polysaccharides content in fruit bodies and their antimicrobial activity of four Ganoderma lucidum (W Curt.: Fr. P. Karst. strains cultivated on different wood type substrates

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Krystyna Skalicka-Woźniak

2012-03-01

Full Text Available Quantitative determination of polysaccharides in Ganoderma lucidum fruit bodies from different sawdust cultivation substrates and their antibacterial activity was done. Thirty six samples were analyzed. Four strains of Ganoderma lucidum (GL01, GL02, GL03 and GL04 were cultivated on the growth substrates of three different sawdust types: birch (Bo, maple (Kl or alder (Ol amended with wheat bran in three different concentrations: 10, 20 and 30% (w/w. Even though the richest in polysaccharides was GL01 strain, the highest yields of the polysaccharides were determined in GL04Kl3 sample and was 112.82 mg/g of dry weight. The antibacterial activity of polysaccharides was determined in vitro using micro-dilution broth method. The panel of eight reference bacterial strains was used. All the polysaccharide samples tested showed the broad spectrum and the moderate antibacterial activity. Micrococcus luteus ATCC 10240 strain was the most sensitive with MIC (minimal inhibitory concentration = 0.63 − 1.25 mg/mL.

The Evolution of the Meningitis Vaccine Project.

Science.gov (United States)

Tiffay, Kathleen; Jodar, Luis; Kieny, Marie-Paule; Socquet, Muriel; LaForce, F Marc

2015-11-15

In 2001, the Meningitis Vaccine Project (MVP) was tasked to develop, test, license, and introduce a group A meningococcal (MenA) conjugate vaccine for sub-Saharan Africa. African public health officials emphasized that a vaccine price of less than US$0.50 per dose was necessary to ensure introduction and sustained use of this new vaccine. Initially, MVP envisioned partnering with a multinational vaccine manufacturer, but the target price and opportunity costs were problematic and formal negotiations ended in 2002. MVP chose to become a "virtual vaccine company," and over the next decade managed a network of public-private and public-public partnerships for pharmaceutical development, clinical development, and regulatory submission. MVP supported the transfer of key know-how for the production of group A polysaccharide and a new conjugation method to the Serum Institute of India, Ltd, based in Pune, India. A robust staff structure supported by technical consultants and overseen by advisory groups in Europe and Africa ensured that the MenA conjugate vaccine would meet all international standards. A robust project structure including a team of technical consultants and 3 advisory groups in Europe and Africa ensured that the MenA conjugate vaccine (PsA-TT, MenAfriVac) was licensed by the Drug Controller General of India and prequalified by the World Health Organization in June 2010. The vaccine was introduced in Burkina Faso, Mali, and Niger in December 2010. The development, through a public-private partnership, of a safe, effective, and affordable vaccine for sub-Saharan Africa, PsA-TT, offers a new paradigm for the development of vaccines specifically targeting populations in resource-poor countries. © The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases Society of America.

Polysaccharide components from the scape of Musa paradisiaca: main structural features of water-soluble polysaccharide component.

Science.gov (United States)

Anjaneyalu, Y V; Jagadish, R L; Raju, T S

1997-06-01

Polysaccharide components present in the pseudo-stem (scape) of M. paradisiaca were purified from acetone powder of the scape by delignification followed by extraction with aqueous solvents into water soluble polysaccharide (WSP), EDTA-soluble polysaccharide (EDTA-SP), alkali-soluble polysaccharide (ASP) and alkali-insoluble polysaccharide (AISP) fractions. Sugar compositional analysis showed that WSP and EDTA-SP contained only D-Glc whereas ASP contained D-Glc, L-Ara and D-Xyl in approximately 1:1:10 ratio, respectively, and AISP contained D-Glc, L-Ara and D-Xyl in approximately 10:1:2 ratio, respectively. WSP was further purified by complexation with iso-amylalcohol and characterized by specific rotation, IR spectroscopy, Iodine affinity, ferricyanide number, blue value, hydrolysis with alpha-amylase and glucoamylase, and methylation linkage analysis, and shown to be a amylopectin type alpha-D-glucan.

Characterization of Two Metal Binding Lipoproteins as Vaccine Candidates for Enterococcal Infections.

Science.gov (United States)

Romero-Saavedra, Felipe; Laverde, Diana; Budin-Verneuil, Aurélie; Muller, Cécile; Bernay, Benoit; Benachour, Abdellah; Hartke, Axel; Huebner, Johannes

2015-01-01

Enterococcus faecium and faecalis are Gram-positive opportunistic pathogens that have become leading causes of nosocomial infections over the last decades. Especially multidrug resistant enterococci have become a challenging clinical problem worldwide. Therefore, new treatment options are needed and the identification of alternative targets for vaccine development has emerged as a feasible alternative to fight the infections caused by these pathogens. We extrapolate the transcriptomic data from a mice peritonitis infection model in E. faecalis to identify putative up-regulated surface proteins under infection conditions in E. faecium. After the bionformatic analyses two metal binding lipoproteins were identified to have a high homology (>72%) between the two species, the manganese ABC transporter substrate-binding lipoprotein (PsaAfm,) and the zinc ABC transporter substrate-binding lipoprotein (AdcAfm). These candidate lipoproteins were overexpressed in Escherichia coli and purified. The recombinant proteins were used to produce rabbit polyclonal antibodies that were able to induce specific opsonic antibodies that mediated killing of the homologous strain E. faecium E155 as well as clinical strains E. faecium E1162, Enterococcus faecalis 12030, type 2 and type 5. Mice were passively immunized with the antibodies raised against recombinant lipoproteins, showing significant reduction of colony counts in mice livers after the bacterial challenge and demonstrating the efficacy of these metal binding lipoproteins as promising vaccine candidates to treat infections caused by these enterococcal pathogens. Overall, our results demonstrate that these two metal binding lipoproteins elicited specific, opsonic and protective antibodies, with an extensive cross-reactivity and serotype-independent coverage among these two important nocosomial pathogens. Pointing these two protein antigens as promising immunogens, that can be used as single components or as carrier proteins

Polysaccharides and bacterial plugging. Final report, 1992--1993

Energy Technology Data Exchange (ETDEWEB)

Fogler, H.S.

1995-02-01

In situ core plugging experiments and transport experiments, using the model bacteria Leuconostoc m., have been conducted. Results demonstrated that cellular polysaccharide production increases cell distribution in porous media and caused an overall decrease in media permeability. Further, a parallel core plugging experiment was conducted and showed the feasibility of this system to divert injection fluid from high permeability zones into low permeability zones within porous media as is needed for profile modification. To implement this type of application, however, controlled placement of cells and rates of polymer production are needed. Therefore, kinetic studies were performed. A kinetic model was subsequently developed for Leuconostoc m. bacteria. This model is based on data generated from batch growth experiments and allows for the prediction of saccharide utilization, cell generation, and dextran production. These predictions can be used to develop injection strategies for field implementation. Transport and in situ growth micromodel experiments have shown how dextran allow cells to remain as clusters after cell division which enhanced cell capture and retention in porous media. Additional Damkohler experiments have been performed to determine the effects of the nutrient injection rate and nutrient concentration on the rate of porous media plugging. As shown experimentally and as predicted by a model for in situ growth, an increase in nutrient concentration and/or its injection rate will result in a faster rate of porous media plugging. Through continuum model simulations, it has been shown that the initial cell profiles play a key role on the core plugging rate. Controlling the location of the inoculating cells is thus another key factor in using bacteria for profile modification.

Immunogenicity and safety of a quadrivalent meningococcal polysaccharide CRM conjugate vaccine in infants and toddlers.

Science.gov (United States)

Tregnaghi, Miguel; Lopez, Pio; Stamboulian, Daniel; Graña, Gabriela; Odrljin, Tatjana; Bedell, Lisa; Dull, Peter M

2014-09-01

This phase III study assessed the safety and immunogenicity of MenACWY-CRM, a quadrivalent meningococcal conjugate vaccine, administered with routine vaccines starting at 2 months of age. Healthy infants received MenACWY-CRM in a two- or three-dose primary infant series plus a single toddler dose. In addition, a two-dose toddler catch-up series was evaluated. Immune responses to MenACWY-CRM were assessed for serum bactericidal activity with human complement (hSBA). Reactogenicity and safety results were collected systematically. After a full infant/toddler series or two-dose toddler catch-up series, MenACWY-CRM elicited immune responses against the four serogroups in 94-100% of subjects. Noninferiority of the two- versus three-dose MenACWY-CRM infant dosing regimen was established for geometric mean titers for all serogroups. Following the three-dose infant primary series, 89-98% of subjects achieved an hSBA ≥ 8 across all serogroups. Immune responses to concomitant routine vaccines given with MenACWY-CRM were noninferior to responses to routine vaccines alone, except for pertactin after the two-dose infant series. Noninferiority criteria were met for all concomitant antigens after the three-dose infant series. MenACWY-CRM vaccination regimens in infants and toddlers were immunogenic and well tolerated. No clinically meaningful effects of concomitant administration with routine infant and toddler vaccines were observed. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

Safety and immunogenicity of an investigational quadrivalent meningococcal CRM(197) conjugate vaccine, MenACWY-CRM, compared with licensed vaccines in adults in Latin America.

Science.gov (United States)

Stamboulian, D; Lopardo, G; Lopez, P; Cortes-Barbosa, C; Valencia, A; Bedell, L; Karsten, A; Dull, P M

2010-10-01

This study compared the investigational quadrivalent meningococcal CRM₁₉₇ conjugate vaccine, MenACWY-CRM, with licensed quadrivalent polysaccharide (MPSV4) and conjugate (MenACWY-D) meningococcal vaccines. In this phase III multicenter study, 2505 adults (aged 19-55 years) were randomized to receive either MenACWY-CRM or MenACWY-D, and 326 adults (aged 56-65 years) were randomized to receive either MenACWY-CRM or MPSV4. Sera obtained pre-vaccination and at 1-month post-vaccination were tested for serogroup-specific serum bactericidal activity using human complement (hSBA) for immunogenicity non-inferiority and superiority analyses. The vaccines in all groups were well tolerated. In the 19-55 years age group, post-vaccination geometric mean titers (GMTs) were consistently higher for MenACWY-CRM than for MenACWY-D for all four serogroups. MenACWY-CRM was non-inferior to MenACWY-D for all serogroups, and superior for serogroup Y. In the 56-65 years age group, post-vaccination GMTs were 1.2- to 5.4-fold higher for MenACWY-CRM than for MPSV4 for the four serogroups. MenACWY-CRM is well tolerated and immunogenic in adults aged 19-65 years, with at least non-inferior immunogenicity compared with the currently licensed meningococcal vaccines. Copyright © 2010 International Society for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

Advances on Bioactive Polysaccharides from Medicinal Plants.

Science.gov (United States)

Xie, Jian-Hua; Jin, Ming-Liang; Morris, Gordon A; Zha, Xue-Qiang; Chen, Han-Qing; Yi, Yang; Li, Jing-En; Wang, Zhi-Jun; Gao, Jie; Nie, Shao-Ping; Shang, Peng; Xie, Ming-Yong

2016-07-29

In recent decades, the polysaccharides from the medicinal plants have attracted a lot of attention due to their significant bioactivities, such as anti-tumor activity, antioxidant activity, anticoagulant activity, antidiabetic activity, radioprotection effect, anti-viral activity, hypolipidemic and immunomodulatory activities, which make them suitable for medicinal applications. Previous studies have also shown that medicinal plant polysaccharides are non-toxic and show no side effects. Based on these encouraging observations, most researches have been focusing on the isolation and identification of polysaccharides, as well as their bioactivities. A large number of bioactive polysaccharides with different structural features and biological effects from medicinal plants have been purified and characterized. This review provides a comprehensive summary of the most recent developments in physiochemical, structural features and biological activities of bioactive polysaccharides from a number of important medicinal plants, such as polysaccharides from Astragalus membranaceus, Dendrobium plants, Bupleurum, Cactus fruits, Acanthopanax senticosus, Angelica sinensis (Oliv.) Diels, Aloe barbadensis Miller, and Dimocarpus longan Lour. Moreover, the paper has also been focused on the applications of bioactive polysaccharides for medicinal applications. Recent studies have provided evidence that polysaccharides from medicinal plants can play a vital role in bioactivities. The contents and data will serve as a useful reference material for further investigation, production, and application of these polysaccharides in functional foods and therapeutic agents.

Structural analysis of cell wall polysaccharides using PACE

Energy Technology Data Exchange (ETDEWEB)

Mortimer, Jennifer C. [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Joint BioEnergy Institute

2017-01-01

The plant cell wall is composed of many complex polysaccharides. The composition and structure of the polysaccharides affect various cell properties including cell shape, cell function and cell adhesion. Many techniques to characterize polysaccharide structure are complicated, requiring expensive equipment and specialized operators e.g. NMR, MALDI-MS. PACE (Polysaccharide Analysis using Carbohydrate gel Electrophoresis) uses a simple, rapid technique to analyze polysaccharide quantity and structure (Goubet et al. 2002). Whilst the method here describes xylan analysis, it can be applied (by use of the appropriate glycosyl hydrolase) to any cell wall polysaccharide.

An exocellular polysaccharide and its interactions with proteins

NARCIS (Netherlands)

Tuinier, R.

1999-01-01

In the food industry polysaccharides are used as thickening or gelling agents. Polysaccharides are usually extracted from plants. Micro-organisms are also capable of excreting polysaccharides: exocellular polysaccharides (EPSs). In some cases EPSs are produced in-situ in food products,

Mathematical Modelling of Bacterial Meningitis Transmission Dynamics with Control Measures

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Joshua Kiddy K. Asamoah

2018-01-01

Full Text Available Vaccination and treatment are the most effective ways of controlling the transmission of most infectious diseases. While vaccination helps susceptible individuals to build either a long-term immunity or short-term immunity, treatment reduces the number of disease-induced deaths and the number of infectious individuals in a community/nation. In this paper, a nonlinear deterministic model with time-dependent controls has been proposed to describe the dynamics of bacterial meningitis in a population. The model is shown to exhibit a unique globally asymptotically stable disease-free equilibrium E0, when the effective reproduction number RVT≤1, and a globally asymptotically stable endemic equilibrium E1, when RVT>1; and it exhibits a transcritical bifurcation at RVT=1. Carriers have been shown (by Tornado plot to have a higher chance of spreading the infection than those with clinical symptoms who will sometimes be bound to bed during the acute phase of the infection. In order to find the best strategy for minimizing the number of carriers and ill individuals and the cost of control implementation, an optimal control problem is set up by defining a Lagrangian function L to be minimized subject to the proposed model. Numerical simulation of the optimal problem demonstrates that the best strategy to control bacterial meningitis is to combine vaccination with other interventions (such as treatment and public health education. Additionally, this research suggests that stakeholders should press hard for the production of existing/new vaccines and antibiotics and their disbursement to areas that are most affected by bacterial meningitis, especially Sub-Saharan Africa; furthermore, individuals who live in communities where the environment is relatively warm (hot/moisture are advised to go for vaccination against bacterial meningitis.

Vaccines for the 21st century

Science.gov (United States)

Delany, Isabel; Rappuoli, Rino; De Gregorio, Ennio

2014-01-01

In the last century, vaccination has been the most effective medical intervention to reduce death and morbidity caused by infectious diseases. It is believed that vaccines save at least 2–3 million lives per year worldwide. Smallpox has been eradicated and polio has almost disappeared worldwide through global vaccine campaigns. Most of the viral and bacterial infections that traditionally affected children have been drastically reduced thanks to national immunization programs in developed countries. However, many diseases are not yet preventable by vaccination, and vaccines have not been fully exploited for target populations such as elderly and pregnant women. This review focuses on the state of the art of recent clinical trials of vaccines for major unmet medical needs such as HIV, malaria, TB, and cancer. In addition, we describe the innovative technologies currently used in vaccine research and development including adjuvants, vectors, nucleic acid vaccines, and structure-based antigen design. The hope is that thanks to these technologies, more diseases will be addressed in the 21st century by novel preventative and therapeutic vaccines. PMID:24803000

Vi-CRM 197 as a new conjugate vaccine against Salmonella Typhi.

Science.gov (United States)

Micoli, F; Rondini, S; Pisoni, I; Proietti, D; Berti, F; Costantino, P; Rappuoli, R; Szu, S; Saul, A; Martin, L B

2011-01-17

An efficacious, low cost vaccine against typhoid fever, especially for young children, would make a major impact on disease burden in developing countries. The virulence capsular polysaccharide of Salmonella Typhi (Vi) coupled to recombinant mutant Pseudomonas aeruginosa exoprotein A (Vi-rEPA) has been shown to be highly efficacious. We investigated the use of carrier proteins included in infant vaccines, standardized the conjugation process and developed key assays required for routine lot release at production scale. Vi from a BSL1 organism, Citrobacter freundii, strain WR7011, was used as an alternative to Vi from S. Typhi. We showed that Vi conjugated to CRM(197), a non-toxic mutant of diphtheria toxin, widely used in commercial vaccines, was produced at high yield. Vi-CRM(197) proved immunogenic in animal studies, even without adjuvant. Thus, Vi-CRM(197) appears to be a suitable candidate for the development of a commercially viable, effective typhoid vaccine for developing countries. Copyright © 2010 Elsevier Ltd. All rights reserved.

Three-Dimensional Structural Aspects of Protein–Polysaccharide Interactions

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Masamichi Nagae

2014-03-01

Full Text Available Linear polysaccharides are typically composed of repeating mono- or disaccharide units and are ubiquitous among living organisms. Polysaccharide diversity arises from chain-length variation, branching, and additional modifications. Structural diversity is associated with various physiological functions, which are often regulated by cognate polysaccharide-binding proteins. Proteins that interact with linear polysaccharides have been identified or developed, such as galectins and polysaccharide-specific antibodies, respectively. Currently, data is accumulating on the three-dimensional structure of polysaccharide-binding proteins. These proteins are classified into two types: exo-type and endo-type. The former group specifically interacts with the terminal units of polysaccharides, whereas the latter with internal units. In this review, we describe the structural aspects of exo-type and endo-type protein-polysaccharide interactions. Further, we discuss the structural basis for affinity and specificity enhancement in the face of inherently weak binding interactions.

Antigen-specific IgA titres after 23-valent pneumococcal vaccine indicate transient antibody deficiency disease in children

NARCIS (Netherlands)

Janssen, Willemijn J M; Nierkens, Stefan; Sanders, Elisabeth A; Boes, Marianne; van Montfrans, Joris M

2015-01-01

Paediatric patients with antibody deficiency may either be delayed in development of humoral immunity or may be persistently deficient in antibody production. To differentiate between these entities, we examined the 23-valent pneumococcal polysaccharide (PnPS) vaccine-induced IgM-, IgG- and IgA

A polysaccharide isolated from the liquid culture of Lentinus edodes (shiitake) mushroom mycelia containing black rice bran protects mice against a Salmonella lipopolysaccharide-induced endotoxemia

Science.gov (United States)

Endotoxemia (sepsis, septic shock) is an inflammatory, virulent disease that results mainly from bacterial infection. The present study investigates the inhibitory effect of the bio-processed polysaccharide (BPP) isolated from the edible Lentinus edodes liquid mycelial mushroom culture supplemented...

Burden of invasive bacterial disease among children younger than 5 ...

African Journals Online (AJOL)

Background: Haemophilus influenzae b (Hib), pneumococcus and meningococcus are responsible for high mortality and morbidity in children younger than 5 years of age worldwide. Hib containing vaccine was introduced in July 2008 in Togo; and baseline data are available on bacterial meningitis prior to PCV13 vaccine ...

Immunogenicity and safety of a novel quadrivalent meningococcal conjugate vaccine (MenACWY-CRM in healthy Korean adolescents and adults

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Hoan Jong Lee

2014-11-01

Conclusions: Findings of this first study of a quadrivalent meningococcal polysaccharide conjugate vaccine in Korean adults and adolescents demonstrated that a single dose of MenACWY-CRM was well tolerated and immunogenic, as indicated by the percentages of subjects with hSBA titers ≥8 (79%, 99%, 98%, and 94% of subjects and geometric mean titers (48, 231, 147, and 107 against serogroups A, C, W, and Y, respectively, at 1 month post-vaccination.

Utilization of polysaccharides by radiation processing

Energy Technology Data Exchange (ETDEWEB)

Kume, Tamikazu [Japan Atomic Energy Research Inst., Takasaki, Gunma (Japan). Takasaki Radiation Chemistry Research Establishment

2000-03-01

Radiation treatment has been applied for improvement or pasteurization of agro-resources to recycle the resources and to reduce the pollution of environment. By using the radiation effect for pasteurization, upgrading of cellulosic wastes of oil palm to animal feeds and mushroom has been studied under the bilateral research cooperation between JAERI and MINT (Malaysian Institute for Nuclear Technology Research). The necessary dose for pasteurization of oil palm empty fruit bunch (EFB), which is a main cellulosic by-product of palm oil industry, was determined as 10 kGy. After pasteurization, the EFB substrate was inoculated with Pleurotus sajor-caju and fermented for 1 month. The digestibility and nutritional value of fermented products were evaluated as ruminant feeds and the mushroom can be produced as by-product. For the improvement of resources, radiation effects on polysaccharides such as chitosan, sodium alginate, carrageenan, cellulose, pectin have been investigated to induce the biological activities. These carbohydrates were easily degraded by irradiation and induced various kinds of biological activities. The anti-bacterial activity and elicitor activity of chitosan were induced by irradiation. The induction of phytoalexins was also observed by irradiated pectin but the higher elicitor activity for pisatin was obtained by chitosan than pectin. For the plant growth promotion, alginate derived from brown marine algae, chitosan and ligno-cellulosic extracts show a strong activity. carrageenan derived from red marine algae can promote growth of rice and the highest effect was obtained with kappa carrageenan irradiated at 100 kGy. Furthermore, some radiation degraded polysaccharides suppressed the damage of environmental stress on plants. (author)

Utilization of polysaccharides by radiation processing

International Nuclear Information System (INIS)

Kume, Tamikazu

2000-01-01

Radiation treatment has been applied for improvement or pasteurization of agro-resources to recycle the resources and to reduce the pollution of environment. By using the radiation effect for pasteurization, upgrading of cellulosic wastes of oil palm to animal feeds and mushroom has been studied under the bilateral research cooperation between JAERI and MINT (Malaysian Institute for Nuclear Technology Research). The necessary dose for pasteurization of oil palm empty fruit bunch (EFB), which is a main cellulosic by-product of palm oil industry, was determined as 10 kGy. After pasteurization, the EFB substrate was inoculated with Pleurotus sajor-caju and fermented for 1 month. The digestibility and nutritional value of fermented products were evaluated as ruminant feeds and the mushroom can be produced as by-product. For the improvement of resources, radiation effects on polysaccharides such as chitosan, sodium alginate, carrageenan, cellulose, pectin have been investigated to induce the biological activities. These carbohydrates were easily degraded by irradiation and induced various kinds of biological activities. The anti-bacterial activity and elicitor activity of chitosan were induced by irradiation. The induction of phytoalexins was also observed by irradiated pectin but the higher elicitor activity for pisatin was obtained by chitosan than pectin. For the plant growth promotion, alginate derived from brown marine algae, chitosan and ligno-cellulosic extracts show a strong activity. carrageenan derived from red marine algae can promote growth of rice and the highest effect was obtained with kappa carrageenan irradiated at 100 kGy. Furthermore, some radiation degraded polysaccharides suppressed the damage of environmental stress on plants. (author)

Phage display as a promising approach for vaccine development

OpenAIRE

Aghebati-Maleki, Leili; Bakhshinejad, Babak; Baradaran, Behzad; Motallebnezhad, Morteza; Aghebati-Maleki, Ali; Nickho, Hamid; Yousefi, Mehdi; Majidi, Jafar

2016-01-01

Bacteriophages are specific antagonists to bacterial hosts. These viral entities have attracted growing interest as optimal vaccine delivery vehicles. Phages are well-matched for vaccine design due to being highly stable under harsh environmental conditions, simple and inexpensive large scale production, and potent adjuvant capacities. Phage vaccines have efficient immunostimulatory effects and present a high safety profile because these viruses have made a constant relationship with the mamm...

Critical appraisal of a quadrivalent CRM197 conjugate vaccine against meningococcal serogroups A, C W-135 and Y (Menveo® in the context of treatment and prevention of invasive disease

Directory of Open Access Journals (Sweden)

Bröker M

2011-07-01

Full Text Available Michael Bröker, Brian Cooper, Lisa M DeTora, Jeffrey J StoddardGlobal Medical Affairs, Novartis Vaccines and Diagnostics, Marburg, Germany, and Cambridge, MA, USAAbstract: Worldwide, invasive meningococcal disease affects about 500,000 people annually. Case fatality in developed countries averages 10%, and higher rates are reported in less prosperous regions. According to the World Health Organization, the most important pathogenic serogroups are A, B, C, W-135, X, and Y. Clinical features of invasive meningococcal disease make diagnosis and management difficult. Antibiotic measures are recommended for prophylaxis after exposure and for treatment of invasive meningococcal disease cases; however, resistant strains may be emerging. Vaccines are generally regarded as the best preventative measure for invasive meningococcal disease. Polysaccharide vaccines against serogroups A, C, W-135, and Y using protein conjugation technology have clear advantages over older plain polysaccharide formulations without a protein component. The first quadrivalent meningococcal conjugate vaccine (MenACWY-D was licensed in the US in 2005. More recently, MenACWY-CRM (Menveo® was licensed in Europe, the US, the Middle East, and Latin America. MenACWY-CRM uses cross-reactive material 197, a nontoxic mutant of diphtheria toxin, as the carrier protein. MenACWY-CRM offers robust immunogenicity in all age groups, with a tolerability profile similar to that of a plain polysaccharide vaccine. Given its potential for protecting persons from infancy to old age, MenACWY-CRM offers the opportunity to protect broad populations against invasive meningococcal disease. The most optimal strategy for use of the vaccine has to be assessed country by country on the basis of local epidemiology, individual health care systems, and need.Keywords: invasive meningococcal disease, quadrivalent meningococcal conjugate vaccine, Neisseria meningitidis

The response to Typhi Vi vaccination is compromised in individuals with primary immunodeficiency.

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Kumarage, Jeevani; Seneviratne, Suranjith L; Senaratne, Vijitha; Fernando, Amitha; Gunasekera, Kirthi; Gunasena, Bandu; Gurugama, Padmalal; Peiris, Sudath; Parker, Antony R; Harding, Stephen; de Silva, Nilhan Rajiva

2017-06-01

Measurement of an individuals ability to respond to polysaccharide antigens is a crucial test to determine adaptive immunity. Currently the response to Pneumovax ® is utilized but with the success of Prevnar ® , measurement of the response to Pneumovax may be challenging. The aim of the study was to assess the response to Typhi Vi vaccination in both children and adult control groups and patients with primary immunodeficiency (PID). In the control groups, >95% of the individuals had pre Typhi Vi vaccination concentrations 94% achieving ≥3 fold increase in concentration (FI). The response to Typhi Vi vaccination was significantly lower in both children ( p = 0.006) and adult ( p = 0.002) PID groups when compared to their control groups. 11% and 55% of the children and adult PID groups respectively did not obtain a response >3FI. There were no significant differences between the responses obtained in the children and adult PID groups. When all individuals with PID were separated into those with either hypogammaglobulinemia (HYPO) or common variable immunodeficiency (CVID), both groups had a significantly lower median FI than the control group (19, 95%CI 5-56 vs 59, 95%CI 7-237; p = 0.01 and 1, 95%CI 1-56 vs 32, 95%CI 5-136; p = 0.005). Further, a >3FI differentiated the antibody responses between both the CVID and HYPO groups and their control groups (AUC: 0.83, 95%CI: 0.65-1.00, p = 0.005 and 0.81, 95% CI: 0.65-0.97, p = 0.01). The data suggests that measurement of the response to Typhi Vi vaccination could represent a complementary assay for the assessment of the response to a polysaccharide vaccine.

