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Sample records for 23-valent polysaccharide vaccine

  1. Safety and immunogenicity of a single dose 23-valent pneumococcal polysaccharide vaccine in Russian subjects.

    PubMed

    Ciprero, Karen; Zykov, Kirill A; Briko, Nikolay I; Shekar, Tulin; Sterling, Tina M; Bitieva, Elizaveta; Stek, Jon E; Musey, Luwy

    2016-08-02

    Pneumococcal infection is a major cause of pneumonia, bacteremia, and meningitis. Incidence of pneumococcal disease (PD) varies worldwide. The 23-valent pneumococcal polysaccharide vaccine (PPV23) displays an acceptable safety profile and has been demonstrated cost-effective in reducing burden of PD.

  2. 23-Valent Pneumococcal Polysaccharide Vaccine Uptake in the United States Air Force HIV Program.

    PubMed

    Ocampo, Thad F; Le, Tuan; Matthews, Peter E; Okulicz, Jason F

    2016-07-01

    Streptococcus pneumoniae infection is a predominant cause of bacterial infection in HIV-infected individuals. However, reported rates of pneumococcal vaccination with 23-valent polysaccharide vaccine (PPV23) are variable. We evaluated uptake of PPV23 in patients diagnosed with HIV between 1996 and 2012 (n = 507) in the United States Air Force, a centralized HIV program with free access to care including vaccines and medications. A total of 411 (81.1%) patients received at least 1 PPV23 dose. The PPV23 vaccination within 1 year of diagnosis was greater for those diagnosed between 2004 and 2012 (n = 184, 86%) compared with 1996 to 2003 (n = 104, 56.5%; P < .001). For those with ≥6 years of follow-up, receipt of a second recommended PPV23 dose was greater for those diagnosed between 1996 and 2003 (n = 52, 57.8%) compared with 2004 to 2012 (n = 9, 28.1%; P = .004). Although first PPV23 vaccination was high in recent years, process improvement efforts are underway to overcome barriers and improve uptake of pneumococcal vaccines in our program.

  3. Expression of hBD-2 induced by 23-valent pneumococcal polysaccharide vaccine, Haemophilus influenzae type b vaccine and split influenza virus vaccine.

    PubMed

    Shen, Zhenwei; Lei, Han

    2012-10-01

    Human β-defensin-2 (hBD-2) is an antimicrobial peptide with high activity and broad spectrum activity. hBD-2 expression may be highly elevated by microorganisms and inflammation. We reported that the majority of common vaccines used, including 23-valent pneumococcal polysaccharide vaccine, Haemophilus influenzae type b vaccine and split influenza virus vaccine, could induce the expression of hBD-2 in epithelial cells. Among them, the 23-valent pneumococcal polysaccharide vaccine was effective at a lower concentration (0.5 µg/ml), while Haemophilus influenzae type b vaccine and split influenza virus vaccine were effective at the concentration of 1 µg/ml. However, bacteriostatic experiments revealed that the split influenza virus vaccine was capable of inducing the highest antimicrobial activity. The medium of the 23-valent pneumococcal polysaccharide vaccine treatment group had a higher antimicrobial activity than the medium of the Haemophilus influenzae type b vaccine treatment group. The transcriptional regulator of hBD-2, that is, the NF-κB subunit, had a high level of activity, while the normal epithelial cells showed barely detectable activity, indicating that these vaccines have potential for clinical application.

  4. Cost-Effectiveness Analysis of Universal Vaccination of Adults Aged 60 Years with 23-Valent Pneumococcal Polysaccharide Vaccine versus Current Practice in Brazil

    PubMed Central

    de Soárez, Patrícia Coelho; Sartori, Ana Marli Christovam; Freitas, Angela Carvalho; Nishikawa, Álvaro Mitsunori; Novaes, Hillegonda Maria Dutilh

    2015-01-01

    Objective To evaluate the cost-effectiveness of introducing universal vaccination of adults aged 60 years with the 23-valent pneumococcal polysaccharide vaccine (PPV23) into the National Immunization Program (NIP) in Brazil. Methods Economic evaluation using a Markov model to compare two strategies: (1) universal vaccination of adults aged 60 years with one dose of PPV23 and 2) current practice (vaccination of institutionalized elderly and elderly with underlying diseases). The perspective was from the health system and society. Temporal horizon was 10 years. Discount rate of 5% was applied to costs and benefits. Clinical syndromes of interest were invasive pneumococcal disease (IPD) including meningitis, sepsis and others and pneumonia. Vaccine efficacy against IPD was obtained from a meta-analysis of randomized control trials and randomized studies, whereas vaccine effectiveness against pneumonia was obtained from cohort studies. Resource utilization and costs were obtained from the Brazilian Health Information Systems. The primary outcome was cost per life year saved (LYS). Univariate and multivariate sensitivity analysis were performed. Results The universal vaccination strategy avoided 7,810 hospitalizations and 514 deaths, saving 3,787 years of life and costing a total of USD$31,507,012 and USD$44,548,180, respectively, from the health system and societal perspective. The universal immunization would result in ICERs of USD$1,297 per LYS, from the perspective of the health system, and USD$904 per LYS, from the societal perspective. Conclusion The results suggest that universal vaccination of adults aged 60 years with the 23-valent pneumococcal polysaccharide vaccine (PPV23) is a very cost-effective intervention for preventing hospitalization and deaths for IPD and pneumonia is this age group in Brazil. PMID:26114297

  5. Elderly-onset neuromyelitis optica which developed after the diagnosis of prostate adenocarcinoma and relapsed after a 23-valent pneumococcal polysaccharide vaccination.

    PubMed

    Kitazawa, Yu; Warabi, Yoko; Bandoh, Mitsuaki; Takahashi, Toshiyuki; Matsubara, Shiro

    2012-01-01

    We report a case of elderly-onset neuromyelitis optica (NMO) positive for the anti-aquaporin-4 (AQP-4) antibody; symptoms developed after the diagnosis of prostate adenocarcinoma and relapsed after a 23-valent pneumococcal polysaccharide vaccination. We suggest that activation of CD4-positive T cells and secretion of interferon-gamma induced by adenocarcinoma and complement activation induced by vaccination are responsible for the onset and relapse of NMO, even if a patient is positive for the anti-AQP-4 antibody. This case supports the previous experimental finding that the anti-AQP-4 antibody does not cause NMO-like lesions when injected alone, but does so after the induction of T cell-mediated experimental autoimmune encephalomyelitis or when co-injected with human complement.

  6. Vaccination of adults with 23-valent pneumococcal polysaccharide vaccine induces robust antibody responses against pneumococcal serotypes associated with serious clinical outcomes

    PubMed Central

    Ciprero, Karen L.; Marchese, Rocio D.; Richard, Patrick; Baudin, Martine; Sterling, Tina M.; Manoff, Susan B.; Radley, David; Stek, Jon E.; Soubeyrand, Benoît; Grabenstein, John D.; Samson, Sandrine I.; Musey, Luwy K.