The clinical impact of bacterial biofilms

DEFF Research Database (Denmark)

Høiby, Niels; Ciofu, Oana; Johansen, Helle Krogh

2011-01-01

Bacteria survive in nature by forming biofilms on surfaces and probably most, if not all, bacteria (and fungi) are capable of forming biofilms. A biofilm is a structured consortium of bacteria embedded in a self-produced polymer matrix consisting of polysaccharide, protein and extracellular DNA....... Bacterial biofilms are resistant to antibiotics, disinfectant chemicals and to phagocytosis and other components of the innate and adaptive inflammatory defense system of the body. It is known, for example, that persistence of staphylococcal infections related to foreign bodies is due to biofilm formation....... Likewise, chronic Pseudomonas aeruginosa lung infections in cystic fibrosis patients are caused by biofilm growing mucoid strains. Gradients of nutrients and oxygen exist from the top to the bottom of biofilms and the bacterial cells located in nutrient poor areas have decreased metabolic activity...

Safety and immunogenicity of typhoid fever and yellow fever vaccines when administered concomitantly with quadrivalent meningococcal ACWY glycoconjugate vaccine in healthy adults.

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Alberer, Martin; Burchard, Gerd; Jelinek, Tomas; Reisinger, Emil; Beran, Jiri; Hlavata, Lucie Cerna; Forleo-Neto, Eduardo; Dagnew, Alemnew F; Arora, Ashwani K

2015-01-01

Compact and short pre-travel immunization schedules, which include several vaccinations in a single visit, are desirable for many travelers. However, concomitant vaccination could potentially compromise immunogenicity and/or safety of the individual vaccines and, therefore, possible vaccine interferences should be carefully assessed. This article discusses the immunogenicity and safety of travel vaccines for typhoid fever (TF) and yellow fever (YF), when administered with or without a quadrivalent meningococcal glycoconjugate ACWY-CRM vaccine (MenACWY-CRM). Healthy adults (18-≤60 years) were randomized to one of three vaccine regimens: TF + YF + MenACWY-CRM (group I; n = 100), TF + YF (group II; n = 101), or MenACWY-CRM (group III; n = 100). Immunogenicity at baseline and 4 weeks post-vaccination (day 29) was assessed by serum bactericidal assay using human complement (hSBA), enzyme-linked immunosorbent assay (ELISA), or a neutralization test. Adverse events (AEs) and serious adverse events (SAEs) were collected throughout the study period. Non-inferiority of post-vaccination geometric mean concentrations (GMCs) and geometric mean titers (GMTs) was established for TF and YF vaccines, respectively, when given concomitantly with MenACWY-CRM vaccine versus when given alone. The percentages of subjects with seroprotective neutralizing titers against YF on day 29 were similar in groups I and II. The antibody responses to meningococcal serogroups A, C, W-135, and Y were within the same range when MenACWY-CRM was given separately or together with TF and YF vaccines. The percentage of subjects reporting AEs was the same for TF and YF vaccines with or without MenACWY-CRM vaccine. There were no reports of SAEs or AEs leading to study withdrawals. These data provide evidence that MenACWY-CRM can be administered with typhoid Vi polysaccharide vaccine and live attenuated YF vaccine without compromising antibody responses stimulated by the

Comparative resistance towards infection with Y. ruckeri in vaccinated and non-vaccinated rainbow trout

DEFF Research Database (Denmark)

Raida, Martin Kristian

2010-01-01

bath challenged with LD50-doses of Y. ruckeri (serotype O1, biotype 1 and 2), after which fish mortality was recorded and individual fish were sampled for both Real-Time Quantitative PCR (RT-qPCR) as well as immunohistochemical analysis. Challenge with biotype 2 resulted in very low mortalities......-vaccinated and vaccinated fish sampled 3 and 7 days after challenge with biotype 1, shows results similar to the RT-qPCR results. Using polyclonal rabbit antibodies against Y. ruckeri, minor points of infection are seen in tissues of non-vaccinated fish after 3 days, and after 7 days massive infections are present...... in several tissues. Minor infections are found in the vaccinated fish after both 3 and 7 days, but to a smaller extend than the ones found in the non-vaccinated group. The results so far, thus indicate that that the survival of the vaccinated fish after bacterial challenge seems to be correlated...

[Bacterial biofilms and infection].

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Lasa, I; Del Pozo, J L; Penadés, J R; Leiva, J

2005-01-01

In developed countries we tend to think of heart disease and the numerous forms of cancer as the main causes of mortality, but on a global scale infectious diseases come close, or may even be ahead: 14.9 million deaths in 2002 compared to cardiovascular diseases (16.9 million deaths) and cancer (7.1 million deaths) (WHO report 2004). The infectious agents responsible for human mortality have evolved as medical techniques and hygienic measures have changed. Modern-day acute infectious diseases caused by specialized bacterial pathogens such as diphtheria, tetanus, cholera, plague, which represented the main causes of death at the beginning of XX century, have been effectively controlled with antibiotics and vaccines. In their place, more than half of the infectious diseases that affect mildly immunocompromised patients involve bacterial species that are commensal with the human body; these can produce chronic infections, are resistant to antimicrobial agents and there is no effective vaccine against them. Examples of these infections are the otitis media, native valve endocarditis, chronic urinary infections, bacterial prostatitis, osteomyelitis and all the infections related to medical devices. Direct analysis of the surface of medical devices or of tissues that have been foci of chronic infections shows the presence of large numbers of bacteria surrounded by an exopolysaccharide matrix, which has been named the "biofilm". Inside the biofilm, bacteria grow protected from the action of the antibodies, phagocytic cells and antimicrobial treatments. In this article, we describe the role of bacterial biofilms in human persistent infections.

Oral vaccination against plague using Yersinia pseudotuberculosis.

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Demeure, Christian E; Derbise, Anne; Carniel, Elisabeth

2017-04-01

Yersinia pestis, the agent of plague, is among the deadliest bacterial pathogens affecting humans, and is a potential biological weapon. Because antibiotic resistant strains of Yersinia pestis have been observed or could be engineered for evil use, vaccination against plague might become the only means to reduce mortality. Although plague is re-emerging in many countries, a vaccine with worldwide license is currently lacking. The vaccine strategy described here is based on an oral vaccination with an attenuated strain of Yersinia pseudotuberculosis. Indeed, this species is genetically almost identical to Y. pestis, but has a much lower pathogenicity and a higher genomic stability. Gradual modifications of the wild-type Yersinia pseudotuberculosis strain IP32953 were performed to generate a safe and immunogenic vaccine. Genes coding for three essential virulence factors were deleted from this strain. To increase cross-species immunogenicity, an F1-encapsulated Y. pseudotuberculosis strain was then generated. For this, the Y. pestis caf operon, which encodes F1, was inserted first on a plasmid, and subsequently into the chromosome. The successive steps achieved to reach maximal vaccine potential are described, and how each step affected bacterial virulence and the development of a protective immune response is discussed. The final version of the vaccine, named VTnF1, provides a highly efficient and long-lasting protection against both bubonic and pneumonic plague after a single oral vaccine dose. Since a Y. pestis strain deprived of F1 exist or could be engineered, we also analyzed the protection conferred by the vaccine against such strain and found that it also confers full protection against the two forms of plague. Thus, the properties of VTnF1 makes it one of the most efficient candidate vaccine for mass vaccination in tropical endemic areas as well as for populations exposed to bioterrorism. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Botanical polysaccharides: macrophage immunomodulation and therapeutic potential.

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Schepetkin, Igor A; Quinn, Mark T

2006-03-01

Botanical polysaccharides exhibit a number of beneficial therapeutic properties, and it is thought that the mechanisms involved in these effects are due to the modulation of innate immunity and, more specifically, macrophage function. In this review, we summarize our current state of understanding of the macrophage modulatory effects of botanical polysaccharides isolated from a wide array of different species of flora, including higher plants, mushrooms, lichens and algae. Overall, the primary effect of botanical polysaccharides is to enhance and/or activate macrophage immune responses, leading to immunomodulation, anti-tumor activity, wound-healing and other therapeutic effects. Furthermore, botanical and microbial polysaccharides bind to common surface receptors and induce similar immunomodulatory responses in macrophages, suggesting that evolutionarily conserved polysaccharide structural features are shared between these organisms. Thus, the evaluation of botanical polysaccharides provides a unique opportunity for the discovery of novel therapeutic agents and adjuvants that exhibit beneficial immunomodulatory properties.

Polysaccharides of algae. Pt. 37. Characterization of hybrid structure of substituted agarose from Polysiphonia morrowii (Rhodophyta, Rhodomelaceae) using. beta. -agarase and /sup 13/C-NMR spectroscopy

Energy Technology Data Exchange (ETDEWEB)

Usov, A.I.; Ivanova, E.G.

1987-09-01

Structure of gel-forming galactan from Polysiphonia morrowii was analysed using bacterial ..beta..-agarase and /sup 13/C-nuclear magnetic resonance (/sup 13/C-NMR) spectroscopy. The polysaccharide was shown to contain: a) blocks composed of agarobiose residues, partly 6-O-methylated and 6-sulfated, which are sensitive to enzymolysis; b) extended blocks composed of agarobiose 6-sulfate residues, which are resistant to ..beta..-agarase action. The latter blocks contain also ..beta..-D-galactopyranosyl-(1->4)-..cap alpha..-L-galactopyranose 6.6'-disulfate residues (biogenetic precursors of agarobiose 6-sulfate), which are hardly detectable by /sup 13/C-NMR spectrum of the starting polysaccharide. Action of alkali on the enzyme-resistant fraction afforded a polysaccharide preparation having /sup 13/C-NMR spectrum of agarose 6-sulfate.

A brief history of vaccines: smallpox to the present.

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Hsu, Jennifer L

2013-01-01

Modern vaccine history began in the late 18th century with the discovery of smallpox immunization by Edward Jenner. This pivotal step led to substantial progress in prevention of infectious diseases with inactivated vaccines for multiple infectious diseases, including typhoid, plague and cholera. Each advance produced significant decreases in infection-associated morbidity and mortality, thus shaping our modem cultures. As knowledge of microbiology and immunology grew through the 20th century, techniques were developed for cell culture of viruses. This allowed for rapid advances in prevention of polio, varicella, influenza and others. Finally, recent research has led to development of alternative vaccine strategies through use of vectored antigens, pathogen subunits (purified proteins or polysaccharides) or genetically engineered antigens. As the science of vaccinology continues to rapidly evolve, knowledge of the past creates added emphasis on the importance of developing safe and effective strategies for infectious disease prevention in the 21st century.

A public health and budget impact analysis of vaccinating the elderly and at-risk adults with the 23-valent pneumococcal polysaccharide vaccine or 13-valent pneumococcal conjugate vaccine in the UK.

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Jiang, Yiling; Gauthier, Aline; Keeping, Sam; Carroll, Stuart

2014-12-01

Since the introduction of the routine childhood immunization, a change in epidemiology of pneumococcal disease has been seen in both children and adults. This study aimed to quantify the public health and budget impact of pneumococcal vaccination of the elderly and those in at risk groups in the UK. The model was adapted from a previous population-based Markov model. At-risk adults and the elderly were assumed to receive PPV23 or PCV13 vaccination or no vaccination. Over the study period (2012-2016), PPV23 vaccination led to a reduction in the number of invasive pneumococcal disease cases in most scenarios. The net budget impact ranged between £15 and £39 million (vs no vaccination) or between -£116 and -£93 million (vs PCV13). PPV23 vaccination program remains the optimal strategy from public health and budgetary perspectives despite epidemiological changes. PCV13 is likely to impose a significant budget with limited health benefits.

Using Dynamic Transmission Modeling to Determine Vaccination Coverage Rate Based on 5-Year Economic Burden of Infectious Disease: An Example of Pneumococcal Vaccine.

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Wen, Yu-Wen; Wu, Hsin; Chang, Chee-Jen

2015-05-01

Vaccination can reduce the incidence and mortality of an infectious disease and thus increase the years of life and productivity for the entire society. But when determining the vaccination coverage rate, its economic burden is usually not taken into account. This article aimed to use a dynamic transmission modeling (DTM), which is based on a susceptible-infectious-recovered model and is a system of differential equations, to find the optimal vaccination coverage rate based on the economic burden of an infectious disease. Vaccination for pneumococcal diseases was used as an example to demonstrate the main purpose. 23-Valent pneumococcal polysaccharide vaccines (PPV23) and 13-valent pneumococcal conjugate vaccines (PCV13) have shown their cost-effectiveness in elderly and children, respectively. Scenarios analysis of PPV23 to elderly aged 65+ years and of PCV13 to children aged 0 to 4 years was applied to assess the optimal vaccination coverage rate based on the 5-year economic burden. Model parameters were derived from Taiwan's National Health Insurance Research Database, government data, and published literature. Various vaccination coverage rates, the vaccine efficacy, and all epidemiologic parameters were substituted into DTM, and all differential equations were solved in R Statistical Software. If the coverage rate of PPV23 for the elderly and of PCV13 for the children both reach 50%, the economic burden due to pneumococcal disease will be acceptable. This article provided an alternative perspective from the economic burden of diseases to obtain a vaccination coverage rate using the DTM. This will provide valuable information for vaccination policy decision makers. Copyright © 2015 International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc. All rights reserved.

Identification of potential new protein vaccine candidates through pan-surfomic analysis of pneumococcal clinical isolates from adults.

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Alfonso Olaya-Abril

Full Text Available Purified polysaccharide and conjugate vaccines are widely used for preventing infections in adults and in children against the Gram-positive bacterium Streptococcus pneumoniae, a pathogen responsible for high morbidity and mortality rates, especially in developing countries. However, these polysaccharide-based vaccines have some important limitations, such as being serotype-dependent, being subjected to losing efficacy because of serotype replacement and high manufacturing complexity and cost. It is expected that protein-based vaccines will overcome these issues by conferring a broad coverage independent of serotype and lowering production costs. In this study, we have applied the "shaving" proteomic approach, consisting of the LC/MS/MS analysis of peptides generated by protease treatment of live cells, to a collection of 16 pneumococcal clinical isolates from adults, representing the most prevalent strains circulating in Spain during the last years. The set of unique proteins identified in all the isolates, called "pan-surfome", consisted of 254 proteins, which included most of the protective protein antigens reported so far. In search of new candidates with vaccine potential, we identified 32 that were present in at least 50% of the clinical isolates analyzed. We selected four of them (Spr0012, Spr0328, Spr0561 and SP670_2141, whose protection capacity has not yet been tested, for assaying immunogenicity in human sera. All of them induced the production of IgM antibodies in infected patients, thus indicating that they could enter the pipeline for vaccine studies. The pan-surfomic approach shows its utility in the discovery of new proteins that can elicit protection against infectious microorganisms.

Potential of nanoparticles for allergen-specific immunotherapy - use of silica nanoparticles as vaccination platform.

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Scheiblhofer, Sandra; Machado, Yoan; Feinle, Andrea; Thalhamer, Josef; Hüsing, Nicola; Weiss, Richard

2016-12-01

Allergen-specific immunotherapy is the only curative approach for the treatment of allergies. There is an urgent need for improved therapies, which increase both, efficacy and patient compliance. Novel routes of immunization and the use of more advanced vaccine platforms have gained heightened interest in this field. Areas covered: The current status of allergen-specific immunotherapy is summarized and novel routes of immunization and their challenges in the clinics are critically discussed. The use of nanoparticles as novel delivery system for allergy vaccines is comprehensively reviewed. Specifically, the advantages of silica nanoparticles as vaccine carriers and adjuvants are summarized. Expert opinion: Future allergen-specific immunotherapy will combine engineered hypoallergenic vaccines with novel routes of administration, such as the skin. Due to their biodegradability, and the easiness to introduce surface modifications, silica nanoparticles are promising candidates for tailor-made vaccines. By covalently linking allergens and polysaccharides to silica nanoparticles, a versatile vaccination platform can be designed to specifically target antigen-presenting cells, render the formulation hypoallergenic, and introduce immunomodulatory functions. Combining potent skin vaccination methods, such as fractional laser ablation, with nanoparticle-based vaccines addresses all the requirements for safe and efficient therapy of allergic diseases.

Critical appraisal of a quadrivalent CRM197 conjugate vaccine against meningococcal serogroups A, C W-135 and Y (Menveo®) in the context of treatment and prevention of invasive disease

Science.gov (United States)

Bröker, Michael; Cooper, Brian; DeTora, Lisa M; Stoddard, Jeffrey J

2011-01-01

Worldwide, invasive meningococcal disease affects about 500,000 people annually. Case fatality in developed countries averages 10%, and higher rates are reported in less prosperous regions. According to the World Health Organization, the most important pathogenic serogroups are A, B, C, W-135, X, and Y. Clinical features of invasive meningococcal disease make diagnosis and management difficult. Antibiotic measures are recommended for prophylaxis after exposure and for treatment of invasive meningococcal disease cases; however, resistant strains may be emerging. Vaccines are generally regarded as the best preventative measure for invasive meningococcal disease. Polysaccharide vaccines against serogroups A, C, W-135, and Y using protein conjugation technology have clear advantages over older plain polysaccharide formulations without a protein component. The first quadrivalent meningococcal conjugate vaccine (MenACWY-D) was licensed in the US in 2005. More recently, MenACWY-CRM (Menveo®) was licensed in Europe, the US, the Middle East, and Latin America. MenACWY-CRM uses cross-reactive material 197, a nontoxic mutant of diphtheria toxin, as the carrier protein. MenACWY-CRM offers robust immunogenicity in all age groups, with a tolerability profile similar to that of a plain polysaccharide vaccine. Given its potential for protecting persons from infancy to old age, MenACWY-CRM offers the opportunity to protect broad populations against invasive meningococcal disease. The most optimal strategy for use of the vaccine has to be assessed country by country on the basis of local epidemiology, individual health care systems, and need. PMID:21904459

Liposome-Based Delivery Systems in Plant Polysaccharides

International Nuclear Information System (INIS)

Meiwan, C.; Yitao, W.; Yanfang, Z.; Xinsheng, P.; Jingjing, H.; Ping, Z.

2012-01-01

Plant polysaccharides consist of many monosaccharide by α or β glycosidic bond which can be extracted by the water, alcohol, lipophile liquid from a variety of plants including Cordyceps sinensis, astragalus, and mushrooms. Recently, many evidences illustrate that natural plant polysaccharides possess various biological activities including strengthening immunity, lowering blood sugar, regulating lipid metabolism, anti oxidation, anti aging, and antitumour. Plant polysaccharides have been widely used in the medical field due to their special features and low toxicity. As an important drug delivery system, liposomes can not only encapsulate small-molecule compound but also big-molecule drug; therefore, they present great promise for the application of plant polysaccharides with unique physical and chemical properties and make remarkable successes. This paper summarized the current progress in plant polysaccharides liposomes, gave an overview on their experiment design method, preparation, and formulation, characterization and quality control, as well as in vivo and in vitro studies. Moreover, the potential application of plant polysaccharides liposomes was prospected as well.

Heavy-chain isotype patterns of human antibody-secreting cells induced by Haemophilus influenzae type b conjugate vaccines in relation to age and preimmunity

DEFF Research Database (Denmark)

Barington, T; Juul, Lars; Gyhrs, A

1994-01-01

The influence of preexisting immunity on the heavy-chain isotypes of circulating antibody-secreting cells (AbSC) induced by vaccination with Haemophilus influenzae type b (Hib) capsular polysaccharide (HibCP) coupled to tetanus toxoid (TT) or diphtheria toxoid (DT) and by vaccination with TT or D...... of natural HibCP antibodies (r = 0.59; P = 0.00002). A possible role of natural exposure for Hib or cross-reactive bacteria on the mucosal surfaces in the shaping of the isotype response to HibCP conjugate vaccines is discussed....

Changes in the incidence of pneumonia, bacterial meningitis, and infant mortality 5 years following introduction of the 13-valent pneumococcal conjugate vaccine in a "3+0" schedule.

Science.gov (United States)

Becker-Dreps, Sylvia; Blette, Bryan; Briceño, Rafaela; Alemán, Jorge; Hudgens, Michael G; Moreno, Gilberto; Ordoñez, Ana; Rocha, Julio; Weber, David J; Amaya, Erick

2017-01-01

Streptococcus pneumoniae causes about 826,000 deaths of children in the world each year and many health facility visits. To reduce the burden of pneumococcal disease, many nations have added pneumococcal conjugate vaccines to their national immunization schedules. Nicaragua was the first country eligible for GAVI Alliance funding to introduce the 13-valent pneumococcal conjugate vaccine (PCV13) in 2010, provided to infants at 2, 4, and 6 months of age. The goal of this study was to evaluate the population impact of the first five years of the program. Numbers of visits for pneumonia, pneumonia-related deaths, and bacterial meningitis in both children and adults, and infant deaths between 2008 and 2015 were collected from all 107 public health facilities in León Department. Vital statistics data provided additional counts of pneumonia-related deaths that occurred outside health facilities. Adjusted incidence rates and incidence rate ratios (IRRa) in the vaccine (2011-2015) and pre-vaccine periods (2008-2010) were estimated retrospectively using official population estimates as exposure time. The IRRa for pneumonia hospitalizations was 0.70 (95% confidence interval [CI]: 0.66, 0.75) for infants, and 0.92 (95% CI: 0.85, 0.99) for one year-olds. The IRRa for post-neonatal infant mortality was 0.56 (95% CI: 0.41, 0.77). In the population as a whole, ambulatory visits and hospitalizations for pneumonia, as well as pneumonia-related mortality and rates of bacterial meningitis were lower in the vaccine period. During the first five years of program implementation, reductions were observed in health facility visits for pneumonia in immunized age groups and infant mortality, which would be hard to achieve with any other single public health intervention. Future study is warranted to understand whether the lack of a booster dose (e.g., at 12 months) may be responsible for the small reductions in pneumonia hospitalizations observed in one year-olds as compared to infants.

Immune enhancement of Taishan Robinia pseudoacacia polysaccharide on recombinant Proteus mirabilis OmpA in chickens.

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Zhang, Yongbing; Yang, Shifa; Zhao, Xue; Yang, Ya; Li, Bing; Zhu, Fujie; Zhu, Ruiliang

2014-09-01

This study was conducted to evaluate the effects of Taishan Robinia pseudoacacia polysaccharide (TRPPS) on immune responses of chickens immunized with Proteus mirabilis outer membrane protein A (OmpA) recombinant protein vaccine. OmpA was expressed in Pichia pastoris and mixed with TRPPS. 360 chickens were randomly divided into six groups. Groups I to IV were treated with OmpA which contained TRPPS of three different dosages, Freund's adjuvant, respectively. Groups V and VI were treated with pure OmpA and physiological saline, respectively. The data showed that the antibody titers against OmpA, the concentration of IL-2, CD4 +, and CD8 +, T lymphocyte proliferation rate in Group II were significantly higher (P < 0.05) than those in the other groups, little difference in SIgA content was observed among groups I to VI. These results indicated that TRPPS strengthened humoral and cellular immune responses against recombinant OmpA vaccine. Moreover, 200 mg/mL TRPPS showed significance (P < 0.05) compared with Freund's adjuvant. Therefore, TRPPS can be developed into an adjuvant for recombinant subunit vaccine. Copyright © 2014 Elsevier B.V. All rights reserved.

Prophylactic Sublingual Immunization with Mycobacterium tuberculosis Subunit Vaccine Incorporating the Natural Killer T Cell Agonist Alpha-Galactosylceramide Enhances Protective Immunity to Limit Pulmonary and Extra-Pulmonary Bacterial Burden in Mice

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Arshad Khan

2017-12-01

Full Text Available Infection by Mycobacterium tuberculosis (Mtb remains a major global concern and the available Bacillus Calmette-Guerin (BCG vaccine is poorly efficacious in adults. Therefore, alternative vaccines and delivery strategies focusing on Mtb antigens and appropriate immune stimulating adjuvants are needed to induce protective immunity targeted to the lungs, the primary sites of infections and pathology. We present here evidence in support of mucosal vaccination by the sublingual route in mice using the subunit Mtb antigens Ag85B and ESAT-6 adjuvanted with the glycolipid alpha-galactosylceramide (α-GalCer, a potent natural killer T (NKT cell agonist. Vaccinated animals exhibited strong antigen-specific CD4 and CD8 T cells responses in the spleen, cervical lymph nodes and lungs. In general, inclusion of the α-GalCer adjuvant significantly enhanced these responses that persisted over 50 days. Furthermore, aerosolized Mtb infection of vaccinated mice resulted in a significant reduction of bacterial load of the lungs and spleens as compared to levels seen in naïve controls or those vaccinated with subunit proteins, adjuvant , or BCG alone. The protection induced by the Mtb antigens and-GalCer vaccine through sublingual route correlated with a TH1-type immunity mediated by antigen-specific IFN-γ and IL-2 producing T cells.

Effect of early measles vaccine on pneumococcal colonization

DEFF Research Database (Denmark)

Hansen, Nadja Skadkær; Byberg, Stine; Hervig Jacobsen, Lars

2017-01-01

BACKGROUND: Measles vaccine (MV) may have non-specific beneficial effects for child health and particularly seems to prevent respiratory infections. Streptococcus pneumoniae is the leading cause of bacterial pneumonia among children worldwide, and nasopharyngeal colonization precedes infection....... OBJECTIVE: We investigated whether providing early MV at 18 weeks of age reduced pneumococcal colonization and/or density up to 9 months of age. METHOD: The study was conducted in 2013-2014 in Guinea-Bissau. Pneumococcal vaccine was not part of the vaccination program. Infants aged 18 weeks were block...

Cytochemical Localization of Polysaccharides in Dendrobium officinale and the Involvement of DoCSLA6 in the Synthesis of Mannan Polysaccharides

OpenAIRE

He, Chunmei; Wu, Kunlin; Zhang, Jianxia; Liu, Xuncheng; Zeng, Songjun; Yu, Zhenming; Zhang, Xinghua; Teixeira da Silva, Jaime A.; Deng, Rufang; Tan, Jianwen; Luo, Jianping; Duan, Jun

2017-01-01

Dendrobium officinale is a precious traditional Chinese medicinal plant because of its abundant polysaccharides found in stems. We determined the composition of water-soluble polysaccharides and starch content in D. officinale stems. The extracted water-soluble polysaccharide content was as high as 35% (w/w). Analysis of the composition of monosaccharides showed that the water-soluble polysaccharides were dominated by mannose, to a lesser extent glucose, and a small amount of galactose, in a ...

The re-emergency and persistence of vaccine preventable diseases

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RODRIGO C.N. BORBA

2015-08-01

Full Text Available The introduction of vaccination worldwide dramatically reduced the incidence of pathogenic bacterial and viral diseases. Despite the highly successful vaccination strategies, the number of cases among vaccine preventable diseases has increased in the last decade and several of those diseases are still endemic in different countries. Here we discuss some epidemiological aspects and possible arguments that may explain why ancient diseases such as, measles, polio, pertussis, diphtheria and tuberculosis are still with us.

Research of polysaccharide complexes from asteraceae family plants

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Світлана Михайлівна Марчишин

2015-10-01

Full Text Available Aim of research. Depth study of polysaccharides in some little-known plant species of Asteraceae family is pressing question, considering that polysaccharides are important biologically active compounds widely used in pharmaceutical and medical practice as remedies and preventive medications. The aim of research was to determinate both quantitative content and monomeric composition of polysaccharide complexes from Asteraceae family plant species – Tagetes genus, Arnica genus, and Bellis genus.Materials and methods. Determination of polysaccharides was carried out by the precipitation reaction, using 96 % ethyl alcohol P and Fehling's solution after acid hydrolysis; quantitative content of this group of compounds was determined by gravimetric analysis. On purpose to identify the monomeric composition hydrolysis under sulfuric acid conditions was conducted. Qualitative monomeric composition of polysaccharides after hydrolysis was carried out by paper chromatography method in n-Butanol – Pyridine – Distilled water P (6:4:3 system along with saccharides reference samples.Results. Polysaccharide complexes from Tagetes erecta, Tagetes patula, Tagetes tenuifolia, Arnica montana, Arnica foliosa, wild and cultivated Bellis perennis herbs were studied. Water-soluble polysaccharides and pectin fractions were isolated from studied objects; their quantitative content and monomeric composition were determined.Conclusion. The highest amount of water-soluble polysaccharides was found in cultivated Bellis perennis herb (10,13 %, the highest amount of pectin compounds – in Tagetes tenuifolia herb (13,62 %; the lowest amount of water-soluble polysaccharides and pectin compounds was found in Arnica montana herb (4,61 % and Tagetes patula herb (3,62 %, respectively. It was found that polysaccharide complexes from all studied species include glucose and arabinose

Immunogenicity and safety of tetravalent dengue vaccine in 2-11 year-olds previously vaccinated against yellow fever: randomized, controlled, phase II study in Piura, Peru.

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Lanata, Claudio F; Andrade, Teresa; Gil, Ana I; Terrones, Cynthia; Valladolid, Omar; Zambrano, Betzana; Saville, Melanie; Crevat, Denis

2012-09-07

In a randomized, placebo-controlled, monocenter, observer blinded study conducted in an area where dengue is endemic, we assessed the safety and immunogenicity of a recombinant, live, attenuated, tetravalent dengue vaccine candidate (CYD-TDV) in 2-11 year-olds with varying levels of pre-existing yellow-fever immunity due to vaccination 1-7 years previously. 199 children received 3 injections of CYD-TDV (months 0, 6 and 12) and 99 received placebo (months 0 and 6) or pneumococcal polysaccharide vaccine (month 12). One month after the third dengue vaccination, serotype specific neutralizing antibody GMTs were in the range of 178-190 (1/dil) (versus 16.7-38.1 in the control group), a 10-20 fold-increase from baseline, and 94% of vaccines were seropositive to all four serotypes (versus 39% in the control group). There were no vaccine-related SAEs. The observed reactogenicity profile was consistent with phase I studies, with severity grade 1-2 injection site pain, headache, malaise and fever most frequently reported and no increase after subsequent vaccinations. Virologically confirmed dengue cases were seen after completion of the 3 doses: 1 in the CYD-TDV group (N=199), and 3 in the control group (N=99). A 3-dose regimen of CYD-TDV had a good safety profile in 2-11 year olds with a history of YF vaccination and elicited robust antibody responses that were balanced against the four serotypes. Copyright © 2012 Elsevier Ltd. All rights reserved.

Patterns of pneumococcal vaccination and revaccination in elderly and non-elderly adults: a Vaccine Safety Datalink study

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Belongia Edward A

2009-03-01

Full Text Available Abstract Background Pneumococcal polysaccharide vaccine (PPV is recommended for all adults 65 years of age and older and for younger adults with high-risk conditions. While data from national surveys provide information on the proportion of adults 65 years of age and older reporting ever receipt of PPV they do not collect more detailed information, such as age at vaccination or the total number of vaccinations received. In addition, there is relatively little information available on PPV coverage in younger adults with chronic conditions. To assess contemporary patterns of pneumococcal vaccination and revaccination of adults, we conducted a cross-sectional study of adults enrolled in medical care organizations (MCOs participating in the Vaccine Safety Datalink project. Methods The study population included 1.5 million adults 25 years of age and older enrolled in the four participating MCOs on December 1, 2006. PPVs administered to members of the study population prior to that date were identified from computerized immunization registries maintained by the MCOs. Results Among the general population of adults 25 through 64 years of age, vaccine coverage increased from 2% in the 25–29 year old age-group to 26% in the 60–64 year old age-group. In all age-groups, coverage was substantially higher in persons defined as having a chronic high risk condition. This was particularly true for diabetes mellitus, with vaccine coverage of over 50% in the lower age-groups and 75% in those 60–64 years of age. Among adults 65 years of age and older, 82% had received at least one PPV and 18% had received two or more PPVs. Conclusion We found higher levels of PPV coverage among adults 65 years of age and older and among younger adults with diabetes mellitus than reported by national surveys and for those groups PPV coverage approached the Healthy People 2010 national objectives. These results suggest that achieving those objectives for PPV is possible and

Noninvasive vaccination against infectious diseases.

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Zheng, Zhichao; Diaz-Arévalo, Diana; Guan, Hongbing; Zeng, Mingtao

2018-04-06

The development of a successful vaccine, which should elicit a combination of humoral and cellular responses to control or prevent infections, is the first step in protecting against infectious diseases. A vaccine may protect against bacterial, fungal, parasitic, or viral infections in animal models, but to be effective in humans there are some issues that should be considered, such as the adjuvant, the route of vaccination, and the antigen-carrier system. While almost all licensed vaccines are injected such that inoculation is by far the most commonly used method, injection has several potential disadvantages, including pain, cross contamination, needlestick injury, under- or overdosing, and increased cost. It is also problematic for patients from rural areas of developing countries, who must travel to a hospital for vaccine administration. Noninvasive immunizations, including oral, intranasal, and transcutaneous administration of vaccines, can reduce or eliminate pain, reduce the cost of vaccinations, and increase their safety. Several preclinical and clinical studies as well as experience with licensed vaccines have demonstrated that noninvasive vaccine immunization activates cellular and humoral immunity, which protect against pathogen infections. Here we review the development of noninvasive immunization with vaccines based on live attenuated virus, recombinant adenovirus, inactivated virus, viral subunits, virus-like particles, DNA, RNA, and antigen expression in rice in preclinical and clinical studies. We predict that noninvasive vaccine administration will be more widely applied in the clinic in the near future.

Extraction, characterisation and antioxidant activity of Allium sativum polysaccharide.

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Cheng, Hao; Huang, Gangliang

2018-07-15

Extraction and antioxidant activity of polysaccharide from Allium sativum were investigated. The crude polysaccharide was obtained by the hot-water extraction method. The molecular weight of polysaccharide deproteinized with CaCl 2 was 7.35×10 3 . It indicated that polysaccharide from Allium sativum consisted of three monosaccharides, namely fructose, glucose, and galactose by HPLC. The polysaccharide had the β-glycosidic bond. Moreover, it was proved that the polysaccharide had the potential scavenging ability to superoxide anions and hydroxyl radicals. So, it should be a potential antioxidant. Copyright © 2018 Elsevier B.V. All rights reserved.

25 years after Vi typhoid vaccine efficacy study, typhoid affects significant number of population in Nepal.

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Deepak Bajracharya

Full Text Available Salmonella Typhi, first isolated in 1884, results in infection of the intestines and can end in death and disability. Due to serious adverse events post vaccination, whole cell killed vaccines have been replaced with new generation vaccines. The efficacy of Vi polysaccharide (ViPS vaccine, a new generation, single-dose intramuscular typhoid vaccine was assessed in Nepal in 1987. However, despite the availability of ViPS vaccine for more than 25 years, Nepal has one of the highest incidence of typhoid fever. Therefore we collected information from hospitals in the Kathmandu Valley from over the past five years. There were 9901 enteric fever cases between January 2008 and July 2012. 1,881 of these were confirmed typhoid cases from five hospitals in the Kathmandu district. Approximately 70% of the cases involved children under 15 years old. 1281 cases were confirmed as S. Paratyphi. Vaccines should be prioritized for control of typhoid in conjunction with improved water and sanitation conditions in Nepal and in endemic countries of Asia and Africa.

Hijacking Complement Regulatory Proteins for Bacterial Immune Evasion.

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Hovingh, Elise S; van den Broek, Bryan; Jongerius, Ilse

2016-01-01

The human complement system plays an important role in the defense against invading pathogens, inflammation and homeostasis. Invading microbes, such as bacteria, directly activate the complement system resulting in the formation of chemoattractants and in effective labeling of the bacteria for phagocytosis. In addition, formation of the membrane attack complex is responsible for direct killing of Gram-negative bacteria. In turn, bacteria have evolved several ways to evade complement activation on their surface in order to be able to colonize and invade the human host. One important mechanism of bacterial escape is attraction of complement regulatory proteins to the microbial surface. These molecules are present in the human body for tight regulation of the complement system to prevent damage to host self-surfaces. Therefore, recruitment of complement regulatory proteins to the bacterial surface results in decreased complement activation on the microbial surface which favors bacterial survival. This review will discuss recent advances in understanding the binding of complement regulatory proteins to the bacterial surface at the molecular level. This includes, new insights that have become available concerning specific conserved motives on complement regulatory proteins that are favorable for microbial binding. Finally, complement evasion molecules are of high importance for vaccine development due to their dominant role in bacterial survival, high immunogenicity and homology as well as their presence on the bacterial surface. Here, the use of complement evasion molecules for vaccine development will be discussed.

Pneumococcal vaccination in adults: rationale, state of the art and perspectives.

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Icardi, G; Sticchi, L; Bagnasco, A; Iudici, R; Durando, P

2012-06-01

Streptococcus pneumoniae (SP) is a leading cause of morbidity and mortality worldwide. Despite the availability, since the early 1980s, of a 23-valent pneumococcal polysaccharide vaccine (PP V23), its recommendation and increased use in the last decades, and the indirect benefits against invasive pneumococcal diseases following the pediatric immunization strategies with the 7-valent pneumococcal conjugate vaccine (PCV7), pneumoccal diseases, particularly Community Acquired Pneumonia (CAP), still remain a substantial burden among older adults in Western countries. The recent availability on the market of a second generation of pneumococcal conjugate vaccines, with an enlarged spectrum of protection against some serotypes not included in the PCV7 (i.e., the 13-valent pneumococcal conjugate vaccine--PCV13), opens new interesting perspectives for improving the control of this significant health-care issue among the entire population. The most interesting and up-dated epidemiological data regarding the impact of SP in adults and the elderly in Western countries, together with the available evidence concerning the efficacy and effectiveness of the PPV23 in the same population, are reported and discussed below.

Lessons and implications from a mass immunization campaign in squatter settlements of Karachi, Pakistan: an experience from a cluster-randomized double-blinded vaccine trial [NCT00125047

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Abu-Elyazeed Remon

2006-05-01

Full Text Available Abstract Objective To determine the safety and logistic feasibility of a mass immunization strategy outside the local immunization program in the pediatric population of urban squatter settlements in Karachi, Pakistan. Methods A cluster-randomized double blind preventive trial was launched in August 2003 in 60 geographic clusters covering 21,059 children ages 2 to 16 years. After consent was obtained from parents or guardians, eligible children were immunized parenterally at vaccination posts in each cluster with Vi polysaccharide or hepatitis A vaccine. Safety, logistics, and standards were monitored and documented. Results The vaccine coverage of the population was 74% and was higher in those under age 10 years. No life-threatening serious adverse events were reported. Adverse events occurred in less than 1% of all vaccine recipients and the main reactions reported were fever and local pain. The proportion of adverse events in Vi polysaccharide and hepatitis A recipients will not be known until the end of the trial when the code is broken. Throughout the vaccination campaign safe injection practices were maintained and the cold chain was not interrupted. Mass vaccination in slums had good acceptance. Because populations in such areas are highly mobile, settlement conditions could affect coverage. Systemic reactions were uncommon and local reactions were mild and transient. Close community involvement was pivotal for information dissemination and immunization coverage. Conclusion This vaccine strategy described together with other information that will soon be available in the area (cost/effectiveness, vaccine delivery costs, etc will make typhoid fever control become a reality in the near future.

Bio-inspired materials engineering using polysaccharide based biotemplates

International Nuclear Information System (INIS)

Zollfrank, C.

2007-01-01

Nano-structured materials with a controlled microstructure and tailored properties at a scale below 100 nm are of interest for applications in micro-mechanical, sensor and biomedical devices. In contrast to top-down manufacturing processes the formation of solid matter structures in nature is templated and directed by biomacromolecules such as polysaccharides and polypeptides. A promising biomimetic route for the directed deposition of ceramic materials is the application of anisotropically structured biomacromolecules as patterned templates. The polysaccharides exhibit a hierarchical multi scale order as well as self-assembly properties. The bio-inspired deposition and formation of ceramic phases on biomolecular polysaccharide templates was investigated. The polysaccharides were used at various structural levels from the molecular scale up to three-dimensional parts in the millimetre range. The versatility of polysaccharide shaping capabilities was explored using dissolved polysaccharide molecules as well as thin films for the or simultaneous or successive formation of inorganic mineral phases. Microalgae with a spherical appearance of 5 micro-m were applied in mineralisation studies. The extracellular polysaccharide (EPS) layers on the microalgae were used as biotemplates for manufacturing of functional ceramics. The obtained results on the mineralisation of inorganic phases on polysaccharides are adapted for novel biomimetic routes used in the fabrication for functional and biomedical ceramics. (author)

Engineering nanoparticle-coated bacteria as oral DNA vaccines for cancer immunotherapy.

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Hu, Qinglian; Wu, Min; Fang, Chun; Cheng, Changyong; Zhao, Mengmeng; Fang, Weihuan; Chu, Paul K; Ping, Yuan; Tang, Guping

2015-04-08

Live attenuated bacteria are of increasing importance in biotechnology and medicine in the emerging field of cancer immunotherapy. Oral DNA vaccination mediated by live attenuated bacteria often suffers from low infection efficiency due to various biological barriers during the infection process. To this end, we herein report, for the first time, a new strategy to engineer cationic nanoparticle-coated bacterial vectors that can efficiently deliver oral DNA vaccine for efficacious cancer immunotherapy. By coating live attenuated bacteria with synthetic nanoparticles self-assembled from cationic polymers and plasmid DNA, the protective nanoparticle coating layer is able to facilitate bacteria to effectively escape phagosomes, significantly enhance the acid tolerance of bacteria in stomach and intestines, and greatly promote dissemination of bacteria into blood circulation after oral administration. Most importantly, oral delivery of DNA vaccines encoding autologous vascular endothelial growth factor receptor 2 (VEGFR2) by this hybrid vector showed remarkable T cell activation and cytokine production. Successful inhibition of tumor growth was also achieved by efficient oral delivery of VEGFR2 with nanoparticle-coated bacterial vectors due to angiogenesis suppression in the tumor vasculature and tumor necrosis. This proof-of-concept work demonstrates that coating live bacterial cells with synthetic nanoparticles represents a promising strategy to engineer efficient and versatile DNA vaccines for the era of immunotherapy.

Cost-Effectiveness of Vaccinating Immunocompetent ≥65 Year Olds with the 13-Valent Pneumococcal Conjugate Vaccine in England.

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Albert Jan van Hoek

Full Text Available Recently a large clinical trial showed that the use of 13-valent pneumococcal conjugate vaccine (PCV13 among immunocompetent individuals aged 65 years and over was safe and efficacious. The aim of this study was to assess the cost-effectiveness of vaccinating immunocompetent 65 year olds with PCV13 vaccine in England. England is a country with universal childhood pneumococcal conjugate vaccination programme in place (7-valent (PCV7 since 2006 and PCV13 since 2010, as well as a 23-valent pneumococcal polysaccharide (PPV23 vaccination programme targeting clinical risk-groups and those ≥65 years.A static cohort cost-effectiveness model was developed to follow a cohort of 65 year olds until death, which will be vaccinated in the autumn of 2016 with PCV13. Sensitivity analysis was performed to test the robustness of the results.The childhood vaccination programme with PCV7 has induced herd protection among older unvaccinated age groups, with a resultant low residual disease burden caused by PCV7 vaccine types. We show similar herd protection effects for the 6 additional serotypes included in PCV13, and project a new low post-introduction equilibrium of vaccine-type disease in 2018/19. Applying these incidence projections for both invasive disease and community-acquired pneumonia (CAP, and using recent measures of vaccine efficacy against these endpoints for ≥65 year olds, we estimate that vaccination of a cohort of immunocompetent 65 year olds with PCV13 would directly prevent 26 cases of IPD, 69 cases of CAP and 15 deaths. The associated cost-effectiveness ratio is £257,771 per QALY gained (using list price of £49.10 per dose and £7.51 administration costs and is therefore considered not cost-effective. To obtain a cost-effective programme the price per dose would need to be negative. The results were sensitive to disease incidence, waning vaccine protection and case fatality rate; despite this, the overall conclusion was robust.Vaccinating

Whooping Cough Vaccine Recommendation for Preteens and Teens

Centers for Disease Control (CDC) Podcasts

2015-01-22

This podcast provides information about whooping cough and the recommendation that all preteens receive the Tdap vaccine when they are 11 or 12 to help protect them from this serious disease.  Created: 1/22/2015 by National Center for Infectious and Respiratory Disease (NCIRD), Division of Bacterial Disease (DBD), Meningitis and Vaccine Preventable Diseases Branch (MVPD).   Date Released: 1/22/2015.

Bacterial superglue enables easy development of efficient virus-like particle based vaccines

DEFF Research Database (Denmark)

Thrane, Susan; Janitzek, Christoph M; Matondo, Sungwa

2016-01-01

BACKGROUND: Virus-like particles (VLPs) represent a significant advance in the development of subunit vaccines, combining high safety and efficacy. Their particulate nature and dense repetitive subunit organization makes them ideal scaffolds for display of vaccine antigens. Traditional approaches...... for VLP-based antigen display require labor-intensive trial-and-error optimization, and often fail to generate dense antigen display. Here we utilize the split-intein (SpyTag/SpyCatcher) conjugation system to generate stable isopeptide bound antigen-VLP complexes by simply mixing of the antigen and VLP......). CONCLUSIONS: The spy-VLP system constitutes a versatile and rapid method to develop highly immunogenic VLP-based vaccines. Our data provide proof-of-concept for the technology's ability to present complex vaccine antigens to the immune system and elicit robust functional antibody responses as well...

A phase II, randomized study on an investigational DTPw-HBV/Hib-MenAC conjugate vaccine administered to infants in Northern Ghana.

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Abraham Hodgson

Full Text Available BACKGROUND: Combining meningococcal vaccination with routine immunization in infancy may reduce the burden of meningococcal meningitis, especially in the meningitis belt of Africa. We have evaluated the immunogenicity, persistence of immune response, immune memory and safety of an investigational DTPw-HBV/Hib-MenAC conjugate vaccine given to infants in Northern Ghana. METHODS AND FINDINGS: In this phase II, double blind, randomized, controlled study, 280 infants were primed with DTPw-HBV/Hib-MenAC or DTPw-HBV/Hib vaccines at 6, 10 and 14 weeks of age. At 12 months of age, children in each group received a challenge dose of serogroup A+C polysaccharides. Antibody responses were assessed pre, and one month-post dose 3 of the priming schedule and pre and 1 month after administration of the challenge dose. One month post-dose 3, 87.8% and 88.2% of subjects in the study group had bactericidal meningococcal serogroup A (SBA-MenA and meningococcal serogroup C (SBA-MenC antibody titres > or = 1:8 respectively. Seroprotection/seropositivity rates to the 5 antigens administered in the routine EPI schedule were non-inferior in children in the study group compared to those in the control group. The percentages of subjects in the study group with persisting SBA-MenA titres > or = 1:8 or SBA-MenC titres > or = 1:8 at the age of 12 months prior to challenge were significantly higher than in control group (47.7% vs 25.7% and 56.4% vs 5.1% respectively. The administration of 10 microg of serogroup A polysaccharide increased the SBA-MenA GMT by 14.0-fold in the DTPW-HBV/HibMenAC-group compared to a 3.8 fold increase in the control-group. Corresponding fold-increases in SBA-MenC titres following challenge with 10 microg of group C polysaccharide were 18.8 and 1.9 respectively. Reactogenicity following primary vaccination or the administration of the challenge dose was similar in both groups, except for swelling (Grade 3 after primary vaccination which was more

Drying a tuberculosis vaccine without freezing.

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Wong, Yun-Ling; Sampson, Samantha; Germishuizen, Willem Andreas; Goonesekera, Sunali; Caponetti, Giovanni; Sadoff, Jerry; Bloom, Barry R; Edwards, David

2007-02-20

With the increasing incidence of tuberculosis and drug resistant disease in developing countries due to HIV/AIDS, there is a need for vaccines that are more effective than the present bacillus Calmette-Guérin (BCG) vaccine. We demonstrate that BCG vaccine can be dried without traditional freezing and maintained with remarkable refrigerated and room-temperature stability for months through spray drying. Studies with a model Mycobacterium (Mycobacterium smegmatis) revealed that by removing salts and cryoprotectant (e.g., glycerol) from bacterial suspensions, the significant osmotic pressures that are normally produced on bacterial membranes through droplet drying can be reduced sufficiently to minimize loss of viability on drying by up to 2 orders of magnitude. By placing the bacteria in a matrix of leucine, high-yield, free-flowing, "vial-fillable" powders of bacteria (including M. smegmatis and M. bovis BCG) can be produced. These powders show relatively minor losses of activity after maintenance at 4 degrees C and 25 degrees C up to and beyond 4 months. Comparisons with lyophilized material prepared both with the same formulation and with a commercial formulation reveal that the spray-dried BCG has better overall viability on drying.

Therapeutic effect of polysaccharide fraction of Atractylodis macrocephalae Koidz. in bovine subclinical mastitis.

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Xu, Wei; Guan, Ran; Lu, Yisong; Su, Xiaoyan; Xu, Ye; Du, Aifang; Hu, Songhua

2015-07-25

Mastitis is considered the most significant and persistent disease in dairy cows, bringing about large economic losses. Subclinical mastitis brings about major cost implications, for it is difficult to detect due to absence of any visible indications and can persist in the mammary tissue throughout lactation. Immunomodulators have been widely used to reduce intramammary infections by modulating bovine mammary gland. Atractylodis macrocephalae Koidz. polysaccharides (RAMP), extracted from herbal medicine, has been used widely especially for its immunomodulatory function for many years. The objective of this study was to estimate an oil emulsified Atractylodis macrocephalae Koidz. polysaccharides (RAMP-O) as a potential therapeutic agent to treat subclinical mastitis by subcutaneous injection of RAMP-O in the area of supramammary lymph node in lactating cows via analysis of SCC, IMIs and NAGase. Injection of RAMP-O in the area of supramammary lymph node significantly reduced milk SCC and NAGase activity compared with control. The quarters with bacterial infection were also progressively reduced in RAMP-O treated cows and only 9 quarters were found to have bacterial infection, while no obvious change was found in the control group. Subcutaneous injection of RAMP-O in the area of supramammary lymph node had therapeutic value in the treatment of bovine subclinical mastitis by reducing SCC, NAGase and IMIs in milk. Considering both the therapeutic effect and the cost of RAMP-O, 32 mg per dose was found most suitable to reduce milk SCC and NAGase. Therefore, RAMP-O deserves further study for its use in treatment of bovine mastitis.

Structures of two cell wall-associated polysaccharides of a Streptococcus mitis biovar 1 strain. A unique teichoic acid-like polysaccharide and the group O antigen which is a C-polysaccharide in common with pneumococci

DEFF Research Database (Denmark)

Bergström, N; Jansson, P.-E.; Kilian, Mogens

2000-01-01

The cell wall of Streptococcus mitis biovar 1 strain SK137 contains the C-polysaccharide known as the common antigen of a closely related species Streptococcus pneumoniae, and a teichoic acid-like polysaccharide with a unique structure. The two polysaccharides are different entities and could...... be partially separated by gel chromatography. The structures of the two polysaccharides were determined by chemical methods and by NMR spectroscopy. The teichoic acid-like polymer has a heptasaccharide phosphate repeating unit with the following structure: The structure neither contains ribitol nor glycerol...... phosphate as classical teichoic acids do, thus we have used the expression teichoic acid-like for this polysaccharide. The following structure of the C-polysaccharide repeating unit was established: where AAT is 2-acetamido-4-amino-2,4, 6-trideoxy-D-galactose. It has a carbohydrate backbone identical...