    2016-01-01

    ABSTRACT PNEUMOVAX™ 23, a 23-valent polysaccharide pneumococcal vaccine (PPV23), covers 65% to 91% of the isolates recovered from adult cases of invasive pneumococcal disease. Several studies have demonstrated that pneumococcal serotypes 31, 11A, 35F, 17F, 3, 16F, 19F, 15B, and 10A are associated with higher case-fatality or meningitis rates than other pneumococcal serotypes. This study (U05-PnPS-403; EudraCT: 2008-003648-12) evaluated the immune response followings administration of PPV23 for 4 of these serotypes (10A, 11A, 15B, and 17F), that are included in PPV23 but not in licensed pneumococcal conjugate vaccines. Serotype-specific IgG geometric mean concentrations (GMCs) and geometric mean fold-rises (GMFRs) for these 4 serotypes were measured by a validated enzyme-linked immunosorbent assay (ELISA) in 104 subjects >50 y of age who were enrolled in a study evaluating the safety and immunogenicity of a single-dose of PPV23. At 1 month post-vaccination, GMCs for serotypes10A, 11A, 15B and 17F were 6.5, 4.3, 14.7, and 5.1 µg/mL, respectively. GMFRs from baseline were 9.0, 4.5, 8.4, and 11.5, respectively. The percentages of subjects achieving >2-fold increases in IgG GMCs between pre-vaccination and 1 month post-vaccination were 90%, 85%, 88% and 89%, respectively. In conclusion, PPV23 induces a robust immune response in adults to pneumococcal serotypes 10A, 11A, 15B, and 17F, which have been associated with elevated case-fatality or meningitis rates. PMID:27002793

  7. Effectiveness of the 23-Valent Pneumococcal Polysaccharide Vaccine (PPV23) against Pneumococcal Disease in the Elderly: Systematic Review and Meta-Analysis

    PubMed Central

    Remschmidt, Cornelius; Harder, Thomas; Hummers-Pradier, Eva; Wichmann, Ole; Bogdan, Christian

    2017-01-01

    Background Routine vaccination of elderly people against pneumococcal diseases is recommended in many countries. National guidelines differ, recommending either the 23-valent polysaccharide vaccine (PPV23), the 13-valent conjugate vaccine (PCV13) or both. Considering the ongoing debate on the effectiveness of PPV23, we performed a systematic literature review and meta-analysis of the vaccine efficacy/effectiveness (VE) of PPV23 against invasive pneumococcal disease (IPD) and pneumococcal pneumonia in adults aged ≥60 years living in industrialized countries. Methods We searched for pertinent clinical trials and observational studies in databases MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, and Cochrane Database of Systematic Reviews. We assessed the risk of bias of individual studies using the Cochrane Risk of Bias tool for randomized controlled trials and the Newcastle-Ottawa Scale for observational studies. We rated the overall quality of the evidence by GRADE criteria. We performed meta-analyses of studies grouped by outcome and study design using random-effects models. We applied a sensitivity analysis excluding studies with high risk of bias. Results We identified 17 eligible studies. Pooled VE against IPD (by any serotype) was 73% (95%CI: 10–92%) in four clinical trials, 45% (95%CI: 15–65%) in three cohort studies, and 59% (95%CI: 35–74%) in three case-control studies. After excluding studies with high risk of bias, pooled VE against pneumococcal pneumonia (by any serotype) was 64% (95%CI: 35–80%) in two clinical trials and 48% (95%CI: 25–63%) in two cohort studies. Higher VE estimates in trials (follow-up ~2.5 years) than in observational studies (follow-up ~5 years) may indicate waning protection. Unlike previous meta-analyses, we excluded two trials with high risk of bias regarding the outcome pneumococcal pneumonia, because diagnosis was based on serologic methods with insufficient specificity. Conclusions Our meta

  8. Comparison of immunogenicity and safety of an influenza vaccine administered concomitantly with a 13-valent pneumococcal conjugate vaccine or 23-valent polysaccharide pneumococcal vaccine in the elderly

    PubMed Central

    2017-01-01

    Purpose Previous studies have demonstrated the immunogenicity and safety of the co-administration of the trivalent inactivated influenza vaccine (IIV3) with the polysaccharide pneumococcal vaccine (PPV) or pneumococcal conjugate vaccine (PCV). However, there is no direct comparison study that evaluates the immunogenicity and safety of IIV3 given concomitantly with PCV13 or PPV23 in the elderly. Materials and Methods During the 2012-2013 influenza vaccination period, 224 healthy elderly volunteers aged 65 years and older randomly received IIV3 given concomitantly with either PCV13 (PCV13+IIV3) or PPV23 (PPV23+IIV3) in a 1:1 ratio. Serum hemagglutination-inhibiting antibodies for IIV3 were measured at the time of vaccination and 1 month after vaccination. Adverse events were recorded prospectively in a clinical diary during a 7-day period. Results A total of 220 participants blood samples for analysis of immunogenicity and kept a clinical diary for safety analysis (PCV13+IIV3, n=110; PPV23+IIV3, n=110). One month after vaccination, both groups satisfied the Committee for Medical Products for Human Use criteria for A/H1N1, A/H3N2 and B strains, showing comparable seroprotection rates, seroconversion rates and geometric mean titer fold. The assessments of immunogenicity were similar in both groups. The most common local and systemic reactions were pain at the injection site and generalized myalgia. They were generally mild or moderate in intensity. The adverse events were not statistically different between the two groups. Conclusion PCV13+IIV3 and PPV23+IIV3 demonstrated similar immunogenicity and safety in the elderly. PMID:28168172

  9. Effectiveness of vaccination with 23-valent pneumococcal polysaccharide vaccine in preventing hospitalization with laboratory confirmed influenza during the 2009-2010 and 2010-2011 seasons

    PubMed Central

    Domínguez, Angela; Castilla, Jesús; Godoy, Pere; Delgado-Rodríguez, Miguel; Saez, Marc; Soldevila, Núria; Astray, Jenaro; Mayoral, José María; Martín, Vicente; Quintana, José María; González-Candelas, Fernando; Galán, Juan Carlos; Tamames, Sonia; Castro, Ady; Baricot, Maretva; Garín, Olatz; Pumarola, Tomas; Working Group (Spain), CIBERESP Cases and Controls in Pandemic Influenza

    2013-01-01

    Background: Since influenza predisposes to bacterial pneumonia caused by Streptococcus pneumoniae, studies have suggested that pneumococcal vaccination might reduce its occurrence during pandemics. We assessed the effectiveness of pneumococcal polysaccharide vaccination alone and in combination with influenza vaccination in preventing influenza hospitalization during the 2009–2010 pandemic wave and 2010–2011 influenza epidemic. Methods: We conducted a multicenter case-control study in 36 Spanish hospitals. We selected patients aged ≥ 18 y hospitalized with confirmed influenza and two hospitalized controls per case, matched according to age, date of hospitalization and province of residence. Multivariate analysis was performed using conditional logistic regression. Subjects were considered vaccinated if they had received the pneumococcal or seasonal influenza vaccine > 14 d (or > 7 d for pandemic influenza vaccine) before the onset of symptoms (cases) or the onset of symptoms in matched cases (controls). Results: 1187 cases and 2328 controls were included. The adjusted estimate of effectiveness of pneumococcal vaccination in preventing influenza hospitalization was 41% (95% CI 8–62) in all patients and 43% (95% CI 2–78) in patients aged ≥ 65 y. The adjusted effectiveness of dual PPV23 and influenza vaccination was 81% (95% CI 65–90) in all patients and 76% (95% CI 46–90) in patients aged ≥ 65 y. The adjusted effectiveness of influenza vaccination alone was 58% (95% CI 38–72). Conclusions: In elderly people and adults with chronic illness, pneumococcal vaccination may reduce hospitalizations during the influenza season. In people vaccinated with both the influenza and pneumococcal vaccines, the benefit in hospitalizations avoided was greater than in those vaccinated only against influenza. PMID:23563516

  10. Safety and immunogenicity of 13-valent pneumococcal conjugate vaccine formulations with and without aluminum phosphate and comparison of the formulation of choice with 23-valent pneumococcal polysaccharide vaccine in elderly adults

    PubMed Central

    Juergens, Christine; de Villiers, Pierre JT; Moodley, Keymanthri; Jayawardene, Deepthi; Jansen, Kathrin U; Scott, Daniel A; Emini, Emilio A; Gruber, William C; Schmoele-Thoma, Beate