Neisseria meningitidis Group A IgG1 and IgG2 Subclass Immune Response in African Children Aged 12–23 Months Following Meningococcal Vaccination

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Holme, Daniel; Findlow, Helen; Sow, Samba O.; Idoko, Olubukola T.; Preziosi, Marie-Pierre; Carlone, George; Plikaytis, Brian D.; Borrow, Ray

2015-01-01

Background. A group A meningococcal conjugate vaccine, PsA-TT, was licensed in 2010 and was previously studied in a phase 2 clinical trial to evaluate its safety and immunogenicity in African children 12–23 months of age. Methods. Subjects received either PsA-TT; meningococcal group A, C, W, Y polysaccharide vaccine (PsACWY); or Haemophilus influenzae type b conjugate vaccine (Hib-TT). Forty weeks following primary vaccination, the 3 groups were further randomized to receive either PsA-TT, one-fifth dose of PsACWY, or Hib-TT. Group A–specific immunoglobulin G (IgG) subclass response was characterized using an enzyme-linked immunosorbent assay. Results. The predominant IgG subclass response, regardless of vaccine, was IgG1. One month following primary vaccination, the geometric mean concentrations (GMCs) of IgG1 and IgG2 in the PsA-TT group were 21.73 µg/mL and 6.27 µg/mL, whereas in the PsACWY group the mean GMCs were 2.01 µg/mL and 0.97 µg/mL, respectively (P Group A–specific IgG1 and IgG2 GMCs remained greater in the PsA-TT group than in the PsACWY group 40 weeks following primary vaccination (P vaccines. Conclusions. Vaccination of African children aged 12–24 months with either PsA-TT or PsACWY elicited a predominantly IgG1 response. The IgG1:IgG2 mean ratio decreased following successive vaccination with PsACWY, indicating a shift toward IgG2, suggestive of the T-cell–independent immune response commonly associated with polysaccharide antigens. Clinical Trials Registration. SRCTN78147026. PMID:26553689

Characterization of active polysaccharides of HemoHIM

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Shin, Kwang Sun; Shin, Myeong Suk; Bae, Beom Seon; Hwang, Yong Cheol [Kyonggi University, Suwon (Korea, Republic of); Ryu, Kwang Won [Chungju University, Chungju (Korea, Republic of)

2007-07-15

In this study, we aimed to elucidate the detailed structure and active moiety of polysaccharide, one of the active constituents of immune and hematopoietic modulating activities of HemoHIM. We first isolated the polysaccharide fractions from the hot water extracts of the each ingredient herbs (A. gigas, P. janonica, C. officinale) of HemoHIM and their mixture. These polysaccharides were composed of neutral (85.32-92.73%) and acidic (4.25-7.88%) saccharides, proteins (0.16-4.02%), and polyphenols (2.09-5.37%). The hydrolytic analysis of polysaccharide fractions showed that they commonly showed higher arabinose, galactose, and galacturonic acid contents. These result suggested that these polysaccharides may have higher contents of rhamnogalacturonan among pectic substances and the main active moiety is composed of polysaccharides. The anion exchange chromatography of HemoHIM and each ingredient herb extract using DEAE-Sepharose FF (Cl- form) column resulted in 1 non-adsorption and 8 adsorption fractions. The analysis of immune activity (lymphocyte proliferation) on these fractions showed that the fractions obtained by higher salt concentration carried the higher activity, but all fractions showed considerable immune activity

Characterization of active polysaccharides of HemoHIM

International Nuclear Information System (INIS)

Shin, Kwang Sun; Shin, Myeong Suk; Bae, Beom Seon; Hwang, Yong Cheol; Ryu, Kwang Won

2007-07-01

In this study, we aimed to elucidate the detailed structure and active moiety of polysaccharide, one of the active constituents of immune and hematopoietic modulating activities of HemoHIM. We first isolated the polysaccharide fractions from the hot water extracts of the each ingredient herbs (A. gigas, P. janonica, C. officinale) of HemoHIM and their mixture. These polysaccharides were composed of neutral (85.32-92.73%) and acidic (4.25-7.88%) saccharides, proteins (0.16-4.02%), and polyphenols (2.09-5.37%). The hydrolytic analysis of polysaccharide fractions showed that they commonly showed higher arabinose, galactose, and galacturonic acid contents. These result suggested that these polysaccharides may have higher contents of rhamnogalacturonan among pectic substances and the main active moiety is composed of polysaccharides. The anion exchange chromatography of HemoHIM and each ingredient herb extract using DEAE-Sepharose FF (Cl- form) column resulted in 1 non-adsorption and 8 adsorption fractions. The analysis of immune activity (lymphocyte proliferation) on these fractions showed that the fractions obtained by higher salt concentration carried the higher activity, but all fractions showed considerable immune activity

Surface contact stimulates the just-in-time deployment of bacterial adhesins.

Science.gov (United States)

Li, Guanglai; Brown, Pamela J B; Tang, Jay X; Xu, Jing; Quardokus, Ellen M; Fuqua, Clay; Brun, Yves V

2012-01-01

The attachment of bacteria to surfaces provides advantages such as increasing nutrient access and resistance to environmental stress. Attachment begins with a reversible phase, often mediated by surface structures such as flagella and pili, followed by a transition to irreversible attachment, typically mediated by polysaccharides. Here we show that the interplay between pili and flagellum rotation stimulates the rapid transition between reversible and polysaccharide-mediated irreversible attachment. We found that reversible attachment of Caulobacter crescentus cells is mediated by motile cells bearing pili and that their contact with a surface results in the rapid pili-dependent arrest of flagellum rotation and concurrent stimulation of polar holdfast adhesive polysaccharide. Similar stimulation of polar adhesin production by surface contact occurs in Asticcacaulis biprosthecum and Agrobacterium tumefaciens. Therefore, single bacterial cells respond to their initial contact with surfaces by triggering just-in-time adhesin production. This mechanism restricts stable attachment to intimate surface interactions, thereby maximizing surface attachment, discouraging non-productive self-adherence, and preventing curing of the adhesive. © 2011 Blackwell Publishing Ltd.

Modified polysaccharides as alternative binders for foundry industry

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K. Kaczmarska

2016-10-01

Full Text Available Polysaccharides constitute a wide group of important polymers with many commercial applications, for example food packaging, fibres, coatings, adhesives etc. This review is devoted to the presentation of polysaccharide application in foundry industry. In this paper the selected properties of foundry moulding sand and core sand containing modified polysaccharides as binders are presented according to foreign literature data. Also, author’s own research about effect of using moulding sand binder consisting of modified polysaccharide (modified starch or its composition with non-toxic synthetic polymers are discussed. Based on technologies taken under consideration in this paper, it could be concluded that polysaccharides are suitable as an alternative for use as binder in foundry moulding applications.

The immunostimulating role of lichen polysaccharides: a review.

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Shrestha, Gajendra; St Clair, Larry L; O'Neill, Kim L

2015-03-01

The immune system has capacity to suppress the development or progression of various malignancies including cancer. Research on the immunomodulating properties of polysaccharides obtained from plants, microorganisms, marine organisms, and fungi is growing rapidly. Among the various potential sources, lichens, symbiotic systems involving a fungus and an alga and/or a cyanobacterium, show promise as a potential source of immunomodulating compounds. It is well known that lichens produce an abundance of structurally diverse polysaccharides. However, only a limited number of studies have explored the immunostimulating properties of lichen polysaccharides. Published studies have shown that some lichen polysaccharides enhance production of nitrous oxide (NO) by macrophages and also alter the production levels of various proinflammatory and antiinflammatory cytokines (IL-10, IL-12, IL-1β, TNF-α, and IFN-α/β) by macrophages and dendritic cells. Although there are only a limited number of studies examining the role of lichen polysaccharides, all results suggest that lichen polysaccharides can induce immunomodulatory responses in macrophages and dendritic cells. Thus, a detailed evaluation of immunomodulatory capacity of lichen polysaccharides could provide a unique opportunity for the discovery of novel therapeutic agents. Copyright © 2014 John Wiley & Sons, Ltd.

Vaccines against enteric infections for the developing world

Science.gov (United States)

Czerkinsky, Cecil; Holmgren, Jan

2015-01-01

Since the first licensure of the Sabin oral polio vaccine more than 50 years ago, only eight enteric vaccines have been licensed for four disease indications, and all are given orally. While mucosal vaccines offer programmatically attractive tools for facilitating vaccine deployment, their development remains hampered by several factors: —limited knowledge regarding the properties of the gut immune system during early life;—lack of mucosal adjuvants, limiting mucosal vaccine development to live-attenuated or killed whole virus and bacterial vaccines;—lack of correlates/surrogates of mucosal immune protection; and—limited knowledge of the factors contributing to oral vaccine underperformance in children from developing countries.There are now reasons to believe that the development of safe and effective mucosal adjuvants and of programmatically sound intervention strategies could enhance the efficacy of current and next-generation enteric vaccines, especially in lesser developed countries which are often co-endemic for enteric infections and malnutrition. These vaccines must be safe and affordable for the world's poorest, confer long-term protection and herd immunity, and must be able to contain epidemics. PMID:25964464

Synthesis, characterization and immunological properties of LPS-based conjugate vaccine composed of O-polysaccharide from pseudomonas aeruginosa IATS 10 bound to recombinant exoprotein A

International Nuclear Information System (INIS)

Abu-baker, N. F.; Masoud, H. A.; Jaber, B. M.

2008-01-01

Pseudomonas aeruginosa is an improtant opportunistic pathogen that can cause infection in immunocompromised patient. Lipopolysaccharide (LPS), the major surface antigen of P. aeruginosa, is immunogenic and elieits protective antibodies in animals. The O-polysaccharids (O-PS) from international Antigenic typing Scheme (IATS) 10, the antigenic determinant of LPS, was coupled to recombinant exoprotein A (rPA) through adipic acid dihydrazide (ADH) mediated by carbodiimide condensation reaction. Mice were immunized with the conjugate emulsifield with monophosphoryl lipid A-trehalose dicorynomycolate (MPL-T) and freund's adjuvants. The conjiugate emulsified with MPL-T adjuvant elicited the highest level of IgG and IgM followed by freuns's adjuvant. IgG titers using both MPL-T and freund's adjuvants were recorded to be higher than IgM titers after the second post of the immunization. Immunization of mice with the prepared conjugates emulsified with MPL-T and freund's adjvaided provide high level of protection (100%) against ten times the LD50 of homologous strain of P. aeruginsoa. the elicited high IgG level and the in vivo protection test results provided good evidences for the possible protection of the conjugate aginst subsequent infection with the pathogen. These findings will enable us to use it as protective vaccine candidate (authors).

Epidemiology of bacterial meningitis among children in Brazil, 1997-1998

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Débora PL Weiss

2001-06-01

Full Text Available OBJECTIVE: To document the incidence and the descriptive epidemiology of bacterial meningitis among individuals under age 20 in a geographically defined region in Brazil during the two-year period immediately preceding the introduction of Haemophilus influenzae type b (Hib vaccines into the national immunization program of Brazil. METHODS: Population-based epidemiological study of all cases of bacterial meningitis reported among residents of Campinas, Brazil, under age 20 (n=316,570 during the period of 1997-98, using comprehensive surveillance records compiled by the Campinas Health Department from cases reported among hospital inpatients, outpatients, emergency room visits, death certificates, and autopsy reports. RESULTS: The incidence of bacterial meningitis (n=274 was 334.9, 115 and 43.5 cases/10(5 person-years (pys for residents of Campinas under age 1, 5 and 20, respectively. All cases were hospitalized, with an average length of stay of 12 days. Documented prior antibiotic use was 4.0%. The case-fatality rate of bacterial meningitis in individuals under age 20 was 9% (24/274 with 75% of deaths occurring in children under the age of five. The incidence of Hib meningitis (n=26 was 62.8 and 17 cases/10(5 pys in children age <1 and <5, respectively. CONCLUSIONS: The incidence of Hib meningitis in children under the age of 5 in Campinas during 1997-98 was similar to that reported in the US, Western Europe, and Israel prior to widespread Hib vaccine use in those regions. This study provides a baseline for later studies to evaluate changes in the etiology and incidence of bacterial meningitis in children after introduction of routine Hib vaccination in Brazil.

Vaccine platform recombinant measles virus.

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Mühlebach, Michael D

2017-10-01

The classic development of vaccines is lengthy, tedious, and may not necessarily be successful as demonstrated by the case of HIV. This is especially a problem for emerging pathogens that are newly introduced into the human population and carry the inherent risk of pandemic spread in a naïve population. For such situations, a considerable number of different platform technologies are under development. These are also under development for pathogens, where directly derived vaccines are regarded as too complicated or even dangerous due to the induction of inefficient or unwanted immune responses causing considerable side-effects as for dengue virus. Among platform technologies are plasmid-based DNA vaccines, RNA replicons, single-round infectious vector particles, or replicating vaccine-based vectors encoding (a) critical antigen(s) of the target pathogens. Among the latter, recombinant measles viruses derived from vaccine strains have been tested. Measles vaccines are among the most effective and safest life-attenuated vaccines known. Therefore, the development of Schwarz-, Moraten-, or AIK-C-strain derived recombinant vaccines against a wide range of mostly viral, but also bacterial pathogens was quite straightforward. These vaccines generally induce powerful humoral and cellular immune responses in appropriate animal models, i.e., transgenic mice or non-human primates. Also in the recent first clinical phase I trial, the results have been quite encouraging. The trial indicated the expected safety and efficacy also in human patients, interestingly independent from the level of prevalent anti-measles immunity before the trial. Thereby, recombinant measles vaccines expressing additional antigens are a promising platform for future vaccines.

Considerations for the rational design of a Chlamydia vaccine.

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Liang, Steven; Bulir, David; Kaushic, Charu; Mahony, James

2017-04-03

Chlamydia trachomatis is the leading cause of preventable blindness and the most common bacterial sexually transmitted infection. Remarkable progress in vaccine research over the past six decades has led to the advancement of novel C. trachomatis vaccine candidates into clinical trials. However, many questions regarding the role of specific cellular populations and molecular mechanisms in protective immunity against human C. trachomatis genital tract infections remain unanswered. Biomarkers of vaccine induced protective immunity are elusive in humans, while a cautionary message on the translatability of data obtained from current animal models has emanated from vaccine research and development efforts against other important human pathogens. In this commentary, we highlight recent advances in Chlamydia vaccine development and discuss their implications in the context of a rational approach to the design of a human C. trachomatis vaccine.

[Comparison on polysaccharide content and PMP-HPLC fingerprints of polysaccharide in stems and leaves of Dendrobium officinale].

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Zhou, Gui-Fen; Pang, Min-Xia; Chen, Su-Hong; Lv, Gui-Yuan; Yan, Mei-Qiu

2014-03-01

In order to provide scientific basics for exploitation and sufficient application of Dendrobium officinale leaves resources, the phenol-sulfuric acid method was applied to determine the polysaccharide content. The monosaccharides were derivated by PMP and the derivatives were identified by HPLC-DAD-ESI-MS(n) and the contents of mannose and glucose were determined simultaneously. Similarity evaluation system for chromatographic fingerprint of traditional Chinese medicine (2004A) was employed to generate the mean chromatogram and similarity analysis of the samples was carried out. The results demonstrated that polysaccharide content, monosaccharide compositions and composition ratio had an obvious difference between stems and leaves. The polysaccharide content of stems was higher than that of leaves. Monosaccharide composition in leaf was significantly different from that in stem. The polysaccharide from stems was composed of mannose and glucose, however the polysaccharide of leaves was acid heteropolysaccharide and was mainly composed of five monosaccharides, including mannose, galacturonic acid, glucose, galactose and arabinose. The similarity value of the 14 batches was above 0.9, indicating that similarity of fingerprints among different samples was high. The study can provide evidence for expanding the medicinal parts of D. officinale.

Impact of a Targeted Typhoid Vaccination Campaign Following Cyclone Tomas, Republic of Fiji, 2010

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Scobie, Heather M.; Nilles, Eric; Kama, Mike; Kool, Jacob L.; Mintz, Eric; Wannemuehler, Kathleen A.; Hyde, Terri B.; Dawainavesi, Akanisi; Singh, Sheetalpreet; Korovou, Samuel; Jenkins, Kylie; Date, Kashmira

2014-01-01

After a category 4 cyclone that caused extensive population displacement and damage to water and sanitation infrastructure in Fiji in March 2010, a typhoid vaccination campaign was conducted as part of the post-disaster response. During June–December 2010, 64,015 doses of typhoid Vi polysaccharide vaccine were administered to persons ≥ 2 years of age, primarily in cyclone-affected areas that were typhoid endemic. Annual typhoid fever incidence decreased during the post-campaign year (2011) relative to preceding years (2008–2009) in three subdivisions where a large proportion of the population was vaccinated (incidence rate ratios and 95% confidence intervals: 0.23, 0.13–0.41; 0.24, 0.14–0.41; 0.58, 0.40–0.86), and increased or remained unchanged in 12 subdivisions where little to no vaccination occurred. Vaccination played a role in reducing typhoid fever incidence in high-incidence areas after a disaster and should be considered in endemic settings, along with comprehensive control measures, as recommended by the World Health Organization. PMID:24710618

In vitro prebiotic effects of seaweed polysaccharides

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Chen, Xiaolin; Sun, Yuhao; Hu, Linfeng; Liu, Song; Yu, Huahua; Xing, Rong'e.; Li, Rongfeng; Wang, Xueqin; Li, Pengcheng

2017-09-01

Although prebiotic activities of alginate and agar oligosaccharides isolated from seaweeds have been reported, it remains unknown whether seaweed polysaccharides have prebiotic activity. In this study, we isolated polysaccharides from four species of seaweeds, such as Grateloupia filicina (GFP), Eucheuma spinosum (ESP), Ulva pertusa (UPP), and Ascophyllum nodosum (ANP), and characterized their structures and prebiotic effects in vitro. The results showed that these polysaccharides were different in total sugar and sulfate contents as well as monosaccharide composition. GFP and ESP significantly promoted bifidobacterium proliferation and 0.1% ESP and 0.4% GFP resulted in the highest proliferation rates of beneficial bacteria, whereas UPP and ANP inhibited the growth of beneficial bacteria at all tested concentrations (0.1%-0.5%). The different behaviors of the four seaweed-originated polysaccharides might be reflected by differences in monosaccharide composition and structure. Therefore, polysaccharides isolated from GFP and ESP could be utilized as prebiotics. However, more studies must be carried out in vivo.

Determinants of adult vaccination at inner-city health centers: A descriptive study

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Raymund Mahlon

2006-01-01

Full Text Available Abstract Background Pneumococcal polysaccharide vaccination rates among adults 65 years and older or less than 65 years with high risk medical conditions are still below Healthy People 2010 recommended levels of 90%. This study was designed to: 1 assess self-reported pneumococcal vaccination rates following health center level interventions to increase adult vaccination rates; and 2 determine factors associated with vaccination. Methods Tailored interventions to increase immunizations were implemented at two inner-city health centers. We surveyed 375 patients 50 years of age and older. Multivariate logistic regression examines the predictors of 1 self-reported pneumococcal vaccination and 2 combined self-reported influenza and pneumococcal vaccination. Both of these models were stratified by age group (50–64 years and 65 years and older. Results Pneumococcal vaccination rates were 45% by self-report, 55% by medical record review, 69% for patients 65 years old and older, 32% for patients 50–64 years; they did not differ by race. Receipt of the previous season's influenza vaccine was significantly related to pneumococcal vaccination among both younger and older patients. Receiving both the pneumococcal vaccine and the most recent influenza vaccine compared with receiving neither, among younger patients was related to unemployment, more frequent physician visits, and belief that those who do not receive the flu shot are more susceptible to the flu. For older patients, receipt of both vaccines was related to nonsmoking status, believing that friends/family think the patient should be vaccinated, seeing posters advertising flu shot clinics, and belief that those who do not receive the flu shot are more susceptible to the flu. Conclusion Our findings suggest that improving overall pneumococcal vaccination rates among eligible adults, has the potential to eliminate racial disparities. Interventions delivering vaccination messages specific to older

Bioactive polysaccharides and gut microbiome (abstract)

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Many polysaccharides have shown the ability to reduce plasma cholesterol or postprandial glycemia. Viscosity in the small intestine seems to be required to slow glucose uptake. Cereal mixed linkage beta-glucans, psyllium, glucomannans, and other polysaccharides also seem to require higher molecula...

Routine Immunization of Adults in Canada: Review of the Epidemiology of Vaccine-Preventable Diseases and Current Recommendations for Primary Prevention

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Michael D Parkins

2009-01-01

Full Text Available Vaccination is one of the greatest achievements in public health of the 20th century. However, the success of vaccine uptake and adherence to immunization guidelines seen in pediatric populations has not been observed among adult Canadians. As a result of the disparity in susceptibility to vaccine-preventable disease, there has been an increasing shift of vaccine-preventable childhood diseases into adult populations. Accordingly, morbidity and mortality due to vaccine-preventable illnesses now occur disproportionately in adults. All Canadians, irrespective of age, should have immunity to measles, mumps, rubella, tetanus, diphtheria, pertussis and varicella. All adult Canadians with significant medical comorbidities or those older than 65 years of age should receive the pneumococcal polysaccharide vaccine and yearly trivalent inactivate influenza vaccines. The present review summarizes the burden of illness of these vaccine-preventable diseases in the Canadian adult population and reviews the current immunization recommendations. Vaccination of all Canadians to these common agents remains a vital tool to decrease individual morbidity and mortality and reduce the overall burden of preventable disease in Canada.

Biochemical Aspects of Non-Starch Polysaccharides

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Rodica Căpriţă

2010-05-01

Full Text Available Polysaccharides are macromolecules of monosaccharides linked by glycosidic bonds. Non-starch polysaccharides (NSP are principally non-α-glucan polysaccharides of the plant cell wall. They are a heterogeneous group of polysaccharides with varying degrees of water solubility, size, and structure. The water insoluble fiber fraction include cellulose, galactomannans, xylans, xyloglucans, and lignin, while the water-soluble fibers are the pectins, arabinogalactans, arabinoxylans, and β-(1,3(1,4-D-glucans (β-glucans. Knowledge of the chemical structure of NSP has permitted the development of enzyme technology to overcome their antinutritional effects. The physiological effects of NSP on the digestion and absorption of nutrients in human and monogastric animals have been attributed to their physicochemical properties: hydration properties, viscosity, cation exchange capacity and organic compound absorptive properties. This paper reviews and presents information on NSPs chemistry, physicochemical properties and physiological effects on the nutrient entrapment.

An Overview of Vaccination Strategies and Antigen Delivery Systems for Streptococcus agalactiae Vaccines in Nile Tilapia (Oreochromis niloticus).

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Munang'andu, Hetron Mweemba; Paul, Joydeb; Evensen, Øystein

2016-12-13

Streptococcus agalactiae is an emerging infectious disease adversely affecting Nile tilapia ( Niloticus oreochromis ) production in aquaculture. Research carried out in the last decade has focused on developing protective vaccines using different strategies, although no review has been carried out to evaluate the efficacy of these strategies. The purpose of this review is to provide a synopsis of vaccination strategies and antigen delivery systems currently used for S. agalactiae vaccines in tilapia. Furthermore, as shown herein, current vaccine designs include the use of replicative antigen delivery systems, such as attenuated virulent strains, heterologous vectors and DNA vaccines, while non-replicative vaccines include the inactivated whole cell (IWC) and subunit vaccines encoding different S. agalactiae immunogenic proteins. Intraperitoneal vaccination is the most widely used immunization strategy, although immersion, spray and oral vaccines have also been tried with variable success. Vaccine efficacy is mostly evaluated by use of the intraperitoneal challenge model aimed at evaluating the relative percent survival (RPS) of vaccinated fish. The major limitation with this approach is that it lacks the ability to elucidate the mechanism of vaccine protection at portals of bacterial entry in mucosal organs and prevention of pathology in target organs. Despite this, indications are that the correlates of vaccine protection can be established based on antibody responses and antigen dose, although these parameters require optimization before they can become an integral part of routine vaccine production. Nevertheless, this review shows that different approaches can be used to produce protective vaccines against S. agalactiae in tilapia although there is a need to optimize the measures of vaccine efficacy.

An Overview of Vaccination Strategies and Antigen Delivery Systems for Streptococcus agalactiae Vaccines in Nile Tilapia (Oreochromis niloticus)

Science.gov (United States)

Munang’andu, Hetron Mweemba; Paul, Joydeb; Evensen, Øystein

2016-01-01

Streptococcus agalactiae is an emerging infectious disease adversely affecting Nile tilapia (Niloticus oreochromis) production in aquaculture. Research carried out in the last decade has focused on developing protective vaccines using different strategies, although no review has been carried out to evaluate the efficacy of these strategies. The purpose of this review is to provide a synopsis of vaccination strategies and antigen delivery systems currently used for S. agalactiae vaccines in tilapia. Furthermore, as shown herein, current vaccine designs include the use of replicative antigen delivery systems, such as attenuated virulent strains, heterologous vectors and DNA vaccines, while non-replicative vaccines include the inactivated whole cell (IWC) and subunit vaccines encoding different S. agalactiae immunogenic proteins. Intraperitoneal vaccination is the most widely used immunization strategy, although immersion, spray and oral vaccines have also been tried with variable success. Vaccine efficacy is mostly evaluated by use of the intraperitoneal challenge model aimed at evaluating the relative percent survival (RPS) of vaccinated fish. The major limitation with this approach is that it lacks the ability to elucidate the mechanism of vaccine protection at portals of bacterial entry in mucosal organs and prevention of pathology in target organs. Despite this, indications are that the correlates of vaccine protection can be established based on antibody responses and antigen dose, although these parameters require optimization before they can become an integral part of routine vaccine production. Nevertheless, this review shows that different approaches can be used to produce protective vaccines against S. agalactiae in tilapia although there is a need to optimize the measures of vaccine efficacy. PMID:27983591

Adsorption of histones on natural polysaccharides: The potential as agent for multiple organ failure in sepsis.

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Isobe, Takashi; Kofuji, Kyoko; Okada, Kenji; Fujimori, Junya; Murata, Mikio; Shigeyama, Masato; Hanioka, Nobumitsu; Murata, Yoshifumi

2016-03-01

Histones are intracellular proteins that are structural elements of nuclear chromatin and regulate gene transcription. However, the extracellular histones released in response to bacterial challenges have been identified as mediators contributing to endothelial dysfunction, organ failure, and death during sepsis. In the present study, the adsorption of histones as well as plasma proteins (α1-acid glycoprotein (AGP), albumin, and γ-globulin) on alginic acid, pectin, dextran, and chitosan was examined in order to evaluate the potential of natural polysaccharides as therapeutic agents for multiple organ failure in sepsis. Alginic acid and pectin strongly adsorbed histones, whereas the adsorption abilities of dextran and chitosan toward histones were very low or negligible. Among the natural polysaccharides examined, only alginic acid did not adsorb any of the plasma proteins. These results demonstrated that alginic acid strongly adsorbed histones, but not plasma proteins; therefore, it has potential as a candidate drug for the treatment of multiple organ failure in sepsis. Copyright © 2015 Elsevier B.V. All rights reserved.

Immunomodulatory dietary polysaccharides: a systematic review of the literature

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Nelson Erika D

2010-11-01

Full Text Available Abstract Background A large body of literature suggests that certain polysaccharides affect immune system function. Much of this literature, however, consists of in vitro studies or studies in which polysaccharides were injected. Their immunologic effects following oral administration is less clear. The purpose of this systematic review was to consolidate and evaluate the available data regarding the specific immunologic effects of dietary polysaccharides. Methods Studies were identified by conducting PubMed and Google Scholar electronic searches and through reviews of polysaccharide article bibliographies. Only articles published in English were included in this review. Two researchers reviewed data on study design, control, sample size, results, and nature of outcome measures. Subsequent searches were conducted to gather information about polysaccharide safety, structure and composition, and disposition. Results We found 62 publications reporting statistically significant effects of orally ingested glucans, pectins, heteroglycans, glucomannans, fucoidans, galactomannans, arabinogalactans and mixed polysaccharide products in rodents. Fifteen controlled human studies reported that oral glucans, arabinogalactans, heteroglycans, and fucoidans exerted significant effects. Although some studies investigated anti-inflammatory effects, most studies investigated the ability of oral polysaccharides to stimulate the immune system. These studies, as well as safety and toxicity studies, suggest that these polysaccharide products appear to be largely well-tolerated. Conclusions Taken as a whole, the oral polysaccharide literature is highly heterogenous and is not sufficient to support broad product structure/function generalizations. Numerous dietary polysaccharides, particularly glucans, appear to elicit diverse immunomodulatory effects in numerous animal tissues, including the blood, GI tract and spleen. Glucan extracts from the Trametes versicolor

Adjuvants and Their Mechanisms of Action

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Masoumeh Foumani

2012-09-01

Full Text Available Adjuvants are chemicals, microbial components, or mammalian proteins that enhance the immune response to vaccine antigens. Reducing vaccine-related adverse effects and inducing specific types of immunity has led to the development of numerous new adjuvants. Adjuvants in experimental and commercial vaccines include aluminum salts (alum, oil emulsions, saponins, immune-stimulating complexes (ISCOMs, liposomes, microparticles, nonionic block copolymers, derivatized polysaccharides, cytokines, and a wide variety of bacterial derivatives. The mechanisms of action of these diverse compounds are different. Factors influencing the selection of an adjuvant include animal species, specific pathogen, vaccine antigen, route of immunization, and type of immunity needed. In this paper we review the current adjuvant types, structure and mechanism of action and their application in the design and production of animal and human vaccines to provide a source for students and researchers in related fields .

Evaluation of bacterial strategies to promote the bioavailability of polycyclic aromatic hydrocarbons

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Johnsen, A.R.; Karlson, U. [Dept. of Environmental Chemistry and Microbiology, National Environmental Research Inst., Roskilde (Denmark)

2004-07-01

Polycyclic aromatic hydrocarbon (PAHs)-degrading bacteria may enhance the bioavailability of PAHs by excreting biosurfactants, by production of extracellular polymeric substances, or by forming biofilms. We tested these hypotheses in pure cultures of PAHs-degrading bacterial strains. Most of the strains did not substantially reduce the surface tension when grown on PAHs in liquid shaken cultures. Thus, pseudo-solubilization of PAHs in biosurfactant micelles seems not to be a general strategy for these isolates to enhance PAHs-bioavailability. Three semi-colloid Sphingomonas polysaccharides all increased the solubility of PAHs (Gellan 1.3- to 5.4-fold, Welan 1.8- to 6.0-fold and Rhamsan 2.4- to 9.0-fold). The increases were most pronounced for the more hydrophobic PAHs. The polysaccharide-sorbed PAHs were bioavailable. Mineralization rates of 9-[{sup 14}C]-phenanthrene and 3-[{sup 14}C]-fluoranthene by Sphingobium EPA505, were similar with and without sphingans, indicating that mass-transfer rates from PAHs crystals to the bulk liquid were unaffected by the polysaccharides. Biofilm formation on PAHs crystals may favor the diffusive mass transfer of PAHs from crystals to the bacterial cells. A majority of the PAHs-degraders tested formed biofilms in microtiter wells coated with PAHs crystals. For strains capable of growing on different PAHs; the more soluble the PAHs, the lower the percentage of cells attached. Biofilm formation on PAHs-sources was the predominant mechanism among the tested bacteria to overcome mass transfer limitations when growing on poorly soluble PAHs. (orig.)

Comparative study of methods for inactivation of vaccines on development process of veterinary “Ghost” vaccine

International Nuclear Information System (INIS)

Pencheva, Daniela; Genova-Kalou, Petia; Bryaskova, Rayna

2016-01-01

Experimental and laboratory tests were carried out in order to identify the advantages of “ghost” antigens obtained by treatment of the bacterial cell with silver nanoparticles in comparison to the inactivated antigens obtained by classical methods as heating or treatment with formalin. The Minimal Bactericidal Concentrations (MBC) of the hybrid material containing silver nanoparticles (PVA/AgNps), used for inactivation of the tested E. coli strains were determined and they were categorized as susceptible to the action of silver nanoparticles. The changes in the structure of the bacterial cells obtained after the treatment with the hybrid material containing silver nanoparticles or with formaldehyde, respectively, were established by TEM (Transmission electron microscopy) analysis. The advantages of the “ghost” vaccines are expressed in undamaged cell wall and better immunogenicity, thus resulting in faster formation of specific titer after immunization of experimental animals. Key words: E. coli O149, E. coli O157H7, “ghost” vaccine, silver nanoparticles, TEM

In vitro fermentation and prebiotic potential of novel low molecular weight polysaccharides derived from agar and alginate seaweeds.

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Ramnani, Priya; Chitarrari, Roberto; Tuohy, Kieran; Grant, John; Hotchkiss, Sarah; Philp, Kevin; Campbell, Ross; Gill, Chris; Rowland, Ian

2012-02-01

Fermentation properties and prebiotic potential of novel low molecular weight polysaccharides (LMWPs) derived from agar and alginate bearing seaweeds was investigated. Ten LMWPs were supplemented to pH, temperature controlled anaerobic batch cultures inoculated with human feces from three donors, in triplicate. Microbiota changes were monitored using Fluorescent in-situ hybridization and short chain fatty acids, the fermentation end products were analysed using gas chromatography. Of the ten LMWPs tested, Gelidium seaweed CC2253 of molecular weight 64.64 KDa showed a significant increase in bifidobacterial populations from log(10) 8.06 at 0 h to log(10) 8.55 at 24 h (p = 0.018). For total bacterial populations, alginate powder CC2238 produced a significant increase from log(10) 9.01 at 0 h to log(10) 9.58 at 24 h (p = 0.032). No changes were observed in the other bacterial groups tested viz. Bacteroides, Lactobacilli/Enterococci, Eubacterium rectale/Clostridium coccoides and Clostridium histolyticum. The polysaccharides also showed significant increases in total SCFA production, particularly acetic and propionic acids, indicating that they were readily fermented. In conclusion, some LMWPs derived from agar and alginate bearing seaweeds were fermented by gut bacteria and exhibited potential to be used a novel source of prebiotics. Copyright © 2011 Elsevier Ltd. All rights reserved.

Protective effect of plant polysaccharides against radiation injury

International Nuclear Information System (INIS)

Wang Bingji; Huang Shafei; Cheng Lurong

1989-01-01

A series of polysaccharides have been isolated from Chinese traditional medicinal herbs and tested in mice subjected to ionizing radiation for their protective action. The polysaccharides from different origins showed various degrees of radioprotection. Those isolated from Hericium erinaceus and Armillaria mellea showed a higher radioprotective effect than some other polysaccharides. They could increase the survival rate of irradiated mice to 60%. But the polysaccheride separated from Apocynum venetum has negligible effect. In general, most of these polysaccharides are effective only on administration before irradiation. No apparent protection was observed when given post irradiation. The polysaccharide isolated from Armillaria venetum could raise the survival rate of mice irradiated by lethal dose of γ-rays to 58%. It is effective even when administered after irradiation. Some work has been carried out to clarify the mechanism of radioprotective action of polysaccharides. Protection of hemapoietic organs, regulation of immunological system, induction of release of some endogeneous bioactive substances in the organism and reduction of oxygen tension in some vital tissues may be correlated with the protection of organism against radiation injury

Global invasive bacterial vaccine-preventable diseases surveillance--2008-2014.

Science.gov (United States)

Murray, Jillian; Agócs, Mary; Serhan, Fatima; Singh, Simarjit; Deloria-Knoll, Maria; O'Brien, Katherine; Mwenda, Jason M; Mihigo, Richard; Oliveira, Lucia; Teleb, Nadia; Ahmed, Hinda; Wasley, Annemarie; Videbaek, Dovile; Wijesinghe, Pushpa; Thapa, Arun Bhadra; Fox, Kimberly; Paladin, Fem Julia; Hajjeh, Rana; Schwartz, Stephanie; Van Beneden, Chris; Hyde, Terri; Broome, Claire; Cherian, Thomas

2014-12-12

Meningitis and pneumonia are leading causes of morbidity and mortality in children globally infected with Streptococcus pneumoniae (pneumococcus), Neisseria meningitidis, and Haemophilus influenzae causing a large proportion of disease. Vaccines are available to prevent many of the common types of these infections. S. pneumoniae was estimated to have caused 11% of deaths in children aged Organization (WHO) has recommended inclusion of PCV in childhood immunization programs worldwide, especially in countries with high child mortality. As of November 26, 2014, a total of 112 (58%) of all 194 WHO member states and 44 (58%) of the 76 member states ever eligible for support from Gavi, the Vaccine Alliance (Gavi), have introduced PCV. Invasive pneumococcal disease (IPD) surveillance that includes data on serotypes, along with meningitis and pneumonia syndromic surveillance, provides important data to guide decisions to introduce PCV and monitor its impact.

Interaction between gut immunity and polysaccharides.

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Huang, Xiaojun; Nie, Shaoping; Xie, Mingyong

2017-09-22

The human gut is colonized with a vast and diverse microbial ecosystem, and these bacteria play fundamental roles in the well being of our bodies. Gut-associated lymphoid tissues, the largest mucosal immune system, should never be overlooked for their profound effect in maintaining the host immunity. Therefore, we discussed the relationship between gut immunity and host health, primarily from two aspects: the homeostasis of gut microbiota, and the function of gut-associated lymphoid tissues. Polysaccharides, widely concerned as bioactive macromolecules in recent centuries, have been proved to benefit the intestinal health. Dietary polysaccharides can improve the ratio of probiotics, regulate the intestinal microenvironment like decreasing the gut pH, and stimulate the macrophages or lymphocytes in gut tissues to fight against diseases like cancer. Based on various experimental and clinical evidence, the impacts of dietary polysaccharides on intestinal health are summarized, in order to reveal the possible immunomodulatory mechanisms of polysaccharides.

In vitro and in vivo effects of macrophage-stimulatory polysaccharide from leaves of Perilla frutescens var. crispa.

Science.gov (United States)

Kwon, Ki Han; Kim, Kyung Im; Jun, Woo Jin; Shin, Dong Hoon; Cho, Hong Yon; Hong, Bum Shik

2002-03-01

The crude polysaccharide (PFB-1) was isolated from the leaves of Perilla frutescens var. crispa by the sequential procedures with hot-water extraction, methanol reflux, and ethanol precipitation. It was further purified by anion column chromatography in order to obtain the partially purified polysaccharide (PFB-1-0). In the presence of PFB-1-0, strong cellular lysosomal enzyme activity of murine peritoneal macrophages was observed in vitro. Compared to bacterial lipopolysaccharide (LPS), its activity was relatively high. The in vitro phagocytic activity was enhanced by PFB-1-0 as the similar pattern in both gram-negative bacteria, E. coli, and gram-positive bacteria, S. aureus with a time-dependent manner. We also investigated the production of several mediators by murine peritoneal macrophages upon stimulation with PFB-1 (in vivo) or PFB-1-0 (in vitro). The levels of nitric oxide (NO) and tumor necrosis factor (TNF)-alpha were increased in the presence of PFB-1-0 in vitro. The PFB-1 stimulated the production of interleukin (IL)-6 and granulocyte-macrophage colony-stimulating factor (GM-CSF) in vivo. Results suggest that the polysaccharide from P. frutescens var. crispa represents an immunopotentiator and biological response modifiers in vitro and in vivo levels.

Development of the ECODAB into a relational database for Escherichia coli O-antigens and other bacterial polysaccharides.

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Rojas-Macias, Miguel A; Ståhle, Jonas; Lütteke, Thomas; Widmalm, Göran

2015-03-01

Escherichia coli O-antigen database (ECODAB) is a web-based application to support the collection of E. coli O-antigen structures, polymerase and flippase amino acid sequences, NMR chemical shift data of O-antigens as well as information on glycosyltransferases (GTs) involved in the assembly of O-antigen polysaccharides. The database content has been compiled from scientific literature. Furthermore, the system has evolved from being a repository to one that can be used for generating novel data on its own. GT specificity is suggested through sequence comparison with GTs whose function is known. The migration of ECODAB to a relational database has allowed the automation of all processes to update, retrieve and present information, thereby, endowing the system with greater flexibility and improved overall performance. ECODAB is freely available at http://www.casper.organ.su.se/ECODAB/. Currently, data on 169 E. coli unique O-antigen entries and 338 GTs is covered. Moreover, the scope of the database has been extended so that polysaccharide structure and related information from other bacteria subsequently can be added, for example, from Streptococcus pneumoniae. © The Author 2014. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Engineering bacterial biopolymers for the biosorption of heavy metals; new products and novel formulations

International Nuclear Information System (INIS)

Gutnick, D.L.; Bach, H.

2000-01-01

Bioremediation of heavy metal pollution remains a major challenge in environmental biotechnology. One of the approaches considered for application involves biosorption either to biomass or to isolated biopolymers. Many bacterial polysaccharides have been shown to bind heavy metals with varying degrees of specificity and affinity. While various approaches have been adopted to generate polysaccharide variants altered in both structure and activity, metal biosorption has not been examined. Polymer engineering has included structural modification through the introduction of heterologous genes of the biosynthetic pathway into specific mutants, leading either to alterations in polysaccharide backbone or side chains, or to sugar modification. In addition, novel formulations can be designed which enlarge the family of available bacterial biopolymers for metal-binding and subsequent recovery. An example discussed here is the use of amphipathic bioemulsifiers such as emulsan, produced by the oil-degrading Acinetobacter lwoffii RAG-1, that forms stable, concentrated (70%), oil-in-water emulsions (emulsanosols). In this system metal ions bind primarily at the oil/water interface, enabling their recovery and concentration from relatively dilute solutions. In addition to the genetic modifications described above, a new approach to the generation of amphipathic bioemulsifying formulations is based on the interaction of native or recombinant esterase and its derivatives with emulsan and other water-soluble biopolymers. Cation-binding emulsions are generated from a variety of hydrophobic substrates. The features of these and other systems will be discussed, together with a brief consideratiton of possible applications. (orig.)

Enzymatic method for improving the injectability of polysaccharides. [US Patent Application

Science.gov (United States)

Griffith, W.L.; Compere, A.L.; Holleman, J.W.

A method for enhancing the ability of polysaccharides in aqueous solution to flow through a porous medium comprises contacting the polysaccharides with an endoenzyme capable of hydrolyzing at least one of the linkages of the sugar units of the polysaccharides and maintaining the polysaccharides in contact with the enzyme under hydrolysis conditions for a time sufficient to decrease the tendency of the polysaccharides to plug the porous medium yet insufficient to decrease the viscosity of the aqueous polysaccharides by more than 25%. The partially hydrolyzed polysaccharides are useful as thickening agents for flooding water used to recover oil from oil-containing subterranean formations.

Recent advances in synthesis of bacterial rare sugar building blocks and their applications.

Science.gov (United States)

Emmadi, Madhu; Kulkarni, Suvarn S

2014-07-01

Covering: 1964 to 2013. Bacteria have unusual glycans on their surfaces which distinguish them from the host cells. These unique structures offer avenues for targeting bacteria with specific therapeutics and vaccine. However, these rare sugars are not accessible in acceptable purity and amounts by isolation from natural sources. Thus, procurement of orthogonally protected rare sugar building blocks through efficient chemical synthesis is regarded as a crucial step towards the development of glycoconjugate vaccines. This Highlight focuses on recent advances in the synthesis of the bacterial deoxy amino hexopyranoside building blocks and their application in constructing various biologically important bacterial O-glycans.

Immunogenicity and safety of a novel quadrivalent meningococcal conjugate vaccine (MenACWY-CRM) in healthy Korean adolescents and adults.

Science.gov (United States)

Lee, Hoan Jong; Chung, Moon-Hyun; Kim, Woo Joo; Hong, Young Jin; Choi, Kyong Min; Lee, Jina; Oh, Chi Eun; Welsch, Jo Anne; Kim, Kyung-Hyo; Hong, Ki Bae; Dagnew, Alemnew F; Bock, Hans; Dull, Peter M; Odrljin, Tatjana

2014-11-01

This phase III placebo-controlled study evaluated the immunogenicity and safety of MenACWY-CRM vaccination in healthy Korean adolescents and adults. Serum bactericidal activity with human complement (hSBA) was measured before and 1 month after vaccination against all four meningococcal serogroups. The IgG concentration specific for serogroup W capsular polysaccharide was measured in a subset of subjects in a post-hoc analysis. Adverse reactions were monitored throughout the study. Four hundred and fifty subjects were randomized 2:1 to receive MenACWY-CRM (N=297) or a saline placebo (N=153). MenACWY-CRM induced a good immune response against all four serogroups, with seroprotection rates (hSBA titers ≥8) of 79%, 99%, 98%, and 94% for serogroups A, C, W, and Y, respectively. Seroresponse rates were high for serogroups A, C, and Y, i.e. 76%, 86%, and 69%, respectively; the rate for serogroup W was 28%. MenACWY-CRM vaccine induced serum bactericidal antibodies against all four serogroups in a majority of subjects regardless of their baseline hSBA titers. MenACWY-CRM was generally well tolerated with most reactions being transient and mild to moderate in severity. Findings of this first study of a quadrivalent meningococcal polysaccharide conjugate vaccine in Korean adults and adolescents demonstrated that a single dose of MenACWY-CRM was well tolerated and immunogenic, as indicated by the percentages of subjects with hSBA titers ≥8 (79%, 99%, 98%, and 94% of subjects) and geometric mean titers (48, 231, 147, and 107) against serogroups A, C, W, and Y, respectively, at 1 month post-vaccination.

Applying Convergent Immunity to Innovative Vaccines Targeting Staphylococcus aureus

Science.gov (United States)

Yeaman, Michael R.; Filler, Scott G.; Schmidt, Clint S.; Ibrahim, Ashraf S.; Edwards, John E.; Hennessey, John P.

2014-01-01

Recent perspectives forecast a new paradigm for future “third generation” vaccines based on commonalities found in diverse pathogens or convergent immune defenses to such pathogens. For Staphylococcus aureus, recurring infections and a limited success of vaccines containing S. aureus antigens imply that native antigens induce immune responses insufficient for optimal efficacy. These perspectives exemplify the need to apply novel vaccine strategies to high-priority pathogens. One such approach can be termed convergent immunity, where antigens from non-target organisms that contain epitope homologs found in the target organism are applied in vaccines. This approach aims to evoke atypical immune defenses via synergistic processes that (1) afford protective efficacy; (2) target an epitope from one organism that contributes to protective immunity against another; (3) cross-protect against multiple pathogens occupying a common anatomic or immunological niche; and/or (4) overcome immune subversion or avoidance strategies of target pathogens. Thus, convergent immunity has a potential to promote protective efficacy not usually elicited by native antigens from a target pathogen. Variations of this concept have been mainstays in the history of viral and bacterial vaccine development. A more far-reaching example is the pre-clinical evidence that specific fungal antigens can induce cross-kingdom protection against bacterial pathogens. This trans-kingdom protection has been demonstrated in pre-clinical studies of the recombinant Candida albicans agglutinin-like sequence 3 protein (rAls3) where it was shown that a vaccine containing rAls3 provides homologous protection against C. albicans, heterologous protection against several other Candida species, and convergent protection against several strains of S. aureus. Convergent immunity reflects an intriguing new approach to designing and developing vaccine antigens and is considered here in the context of vaccines to target S

Applying Convergent Immunity to Innovative Vaccines Targeting Staphylococcus aureus

Directory of Open Access Journals (Sweden)

Michael R Yeaman

2014-09-01

Full Text Available Recent perspectives forecast a new paradigm for future 3rd generation vaccines based on commonalities found in diverse pathogens or convergent immune defenses to such pathogens. For Staphylococcus aureus, recurring infections and a limited success of vaccines containing S. aureus antigens imply that native antigens induce immune responses insufficient for optimal efficacy. These perspectives exemplify the need to apply novel vaccine strategies to high priority pathogens. One such approach can be termed convergent immunity, where antigens from non-target organisms that contain epitope homologues found in the target organism are applied in vaccines. This approach aims to evoke atypical immune defenses via synergistic processes that 1 afford protective efficacy; 2 target an epitope from one organism that contributes to protective immunity against another; 3 cross-protect against multiple pathogens occupying a common anatomic or immunologic niche; and/or 4 overcome immune subversion or avoidance strategies of target pathogens. Thus, convergent immunity has a potential to promote protective efficacy not usually elicited by native antigens from a target pathogen. Variations of this concept have been mainstays in the history of viral and bacterial vaccine development. A more far-reaching example is the pre–clinical evidence that specific fungal antigens can induce cross-kingdom protection against bacterial pathogens. This trans-kingdom protection has been demonstrated in preclinical studies of the recombinant Candida albicans agglutinin-like sequence 3 protein (rAls3 where it was shown that a vaccine containing rAls3 provides homologous protection against C. albicans, heterologous protection against several other Candida species, and convergent protection against several strains of S. aureus. Convergent immunity reflects an intriguing new approach to designing and developing vaccine antigens and is considered here in the context of vaccines to target

Viral Vectors for Use in the Development of Biodefense Vaccines

National Research Council Canada - National Science Library

Lee, John S; Hadjipanayis, Angela G; Parker, Michael D

2005-01-01

.... DNA vectors, live-attenuated viruses and bacteria, recombinant proteins combined with adjuvant, and viral- or bacterial-vectored vaccines have been developed as countermeasures against many potential...

Polymeric nanoparticles: potent vectors for vaccine delivery targeting cancer and infectious diseases.

Science.gov (United States)

Bolhassani, Azam; Javanzad, Shabnam; Saleh, Tayebeh; Hashemi, Mehrdad; Aghasadeghi, Mohammad Reza; Sadat, Seyed Mehdi

2014-01-01

Nanocarriers with various compositions and biological properties have been extensively applied for in vitro/in vivo drug and gene delivery. The family of nanocarriers includes polymeric nanoparticles, lipid-based carriers (liposomes/micelles), dendrimers, carbon nanotubes, and gold nanoparticles (nanoshells/nanocages). Among different delivery systems, polymeric carriers have several properties such as: easy to synthesize, inexpensive, biocompatible, biodegradable, non-immunogenic, non-toxic, and water soluble. In addition, cationic polymers seem to produce more stable complexes led to a more protection during cellular trafficking than cationic lipids. Nanoparticles often show significant adjuvant effects in vaccine delivery since they may be easily taken up by antigen presenting cells (APCs). Natural polymers such as polysaccharides and synthetic polymers have demonstrated great potential to form vaccine nanoparticles. The development of new adjuvants or delivery systems for DNA and protein immunization is an expanding research field. This review describes polymeric carriers especially PLGA, chitosan, and PEI as vaccine delivery systems.

Vaccines against enteric infections for the developing world.

Science.gov (United States)

Czerkinsky, Cecil; Holmgren, Jan

2015-06-19

Since the first licensure of the Sabin oral polio vaccine more than 50 years ago, only eight enteric vaccines have been licensed for four disease indications, and all are given orally. While mucosal vaccines offer programmatically attractive tools for facilitating vaccine deployment, their development remains hampered by several factors: -limited knowledge regarding the properties of the gut immune system during early life; -lack of mucosal adjuvants, limiting mucosal vaccine development to live-attenuated or killed whole virus and bacterial vaccines; -lack of correlates/surrogates of mucosal immune protection; and -limited knowledge of the factors contributing to oral vaccine underperformance in children from developing countries. There are now reasons to believe that the development of safe and effective mucosal adjuvants and of programmatically sound intervention strategies could enhance the efficacy of current and next-generation enteric vaccines, especially in lesser developed countries which are often co-endemic for enteric infections and malnutrition. These vaccines must be safe and affordable for the world's poorest, confer long-term protection and herd immunity, and must be able to contain epidemics. © 2015 The Author(s) Published by the Royal Society. All rights reserved.

Regulation and diversity of plant polysaccharide utilisation in fungi

NARCIS (Netherlands)

Battaglia, E.

2011-01-01

Filamentous fungi obtain their nutrients by degrading dead or living plant material. Plant material consists of different cell wall and storage polysaccharides. Due to the complex structure and the variety of plant polysaccharides, filamentous fungi secrete a wide range of plant polysaccharide

Safety Evaluation of Turmeric Polysaccharide Extract: Assessment of Mutagenicity and Acute Oral Toxicity

Science.gov (United States)

Velusami, Chandrasekaran Chinampudur; Boddapati, Srinivasa Rao; Hongasandra Srinivasa, Srikanth; Richard, Edwin Jothie; Balasubramanian, Murali

2013-01-01

Curcuma longa Linn. (Zingiberaceae) commonly known as turmeric has long been used for centuries as a spice and household remedy. The present study was carried out to assess the possible mutagenic potential and acute oral toxicity of polysaccharide extract of turmeric rhizome (NR-INF-02) using standard tests. The standard battery of in vitro genotoxicity tests, bacterial reverse mutation test (BRMT), chromosome aberration (CA), and micronucleus (MN) tests were employed to assess the possible mutagenic activity of NR-INF-02 (Turmacin). The results showed no mutagenic effect with NR-INF-02 up to a dose of 5000 µg/mL in BRMT. The results on CA and MN tests revealed the non clastogenic activity of NR-INF-02 in a dose range of 250.36 to 2500 µg/mL with and without metabolic activation (S9). In acute oral toxicity study, NR-INF-02 was found to be safe up to 5 g/kg body weight in Wistar rats. Overall, results indicated that polysaccharide extract of C. longa was found to be genotoxically safe and also exhibited maximum tolerable dose of more than 5 g/kg rat body weight. PMID:24455673

Helicobacter pylori vaccine: from past to future.

Science.gov (United States)

Agarwal, Kanishtha; Agarwal, Shvetank

2008-02-01

Helicobacter pylori infection is highly prevalent worldwide and is an important cause of gastritis, peptic ulcer disease, gastric mucosa-associated lymphoid tissue lymphoma (MALToma), and gastric adenocarcinoma. Infection is usually acquired during childhood and tends to persist unless treated. Because eradication requires treatment with multidrug regimens, prevention of initial infection by a suitable vaccine is attractive. Although immunization with H pylori protein subunits has been encouraging in animals, similar vaccine trials in humans have shown adjuvant-related adverse effects and only moderate effectiveness. Newer immunization approaches (use of DNA, live vectors, bacterial ghosts, and microspheres) are being developed. Several questions about when and whom to vaccinate will need to be appropriately answered, and a cost-effective vaccine production and delivery strategy will have to be useful for developing countries. For this review, we searched MEDLINE using the Medical Subject Heading (MeSH) terms Helicobacter pylori and vaccines for articles in English from 1990 to 2007.

Reproductive toxicity testing of vaccines

International Nuclear Information System (INIS)

Verdier, Francois; Barrow, Paul C.; Burge, Joeelle

2003-01-01

Vaccines play a major role in the prevention of human birth defects by protecting the pregnant woman from teratogenic or otherwise harmful infections. Until now, it has not been common practice to perform preclinical developmental toxicity tests for new vaccines. Despite the excellent safety record of vaccines, increased attention is now being given to the feasibility of screening new vaccines for developmental hazards in animals before their use in humans. Contrary to previous assumptions, many vaccines are now given to potentially pregnant women. Any new components of the vaccine formulation (adjuvants, excipients, stabilisers, preservatives, etc...) could also be tested for influences on development, although based on past experience the risks are limited by the very low dosages used. The conferred immunity following vaccination lasts for several years. Therefore, the developing conceptus may theoretically be exposed to the induced antibodies and/or sensitised T-cells, even if the pregnant woman was last vaccinated during childhood (particularly if she encounters the antigen during pregnancy through exposure to infection). However, it should be kept in mind that viral or bacterial infections represent a higher risk for a pregnant woman than the potential adverse effects related to vaccination or the associated immune response. Non-clinical safety studies may be employed as an aid for hazard identification. In these studies interactions of the vaccine with the maternal immune system or with the developmental systems of the offspring are considered. Post-natal examinations are necessary to detect all possible manifestations of developmental toxicity, such as effects on the immune system. Species selection for the preclinical studies is based on immunogenicity to the vaccine and the relative timing and rate of transfer of maternal antibodies to the offspring. A single study design is proposed for the pre- and post-natal developmental assessments of vaccines in

Considerations for the rational design of a Chlamydia vaccine

OpenAIRE

Liang, Steven; Bulir, David; Kaushic, Charu; Mahony, James

2016-01-01

ABSTRACT Chlamydia trachomatis is the leading cause of preventable blindness and the most common bacterial sexually transmitted infection. Remarkable progress in vaccine research over the past six?decades has led to the advancement of novel C. trachomatis vaccine candidates into clinical trials. However, many questions regarding the role of specific cellular populations and molecular mechanisms in protective immunity against human C. trachomatis genital tract infections remain unanswered. Bio...