    2014-01-01

    This randomized open-label trial was designed to provide preliminary immunogenicity and safety data to support development of the pediatric 13-valent pneumococcal conjugate vaccine (PCV13) for adults. The aims were to: identify an age-appropriate PCV13 formulation, i.e., with (n = 309) or without (n = 304) aluminum phosphate (AlPO4); compare the selected PCV13 formulation (n = 309) with 23-valent pneumococcal polysaccharide vaccine (PPSV23; n = 301); and, together with an extension study, assess sequential use of pneumococcal vaccines at 1-year intervals in adults aged ≥65 years (n = 105) not pre-vaccinated with PPSV23. Immune responses were measured by ELISA and opsonophagocytic activity assays 1 month postvaccination. Immunoglobulin G responses elicited by PCV13 with AlPO4 and PCV13 without AlPO4 were similar for the majority, and noninferior for all PCV13 serotypes. PCV13 with AlPO4 was generally more reactogenic, with reactions mainly mild or moderate. Thus, PCV13 with AlPO4 (hereafter PCV13) became the selected formulation. Immune responses to PCV13 were noninferior for all but one serotype and for most PCV13 serotypes superior to PPSV23. Vaccine sequence assessments showed that for PCV13/PPSV23, the initial PCV13 dose generally enhanced responses to a subsequent PPSV23 dose, compared with PPSV23 alone. For PCV13/PCV13, a second dose did not enhance the first dose response when given after 1 year. For PCV13/PPSV23/PCV13, priming with PCV13 (vaccination 1) did not protect against lower responses induced by PPSV23 to subsequent PCV13 (vaccination 3). In conclusion, the pediatric PCV13 formulation with AlPO4 is well tolerated and immunogenic in adults, is generally more immunogenic than PPSV23, and subsequent vaccination with PPSV23 is possible if required. PMID:24576885

  11. Immunogenicity and safety of 23-valent pneumococcal polysaccharide vaccine as a booster dose in 12- to 18-month-old children primed with 3 doses of 7-valent pneumococcal conjugate vaccine.

    PubMed

    Thisyakorn, Usa; Chokephaibulkit, Kulkanya; Kosalaraksa, Pope; Benjaponpitak, Suwat; Pancharoen, Chitsanu; Chuenkitmongkol, Sunate

    2014-01-01

    The current study examined the safety and immunogenicity of 23-valent pneumococcal capsular polysaccharide vaccine (Pneumo23(®) [PPV23], Sanofi Pasteur) as a booster dose in 12- to 18-month-old children primed with heptavalent pneumococcal vaccine (PCV7; Prevnar(®), Pfizer). This was a randomized, observer-blinded, 2-arm, controlled, multicenter phase III study performed in Thailand to assess and describe the immunogenicity and safety of PPV23 as a booster dose in children who had received the 3 primary doses of PCV7, the pneumococcal vaccine available during the study period. Children primed with 3 doses of PCV7 were randomized 1:1 to receive a booster immunization with PPV23 or PCV7. Pneumococcal antibody concentrations were measured by enzyme-linked immunosorbent assay and functional antibody levels by multiplex opsonophagocytosis assay on day 30. A total of 339 children were enrolled. Geometric mean serum antibody concentrations against serotypes common to PCV7 and PPV23 (4, 6B, 9V, 14, 18C, 19F, and 23F) increased in both groups but they were higher for serotypes 4, 9V, 18C, and 19F in the PPV23 group. Opsonization indices increased in both groups for all measured serotypes (1, 6B, 14, 19A, and 23F) and were higher for serotypes 6B, 14, and 23F in the PCV7 group and for serotypes 1 and 19A in PPV23 group. Solicited reactions and unsolicited adverse events were similar in the 2 groups and generally mild and transient. No treatment-related serious adverse events were reported. These results confirm that boosting with PPV23 is immunogenic and well tolerated in healthy toddlers primed with PCV7.

  12. Immunogenicity and safety of 23-valent pneumococcal polysaccharide vaccine as a booster dose in 12- to 18-month-old children primed with 3 doses of 7-valent pneumococcal conjugate vaccine

    PubMed Central

    Thisyakorn, Usa; Chokephaibulkit, Kulkanya; Kosalaraksa, Pope; Benjaponpitak, Suwat; Pancharoen, Chitsanu; Chuenkitmongkol, Sunate

    2014-01-01

    The current study examined the safety and immunogenicity of 23-valent pneumococcal capsular polysaccharide vaccine (Pneumo23® [PPV23], Sanofi Pasteur) as a booster dose in 12- to 18-month-old children primed with heptavalent pneumococcal vaccine (PCV7; Prevnar®, Pfizer). This was a randomized, observer-blinded, 2-arm, controlled, multicenter phase III study performed in Thailand to assess and describe the immunogenicity and safety of PPV23 as a booster dose in children who had received the 3 primary doses of PCV7, the pneumococcal vaccine available during the study period. Children primed with 3 doses of PCV7 were randomized 1:1 to receive a booster immunization with PPV23 or PCV7. Pneumococcal antibody concentrations were measured by enzyme-linked immunosorbent assay and functional antibody levels by multiplex opsonophagocytosis assay on day 30. A total of 339 children were enrolled. Geometric mean serum antibody concentrations against serotypes common to PCV7 and PPV23 (4, 6B, 9V, 14, 18C, 19F, and 23F) increased in both groups but they were higher for serotypes 4, 9V, 18C, and 19F in the PPV23 group. Opsonization indices increased in both groups for all measured serotypes (1, 6B, 14, 19A, and 23F) and were higher for serotypes 6B, 14, and 23F in the PCV7 group and for serotypes 1 and 19A in PPV23 group. Solicited reactions and unsolicited adverse events were similar in the 2 groups and generally mild and transient. No treatment-related serious adverse events were reported. These results confirm that boosting with PPV23 is immunogenic and well tolerated in healthy toddlers primed with PCV7. PMID:25424793

  13. Effectiveness of 23-valent pneumococcal polysaccharide vaccination in preventing community-acquired pneumonia hospitalization and severe outcomes in the elderly in Spain.

    PubMed

    Domínguez, Àngela; Soldevila, Núria; Toledo, Diana; Torner, Núria; Force, Luis; Pérez, María José; Martín, Vicente; Rodríguez-Rojas, Lourdes; Astray, Jenaro; Egurrola, Mikel; Sanz, Francisco; Castilla, Jesús

    2017-01-01

    Pneumococcal pneumonia is a serious cause of morbidity and mortality in the elderly, but investigation of the etiological agent of community-acquired pneumonia (CAP) is not possible in most hospitalized patients. The aim of this study was to estimate the effect of pneumococcal polysaccharide vaccination (PPSV23) in preventing CAP hospitalization and reducing the risk of intensive care unit admission (ICU) and fatal outcomes in hospitalized people aged ≥65 years. We made a multicenter case-control study in 20 Spanish hospitals during 2013-2014 and 2014-2015. We selected patients aged ≥65 years hospitalized with a diagnosis of pneumonia and controls matched by sex, age and date of hospitalization. Multivariate analysis was performed using conditional logistic regression to estimate vaccine effectiveness and unconditional logistic regression to evaluate the reduction in the risk of severe and fatal outcomes. 1895 cases and 1895 controls were included; 13.7% of cases and 14.4% of controls had received PPSV23 in the last five years. The effectiveness of PPSV23 in preventing CAP hospitalization was 15.2% (95% CI -3.1-30.3). The benefit of PPSV23 in avoiding ICU admission or death was 28.1% (95% CI -14.3-56.9) in all patients, 30.9% (95% CI -32.2-67.4) in immunocompetent patients and 26.9% (95% CI -38.6-64.8) in immunocompromised patients. In conclusion, PPSV23 showed a modest trend to avoidance of hospitalizations due to CAP and to the prevention of death or ICU admission in elderly patients hospitalized with a diagnosis of CAP.