Whooping Cough Vaccine Recommendation for Babies and Young Children

Centers for Disease Control (CDC) Podcasts

2015-01-22

This podcast provides information about whooping cough and the recommendation that all children receive the DTaP vaccine, according to CDC’s recommended schedule, to help protect them from this serious disease.  Created: 1/22/2015 by National Center for Immunization and Respiratory Diseases (NCIRD), Division of Bacterial Diseases (DBD), Meningitis and Vaccine Preventable Diseases Branch (MVPDB).   Date Released: 1/22/2015.

Withania somnifera attenuates acid production, acid tolerance and extra-cellular polysaccharide formation of Streptococcus mutans biofilms.

Science.gov (United States)

Pandit, Santosh; Song, Kwang-Yeob; Jeon, Jae-Gyu

2014-01-01

Withania somnifera (Ashwagandha) is a plant of the Solanaceae family. It has been widely used as a remedy for a variety of ailments in India and Nepal. The plant has also been used as a controlling agent for dental diseases. The aim of the present study was to evaluate the activity of the methanol extract of W. somnifera against the physiological ability of cariogenic biofilms and to identify the components of the extract. To determine the activity of the extract, assays for sucrose-dependent bacterial adherence, glycolytic acid production, acid tolerance, and extracellular polysaccharide formation were performed using Streptococcus mutans biofilms. The viability change of S. mutans biofilms cells was also determined. A phytochemical analysis of the extract was performed using TLC and LC/MS/MS. The extract showed inhibitory effects on sucrose-dependent bacterial adherence (≥ 100 μg/ml), glycolytic acid production (≥ 300 μg/ml), acid tolerance (≥ 300 μg/ml), and extracellular polysaccharide formation (≥ 300 μg/ml) of S. mutans biofilms. However, the extract did not alter the viability of S. mutans biofilms cells in all concentrations tested. Based on the phytochemical analysis, the activity of the extract may be related to the presence of alkaloids, anthrones, coumarines, anthraquinones, terpenoids, flavonoids, and steroid lactones (withanolide A, withaferin A, withanolide B, withanoside IV, and 12-deoxy withastramonolide). These data indicate that W. somnifera may be a potential agent for restraining the physiological ability of cariogenic biofilms.

Assessing Bacterial Interactions Using Carbohydrate-Based Microarrays

Directory of Open Access Journals (Sweden)

Andrea Flannery

2015-12-01

Full Text Available Carbohydrates play a crucial role in host-microorganism interactions and many host glycoconjugates are receptors or co-receptors for microbial binding. Host glycosylation varies with species and location in the body, and this contributes to species specificity and tropism of commensal and pathogenic bacteria. Additionally, bacterial glycosylation is often the first bacterial molecular species encountered and responded to by the host system. Accordingly, characterising and identifying the exact structures involved in these critical interactions is an important priority in deciphering microbial pathogenesis. Carbohydrate-based microarray platforms have been an underused tool for screening bacterial interactions with specific carbohydrate structures, but they are growing in popularity in recent years. In this review, we discuss carbohydrate-based microarrays that have been profiled with whole bacteria, recombinantly expressed adhesins or serum antibodies. Three main types of carbohydrate-based microarray platform are considered; (i conventional carbohydrate or glycan microarrays; (ii whole mucin microarrays; and (iii microarrays constructed from bacterial polysaccharides or their components. Determining the nature of the interactions between bacteria and host can help clarify the molecular mechanisms of carbohydrate-mediated interactions in microbial pathogenesis, infectious disease and host immune response and may lead to new strategies to boost therapeutic treatments.

Screening of Viral Pathogens from Pediatric Ileal Tissue Samples after Vaccination

Directory of Open Access Journals (Sweden)

Laura Hewitson

2014-01-01

Full Text Available In 2010, researchers reported that the two US-licensed rotavirus vaccines contained DNA or DNA fragments from porcine circovirus (PCV. Although PCV, a common virus among pigs, is not thought to cause illness in humans, these findings raised several safety concerns. In this study, we sought to determine whether viruses, including PCV, could be detected in ileal tissue samples of children vaccinated with one of the two rotavirus vaccines. A broad spectrum, novel DNA detection technology, the Lawrence Livermore Microbial Detection Array (LLMDA, was utilized, and confirmation of viral pathogens using the polymerase chain reaction (PCR was conducted. The LLMDA technology was recently used to identify PCV from one rotavirus vaccine. Ileal tissue samples were analyzed from 21 subjects, aged 15–62 months. PCV was not detected in any ileal tissue samples by the LLMDA or PCR. LLMDA identified a human rotavirus A from one of the vaccinated subjects, which is likely due to a recent infection from a wild type rotavirus. LLMDA also identified human parechovirus, a common gastroenteritis viral infection, from two subjects. Additionally, LLMDA detected common gastrointestinal bacterial organisms from the Enterobacteriaceae, Bacteroidaceae, and Streptococcaceae families from several subjects. This study provides a survey of viral and bacterial pathogens from pediatric ileal samples, and may shed light on future studies to identify pathogen associations with pediatric vaccinations.

Radiation degradation of marine polysaccharides by low energy electron beam

International Nuclear Information System (INIS)

Yoshii, Fumio; Nagasawa, Naotsugu; Kume, Tamikazu

2003-01-01

The radiation degradations of marine polysaccharides by both gamma Co-60 and electron beam irradiations are investigated. Polysaccharides and oligosaccharides can be produced by degradation of corresponding polysaccharides including marine polysaccharides such as alginates, chitin chitosan and carrageenan. The viscosity of alginate, chitosan and carrageenan solution decreases markedly with increase of the low energy electron beam irradiation time and the beam current. Furthermore, the viscosity is reduced sharply in short time for polysaccharide solution with low concentration, for instance carrageenan solution of 1%. (author)

Lipoprotein NMB0928 from Neisseria meningitidis serogroup B as a novel vaccine candidate.

Science.gov (United States)

Delgado, Maité; Yero, Daniel; Niebla, Olivia; González, Sonia; Climent, Yanet; Pérez, Yusleydis; Cobas, Karem; Caballero, Evelín; García, Darien; Pajón, Rolando

2007-12-05

Polysaccharide-based vaccines for serogroup B Neisseria meningitidis have failed to induce protective immunity. As a result, efforts to develop vaccines for serogroup B meningococcal disease have mostly focused on outer membrane proteins (OMP). Vaccine candidates based on meningococcal OMP have emerged in the form of outer membrane vesicles (OMVs) or, more recently, purified recombinant proteins, as alternative strategies for serogroup B vaccine development. In our group, the protein composition of the Cuban OMVs-based vaccine VA-MENGOC-BC was elucidated using two-dimensional gel electrophoresis and mass spectrometry. The proteomic map of this product allowed the identification of new putative protective proteins not previously reported as components of an antimeningococcal vaccine. In the present study, we have determined the immunogenicity and protective capacity of NMB0928, one of those proteins present in the OMVs. The antigen was obtained as a recombinant protein in Escherichia coli, purified and used to immunize mice. The antiserum produced against the protein was capable to recognize the natural protein in different meningococcal strains by whole-cell ELISA and Western blotting. After immunization, recombinant NMB0928 induced bactericidal antibodies, and when the protein was administered inserted into liposomes, the elicited antibodies were protective in the infant rat model. These results suggest that NMB0928 is a novel antigen worth to be included in a broadly protective meningococcal vaccine.

Immunochemical studies and genetic background of two Neisseria meningitidis isolates expressing unusual capsule polysaccharide antigens with specificities of both serogroup Y and W135.

Science.gov (United States)

Tsang, Raymond S W; Tsai, Chao Ming; Henderson, Averil M; Tyler, Shaun; Law, Dennis K S; Zollinger, Wendell; Jamieson, Frances

2008-03-01

We described 2 unusual Neisseria meningitidis strains isolated from epidemiologically unrelated invasive meningococcal disease cases in Ontario, Canada. Both isolates have features typical of serogroup Y N. meningitidis: are of serotype 2c, are of the multi-locus sequence types typical of the serogroup Y strains in Canada, and are genotyped as serogroup Y based on a previously described PCR-ELISA method that detects the serogroup-Y-specific siaD gene. However, both strains were poly-agglutinable in both anti-Y and anti-W135 antisera. Further studies on 1 of these 2 isolates showed the presence of glucose and galactose as well as sialic acids in its purified capsular polysaccharide, suggesting the presence of both serogroup Y and serogroup W135 polysaccharides. Rabbit antisera produced to this strain contained antibodies to both purified serogroup Y and serogroup W135 capsular polysaccharides. Absorption experiments with either serogroup Y or serogroup W135 bacteria confirmed the presence of antibodies to these 2 different polysaccharides. DNA sequencing of the cps operon from both isolates revealed a siaD gene with 99.7% homology to the published siaD sequence from a serogroup Y strain but with 3 point mutations that all resulted in amino acid changes. How these strains may affect results of routine surveillance, PCR diagnosis, and immuno-protection by vaccination are discussed.

Plant-Polysaccharide-Degrading Enzymes from Basidiomycetes

Science.gov (United States)

Rytioja, Johanna; Hildén, Kristiina; Yuzon, Jennifer; Hatakka, Annele; de Vries, Ronald P.

2014-01-01

SUMMARY Basidiomycete fungi subsist on various types of plant material in diverse environments, from living and dead trees and forest litter to crops and grasses and to decaying plant matter in soils. Due to the variation in their natural carbon sources, basidiomycetes have highly varied plant-polysaccharide-degrading capabilities. This topic is not as well studied for basidiomycetes as for ascomycete fungi, which are the main sources of knowledge on fungal plant polysaccharide degradation. Research on plant-biomass-decaying fungi has focused on isolating enzymes for current and future applications, such as for the production of fuels, the food industry, and waste treatment. More recently, genomic studies of basidiomycete fungi have provided a profound view of the plant-biomass-degrading potential of wood-rotting, litter-decomposing, plant-pathogenic, and ectomycorrhizal (ECM) basidiomycetes. This review summarizes the current knowledge on plant polysaccharide depolymerization by basidiomycete species from diverse habitats. In addition, these data are compared to those for the most broadly studied ascomycete genus, Aspergillus, to provide insight into specific features of basidiomycetes with respect to plant polysaccharide degradation. PMID:25428937

Anti-radiation effect of hericium erinaceus polysaccharide

International Nuclear Information System (INIS)

Liu Shuchen; Zhang Huijuan; Luo Chuanhuan; Wang Bingji

1999-01-01

Objective: To study the anti-radiation effect of hericium erinaceus polysaccharide on irradiated mice. Methods: 520 female mice were randomized to several groups and exposed to 6.25-8.5 Gy whole-body γ-rays. The hericium erinaceus polysaccharide was injected i.p before or after irradiation. The 30-day survival rate of mice was determined, and DNA content of bone marrow was observed as well at seventh day after irradiation. Results: It was showed that the 30-day survival rate and DNA content of bone marrow were all significantly higher in 30 mg or 15 mg hericium erinaceus polysaccharide-treated groups than those in the corresponding irradiated controls (P < 0.01). The 30-day survival rate increased from 35% to 97.5%. Conclusion: The hericium erinaceus polysaccharide has marked anti-radiation effect. Further investigation is worthwhile

Programmatic challenges in obtaining and confirming the pneumococcal vaccination status of cochlear implant recipients.

Science.gov (United States)

Carpenter, Ryan M; Limb, Charles J; Francis, Howard W; Gottschalk, Barbara; Niparko, John K

2010-10-01

Bacterial meningitis represents a substantial concern for individuals with cochlear implants (CIs). Chart review and direct patient and family correspondence to ascertain vaccination status. Information dissemination via brochure and electronic media, ongoing reminders of the importance of vaccination when confirmation of vaccination was not received. Marked improvement in vaccination rates ranging from 49% to 99% across different patient populations. Importantly, many patients received their vaccinations only after follow-up reminders. Ensuring optimal vaccination of all CI recipients against high-risk pathogens is a significantly challenging task. Maximizing vaccination rates in CI users will require an ongoing, active effort of information dissemination, documentation of compliance, and well-designed behavioral systems to streamline the pragmatic challenges in vaccination delivery.

Chemical studies on the polysaccharides of Salicornia brachiata.

Science.gov (United States)

Sanandiya, Naresh D; Siddhanta, A K

2014-11-04

A group of 12 polysaccharide extracts were prepared from the tips, stem and roots of an Indian halophyte Salicornia brachiata Roxb. obtained by sequential extractions with cold water (CW), hot water (HW), aqueous ammonium oxalate (OX) and aqueous sodium hydroxide (ALK) solutions. Monosaccharide composition analysis revealed that all the polysaccharide extract samples consisted primarily of rhamnose, arabinose, mannose, galactose, glucose, whereas ribose and xylose were present only in some of the extracts. All the extracts exhibited low apparent viscosity (1.47-2.02 cP) and sulphate and contained no prominent toxic metal ions. Fucose was detected only in OX extract of the roots. These polysaccharides were found to be heterogeneous and highly branched (glycoside linkage analysis, size-exclusion chromatography, (13)C-NMR, FT-IR, circular dichroism and optical rotation data). Physico-chemical analyses of these polysaccharides including uronic acid, sulphate and protein contents were also carried out. This constitutes the first report on the profiling of Salicornia polysaccharides. Copyright © 2014 Elsevier Ltd. All rights reserved.

Comparison of polysaccharides from two species of Ganoderma.

Science.gov (United States)

Xie, Jing; Zhao, Jing; Hu, De-Jun; Duan, Jin-Ao; Tang, Yu-Ping; Li, Shao-Ping

2012-01-13

Ganoderma lucidum and Ganoderma sinense, known as Lingzhi in Chinese, are commonly used Chinese medicines with excellent beneficial health effects. Triterpenes and polysaccharides are usually considered as their main active components. However, the content of triterpenes differs significantly between the two species of Ganoderma. To date, a careful comparison of polysaccharides from the two species of Ganoderma has not been performed. In this study, polysaccharides from fruiting bodies of two species of Lingzhi collected from different regions of China were analyzed and compared based on HPSEC-ELSD and HPSEC-MALLS-RI analyses, as well as enzymatic digestion and HPTLC of acid hydrolysates. The results indicated that both the HPSEC-ELSD profiles and the molecular weights of the polysaccharides were similar. Enzymatic digestion showed that polysaccharides from all samples of Lingzhi could be hydrolyzed by pectinase and dextranase. HPTLC profiles of their TFA hydrolysates colored with different reagents and their monosaccharides composition were also similar.

Pneumococcal conjugate vaccines; impact on nasopharyngeal bacterial carriage and optimizing vaccination strategies

NARCIS (Netherlands)

Spijkerman, J.

2013-01-01

The aim of this thesis was to first assess nasopharyngeal bacterial carriage to evaluate population effects after introduction of PCV7 in the NIP in 2006 and to assess the potential impact of PCV10 as introduced in 2011 on carriage of NTHi in a randomized trial (Part One) and second, to assess

Comparison of Polysaccharides from Two Species of Ganoderma

OpenAIRE

Xie, Jing; Zhao, Jing; Hu, De-Jun; Duan, Jin-Ao; Tang, Yu-Ping; Li, Shao-Ping

2012-01-01

Ganoderma lucidum and Ganoderma sinense, known as Lingzhi in Chinese, are commonly used Chinese medicines with excellent beneficial health effects. Triterpenes and polysaccharides are usually considered as their main active components. However, the content of triterpenes differs significantly between the two species of Ganoderma. To date, a careful comparison of polysaccharides from the two species of Ganoderma has not been performed. In this study, polysaccharides from fruiting bodies of two...

Testing experimental subunit furunculosis vaccines for rainbow trout

DEFF Research Database (Denmark)

Marana, Moonika H.; Chettri, Jiwan Kumar; Skov, Jakob

2016-01-01

Aeromonas salmonicida subsp. salmonicida (AS) is the etiological agent of typical furunculosis in salmonid fish. The disease causes bacterial septicemia and is a major fish health problem in salmonid aquaculture worldwide, inducing high morbidity and mortality. In this study we vaccinated rainbow...... trout with subunit vaccines containing protein antigens that were selected based on an in silico antigen discovery approach. Thus, the proteome of AS strain A449 was analyzed by an antigen discovery platform and its proteins consequently ranked by their predicted ability to evoke protective immune...... response against AS. Fourteen proteins were prepared in 3 different experimental subunit vaccine combinations and used to vaccinate rainbow trout by intraperitoneal (i.p.) injection. We tested the proteins for their ability to elicit antibody production and protection. Thus, fish were exposed to virulent...

Polysaccharides in fungi. XXXII. Hypoglycemic activity and chemical properties of a polysaccharide from the cultural mycelium of Cordyceps sinensis.

Science.gov (United States)

Kiho, T; Hui, J; Yamane, A; Ukai, S

1993-12-01

Crude polysaccharides were obtained from a hot-water extract and alkaline extracts of the cultural mycelium of Cordyceps sinensis. They showed significant activity in normal mice and streptozotocin-induced diabetic mice as a result of intraperitoneal (i.p.) injection. A crude polysaccharide (CS-OHEP) obtained from 5% sodium hydroxide extract slightly lowered the plasma glucose level in normal mice by oral (p.o.) administration. A neutral polysaccharide (CS-F30) exhibited higher hypoglycemic activity than its crude polysaccharide (CS-OHEP), exhibited by i.p. injection, and it significantly lowered the glucose level by p.o. administration (50 mg/kg). However, it hardly affected the plasma insulin level in normal mice. CS-F30 ([alpha]D + 21 degrees in water) is composed of galactose, glucose and mannose (molar percent, 62:28:10), and its molecular weight is about 45000.

Decades of Hepatitis B Vaccination in China

Centers for Disease Control (CDC) Podcasts

2017-07-19

Dr. Stephen Hadler, deputy director for the Division of Bacterial Diseases at CDC, discusses a hepatitis B vaccination program in China.  Created: 7/19/2017 by National Center for Emerging and Zoonotic Infectious Diseases (NCEZID).   Date Released: 7/19/2017.

Radiation-chemical destruction of cellulose and other polysaccharides

International Nuclear Information System (INIS)

Ershov, B.G.

1998-01-01

The studies concerning the radiation-chemical destruction of cellulose, its ethers and some polysaccharides (xylan, starch, decstrans, chitin, chitosan and geparin) are discussed. Ionising irradiation causes the destruction of these compounds with the decay of pyranose ring, accompanied by the formation of compounds containing carbonyl or carboxyl groups, as well as hydrogen, carbon dioxide, and carbon oxide. The efficiency of radiation degradation increases with increasing the temperature and depends on the structure of polysaccharides and the nature of substituents. The mechanism of radiation-chemical transformations of cellulose and others polysaccharides is proposed. Prospects of the application of radiation-chemical methods of treatment of cellulose and other polysaccharides in industry and agriculture considered [ru

Revealing the ability of a novel polysaccharide bioflocculant in bioremediation of heavy metals sensed in a Vibrio bioluminescence reporter assay.

Science.gov (United States)

Sajayan, Arya; Seghal Kiran, G; Priyadharshini, S; Poulose, Navya; Selvin, Joseph

2017-09-01

A bioflocculant-producing bacterial strain, designated MSI021, was isolated from the marine sponge Dendrilla nigra and demonstrated 94% flocculation activity in a kaolin clay suspension. MSI021 was identified as Bacillus cereus based on phylogenetic affiliation and biochemical characteristics. The purified extra-cellular bioflocculant was chemically elucidated as a polysaccharide molecule. The polysaccharide bioflocculant was stable under both acidic and alkaline conditions (pH 2.0-10.0) and temperatures up to 100 °C. The purified bioflocculant efficiently nucleated the formation of silver nanoparticles which showed broad spectrum antibacterial activity. The ability of the bioflocculant to remediate heavy metal toxicity was evaluated by measuring the inhibition of bioluminescence expression in Vibrio harveyi. Enrichment of heavy metals such as zinc, mercury and copper at concentrations of 1, 2 and 3 mM in culture media showed significant reduction of bioluminescence in Vibrio, whereas media enriched with heavy metals and bioflocculant showed dose dependent improvement in the expression of bioluminescence. The assay results demonstrated that the polysaccharide bioflocculant effectively mitigates heavy metal toxicity, thereby improving the expression of bioluminescence in Vibrio. This bioluminescence reporter assay can be developed into a high-throughput format to monitor and evaluate of heavy metal toxicity. The findings of this study revealed that a novel polysaccharide bioflocculant produced by a marine B. cereus demonstrated strong flocculating performance and was effective in nucleating the formation antibacterial silver nanoparticles and removing heavy metals. These results suggest that the MSI021 polysaccharide bioflocculant can be used to develop greener waste water treatment systems. Copyright © 2017 Elsevier Ltd. All rights reserved.

Use of vaccines as a key antimicrobial stewardship strategy

African Journals Online (AJOL)

The efficacy of both bacterial and viral vaccines in the reduction of antimicrobial ... mucosal trio' of nasopharyngeal carriage, subsequent acute otitis media (AOM) .... results of the Community Acquired Pneumonia Immunization Trial in Adults ...

Synthesis of orthogonally protected bacterial, rare-sugar and D-glycosamine building blocks.

Science.gov (United States)

Emmadi, Madhu; Kulkarni, Suvarn S

2013-10-01

Bacterial glycoconjugates comprise atypical deoxy amino sugars that are not present on the human cell surface, making them good targets for drug discovery and carbohydrate-based vaccine development. Unfortunately, they cannot be isolated with sufficient purity in acceptable amounts, and therefore chemical synthesis is a crucial step toward the development of these products. Here we describe a detailed protocol for the synthesis of orthogonally protected bacterial deoxy amino hexopyranoside (2,4-diacetamido-2,4,6-trideoxyhexose (DATDH), D-bacillosamine, D-fucosamine, and 2-acetamido-4-amino-2,4,6-trideoxy-D-galactose (AAT)), D-glucosamine and D-galactosamine building blocks starting from β-D-thiophenylmannoside. Readily available β-D-thiophenylmannoside was first converted into the corresponding 2,4-diols via deoxygenation or silylation at C6, followed by O3 acylation. The 2,4-diols were converted into 2,4-bis-trifluoromethanesulfonates, which underwent highly regioselective, one-pot, double-serial and double-parallel displacements by azide, phthalimide, acetate and nitrite ions as nucleophiles. Thus, D-rhamnosyl- and D-mannosyl 2,4-diols can be efficiently transformed into various rare sugars and D-galactosamine, respectively, as orthogonally protected thioglycoside building blocks on a gram scale in 1-2 d, in 54-85% overall yields, after a single chromatographic purification. This would otherwise take 1-2 weeks. D-Glucosamine building blocks can be prepared from β-D-thiophenylmannoside in four steps via C2 displacement of triflates by azide in 2 d and in 66-70% overall yields. These procedures have been applied to the synthesis of L-serine-linked trisaccharide of Neisseria meningitidis and a rare disaccharide fragment of the zwitterionic polysaccharide (ZPS) A1 (ZPS A1) of Bacteroides fragilis.

Characterization of polysaccharides from Ganoderma spp. using saccharide mapping.

Science.gov (United States)

Wu, Ding-Tao; Xie, Jing; Hu, De-Jun; Zhao, Jing; Li, Shao-Ping

2013-09-12

Polysaccharides from Ganoderma spp. and their adulterants were firstly investigated and compared using saccharide mapping, enzymatic (endo-1,3-β-D-glucanase and pectinase) digestion followed by polysaccharide analysis using carbohydrate gel electrophoresis analysis. The results showed that both 1,3-β-D-glucosidic and 1,4-α-D-galactosiduronic linkages were existed in Lingzhi (Ganoderma lucidum and Ganoderma sinense), and the similarity of polysaccharides from G. lucidum and G. sinense was high, which may contribute to rational use of Lingzhi. Different species of Ganoderma and their adulterants can be differentiated based on the saccharide mapping, which is helpful to well understand the structural characters of polysaccharides from different species of Ganoderma and to improve the quality control of polysaccharides in Lingzhi. Copyright © 2013 Elsevier Ltd. All rights reserved.

A randomized study to assess the immunogenicity, antibody persistence and safety of a tetravalent meningococcal serogroups A, C, W-135 and Y tetanus toxoid conjugate vaccine in children aged 2–10 years

Science.gov (United States)

Vesikari, Timo; Forstén, Aino; Boutriau, Dominique; Bianco, Véronique; Van der Wielen, Marie; Miller, Jacqueline M.

2012-01-01

Incidence of meningococcal diseases is high in children, and effective vaccines are needed for this age group. In this phase II, open, controlled study, 309 children aged 2–10 y from Finland were randomized (3:1) into two parallel groups to receive one dose of meningococcal ACWY-tetanus toxoid conjugate vaccine (ACWY-TT group; n = 231) or a licensed meningococcal ACWY polysaccharide vaccine (Men-PS group; n = 78). Serum bactericidal activity using rabbit complement (rSBA) was evaluated up to three years post-vaccination. Exploratory comparisons suggested that rSBA vaccine response rates and geometric mean titers (GMTs) for each serogroup at one month post-vaccination and rSBA GMTs for serogroups A, W-135 and Y up to three years post-vaccination were higher in the ACWY-TT compared with Men-PS group, but did not detect any difference between groups in terms of rSBA-MenC GMTs at three years post-vaccination; this is explained by the higher proportion of children from the Men-PS group who were excluded because they were re-vaccinated with a monovalent meningococcal serogroup C vaccine due to loss of protective antibody levels against this serogroup. Although there was a higher incidence of local reactogenicity in the ACWY-TT group, general and unsolicited symptoms reporting rates were comparable in both groups. This study showed that MenACWY-TT was immunogenic with a clinically acceptable safety profile in children aged 2–10 y. MenACWY-TT induced higher functional antibody titers for all serogroups, which persisted longer for serogroups A, W-135 and Y, than the MenACWY polysaccharide vaccine. This study has been registered at www.clinicaltrials.gov NCT00427908. PMID:23032168

Evaluation of the Mycobacterium tuberculosis SO2 vaccine using a natural tuberculosis infection model in goats.

Science.gov (United States)

Bezos, J; Casal, C; Álvarez, J; Roy, A; Romero, B; Rodríguez-Bertos, A; Bárcena, C; Díez, A; Juste, R; Gortázar, C; Puentes, E; Aguiló, N; Martín, C; de Juan, L; Domínguez, L

2017-05-01

The development of new vaccines against animal tuberculosis (TB) is a priority for improving the control and eradication of this disease, particularly in those species not subjected to compulsory eradication programmes. In this study, the protection conferred by the Mycobacterium tuberculosis SO 2 experimental vaccine was evaluated using a natural infection model in goats. Twenty-six goats were distributed in three groups: (1) 10 goats served as a control group; (2) six goats were subcutaneously vaccinated with BCG; and (3) 10 goats were subcutaneously vaccinated with SO 2 . Four months after vaccination, all groups were merged with goats infected with Mycobacterium bovis or Mycobacterium caprae, and tested over a 40 week period using a tuberculin intradermal test and an interferon-γ assay for mycobacterial reactivity. The severity of lesions was determined at post-mortem examination and the bacterial load in tissues were evaluated by culture. The two vaccinated groups had significantly lower lesion and bacterial culture scores than the control group (P<0.05); at the end of the study, the SO 2 vaccinated goats had the lowest lesion and culture scores. These results suggest that the SO 2 vaccine provides some protection against TB infection acquired from natural exposure. Copyright © 2017 Elsevier Ltd. All rights reserved.

Chemical characteristics and anti-proliferation activities of Ganoderma tsugae polysaccharides.

Science.gov (United States)

Chien, Rao-Chi; Yen, Ming-Tsung; Tseng, Yu-Hsiu; Mau, Jeng-Leun

2015-09-05

Polysaccharides were extracted by hot-water and hot-alkali from four forms of Ganoderma tsugae including mature and baby Ling chih, mycelium and filtrate. Different profiles of proximate composition and monosaccharide constituents, and element contents were found in the extracted polysaccharides from different extractions and different forms. The molecular weight distributions of polysaccharides were 2.8×10(4)-6.5×10(5)Da and their infrared spectra were comparable. The hot-alkali extracted polysaccharides exhibited better anti-proliferation on IMR32 cells than the hot-water extracted polysaccharides, which were in turn more effective than the hot-water extracts. Besides, most hot-water extracts and both extracted polysaccharides exhibited an anti-proliferation effect on Hep G2 cells. However, the hot-water extracts showed less effective in anti-proliferation of IMR32 and Hep G2 cells. Based on the anti-tumor effects, both polysaccharides could be prepared for use in the formulation of nutraceuticals and functional foods. Copyright © 2015 Elsevier Ltd. All rights reserved.

Structure of polysaccharide antibiotics

International Nuclear Information System (INIS)

Matutano, L.

1966-01-01

Study of the structure of antibiotics having two or several sugars in their molecule. One may distinguish: the polysaccharide antibiotics themselves, made up of two or several sugars either with or without nitrogen, such as streptomycin, neomycins, paromomycine, kanamycin, chalcomycin; the hetero-polysaccharide antibiotics made up of one saccharide part linked to an aglycone of various type through a glucoside: macrolide, pigment, pyrimidine purine. Amongst these latter are: erythromycin, magnamycin, spiramycin, oleandomycin, cinerubin and amicetin. The sugars can either play a direct role in biochemical reactions or act as a dissolving agent, as far as the anti-microbe power of these antibiotics is concerned. (author) [fr

Polysaccharides from Traditional Chinese Medicines: Extraction, Purification, Modification, and Biological Activity.

Science.gov (United States)

Chen, Yun; Yao, Fangke; Ming, Ke; Wang, Deyun; Hu, Yuanliang; Liu, Jiaguo

2016-12-13

Traditional Chinese Medicine (TCM) has been used to treat diseases in China for thousands of years. TCM compositions are complex, using as their various sources plants, animals, fungi, and minerals. Polysaccharides are one of the active and important ingredients of TCMs. Polysaccharides from TCMs exhibit a wide range of biological activities in terms of immunity- modifying, antiviral, anti-inflammatory, anti-oxidative, and anti-tumor properties. With their widespread biological activities, polysaccharides consistently attract scientist's interests, and the studies often concentrate on the extraction, purification, and biological activity of TCM polysaccharides. Currently, numerous studies have shown that the modification of polysaccharides can heighten or change the biological activities, which is a new angle of polysaccharide research. This review highlights the current knowledge of TCM polysaccharides, including their extraction, purification, modification, and biological activity, which will hopefully provide profound insights facilitating further research and development.

Recombinant Lipoproteins as Novel Vaccines with Intrinsic Adjuvant.

Science.gov (United States)

Chong, Pele; Huang, Jui-Hsin; Leng, Chih-Hsiang; Liu, Shih-Jen; Chen, Hsin-Wei

2015-01-01

A core platform technology for high production of recombinant lipoproteins with built-in immunostimulator for novel subunit vaccine development has been established. This platform technology has the following advantages: (1) easily convert antigen into lipidated recombinant protein using a fusion sequence containing lipobox and express high level (50-150mg/L) in Escherichia coli; (2) a robust high-yield up- and downstream bioprocess for lipoprotein production is successfully developed to devoid endotoxin contamination; (3) the lipid moiety of recombinant lipoproteins, which is identical to that of bacterial lipoproteins is recognized as danger signals by the immune system (Toll-like receptor 2 agonist), so both innate and adaptive immune responses can be induced by lipoproteins; and (4) successfully demonstrate the feasibility and safety of this core platform technology in meningococcal group B subunit vaccine, dengue subunit vaccine, novel subunit vaccine against Clostridium difficile-associated diseases, and HPV-based immunotherapeutic vaccines in animal model studies. © 2015 Elsevier Inc. All rights reserved.

Molecular mapping of the cell wall polysaccharides of the human pathogen Streptococcus agalactiae

Science.gov (United States)

Beaussart, Audrey; Péchoux, Christine; Trieu-Cuot, Patrick; Hols, Pascal; Mistou, Michel-Yves; Dufrêne, Yves F.

2014-11-01

The surface of many bacterial pathogens is covered with polysaccharides that play important roles in mediating pathogen-host interactions. In Streptococcus agalactiae, the capsular polysaccharide (CPS) is recognized as a major virulence factor while the group B carbohydrate (GBC) is crucial for peptidoglycan biosynthesis and cell division. Despite the important roles of CPS and GBC, there is little information available on the molecular organization of these glycopolymers on the cell surface. Here, we use atomic force microscopy (AFM) and transmission electron microscopy (TEM) to analyze the nanoscale distribution of CPS and GBC in wild-type (WT) and mutant strains of S. agalactiae. TEM analyses reveal that in WT bacteria, peptidoglycan is covered with a very thin (few nm) layer of GBC (the ``pellicle'') overlaid by a 15-45 nm thick layer of CPS (the ``capsule''). AFM-based single-molecule mapping with specific antibody probes shows that CPS is exposed on WT cells, while it is hardly detected on mutant cells impaired in CPS production (ΔcpsE mutant). By contrast, both TEM and AFM show that CPS is over-expressed in mutant cells altered in GBC expression (ΔgbcO mutant), indicating that the production of the two surface glycopolymers is coordinated in WT cells. In addition, AFM topographic imaging and molecular mapping with specific lectin probes demonstrate that removal of CPS (ΔcpsE), but not of GBC (ΔgbcO), leads to the exposure of peptidoglycan, organized into 25 nm wide bands running parallel to the septum. These results indicate that CPS forms a homogeneous barrier protecting the underlying peptidoglycan from environmental exposure, while the presence of GBC does not prevent peptidoglycan detection. This work shows that single-molecule AFM, combined with high-resolution TEM, represents a powerful platform for analysing the molecular arrangement of the cell wall polymers of bacterial pathogens.

Crosslinked ionic polysaccharides for stimuli-sensitive drug delivery.

Science.gov (United States)

Alvarez-Lorenzo, Carmen; Blanco-Fernandez, Barbara; Puga, Ana M; Concheiro, Angel

2013-08-01

Polysaccharides are gaining increasing attention as components of stimuli-responsive drug delivery systems, particularly since they can be obtained in a well characterized and reproducible way from the natural sources. Ionic polysaccharides can be readily crosslinked to render hydrogel networks sensitive to a variety of internal and external variables, and thus suitable for switching drug release on-off through diverse mechanisms. Hybrids, composites and grafted polymers can reinforce the responsiveness and widen the range of stimuli to which polysaccharide-based systems can respond. This review analyzes the state of the art of crosslinked ionic polysaccharides as components of delivery systems that can regulate drug release as a function of changes in pH, ion nature and concentration, electric and magnetic field intensity, light wavelength, temperature, redox potential, and certain molecules (enzymes, illness markers, and so on). Examples of specific applications are provided. The information compiled demonstrates that crosslinked networks of ionic polysaccharides are suitable building blocks for developing advanced externally activated and feed-back modulated drug delivery systems. Copyright © 2013 Elsevier B.V. All rights reserved.

Application of new vaccine technologies for the control of transboundary diseases.

Science.gov (United States)

Swayne, D E

2004-01-01

Vaccines have played an important role in the control of diseases of livestock and poultry, including Transboundary Diseases. In the future, vaccines will play a greater role in controlling these diseases. Historically, inactivated whole viruses in various adjuvant systems have been used and will continue to be used in the near future. For the future, emerging technologies will allow targeted use of only the protective antigens of the pathogen and will provide the opportunity for differentiating between vaccinated and field-exposed animals. Furthermore, the expression of cytokines by vaccines will afford earlier or greater enhancement of protection than can be achieved by the protective response elicited by the antigenic epitopes of the pathogen alone. Avian influenza (AI) is a good case for studying future trends in vaccine design and use. Inactivated AI virus (AIV) vaccines will continue as the primary vaccines used over the next 10 years. These vaccines will use homologous haemagglutinin sub-types, either from the use of field strains or the generation of new strains through the use of infectious clones produced in the laboratory. The latter will allow creation of high growth reassortants, which will provide consistent high yields of antigen and result in potent vaccines. New viral and bacterial vectors with inserts of AIV haemagglutinin gene will be developed and potentially used in the field. Such new vectors will include herpesvirus-turkey, infectious laryngotracheitis virus, adenoviruses, various types of paramyxoviruses and Salmonella sp. In addition, there is a theoretical possibility of gene-deleted mutants that would allow the use of live AIV vaccines, but the application of such vaccines has inherent dangers for gene reassortment with field viruses in the generation of disease-causing strains. Subunit haemagglutinin protein and DNA haemagglutinin gene vaccines are possible, but with current technologies, the cost is prohibitive. In the future, effective

Vaccination against Salmonella Infection: the Mucosal Way.

Science.gov (United States)

Gayet, Rémi; Bioley, Gilles; Rochereau, Nicolas; Paul, Stéphane; Corthésy, Blaise

2017-09-01

Salmonella enterica subspecies enterica includes several serovars infecting both humans and other animals and leading to typhoid fever or gastroenteritis. The high prevalence of associated morbidity and mortality, together with an increased emergence of multidrug-resistant strains, is a current global health issue that has prompted the development of vaccination strategies that confer protection against most serovars. Currently available systemic vaccine approaches have major limitations, including a reduced effectiveness in young children and a lack of cross-protection among different strains. Having studied host-pathogen interactions, microbiologists and immunologists argue in favor of topical gastrointestinal administration for improvement in vaccine efficacy. Here, recent advances in this field are summarized, including mechanisms of bacterial uptake at the intestinal epithelium, the assessment of protective host immunity, and improved animal models that closely mimic infection in humans. The pros and cons of existing vaccines are presented, along with recent progress made with novel formulations. Finally, new candidate antigens and their relevance in the refined design of anti- Salmonella vaccines are discussed, along with antigen vectorization strategies such as nanoparticles or secretory immunoglobulins, with a focus on potentiating mucosal vaccine efficacy. Copyright © 2017 American Society for Microbiology.

An overview of adjuvants utilized in prophylactic vaccine formulation as immunomodulators.

Science.gov (United States)

Chauhan, Nidhi; Tiwari, Sukirti; Iype, Tessy; Jain, Utkarsh

2017-05-01

Development of efficient and cost effective vaccines have been recognized as the primary concern to improve the overall healthcare in a country. In order to achieve this goal, more improved and powerful adjuvants need to be developed. Lacking in the self-adjuvanting immuno-modulatory constituents, vaccines exhibit lower immunogenicity. Combining potent adjuvants with vaccines is the most appropriate method to enhance the efficacy of the vaccines. Hence, this review is focussed on the most potent adjuvants for the formulation of vaccines. Areas covered: This review focuses on Oil-based emulsions, Mineral compounds, Liposomes, Bacterial products, ISCOMs and most recently used nanomaterials as adjuvants for enhancing the antigenicity of vaccines. Furthermore, this review explains the immunological response elicited by various particles. Moreover, case studies are incorporated providing an in depth analyses of various adjuvant-containing vaccines which are currently used. Expert commentary: Enhanced fundamental knowledge about the adjuvants and their immuno-stimulatory capabilities and delivery mechanisms will facilitate the rational designing of prophylactic vaccines with better efficacy.

[Effects of tree species on polysaccharides content of epiphytic Dendrobium officinale].

Science.gov (United States)

Guo, Ying-Ying; Zhu, Yan; Si, Jin-Ping; Liu, Jing-Jing; Wu, Cheng-Yong; Li, Hui

2014-11-01

To reveals the effects of tree species on polysaccharides content of epiphytic Dendrobium officinale. The polysaccharides content of D. officinale attached to living tress in wild or stumps in bionic-facility was determined by phenol-sulfuric acid method. There were extremely significant differences of polysaccharides content of D. officinale attached to different tree species, but the differences had no relationship with the form and nutrition of barks. The polysaccharides content of D. officinale mainly affected by the light intensity of environment, so reasonable illumination favored the accumulation of polysaccharides. Various polysaccharides content of D. officinal from different attached trees is due to the difference of light regulation, but not the form and nutrition of barks.

Of the Phrensy: an update on the epidemiology and pathogenesis of bacterial meningitis in the pediatric population [version 1; referees: 3 approved

Directory of Open Access Journals (Sweden)

Andrew Janowski

2017-01-01

Full Text Available In the past century, advances in antibiotics and vaccination have dramatically altered the incidence and clinical outcomes of bacterial meningitis. We review the shifting epidemiology of meningitis in children, including after the implementation of vaccines that target common meningitic pathogens and the introduction of intrapartum antibiotic prophylaxis offered to mothers colonized with Streptococcus agalactiae. We also discuss what is currently known about the pathogenesis of meningitis. Recent studies of the human microbiome have illustrated dynamic relationships of bacterial and viral populations with the host, which may potentiate the risk of bacterial meningitis.

Extracellular polysaccharides are involved in the attachment of Azospirillum brasilense and Rhizobium leguminosarum to arbuscular mycorrhizal structures

Directory of Open Access Journals (Sweden)

V Bianciotto

2009-12-01

Full Text Available Arbuscular mycorrhizal (AM fungi, one of the most important component of the soil microbial community, establish physical interactions with naturally occurring and genetically modified bacterial biofertilizers and biopesticides, commonly referred to as plant growth-promoting rhizobacteria (PGPR. We have used a genetic approach to investigate the bacterial components possibly involved in the attachment of two PGPR (Azospirillum and Rhizobium to AM roots and AM fungal structures. Mutants affected in extracellular polysaccharides (EPS have been tested in in vitro adhesion assays and shown to be strongly impaired in the attachment to both types of surfaces as well as to quartz fibers. Anchoring of rhizobacteria to AM fungal structures may have special ecological and biotechnological significance because it may facilitate colonisation of new rhizospheres by the bacteria, and may be an essential trait for the development of mixed inocula.

Polysaccharides from Traditional Chinese Medicines: Extraction, Purification, Modification, and Biological Activity

Directory of Open Access Journals (Sweden)

Yun Chen

2016-12-01

Full Text Available Traditional Chinese Medicine (TCM has been used to treat diseases in China for thousands of years. TCM compositions are complex, using as their various sources plants, animals, fungi, and minerals. Polysaccharides are one of the active and important ingredients of TCMs. Polysaccharides from TCMs exhibit a wide range of biological activities in terms of immunity- modifying, antiviral, anti-inflammatory, anti-oxidative, and anti-tumor properties. With their widespread biological activities, polysaccharides consistently attract scientist's interests, and the studies often concentrate on the extraction, purification, and biological activity of TCM polysaccharides. Currently, numerous studies have shown that the modification of polysaccharides can heighten or change the biological activities, which is a new angle of polysaccharide research. This review highlights the current knowledge of TCM polysaccharides, including their extraction, purification, modification, and biological activity, which will hopefully provide profound insights facilitating further research and development.

Chromatography in characterization of polysaccharides from medicinal plants and fungi.

Science.gov (United States)

Hu, De-jun; Cheong, Kit-leong; Zhao, Jing; Li, Shao-ping

2013-01-01

Polysaccharides isolated from medicinal plants and fungi exhibit multiple pharmacological activities. The biological activities of polysaccharides depend on their chemical characteristics. However, characterization of polysaccahrides is a challenge because of their complicated structure and macromolecular mass. In this review, chromatography in characterization of polysaccharides, including physicochemical characterization (purity, molecular mass, and distribution), structural characterization (constituent monosaccharide composition and the ratio, the features of glycosidic linkages), and fingerprint of polysaccharides (acidic and enzymatic hydrolysates), from medicinal plants and fungi were reviewed and discussed according to the publications collected in Web of Science since 2007. The perspective for characterization of polysaccharides has also been described. © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Lytic polysaccharide monooxygenases from Myceliophthora thermophila C1

NARCIS (Netherlands)

Frommhagen, Matthias

2017-01-01

Current developments aim at the effective enzymatic degradation of plant biomass polysaccharides into fermentable monosaccharides for biofuels and biochemicals. Recently discovered lytic polysaccharide monooxgygenases (LPMOs) boost the hydrolytic breakdown of lignocellulosic biomass, especially

Structural Characterization and Enzymatic Modification of Soybean Polysaccharides

DEFF Research Database (Denmark)

Pierce, Brian; Wichmann, Jesper

% galacturonic acid, 8% xylose, 3% rhamnose, and 3% fucose. Currently, the majority of this material is disposed of as waste, increasing production costs. Opportunities exist for the develop-ment of novel functional ingredients from this abundant and underutilized ma-terial; however, efforts in this area......The work in this thesis explores the structure of soybean polysaccharides, and examines approaches for the chemical and enzymatic degradation and solu-bilization of this material. Soybean polysaccharides are produced in large quantities globally as a by-product of various soy production processes...... are currently limited by the material’s insol-ubility. A central hypothesis of this work was that by obtaining a more complete understanding of the structure of this material, chemical and enzymatic ap-proaches could be developed to modify the polysaccharides, creating soluble polysaccharide fractions...

Complement evasion by Bordetella pertussis: implications for improving current vaccines.

Science.gov (United States)

Jongerius, Ilse; Schuijt, Tim J; Mooi, Frits R; Pinelli, Elena

2015-04-01

Bordetella pertussis causes whooping cough or pertussis, a highly contagious disease of the respiratory tract. Despite high vaccination coverage, reported cases of pertussis are rising worldwide and it has become clear that the current vaccines must be improved. In addition to the well-known protective role of antibodies and T cells during B. pertussis infection, innate immune responses such as the complement system play an essential role in B. pertussis killing. In order to evade this complement activation and colonize the human host, B. pertussis expresses several molecules that inhibit complement activation. Interestingly, one of the known complement evasion proteins, autotransporter Vag8, is highly expressed in the recently emerged B. pertussis isolates. Here, we describe the current knowledge on how B. pertussis evades complement-mediated killing. In addition, we compare this to complement evasion strategies used by other bacterial species. Finally, we discuss the consequences of complement evasion by B. pertussis on adaptive immunity and how identification of the bacterial molecules and the mechanisms involved in complement evasion might help improve pertussis vaccines.

Update on the current status of cytomegalovirus vaccines.

Science.gov (United States)

Sung, Heungsup; Schleiss, Mark R

2010-11-01

Human cytomegalovirus (HCMV) is ubiquitous in all populations, and is the most commonly recognized cause of congenital viral infection in developed countries. On the basis of the economic costs saved and the improvement in quality of life that could potentially be conferred by a successful vaccine for prevention of congenital HCMV infection, the Institute of Medicine has identified HCMV vaccine development as a major public health priority. An effective vaccine could potentially also be beneficial in preventing or ameliorating HCMV disease in immunocompromised individuals. Although there are no licensed HCMV vaccines currently available, enormous progress has been made in the last decade, as evidenced by the recently reported results of a Phase II trial of a glycoprotein B vaccine for the prevention of HCMV infection in seronegative women of childbearing age. HCMV vaccines currently in clinical trials include: glycoprotein B subunit vaccines; alphavirus replicon particle vaccines; DNA vaccines; and live-attenuated vaccines. A variety of vaccine strategies are also being examined in preclinical systems and animal models of infection. These include: recombinant vesicular stomatitis virus vaccines; recombinant modified vaccinia virus Ankara; replication-deficient adenovirus-vectored vaccines; and recombinant live-attenuated virus vaccines generated by mutagenesis of cloned rodent CMV genomes maintained as bacterial artificial chromosomes in Escherichia coli. In this article, we provide an overview of the current state of clinical trials and preclinical development of vaccines against HCMV, with an emphasis on studies that have been conducted in the past 5 years. We also summarize a number of recent advances in the study of the biology of HCMV, particularly with respect to epithelial and endothelial cell entry of the virus, which have implications for future vaccine design.

Total synthesis of a Streptococcus pneumoniae serotype 12F CPS repeating unit hexasaccharide

Directory of Open Access Journals (Sweden)

Peter H. Seeberger

2017-01-01

Full Text Available The Gram-positive bacterium Streptococcus pneumoniae causes severe disease globally. Vaccines that prevent S. pneumoniae infections induce antibodies against epitopes within the bacterial capsular polysaccharide (CPS. A better immunological understanding of the epitopes that protect from bacterial infection requires defined oligosaccharides obtained by total synthesis. The key to the synthesis of the S. pneumoniae serotype 12F CPS hexasaccharide repeating unit that is not contained in currently used glycoconjugate vaccines is the assembly of the trisaccharide β-D-GalpNAc-(1→4-[α-D-Glcp-(1→3]-β-D-ManpNAcA, in which the branching points are equipped with orthogonal protecting groups. A linear approach relying on the sequential assembly of monosaccharide building blocks proved superior to a convergent [3 + 3] strategy that was not successful due to steric constraints. The synthetic hexasaccharide is the starting point for further immunological investigations.

The Vi capsular polysaccharide enables Salmonella enterica serovar typhi to evade microbe-guided neutrophil chemotaxis.

Directory of Open Access Journals (Sweden)

Tamding Wangdi

2014-08-01

Full Text Available Salmonella enterica serovar Typhi (S. Typhi causes typhoid fever, a disseminated infection, while the closely related pathogen S. enterica serovar Typhimurium (S. Typhimurium is associated with a localized gastroenteritis in humans. Here we investigated whether both pathogens differ in the chemotactic response they induce in neutrophils using a single-cell experimental approach. Surprisingly, neutrophils extended chemotactic pseudopodia toward Escherichia coli and S. Typhimurium, but not toward S. Typhi. Bacterial-guided chemotaxis was dependent on the presence of complement component 5a (C5a and C5a receptor (C5aR. Deletion of S. Typhi capsule biosynthesis genes markedly enhanced the chemotactic response of neutrophils in vitro. Furthermore, deletion of capsule biosynthesis genes heightened the association of S. Typhi with neutrophils in vivo through a C5aR-dependent mechanism. Collectively, these data suggest that expression of the virulence-associated (Vi capsular polysaccharide of S. Typhi obstructs bacterial-guided neutrophil chemotaxis.

Bacterial meningitis: epidemiology, herd protection, clinical characteristics, and risk assessment

NARCIS (Netherlands)

Bijlsma, M.W.

2016-01-01

This thesis studied the epidemiology of community-acquired bacterial meningitis after the nationwide implementation of paediatric conjugate vaccines, as well as the long-term epidemiology of invasive meningococcal disease and neonatal group B streptococcal disease in the Netherlands. Furthermore,

Characterization and antioxidant activities of polysaccharides from thirteen boletus mushrooms.

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Zhang, Lan; Hu, Yu; Duan, Xiaoyu; Tang, Tingting; Shen, Yingbin; Hu, Bin; Liu, Aiping; Chen, Hong; Li, Cheng; Liu, Yuntao

2018-07-01

Water-soluble polysaccharides were extracted from the caps and stipes of thirteen boletus mushrooms representing five different species collected in Southwest China. Investigations of their structures and antioxidant activities allowed an evaluation of structure-function relationships. The polysaccharides were composed mainly of the monosaccharides arabinose, xylose, mannose, glucose and galactose. Most samples displayed a broad molecular weight range, with significant differences observed between the molecular weight ranges of the polysaccharides from the caps and the stipes. FT-IR spectral analysis of the polysaccharides revealed that most of polysaccharides from boletus mushrooms (except Boletus edulis) contained a pyranose ring. The antioxidant activities of the polysaccharides in stipes showed a significant correlation with their monosaccharide composition, and were also related to their molecular weight and anomeric configuration. Suillellus luridus collected in Pingwu, Mianyang, Sichuan, China had remarkably superior antioxidant activity and might be developed as a natural antioxidant. Copyright © 2018 Elsevier B.V. All rights reserved.

Immunogenicity and tolerability of recombinant serogroup B meningococcal vaccine administered with or without routine infant vaccinations according to different immunization schedules: a randomized controlled trial.

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Gossger, Nicoletta; Snape, Matthew D; Yu, Ly-Mee; Finn, Adam; Bona, Gianni; Esposito, Susanna; Principi, Nicola; Diez-Domingo, Javier; Sokal, Etienne; Becker, Birgitta; Kieninger, Dorothee; Prymula, Roman; Dull, Peter; Ypma, Ellen; Toneatto, Daniela; Kimura, Alan; Pollard, Andrew J

2012-02-08

In the absence of an effective vaccine, serogroup B Neisseria meningitidis (MenB) remains a major cause of invasive disease in early childhood in developed countries. To determine the immunogenicity and reactogenicity of a multicomponent MenB vaccine (4CMenB) and routine infant vaccines when given either concomitantly or separately. Phase 2b, multicenter, open-label, parallel-group, randomized controlled study of 1885 infants enrolled at age 2 months from August 2008 to July 2010 in Europe. Participants were randomized 2:2:1:1 to receive (1) 4CMenB at 2, 4, and 6 months with routine vaccines (7-valent pneumococcal and combined diphtheria, tetanus, acellular pertussis, inactivated polio, hepatitis B, Haemophilus influenzae type b vaccines); (2) 4CMenB at 2, 4, and 6 months and routine vaccines at 3, 5, and 7 months; (3) 4CMenB with routine vaccines at 2, 3, and 4 months; or (4) routine vaccines alone at 2, 3, and 4 months. Percentage of participants with human complement serum bactericidal activity (hSBA) titer of 1:5 or greater against 3 MenB strains specific for vaccine antigens (NZ98/254, 44/76-SL, and 5/99). After three 4CMenB vaccinations, 99% or more of infants developed hSBA titers of 1:5 or greater against strains 44/76-SL and 5/99. For NZ98/254, this proportion was 79% (95% CI, 75.2%-82.4%) for vaccination at 2, 4, and 6 months with routine vaccines, 86.1% (95% CI, 82.9%-89.0%) for vaccination at 2, 4, and 6 months without routine vaccines, and 81.7% (95% CI, 76.6%-86.2%) for vaccination at 2, 3, and 4 months with routine vaccines. Responses to routine vaccines given with 4CMenB were noninferior to routine vaccines alone for all antigens, except for the responses to pertactin and serotype 6B pneumococcal polysaccharide. Fever was seen following 26% (158/602) to 41% (247/607) of 4CMenB doses when administered alone, compared with 23% (69/304) to 36% (109/306) after routine vaccines given alone and 51% (306/605) to 61% (380/624) after 4CMenB and routine

Studies on water soluble polysaccharides from Pithecellobium dulce (Roxb.) Benth. seeds.