  14. Effectiveness of 23-valent pneumococcal polysaccharide vaccination in preventing community-acquired pneumonia hospitalization and severe outcomes in the elderly in Spain

    PubMed Central

    Soldevila, Núria; Toledo, Diana; Torner, Núria; Force, Luis; Pérez, María José; Martín, Vicente; Rodríguez-Rojas, Lourdes; Astray, Jenaro; Egurrola, Mikel; Sanz, Francisco; Castilla, Jesús

    2017-01-01

    Pneumococcal pneumonia is a serious cause of morbidity and mortality in the elderly, but investigation of the etiological agent of community-acquired pneumonia (CAP) is not possible in most hospitalized patients. The aim of this study was to estimate the effect of pneumococcal polysaccharide vaccination (PPSV23) in preventing CAP hospitalization and reducing the risk of intensive care unit admission (ICU) and fatal outcomes in hospitalized people aged ≥65 years. We made a multicenter case-control study in 20 Spanish hospitals during 2013–2014 and 2014–2015. We selected patients aged ≥65 years hospitalized with a diagnosis of pneumonia and controls matched by sex, age and date of hospitalization. Multivariate analysis was performed using conditional logistic regression to estimate vaccine effectiveness and unconditional logistic regression to evaluate the reduction in the risk of severe and fatal outcomes. 1895 cases and 1895 controls were included; 13.7% of cases and 14.4% of controls had received PPSV23 in the last five years. The effectiveness of PPSV23 in preventing CAP hospitalization was 15.2% (95% CI -3.1–30.3). The benefit of PPSV23 in avoiding ICU admission or death was 28.1% (95% CI -14.3–56.9) in all patients, 30.9% (95% CI -32.2–67.4) in immunocompetent patients and 26.9% (95% CI -38.6–64.8) in immunocompromised patients. In conclusion, PPSV23 showed a modest trend to avoidance of hospitalizations due to CAP and to the prevention of death or ICU admission in elderly patients hospitalized with a diagnosis of CAP. PMID:28187206

  15. Immunogenicity and safety of a 23-valent pneumococcal polysaccharide vaccine in Chinese healthy population aged >2 years: A randomized, double-blinded, active control, phase III trial

    PubMed Central

    Kong, Yujia; Zhang, Wei; Jiang, Zhiwei; Wang, Ling; Li, Chanjuan; Li, Yanping; Xia, Jielai

    2015-01-01

    Streptococcus pneumoniae is an important pathogen causing invasive diseases such as sepsis, meningitis, and pneumonia. Vaccines have become the most effective way to prevent pneumococcal infections. This phase III trial was designed to evaluate the immunogenicity and safety of a 23-valent pneumococcal polysaccharide vaccine in Chinese healthy population aged >2 years. We conducted a randomized, double-blinded, active-controlled, multicenter trial in which 1660 healthy population (>2 years of age) were randomly assigned in a 1 : 1 ratio to receive 2 intramuscular doses of either the treatment vaccine or the active control vaccine, PNEUMOVAX 23. The surveillance period was 30 days. The primary end point was the 2-fold increase rate of anti-pneumococcal antibody for all 23 included serotypes in each group. In the intention-to-treat cohort, the 2-fold increase rate of anti-pneumococcal antibody for 23 included serotypes varied from 62.47% to 97.01% in the treatment group, and from 51.49% to 95.77% in the control group. According to −10% non-inferiority margin and 95% confidence intervals of rate difference, almost all included serotypes of the treatment group reached non-inferiority to control group except for serotype 6B, the lower limit of rate difference of which was −10.00%, equal to the non-inferiority margin. The 2-fold increase rates of anti-pneumococcal antibody were significantly higher in the treatment group for serotype 2, 3, 4, 10A, 11A and 20. Furthermore, for all 23 serotypes, IgG geometric mean concentrations (GMCs) at day 30 were significantly higher in treatment group for serotype 2, 3, 4, 9V, 10A, 11A, 15B, 18C, 19A, 22F and 33F. Higher geometric mean fold increase (GMFI) were also observed in the treatment group correspondingly. Serious adverse events occurred in 3 of 830 participants in the treatment group (0.36%) and 2 of 830 participants in the control group (0.24%). No death occurred during the trial. The frequencies of both solicited and

  16. Immunogenicity and Tolerance of a 7-Valent Pneumococcal Conjugate Vaccine in Nonresponders to the 23-Valent Pneumococcal Vaccine

    PubMed Central

    Zielen, S.; Bühring, I.; Strnad, N.; Reichenbach, J.; Hofmann, D.

    2000-01-01

    There is still a lack of effective vaccination strategies for patients with a deficient antibody response to bacterial polysaccharide antigens. In an open trial, we evaluated the immunogenicity and tolerance of a new 7-valent pneumococcal conjugate vaccine in 22 infection-prone nonresponders to pneumococcal polysaccharide vaccine and 21 controls. In the patient group, nonresponsiveness was confirmed by repeated vaccination with a 23-valent pneumococcal polysaccharide vaccine. The study protocol provided two doses of the pneumococcal conjugate vaccine, given 4 to 6 weeks apart, for both groups. The antibody response was determined before each vaccination and on follow-up by an enzyme-linked immunosorbent assay and compared to the response in a functional opsonophagocytosis assay. Patients showed a significantly lower postvaccination immune response for all serotypes than did controls. The postvaccination response was serotype dependent. A median titer of >1 μg/ml in patients was recorded only for serotypes 4, 9V, 14, and 19F, which are known to be more immunogenic than serotypes 6B, 18C, and 23F. In the patient group, 70% responded to serotype 19F (Pnc 19F), 65% responded to Pnc 14 and 4, 60% responded to Pnc 9V, 55% responded to Pnc 18C, 50% responded to Pnc 23F, and 25% responded to Pnc 6B. In the control group >95% of individuals showed a titer of >1 μg/ml to every serotype. The vaccine was tolerated well, and no major side effects have been reported. The new pneumococcal conjugate vaccine is clearly more immunogenic in previous nonresponders than is the 23-valent pneumococcal vaccine. Immunization with a pneumococcal conjugate vaccine should be considered as a strategy to protect high-risk patients. PMID:10678957

  17. Anaphylaxis to the 23-valent pneumococcal vaccine: a second explored case by means of immediate-reading skin tests with pneumococcal vaccines.

    PubMed

    Ponvert, C; Scheinmann, P; de Blic, J

    2010-12-06

    Anaphylaxis to pneumococcal vaccines is rare. In the only one child with anaphylaxis to a first injection of the 23-valent pneumococcal vaccine that has been explored, skin tests and specific IgE determination diagnosed immediate-type hypersensitivity to pneumococcal antigens. We report the case of a child who tolerated three injections of the 7-valent pneumococcal vaccine, but experienced anaphylaxis to a fourth injection of the 23-valent vaccine. Immediate responses in skin tests diagnosed immediate-type hypersensitivity to the two vaccines. Immunizations with the 7-valent pneumococcal vaccine may induce IgE-dependent sensitization to pneumococcal antigens, responsible for anaphylaxis to subsequent injections of pneumococcal vaccines.

  18. Lack of Effectiveness of the 23-Valent Polysaccharide Pneumococcal Vaccine in Reducing All-Cause Pneumonias Among Healthy Young Military Recruits: A Randomized, Double-Blind, Placebo-Controlled Trial

    DTIC Science & Technology

    2015-01-08

    his pathogen [14]. Civilian cost-benefit and cost-effectiveness studies performed rior to this study suggested that vaccination against pneumococ- al...pneumonia would create net health improvements in every ge group and that vaccination programs for those considered at igh risk were economically...justified [22,23]. Beutels and Postma emonstrated that vaccination of those between 65 and 75 years f age, immunocompromised individuals, and military

  19. Relationship between public subsidies and vaccination rates with the 23-valent pneumococcal vaccine in elderly persons, including the influence of the free vaccination campaign after the Great East Japan Earthquake.

    PubMed

    Naito, Toshio; Matsuda, Naoto; Tanei, Mika; Watanabe, Yukiko; Watanabe, Akira

    2014-07-01

    Low vaccination rates with pneumococcal vaccine in elderly persons in Japan are thought to be related to low levels of public subsidy. To identify strategies to increase future pneumococcal vaccination rates, we examined the relationship between public subsidies and vaccination rates. We also investigated the influence of free vaccinations after the 2011 Great East Japan Earthquake on vaccination rates in the three Tohoku prefectures of Japan. We surveyed a total of 1742 municipalities in Japan about whether public subsidies were available and their monetary amount. Vaccination rates with the 23-valent pneumococcal vaccine were calculated as the "cumulative amount shipped to each municipality divided by the population aged ≥65 years." There were no subsidies in 773 municipalities (44.4%). In those municipalities with public subsidies, larger subsidies were significantly associated with elevated vaccination rates (p < 0.0001). Compared to a mean vaccination rate of 25.4% throughout Japan, the vaccination rate was 52.1% in municipalities where the full cost was subsidized. The three prefectures (Iwate, Miyagi, and Fukushima) most affected by the Great East Japan Earthquake ranked as the top three prefectures for vaccination rates in Japan, presumably as a result of the free vaccination campaign for disaster victims. Our findings show that public subsidies play an important role in increasing the vaccination rate. The free vaccinations given to disaster victims after the Great East Japan Earthquake helped to achieve extremely high vaccination rates in the three Tohoku prefectures. We suggest that such public subsidies should be promoted throughout Japan.

  20. Polysaccharide-Based Vaccines

    NASA Astrophysics Data System (ADS)

    Santana, Violeta Fernández; Balbin, Yury Valdés; Calderón, Janoi Chang; Icart, Luis Peña; Verez-Bencomo, Vicente

    Capsular polysaccharides (CPS) and lipopolysaccharides from bacteria are employed for the production of vaccines against human diseases. Initial development of CPS as a vaccine was followed by the development and introduction of conjugate polysaccharide-protein vaccines. The principles leading to both developments are reviewed.

  1. Experience with pneumococcal polysaccharide conjugate vaccine (conjugated to CRM197 carrier protein) in children and adults.

    PubMed

    Durando, P; Faust, S N; Fletcher, M; Krizova, P; Torres, A; Welte, T

    2013-10-01

    Streptococcus pneumoniae-related infections are a major cause of morbidity and mortality in people of all ages worldwide. Pneumococcal vaccine development started in 1911 with a whole cell vaccine and more recently multivalent plain polysaccharide and polysaccharide conjugate vaccines have been developed. The recent vaccines rely on capsular polysaccharide antigens to induce serotype-specific immune responses. We summarize here the presentations on pneumococcal polysaccharide conjugate vaccine (conjugated to CRM197 carrier protein) given during the integrated symposium organized and funded by Pfizer International Operations during the 22nd European Congress of Clinical Microbiology and Infectious Diseases (ECCMID) 31 March to 3 April 2012, London, UK. A dramatic reduction in the incidence of invasive pneumococcal diseases (IPD) due to vaccine serotypes (VST-IPD) has been reported since the introduction of a hepta-valent pneumococcal conjugate vaccine (PCV7). An indirect (herd) effect has been demonstrated to be associated with PCV7 infant vaccination programmes, with many studies reporting reductions in VST-IPD in populations that are not eligible for PCV7 vaccination. Since 2010, a 13-valent pneumococcal conjugate vaccine (PCV13) has been introduced into national immunization programmes and results from early surveillance suggest that this vaccine also has an impact on the serotypes unique to PCV13, as well as continuing to protect against the PCV7 serotypes. Data from a passive surveillance system in Europe in 2009, for instance, showed that the highest incidence of IPD remains in those aged >65 years and in children <5 years. PCV13 has now been licensed for vaccination of adults >50 years based on safety and immunogenicity data; an efficacy trial is being conducted. Regardless of previous pneumococcal vaccination status, if the use of 23-valent polysaccharide is considered appropriate, it is recommended to give PCV13 first. Novel immunization strategies remain

  2. A comparison of multiple regimens of pneumococcal polysaccharide-meningococcal outer membrane protein complex conjugate vaccine and pneumococcal polysaccharide vaccine in toddlers.

    PubMed

    Blum, M D; Dagan, R; Mendelman, P M; Pinsk, V; Giordani, M; Li, S; Bohidar, N; McNeely, T B

    2000-05-08

    Children who had been randomized to receive one dose of either heptavalent pneumococcal polysaccharide-meningococcal outer membrane protein complex conjugate vaccine (PCV) or 23-valent pneumococcal polysaccharide vaccine (PN23) at 12, 15, or 18 months of age were subsequently randomized to receive a booster injection of either PCV or PN23 12 months later. For those children who received a priming dose of PCV (N=75) compared to PN23 (N=48) at 12, 15, or 18 months of age, higher serum antibody concentrations were achieved 1 month following a booster injection of either PCV or PN23 for all serotypes tested (p<0.001). Within the group of children receiving a priming dose of PCV, those children who received a booster dose of PN23 developed higher serum antibody concentrations for four of the seven serotypes tested and similar opsonic antibody titers to serotype 6B, yet more frequent erythema (p=0.030) and pain or soreness (p=0.024) at the injection site compared to those boosted with PCV. In conclusion, a single dose of PCV at 12-18 months of age primed for responses to booster doses of either PCV or PN23 12 months later. For those children who received a priming dose of PCV, boosting with PN23 resulted in more frequent injection site pain and erythema than boosting with PCV, yet higher antibody concentrations for most of the serotypes tested.

  3. Cost-effectiveness analysis of pneumococcal polysaccharide vaccination from age 60 in São Paulo State, Brazil

    PubMed Central

    Neto, Joao Tonolio; Gagliardi, Anna; Pinho, Amanda; Durand, Laure; Fonseca, Marcelo

    2011-01-01

    Vaccination of adults aged 60 years and older against Streptococcus pneumonia is not recommended in Brazil. The 23-valent polysaccharide pneumococcal vaccine (PPV23) is only available for institutionalized persons or with underlying diseases despite the substantial medical and economic burden related to pneumococcal infections in adults over than 59 years. The study aimed at evaluating the cost effectiveness of implementing a large PPV program in this population. This analysis was performed using a static decision tree model. Demographic and epidemiological data were obtained from Brazilian official sources and international literature. Economic data were obtained from a study performed in 2007 in a public and a private hospital located in Sao Paulo. Vaccination was assumed to protect for 5 years with 60% effectiveness against bacteremic pneumococcal pneumonia (BPP) and 21% effectiveness against non bacteremic pneumococcal pneumonia (NBPP). Deterministic and sensitivity analyses were performed. The pneumococcal polysaccharide vaccination saved 5,218 life year gained (LYG). The vaccination program was found to be cost effective in the social security and public health care perspectives with a mean incremental cost-effectiveness ratio of R$10,887 and R$8,281 per LYG respectively. Results were sensitive to the vaccine effectiveness against NBPP, the incidence and case-fatality rate of NBPP. From a societal perspective, PPV23 program for adults 60 and older was found to be cost-saving. Pneumococcal polysaccharide vaccination is clinically and economically favored over the present vaccination strategy, in which persons aged over 59 years in Sao Paulo have not been vaccinated. PMID:21941088