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Bagchi, S; Kumar, K Jayaram

2016-03-15

In this existing experimental work, water soluble PDP polysaccharides were secluded from Pithecellobium dulce (Roxb.) Benth. seeds. The physicochemical properties were analyzed in terms of swelling power, solubility, pH and water holding capacity. Micromeretic studies proved the polysaccharide may be used a potential pharmaceutical adjuvant. The polysaccharide was characterized by FT-IR, SEM, TGA and NMR techniques. Methylation analysis confirmed that the polysaccharide is composed of Arabinose (Araf) units. The chemical shifts of anomeric proton region were found in the region of 4.4-5.5ppm. Thermogravimetric analysis showed that PDP polysaccharide was thermally stable. The in vitro antioxidant capacities of the polysaccharide were investigated in terms of scavenging of hydroxyl radicals, 2, 2-diphenyl-1-picrylhydrazyl (DPPH) radicals, hydrogen peroxide (H2O2) and reducing power assay. The polysaccharide fractions showed activity in a concentration dependent manner which was comparable to the standard, ascorbic acid. Copyright © 2015 Elsevier Ltd. All rights reserved.

Bacteriological cure rate and changes in milk composition in mastitis vaccinated ewes affected with subclinical mastitis.

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Alekish, Myassar O; Ismail, Z Bani; Hammouri, H M; Daradka, M H; Taha, S Al; Olymat, I

2018-02-01

The aim of this study was to investigate the effects of using a commercially-available polyvalent mastitis vaccine on the bacteriological cure rate of existing subclinical mastitis in Awassi sheep. A total of 164 lactating ewes were divided into two main groups according to udder health and milk somatic cell count (SCC): Group 1=normal (N; n=80) and Group 2=subclinical mastitis (SC; n=84). Each group was then subdivided randomly into two treatment groups: N vaccinated (N vax ; n=38), N non-vaccinated (N nvax ; n=42), SC vaccinated (SC vax ; n=42), and SC non-vaccinated (SC nvax ; n=42). The vaccine was administered as per manufacturer's recommendations. Milk samples were collected aseptically from all ewes before vaccine administration (T0) and again on days 28 (T2) and 42 (T3) of the experiment. In the SC group, the bacteriological cure rates in vaccinated and non-vaccinated ewes were 76% and 69%, respectively. In N group, the new intramammary infection rates in vaccinated and non-vaccinated ewes were 48% and 50%, respectively. Vaccination of normal ewes resulted in a significant (pewes on days 28 and 42 was 19% and 20%, respectively. The prevalence of new intramammary infection rate in N nvax group on days 28 and 42 was 33% and 30%, respectively. In SC vax group, the bacterial growth rate on days 28 and 42 was 44% and 35%, respectively. In SC nvax group, the bacterial growth rate on days 28 and 42 was 27% and 32%, respectively. There was no statistically significant effect of vaccination on any of the studied milk composition parameters. This is a preliminary study that indicated a possible protective effect of vaccination against mastitis in sheep. Further, case-controlled studies are indicated to estimate the level of immunity this vaccine provides to vaccinated sheep.

[Analysis of Koch phenomenon of Mycobacterium tuberculosis-infected guinea pigs vaccinated with recombinant tuberculosis vaccine AEC/BC02].

Science.gov (United States)

Lu, J B; Cheng, B W; Deng, H Q; Su, C; Shen, X B; Du, W X; Yang, L; Wang, G Z; Xu, M

2016-07-01

To observe the Koch phenomenon of Mycobacterium tuberculosis(MTB)-infected guinea pigs after vaccinated with killed H37Ra bacteria or tuberculosis vaccine candidate AEC/BC02. Eighteen guinea pigs were challenged subcutaneously with 5.0×10(3) CFU MTB and after 40 days were divided into 3 groups (6 per group): NS group, AEC/BC02 group and H37Ra group, which were injected intramuscularly 3 times at 1 day interval with normal saline, AEC/BC02 vaccine and killed H37Ra bacteria respectively. Three weeks after the first vaccination, all guinea pigs were sacrificed to evaluate gross pathological scores for liver, spleen and lung, bacterial loads in lung and spleen, and lung inflammation. The gross pathological score in H37Ra group (48±26) was lower than that in NS group(62±15), but the difference was not significant (t=1.093, P=0.300). The AEC/BC02 group had a significantly lower gross pathological score (36±15) than NS group (t=2.980, P=0.014). No significant difference between H37Ra group and AEC/BC02 group was observed (t=1.009, P=0.337). The spleen bacterial load [(5.31±0.80) log10 CFU]in H37Ra group was slightly lower than that in NS group[(5.57±0.75) log10 CFU] but the difference was not significant (t=1.581, P=0.574). In AEC/BC02 group bacterial load in the spleen was (4.64±0.64) log10 CFU and significantly lower than NS group (t=2.306, P=0.044) and no significant difference between H37Ra group and AEC/BC02 group was observed (t=1.602, P=0.140). Meanwhile, the lung bacterial load in AEC/BC02 group was (3.71±1.01) log10 CFU and in H37Ra group was (3.82±1.25) log10 CFU. Compared to (4.15±0.69) log10 CFU in the NS group, no significant differences were found (t=0.881, P=0.399; t=0.566, P=0.584, respectively). For the lung inflammation, the inflamed areas in H37Ra group were significantly larger [(33.0±4.4%)] than those in both NS group [(14.8±8.4) %, t=4.719, P=0.001] and AEC/BC02 group [(14.8±8.4) %, t=3.616, P=0.005], and no significant differences were

Non-cellulosic polysaccharides from cotton fibre are differently impacted by textile processing

DEFF Research Database (Denmark)

Runavot, Jean-Luc; Guo, Xiaoyuan; Willats, William George Tycho

2014-01-01

-cellulosic cotton fibre polysaccharides during different steps of cotton textile processing using GC-MS, HPLC and comprehensive microarray polymer profiling to obtain monosaccharide and polysaccharide amounts and linkage compositions. Additionally, in situ detection was used to obtain information on polysaccharide......Cotton fibre is mainly composed of cellulose, although non-cellulosic polysaccharides play key roles during fibre development and are still present in the harvested fibre. This study aimed at determining the fate of non-cellulosic polysaccharides during cotton textile processing. We analyzed non...... localization and accessibility. We show that pectic and hemicellulosic polysaccharide levels decrease during cotton textile processing and that some processing steps have more impact than others. Pectins and arabinose-containing polysaccharides are strongly impacted by the chemical treatments, with most being...

Polysaccharides isolated from Açaí fruit induce innate immune responses.

Directory of Open Access Journals (Sweden)

Jeff Holderness

2011-02-01

Full Text Available The Açaí (Acai fruit is a popular nutritional supplement that purportedly enhances immune system function. These anecdotal claims are supported by limited studies describing immune responses to the Acai polyphenol fraction. Previously, we characterized γδ T cell responses to both polyphenol and polysaccharide fractions from several plant-derived nutritional supplements. Similar polyphenol and polysaccharide fractions are found in Acai fruit. Thus, we hypothesized that one or both of these fractions could activate γδ T cells. Contrary to previous reports, we did not identify agonist activity in the polyphenol fraction; however, the Acai polysaccharide fraction induced robust γδ T cell stimulatory activity in human, mouse, and bovine PBMC cultures. To characterize the immune response to Acai polysaccharides, we fractionated the crude polysaccharide preparation and tested these fractions for activity in human PBMC cultures. The largest Acai polysaccharides were the most active in vitro as indicated by activation of myeloid and γδ T cells. When delivered in vivo, Acai polysaccharide induced myeloid cell recruitment and IL-12 production. These results define innate immune responses induced by the polysaccharide component of Acai and have implications for the treatment of asthma and infectious disease.

Improving the Immunogenicity of the Mycobacterium bovis BCG Vaccine by Non-Genetic Bacterial Surface Decoration Using the Avidin-Biotin System.

Directory of Open Access Journals (Sweden)

Ting-Yu Angela Liao

Full Text Available Current strategies to improve the current BCG vaccine attempt to over-express genes encoding specific M. tuberculosis (Mtb antigens and/or regulators of antigen presentation function, which indeed have the potential to reshape BCG in many ways. However, these approaches often face serious difficulties, in particular the efficiency and stability of gene expression via nucleic acid complementation and safety concerns associated with the introduction of exogenous DNA. As an alternative, we developed a novel non-genetic approach for rapid and efficient display of exogenous proteins on bacterial cell surface. The technology involves expression of proteins of interest in fusion with a mutant version of monomeric avidin that has the feature of reversible binding to biotin. Fusion proteins are then used to decorate the surface of biotinylated BCG. Surface coating of BCG with recombinant proteins was highly reproducible and stable. It also resisted to the freeze-drying shock routinely used in manufacturing conventional BCG. Modifications of BCG surface did not affect its growth in culture media neither its survival within the host cell. Macrophages phagocytized coated BCG bacteria, which efficiently delivered their surface cargo of avidin fusion proteins to MHC class I and class II antigen presentation compartments. Thereafter, chimeric proteins corresponding to a surrogate antigen derived from ovalbumin and the Mtb specific ESAT6 antigen were generated and tested for immunogenicity in vaccinated mice. We found that BCG displaying ovalbumin antigen induces an immune response with a magnitude similar to that induced by BCG genetically expressing the same surrogate antigen. We also found that BCG decorated with Mtb specific antigen ESAT6 successfully induces the expansion of specific T cell responses. This novel technology, therefore, represents a practical and effective alternative to DNA-based gene expression for upgrading the current BCG vaccine.

Improving the Immunogenicity of the Mycobacterium bovis BCG Vaccine by Non-Genetic Bacterial Surface Decoration Using the Avidin-Biotin System.

Science.gov (United States)

Liao, Ting-Yu Angela; Lau, Alice; Joseph, Sunil; Hytönen, Vesa; Hmama, Zakaria

2015-01-01

Current strategies to improve the current BCG vaccine attempt to over-express genes encoding specific M. tuberculosis (Mtb) antigens and/or regulators of antigen presentation function, which indeed have the potential to reshape BCG in many ways. However, these approaches often face serious difficulties, in particular the efficiency and stability of gene expression via nucleic acid complementation and safety concerns associated with the introduction of exogenous DNA. As an alternative, we developed a novel non-genetic approach for rapid and efficient display of exogenous proteins on bacterial cell surface. The technology involves expression of proteins of interest in fusion with a mutant version of monomeric avidin that has the feature of reversible binding to biotin. Fusion proteins are then used to decorate the surface of biotinylated BCG. Surface coating of BCG with recombinant proteins was highly reproducible and stable. It also resisted to the freeze-drying shock routinely used in manufacturing conventional BCG. Modifications of BCG surface did not affect its growth in culture media neither its survival within the host cell. Macrophages phagocytized coated BCG bacteria, which efficiently delivered their surface cargo of avidin fusion proteins to MHC class I and class II antigen presentation compartments. Thereafter, chimeric proteins corresponding to a surrogate antigen derived from ovalbumin and the Mtb specific ESAT6 antigen were generated and tested for immunogenicity in vaccinated mice. We found that BCG displaying ovalbumin antigen induces an immune response with a magnitude similar to that induced by BCG genetically expressing the same surrogate antigen. We also found that BCG decorated with Mtb specific antigen ESAT6 successfully induces the expansion of specific T cell responses. This novel technology, therefore, represents a practical and effective alternative to DNA-based gene expression for upgrading the current BCG vaccine.

Mapping the polysaccharide degradation potential of Aspergillus niger

Science.gov (United States)

2012-01-01

Background The degradation of plant materials by enzymes is an industry of increasing importance. For sustainable production of second generation biofuels and other products of industrial biotechnology, efficient degradation of non-edible plant polysaccharides such as hemicellulose is required. For each type of hemicellulose, a complex mixture of enzymes is required for complete conversion to fermentable monosaccharides. In plant-biomass degrading fungi, these enzymes are regulated and released by complex regulatory structures. In this study, we present a methodology for evaluating the potential of a given fungus for polysaccharide degradation. Results Through the compilation of information from 203 articles, we have systematized knowledge on the structure and degradation of 16 major types of plant polysaccharides to form a graphical overview. As a case example, we have combined this with a list of 188 genes coding for carbohydrate-active enzymes from Aspergillus niger, thus forming an analysis framework, which can be queried. Combination of this information network with gene expression analysis on mono- and polysaccharide substrates has allowed elucidation of concerted gene expression from this organism. One such example is the identification of a full set of extracellular polysaccharide-acting genes for the degradation of oat spelt xylan. Conclusions The mapping of plant polysaccharide structures along with the corresponding enzymatic activities is a powerful framework for expression analysis of carbohydrate-active enzymes. Applying this network-based approach, we provide the first genome-scale characterization of all genes coding for carbohydrate-active enzymes identified in A. niger. PMID:22799883

The Use of Xanthan Gum as Vaccine Adjuvant: An Evaluation of Immunostimulatory Potential in BALB/c Mice and Cytotoxicity In Vitro.

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Schuch, Rodrigo Andrade; Oliveira, Thaís Larré; Collares, Thaís Farias; Monte, Leonardo Garcia; Inda, Guilherme Roig; Dellagostin, Odir Antonio; Vendruscolo, Claire Tondo; Moreira, Angelita da Silveira; Hartwig, Daiane Drawanz

2017-01-01

The successful production of new, safe, and effective vaccines that generate immunological memory is directly related to adjuvant feature, which is responsible for increasing and/or modulating the immune response. Several compounds display adjuvant activity, including carbohydrates. These compounds play important roles in the immune response, as well as having biocompatible properties in vaccine formulations. One such carbohydrate is xanthan gum, a polysaccharide that is produced by the plant-pathogenic bacterium Xanthomonas spp., which has adjuvant attributes. This study evaluated the immune response induced by xanthan gum associated with ovalbumin in BALB/c mice, which were subcutaneously immunized, in terms of antibody production (IgG1, IgG2a, IgG2b, and IgG3), and assessed the levels of IFN- γ in the splenocyte culture using indirect ELISA. Furthermore, we investigated in vitro cytotoxicity of xanthan in the embryo fibroblasts cell line of the NIH/3T3 mouse by MTT assay and propidium iodide uptake assay. The mice immunized with ovalbumin plus xanthan gum exhibited higher antibody IgG1 responses than control groups. Furthermore, the xanthan polysaccharide was capable of increasing the immunogenicity of antigens by producing IFN- γ and did not exhibit cytotoxicity effects in NIH/3T3 mouse fibroblast cells, considered a promising candidate for vaccine adjuvant.

The Use of Xanthan Gum as Vaccine Adjuvant: An Evaluation of Immunostimulatory Potential in BALB/c Mice and Cytotoxicity In Vitro

Directory of Open Access Journals (Sweden)

Rodrigo Andrade Schuch

2017-01-01

Full Text Available The successful production of new, safe, and effective vaccines that generate immunological memory is directly related to adjuvant feature, which is responsible for increasing and/or modulating the immune response. Several compounds display adjuvant activity, including carbohydrates. These compounds play important roles in the immune response, as well as having biocompatible properties in vaccine formulations. One such carbohydrate is xanthan gum, a polysaccharide that is produced by the plant-pathogenic bacterium Xanthomonas spp., which has adjuvant attributes. This study evaluated the immune response induced by xanthan gum associated with ovalbumin in BALB/c mice, which were subcutaneously immunized, in terms of antibody production (IgG1, IgG2a, IgG2b, and IgG3, and assessed the levels of IFN-γ in the splenocyte culture using indirect ELISA. Furthermore, we investigated in vitro cytotoxicity of xanthan in the embryo fibroblasts cell line of the NIH/3T3 mouse by MTT assay and propidium iodide uptake assay. The mice immunized with ovalbumin plus xanthan gum exhibited higher antibody IgG1 responses than control groups. Furthermore, the xanthan polysaccharide was capable of increasing the immunogenicity of antigens by producing IFN-γ and did not exhibit cytotoxicity effects in NIH/3T3 mouse fibroblast cells, considered a promising candidate for vaccine adjuvant.

The cost-effectiveness of alternative vaccination strategies for polyvalent meningococcal vaccines in Burkina Faso: A transmission dynamic modeling study.

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Yaesoubi, Reza; Trotter, Caroline; Colijn, Caroline; Yaesoubi, Maziar; Colombini, Anaïs; Resch, Stephen; Kristiansen, Paul A; LaForce, F Marc; Cohen, Ted

2018-01-01

The introduction of a conjugate vaccine for serogroup A Neisseria meningitidis has dramatically reduced disease in the African meningitis belt. In this context, important questions remain about the performance of different vaccine policies that target remaining serogroups. Here, we estimate the health impact and cost associated with several alternative vaccination policies in Burkina Faso. We developed and calibrated a mathematical model of meningococcal transmission to project the disability-adjusted life years (DALYs) averted and costs associated with the current Base policy (serogroup A conjugate vaccination at 9 months, as part of the Expanded Program on Immunization [EPI], plus district-specific reactive vaccination campaigns using polyvalent meningococcal polysaccharide [PMP] vaccine in response to outbreaks) and three alternative policies: (1) Base Prime: novel polyvalent meningococcal conjugate (PMC) vaccine replaces the serogroup A conjugate in EPI and is also used in reactive campaigns; (2) Prevention 1: PMC used in EPI and in a nationwide catch-up campaign for 1-18-year-olds; and (3) Prevention 2: Prevention 1, except the nationwide campaign includes individuals up to 29 years old. Over a 30-year simulation period, Prevention 2 would avert 78% of the meningococcal cases (95% prediction interval: 63%-90%) expected under the Base policy if serogroup A is not replaced by remaining serogroups after elimination, and would avert 87% (77%-93%) of meningococcal cases if complete strain replacement occurs. Compared to the Base policy and at the PMC vaccine price of US$4 per dose, strategies that use PMC vaccine (i.e., Base Prime and Preventions 1 and 2) are expected to be cost saving if strain replacement occurs, and would cost US$51 (-US$236, US$490), US$188 (-US$97, US$626), and US$246 (-US$53, US$703) per DALY averted, respectively, if strain replacement does not occur. An important potential limitation of our study is the simplifying assumption that all

Bacillus subtilis biofilm induction by plant polysaccharides.

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Beauregard, Pascale B; Chai, Yunrong; Vlamakis, Hera; Losick, Richard; Kolter, Roberto

2013-04-23

Bacillus subtilis is a plant-beneficial Gram-positive bacterium widely used as a biofertilizer. However, relatively little is known regarding the molecular processes underlying this bacterium's ability to colonize roots. In contrast, much is known about how this bacterium forms matrix-enclosed multicellular communities (biofilms) in vitro. Here, we show that, when B. subtilis colonizes Arabidopsis thaliana roots it forms biofilms that depend on the same matrix genes required in vitro. B. subtilis biofilm formation was triggered by certain plant polysaccharides. These polysaccharides served as a signal for biofilm formation transduced via the kinases controlling the phosphorylation state of the master regulator Spo0A. In addition, plant polysaccharides are used as a source of sugars for the synthesis of the matrix exopolysaccharide. The bacterium's response to plant polysaccharides was observed across several different strains of the species, some of which are known to have beneficial effects on plants. These observations provide evidence that biofilm genes are crucial for Arabidopsis root colonization by B. subtilis and provide insights into how matrix synthesis may be triggered by this plant.

Vaccination evokes gender-dependent protection against tularemia infection in C57BL/6Tac mice.

Science.gov (United States)

Sunagar, Raju; Kumar, Sudeep; Franz, Brian J; Gosselin, Edmund J

2016-06-17

Francisella tularensis (Ft) is a Category A biothreat agent for which there currently is no FDA-approved vaccine. Thus, there is a substantial effort underway to develop an effective tularemia vaccine. While it is well established that gender can significantly impact susceptibility to primary infection, the impact of gender on vaccine efficacy is not well established. Thus, development of a successful vaccine against tularemia will require an understanding of the impact gender has on vaccine-induced protection against this organism. In this study, a role for gender in vaccine-induced protection following Ft challenge is identified for the first time. In the present study, mucosal vaccination with inactivated Ft (iFt) LVS elicited gender-based protection in C57BL/6Tac mice against respiratory challenge with Ft LVS. Specifically, vaccinated male mice were more susceptible to subsequent Ft LVS challenge. This increased susceptibility in male mice correlated with increased bacterial burden, increased tissue inflammation, and increased proinflammatory cytokine production late in post-challenge infection. In contrast, improved survival of iFt-vaccinated female mice correlated with reduced bacterial burden and enhanced levels of Ft-specific Abs in serum and broncho-alveolar lavage (BAL) fluid post-challenge. Furthermore, vaccination with a live attenuated vaccine consisting of an Ft LVS superoxide dismutase (SodB) mutant, which has proven efficacious against the highly virulent Ft SchuS4 strain, demonstrated similar gender bias in protection post-Ft SchuS4 challenge. Of particular significance is the fact that these are the first studies to demonstrate that gender differences impact disease outcome in the case of lethal respiratory tularemia following mucosal vaccination. In addition, these studies further emphasize the fact that gender differences must be a serious consideration in any future tularemia vaccine development studies. Copyright © 2016 Elsevier Ltd. All

Extraction, purification and antioxidant activities of the polysaccharides from maca (Lepidium meyenii).

Science.gov (United States)

Zha, Shenghua; Zhao, Qingsheng; Chen, Jinjin; Wang, Liwei; Zhang, Guifeng; Zhang, Hong; Zhao, Bing

2014-10-13

Water-soluble polysaccharides were separated from maca (Lepidium meyenii) aqueous extract (MAE). The crude polysaccharides were deproteinized by Sevag method. During the preparation process of maca polysaccharides, amylase and glucoamylase effectively removed starch in maca polysaccharides. Four Lepidium meyenii polysaccharides (LMPs) were obtained by changing the concentration of ethanol in the process of polysaccharide precipitation. All of the LMPs were composed of rhamnose, arabinose, glucose and galactose. Antioxidant activity tests revealed that LMP-60 showed good capability of scavenging hydroxyl free radical and superoxide radical at 2.0mg/mL, the scavenging rate was 52.9% and 85.8%, respectively. Therefore, the results showed that maca polysaccharides had a high antioxidant activity and could be explored as the source of bioactive compounds. Copyright © 2014 Elsevier Ltd. All rights reserved.

Use of a booster dose of capsular group C meningococcal glycoconjugate vaccine to demonstrate immunologic memory in children primed with one or two vaccine doses in infancy.

Science.gov (United States)

Pace, David; Khatami, Ameneh; Attard-Montalto, Simon; Voysey, Merryn; Finn, Adam; Faust, Saul N; Heath, Paul T; Borrow, Ray; Snape, Matthew D; Pollard, Andrew J

2016-12-07

Use of a polysaccharide vaccine challenge to demonstrate immunologic memory after priming with capsular group C meningococcal conjugate vaccines (MenCC) risks induction of immunologic hyporesponsiveness. For this reason, MenCC vaccines are now used as probes of immunologic memory, however, no studies have demonstrated their ability to distinguish primed from unprimed children. This study was part of a randomised controlled trial investigating the immunogenicity of a booster dose of the combined Haemophilus influenzae type b and MenC-tetanus toxoid vaccine (Hib-MenC-TT) in infants receiving reduced dose MenCC vaccine priming schedules (one MenC-CRM/MenC-TT or two MenC-CRM vaccine doses) compared with an unprimed group. Antibody kinetics were studied in a subset of 269 children by measuring changes in the MenC serum bactericidal antibody, using rabbit complement, (MenC rSBA) titres and MenC specific IgG memory B-cells before and at 6 and 28days following the 12month booster vaccination. At 6days after the 12monthMenCC vaccine, the rise in MenC rSBA titres and MenC specific IgG memory B-cells of the primed groups were significantly higher than the infant MenCC naïve group. Participants primed with one MenC-TT dose had the highest increase in MenC rSBA titres compared with all other groups. The MenC rSBA titres at the 28th compared with the 6th day after boosting was significantly higher in those primed with a single MenC-TT/MenC-CRM vaccine in infancy compared with those who were not primed or who were primed with two doses of the MenC-CRM vaccine. Immunologic memory can be demonstrated by a MenCC booster vaccination but is affected by the type and number of MenCC doses used for infant priming. The MenC rSBA responses can be used to demonstrate successful immunologic priming. Copyright © 2016 Elsevier Ltd. All rights reserved.

Detection of Inulin, a Prebiotic Polysaccharide, in Maple Syrup.

Science.gov (United States)

Sun, Jiadong; Ma, Hang; Seeram, Navindra P; Rowley, David C

2016-09-28

Maple syrup is a widely consumed plant-derived natural sweetener produced by concentrating xylem sap collected from certain maple (Acer) species. During thermal evaporation of water, natural phytochemical components are concentrated in maple syrup. The polymeric components from maple syrup were isolated by ethanol precipitation, dialysis, and anion exchange chromatography and structurally characterized by glycosyl composition analysis, glycosyl linkage analysis, and nuclear magnetic resonance spectroscopy. Among the maple syrup polysaccharides, one neutral polysaccharide was characterized as inulin with a broad molecular weight distribution, representing the first isolation of this prebiotic carbohydrate from a xylem sap. In addition, two acidic polysaccharides with structural similarity were identified as arabinogalactans derived from rhamnogalacturonan type I pectic polysaccharides.

Veterinary vaccine nanotechnology: pulmonary and nasal delivery in livestock animals.

Science.gov (United States)

Calderon-Nieva, Daniella; Goonewardene, Kalhari Bandara; Gomis, Susantha; Foldvari, Marianna

2017-08-01

Veterinary vaccine development has several similarities with human vaccine development to improve the overall health and well-being of species. However, veterinary goals lean more toward feasible large-scale administration methods and low cost to high benefit immunization. Since the respiratory mucosa is easily accessible and most infectious agents begin their infection cycle at the mucosa, immunization through the respiratory route has been a highly attractive vaccine delivery strategy against infectious diseases. Additionally, vaccines administered via the respiratory mucosa could lower costs by removing the need of trained medical personnel, and lowering doses yet achieving similar or increased immune stimulation. The respiratory route often brings challenges in antigen delivery efficiency with enough potency to induce immunity. Nanoparticle (NP) technology has been shown to enhance immune activation by producing higher antibody titers and protection. Although specific mechanisms between NPs and biological membranes are still under investigation, physical parameters such as particle size and shape, as well as biological tissue distribution including mucociliary clearance influence the protection and delivery of antigens to the site of action and uptake by target cells. For respiratory delivery, various biomaterials such as mucoadhesive polymers, lipids, and polysaccharides have shown enhanced antibody production or protection in comparison to antigen alone. This review presents promising NPs administered via the nasal or pulmonary routes for veterinary applications specifically focusing on livestock animals including poultry.

Protective immunity induced by the vaccination of recombinant Proteus mirabilis OmpA expressed in Pichia pastoris.