  4. Nanoengineering of vaccines using natural polysaccharides.

    PubMed

    Cordeiro, Ana Sara; Alonso, María José; de la Fuente, María

    2015-11-01

    Currently, there are over 70 licensed vaccines, which prevent the pathogenesis of around 30 viruses and bacteria. Nevertheless, there are still important challenges in this area, which include the development of more active, non-invasive, and thermo-resistant vaccines. Important biotechnological advances have led to safer subunit antigens, such as proteins, peptides, and nucleic acids. However, their limited immunogenicity has demanded potent adjuvants that can strengthen the immune response. Particulate nanocarriers hold a high potential as adjuvants in vaccination. Due to their pathogen-like size and structure, they can enhance immune responses by mimicking the natural infection process. Additionally, they can be tailored for non-invasive mucosal administration (needle-free vaccination), and control the delivery of the associated antigens to a specific location and for prolonged times, opening room for single-dose vaccination. Moreover, they allow co-association of immunostimulatory molecules to improve the overall adjuvant capacity. The natural and ubiquitous character of polysaccharides, together with their intrinsic immunomodulating properties, their biocompatibility, and biodegradability, justify their interest in the engineering of nanovaccines. In this review, we aim to provide a state-of-the-art overview regarding the application of nanotechnology in vaccine delivery, with a focus on the most recent advances in the development and application of polysaccharide-based antigen nanocarriers.

  5. Serogroup quantitation of multivalent polysaccharide and polysaccharide-conjugate meningococcal vaccines from China.

    PubMed

    Cook, Matthew C; Gibeault, Sabrina; Filippenko, Vasilisa; Ye, Qiang; Wang, Junzhi; Kunkel, Jeremy P

    2013-07-01

    The active components of most meningococcal vaccines are four antigenic serogroup capsular polysaccharides (A, C, Y, W135). The vaccines, monovalent or multivalent mixtures of either free polysaccharides or polysaccharides conjugated to antigenic carrier proteins, may be in liquid or lyophilised formulations, with or without excipients. Acid hydrolysis and chromatographic methods for serogroup quantitation, which were previously optimised and qualified using polysaccharide-based standards and a narrow range of real vaccines, are here challenged with multiple lots of a broad assortment of additional multivalent polysaccharide-based meningococcal vaccine products. Centrifugal filtration successfully removed all interfering lactose excipient without loss of polysaccharides to allow for the determination of Y and W135 serogroups. Replicate operations by three different analysts indicated high method reproducibility. Results indicated some lot-to-lot and product-to-product variations. However, all vaccines were within general specifications for each serogroup polysaccharide, with the exception of all lots of one polysaccharide vaccine - which by these methods were found to be deficient in the serogroup A component only. These robust techniques are very useful for the evaluation of antigen content and consistency of manufacture. The deformulation, hydrolysis and chromatographic methods may be adaptable for the evaluation of other types of polysaccharide-based vaccines.

  6. Polysaccharides, mimotopes and vaccines for fungal and encapsulated pathogens.

    PubMed

    Pirofski, L A

    2001-09-01

    Vaccination is a rational alternative to treatment for Cryptococcus neoformans infections, as these infections are currently intractable in immunocompromised (including HIV-infected) individuals. Vaccines composed of the cryptococcal capsular polysaccharide glucuronoxylomannan (GXM), the key C. neoformans virulence factor, elicit protective antibodies in mice, although deleterious antibodies can also be induced. By contrast, polysaccharides are poor immunogens in HIV-infected humans and others with B-cell defects. Peptide mimotopes of GXM can induce protective immunity to C. neoformans in mice, however, our knowledge of the mechanisms of mimotope-induced protection is incomplete and further work is needed if polysaccharide- or mimotope-based vaccines are to be used to manage C. neoformans infection.

  7. Conjugate and polysaccharide pneumococcal vaccines do not improve initial response of the polysaccharide vaccine in HIV-infected adults.

    PubMed

    Peñaranda, Maria; Payeras, Antoni; Cambra, Ana; Mila, Joan; Riera, Melcior

    2010-05-15

    This is a randomized trial to compare the immunoglobulin G response and the antibody avidity after two pneumococcal vaccinations, conjugated pneumococcal vaccine (CPV) and polysaccharide pneumococcal vaccine (PPV) 4 weeks after vs. PPV alone in 202 HIV-infected adults. There were no differences in the two strategies, either in the percentage of immunoglobulin G two-fold increase for the CPV included serotypes or immunoglobulin G two-fold increase, reaching the level of 1 microg/ml except for serotype 23F (26% responded after conjugated pneumococcal vaccine + PPV vs. 14% after PPV). No avidity increases were seen in any strategy.

  8. Polysaccharide Responsiveness Is Not Biased by Prior Pneumococcal-Conjugate Vaccination

    PubMed Central

    Bernth-Jensen, Jens Magnus; Søgaard, Ole Schmeltz

    2013-01-01

    Polysaccharide responsiveness is tested by measuring antibody responses to polysaccharide vaccines to diagnose for humoral immunodeficiency. A common assumption is that this responsiveness is biased by any previous exposure to the polysaccharides in the form of protein-coupled polysaccharide vaccines, such as those used in many childhood vaccination programmes. To examine this assumption, we investigated the effect of protein-coupled polysaccharide vaccination on subsequent polysaccharide responsiveness. HIV-infected adults (n = 47) were vaccinated twice with protein-coupled polysaccharides and six months later with pure polysaccharides. We measured immunoglobulin G responses against three polysaccharides present in only the polysaccharide vaccine (non-memory polysaccharides) and seven recurring polysaccharides (memory polysaccharides). Responsiveness was evaluated according to the consensus guidelines published by the American immunology societies. Impaired responsiveness to non-memory polysaccharides was more frequent than to memory polysaccharides (51% versus 28%, P = 0.015), but the individual polysaccharides did not differ in triggering sufficient responses (74% versus 77%, P = 0.53). Closer analysis revealed important shortcomings of the current evaluation guidelines. The interpreted responseś number and their specificities influenced the likelihood of impaired responsiveness in a complex manor. This influence was propelled by the dichotomous approaches inherent to the American guidelines. We therefore define a novel more robust polysaccharide responsiveness measure, the Z-score, which condenses multiple, uniformly weighted responses into one continuous variable. Using the Z-score, responsiveness to non-memory polysaccharides and memory-polysaccharides were found to correlate (R2 = 0.59, P<0.0001). We found that polysaccharide responsiveness was not biased by prior protein-coupled polysaccharide vaccination in HIV-infected adults. Studies in

  9. Quantitative and Qualitative Antibody Responses to Immunization With the Pneumococcal Polysaccharide Vaccine in HIV-Infected Patients After Initiation of Antiretroviral Treatment: Results From a Randomized Clinical Trial

    PubMed Central

    Rodriguez-Barradas, Maria C.; Serpa, Jose A.; Munjal, Iona; Mendoza, Daniel; Rueda, Adriana M.; Mushtaq, Mahwish; Pirofski, Liise-anne

    2015-01-01

    Background. Pneumococcal vaccination is recommended for human immunodeficiency virus-infected (HIV+) persons; the best timing for immunization with respect to initiation of antiretroviral therapy (ART) is unknown. Methods. Double-blind, placebo-controlled trial in HIV+ with CD4+ T cells/µL (CD4) ≥ 200 randomized to receive the 23-valent pneumococcal polysaccharide vaccine (PPV23) or placebo at enrollment, followed by placebo or PPV23, respectively, 9–12 months later (after ≥6 months of ART). Capsular polysaccharide-specific immunoglobin (Ig) G and IgM levels to serotypes 1, 3, 4, 6B, and 23F, and opsonophagocytic killing activity (OPA) to serotypes 6B and 23F were evaluated 1 month postvaccination. Results. One hundred seven subjects were enrolled, 72 (67.3%) were evaluable (36/group). Both groups had significant increases in pre- to 1-month postvaccination IgG levels, but negligible to IgM, and significant increases in OPA titers to serotype 6B but not to 23F. There were no significant differences between groups in serotype-specific IgM or IgG levels or OPA titers. For the combined groups, there was a significant correlation between serotype-specific IgG and OPA titers to 23F but not to 6B. There was no correlation between CD4, viral load and IgG responses. Conclusions. In HIV+ with CD4 ≥ 200, delaying PPV23 until ≥6 months of ART does not improve responses and may lead to missed opportunities for immunization. PMID:25538270

  10. Pneumococcal Vaccination in High-Risk Individuals: Are We Doing It Right?

    PubMed

    Papadatou, Ioanna; Spoulou, Vana

    2016-05-01

    Controversy exists regarding the optimal use of the 23-valent pneumococcal conjugate vaccine for the protection of high-risk individuals, such as children and adults with immunocompromising conditions and the elderly. The effectiveness and immunogenicity of 23-valent pneumococcal polysaccharide vaccine (PPV23) are limited in such high-risk populations compared to the healthy, with meta-analyses failing to provide robust evidence on vaccine efficacy against invasive pneumococcal disease (IPD) or pneumonia. Moreover, several studies have demonstrated a PPV23-induced state of immune tolerance or hyporesponsiveness to subsequent vaccination, where the response to revaccination does not reach the levels achieved with primary vaccination. The clinical significance of hyporesponsiveness is not yet clarified, but attenuated humoral and cellular response could lead to reduced levels of protection and increased susceptibility to pneumococcal disease. As disease epidemiology among high-risk groups shows that we are still in need of maximum serotype coverage, the optimal use of PPV23 in the context of combined conjugate/polysaccharide vaccine schedules is an important priority. In this minireview, we discuss PPV23-induced hyporesponsiveness and its implications in designing highly effective vaccination schedules for the optimal protection for high-risk individuals.

  11. Reversal of age-associated decline in immune response to Pnu-imune vaccine by supplementation with the steroid hormone dehydroepiandrosterone.

    PubMed Central

    Garg, M; Bondada, S

    1993-01-01

    Recently, we reported that murine antibody responses to the 23-valent pneumococcal polysaccharide (Pnu-Imune) vaccine declined with age. Here we present data to support the concept that age-associated immune defects are not only due to intrinsic defects in immune cells but are also due to extrinsic factors emanating from the neuroendocrine system. We found that supplementation with dehydroepiandrosterone, a steroid hormone known to be reduced in the aged, corrects the immune deficiency of aged mice and significantly enhanced their splenic immune responses to the Pnu-Imune vaccine. PMID:8478117

  12. Vaccination with peptide mimotopes produces antibodies recognizing bacterial capsular polysaccharides.

    PubMed

    Wu, Yang; Zhang, Qibo; Sales, Debra; Bianco, Albert Edward; Craig, Alister

    2010-09-07

    A phage display peptide library was screened using a panel of antibodies to the capsular polysaccharides of Streptococcus agalactiae and Neisseria meningitidis. Mimotopes NPDHPRVPTFMA (2-8), LIPFHKHPHHRG (3-2) and EQEIFTNITDRV (G3) showing the highest binding capacity and strongest ELISA reaction were selected for immunization experiments. These mimotopes were either synthesised as oligodeoxynucleotides for DNA immunization or MAP (multiple antigen peptide) for peptide immunization. Mimotope-DNA vaccination, particularly for G3, induced antibodies recognizing a number of target bacteria. This response was seen after the second boost injection and was significantly enhanced by the 3rd boost injection with a Th1-associated profile, which was dominated by IgG2a, followed by IgG1. Mimotope-MAP immunization also produced strong humoral immune responses to the bacteria. Antibodies from G3 DNA immunization reacted with the surface molecules of S. agalactiae, N. meningitidis and Escherichia coli K5 shown by indirect immunofluorescence staining, indicating a possible localization to the bacterial capsule. Antibodies produced both from DNA/MAP immunization reacted with purified bacterial capsular polysaccharides by ELISA and were of high avidity. We have further characterized peptide G3 by a 'tiling path' study to examine the effect of changing individual residues in the peptide in raising antibodies, which showed that the EIFTN motif in G3 was important in generating antibodies to several capsulated bacteria. We conclude that mimotope immunization with DNA or MAP potentially induces strong antibody responses against encapsulated bacteria. It is suggested that the antibody targets are polysaccharides, and these antibodies may cross react at least among closely related species of bacteria.

  13. A universal polysaccharide conjugated vaccine against O111 E. coli.

    PubMed

    Andrade, Gabrielle R; New, Roger R C; Sant'Anna, Osvaldo A; Williams, Neil A; Alves, Rosely C B; Pimenta, Daniel C; Vigerelli, Hugo; Melo, Bruna S; Rocha, Letícia B; Piazza, Roxane M F; Mendonça-Previato, Lucia; Domingos, Marta O

    2014-01-01

    E. coli O111 strains are responsible for outbreaks of blood diarrhea and hemolytic uremic syndrome throughout the world. Because of their phenotypic variability, the development of a vaccine against these strains which targets an antigen that is common to all of them is quite a challenge. Previous results have indicated, however, that O111 LPS is such a candidate, but its toxicity makes LPS forbidden for human use. To overcome this problem, O111 polysaccharides were conjugated either to cytochrome C or to EtxB (a recombinant B subunit of LT) as carrier proteins. The O111-cytochrome C conjugate was incorporated in silica SBA-15 nanoparticles and administered subcutaneously in rabbits, while the O111-EtxB conjugate was incorporated in Vaxcine(TM), an oil-based delivery system, and administered orally in mice. The results showed that one year post-vaccination, the conjugate incorporated in silica SBA-15 generated antibodies in rabbits able to inhibit the adhesion of all categories of O111 E. coli to epithelial cells. Importantly, mice immunized orally with the O111-EtxB conjugate in Vaxcine(TM) generated systemic and mucosal humoral responses against all categories of O111 E. coli as well as antibodies able to inhibit the toxic effect of LT in vitro. In summary, the results obtained by using 2 different approaches indicate that a vaccine that targets the O111 antigen has the potential to prevent diarrhea induced by O111 E. coli strains regardless their mechanism of virulence. They also suggest that a conjugated vaccine that uses EtxB as a carrier protein has potential to combat diarrhea induced by ETEC.

  14. A public health and budget impact analysis of vaccinating at-risk adults and the elderly against pneumococcal diseases in Germany.

    PubMed

    Jiang, Yiling; Gauthier, Aline; Annemans, Lieven; van der Linden, Mark; Nicolas-Spony, Laurence; Bresse, Xavier

    2012-10-01

    To assess the comparative public health and budget impact over 5 years of several pneumococcal vaccination strategies (23-valent pneumococcal polysaccharide vaccine [PPV23] and/or 13-valent pneumococcal conjugate vaccine [PCV13]) in Germany, within the context of changing invasive pneumococcal disease (IPD) incidence over time. A multi-cohort, population-based Markov model was developed. Uncertainty around vaccine effectiveness, costs and IPD incidence change was handled through scenario analyses. Between 2012 and 2016, the introduction of PCV13 in adults, compared with the use of PPV23, would be associated with a net estimated budget increase of €59.7 million (+6.7%) to €151.6 million (+13.7%). Impact on IPD incidence ranged from -113 cases (-0.8%) to +298 cases (+2.8%). Introducing PCV13 in adults is expected to significantly affect healthcare budgets. Adult vaccination with PPV23 remains the optimal vaccination strategy from public health and budget perspectives.

  15. Factors associated with pneumococcal polysaccharide vaccination of the elderly in Spain: A cross-sectional study.

    PubMed

    Domínguez, Angela; Soldevila, Núria; Toledo, Diana; Godoy, Pere; Torner, Núria; Force, Luis; Castilla, Jesús; Mayoral, José María; Tamames, Sonia; Martín, Vicente; Egurrola, Mikel; Sanz, Francisco; Astray, Jenaro; Project Pi12/02079 Working Group

    2016-07-02

    Vaccination of the elderly is an important factor in limiting the impact of pneumonia in the community. The aim of this study was to investigate the factors associated with pneumococcal polysaccharide vaccination in patients aged ≥ 65 years hospitalized for causes unrelated to pneumonia, acute respiratory disease, or influenza-like illness in Spain. We made a cross-sectional study during 2013-2014. A bivariate analysis was performed comparing vaccinated and unvaccinated patients, taking into account sociodemographic variables and risk medical conditions. A multivariate analysis was performed using multilevel regression models. 921 patients were included; 403 (43.8%) had received the pneumococcal vaccine (394 received the polysaccharide vaccine). Visiting the general practitioner ≥ 3 times during the last year (OR = 1.79; 95% CI 1.25-2.57); having received the influenza vaccination in the 2013-14 season (OR = 2.57; 95% CI 1.72-3.84) or in any of the 3 previous seasons (OR = 11.70; 95% CI 7.42-18.45) were associated with receiving the pneumococcal polysaccharide vaccine. Pneumococcal vaccination coverage of hospitalized elderly people is low. The elderly need to be targeted about pneumococcal vaccination and activities that encourage healthcare workers to proactively propose vaccination might be useful. Educational campaigns aimed at the elderly could also help to increase vaccination coverages and reduce the burden of pneumococcal disease in the community.

  16. An evaluation of the immunogenicity and safety of a new trivalent meningococcal polysaccharide vaccine.

    PubMed

    Chandramohan, Daniel; Hodgson, Abraham; Coleman, Paul; Baiden, Rita; Asante, Kwaku; Awine, Elizabeth; Owusu-Agyei, Seth; Boutriau, Dominique; Nelson, Christopher B; Greenwood, Brain

    2007-09-03

    The immunogenicity and safety of a meningococcal trivalent A/C/W135 polysaccharide vaccine was compared with that of a tetravalent A/C/Y/W135 polysaccharide vaccine in a randomised, double blind trial. The study included 360 adults, who received either a trivalent or tetravalent polysaccharide meningococcal vaccine. Antibody responses were determined by serum bactericidal antibody (rSBA) assays prior to vaccination and on day 28 and month 11 after vaccination. The percentage of participants in the trivalent vaccine group who had rSBA titres >or=8 on day 28 post-vaccination against serogroups A, C and W135 meningococci were 99, 98 and 91%, respectively. The corresponding figures in the tetravalent vaccine group were 99, 99 and 90%. The percentage of participants with various cut off levels of rSBA against serogroups A, W135 and C meningococci on day 28 and 11-month post-vaccination and the incidence of adverse events did not differ significantly between the two groups.

  17. Pneumococcal Vaccine to Counter Emerging Infectious Disease Threat in the Military

    DTIC Science & Technology

    2001-12-01

    clinical trial of the currently In 1945, the first successful trial of a polyvalent polysaccha- available 23- valent pneumococcal vaccine . The purpose...December 2001 1088 Pneumococcal Vaccine bers are affected by pneumococcal disease; however, because of Board 35 recommended that the 23- valent ...pnoeumococcal vaccines years studied to date. The efficacy of the conjugate 7- valent Athe bi-oeti peuis cc vacspcilcone, witvaccine in children appears to also

  18. A second controlled field trial of a serogroup A meningococcal polysaccharide vaccine in Alexandria

    PubMed Central

    Wahdan, M. H.; Sallam, S. A.; Hassan, M. N.; Abdel Gawad, A.; Rakha, A. S.; Sippel, J. E.; Hablas, R.; Sanborn, W. R.; Kassem, N. M.; Riad, S. M.; Cvjetanović, B.

    1977-01-01

    The encouraging results of an earlier controlled field trial of the serogroup A meningococcal polysaccharide vaccine in the prevention of clinical disease prompted this study, the aim of which was to evaluate further the effectiveness of another lot of this type of vaccine, the duration of immunity, and the effectiveness against meningococcal carriage. A controlled field trial was carried out in early 1973 on 176 646 schoolchildren 6-15 years of age, of whom half received the serogroup A polysaccharide vaccine and the other half tetanus toxoid as a control. The incidence of cerebrospinal meningitis caused by serogroup A meningococci was 89% lower in the immunized group than in the controls for one year only. With regard to its effect on carriage, the vaccine was found to reduce to less than half the rate of new acquisition of serogroup A meningococci during the period immediately following immunization. The duration of the carrier state was also shortened in the immunized group. PMID:413639

  19. Maternal group B streptococcal immunization: capsular polysaccharide (CPS)-based vaccines and their implications on prevention.

    PubMed

    Palmeiro, Jussara K; De Carvalho, Newton S; Botelho, Ana C N; Fracalanzza, Sérgio E L; Madeira, Humberto M F; Dalla-Costa, Libera M

    2011-05-12

    Group B streptococcal (GBS) capsular polysaccharide (CPS)-based conjugate vaccine, which includes types Ia, Ib, II, III, and V, could potentially prevent neonatal, pediatric, adult, and pregnancy-associated diseases. However, since GBS CPS types included in that vaccine are prevalent serotypes found in North America and Europe, it may not provide the necessary protection for individuals in countries in which other capsular types have been found.

  20. The impact of protein-conjugate polysaccharide vaccines: an endgame for meningitis?

    PubMed Central

    Maiden, Martin C. J.

    2013-01-01

    The development and implementation of conjugate polysaccharide vaccines against invasive bacterial diseases, specifically those caused by the encapsulated bacteria Neisseria meningitidis, Haemophilus influenzae and Streptococcus pneumoniae, has been one of the most effective public health innovations of the last 25 years. These vaccines have resulted in significant reductions in childhood morbidity and mortality worldwide, with their effectiveness due in large part to their ability to induce long-lasting immunity in a range of age groups. At the population level this immunity reduces carriage and interrupts transmission resulting in herd immunity; however, these beneficial effects can be counterbalanced by the selection pressures that immunity against carriage can impose, potentially promoting the emergence and spread of virulent vaccine escape variants. Studies following the implementation of meningococcal serogroup C vaccines improved our understanding of these effects in relation to the biology of accidental pathogens such as the meningococcus. This understanding has enabled the refinement of the implementation of conjugate polysaccharide vaccines against meningitis-associated bacteria, and will be crucial in maintaining and improving vaccine control of these infections. To date there is little evidence for the spread of virulent vaccine escape variants of the meningococcus and H. influenzae, although this has been reported in pneumococci. PMID:23798695

  1. [Pneumococcal disease in adults: Risk levels and vaccine recommendations].

    PubMed

    Vila-Córcoles, Angel; Ochoa-Gondar, Olga

    2017-02-01

    There are currently two anti-pneumococcal vaccines available for use in adults: the classical 23-valent polysaccharide pneumococcal vaccine (PPV23) and the new 13-valent pneumococcal conjugate vaccine (PCV13). The main advantage of the PCV13 is the potentially better immunogenicity, with its major disadvantages being the higher cost and the lower serotype-coverage than the PPV23. The currently available scientific evidence supports the following basic recommendations: (i)among adults with greatest risk (basically asplenia and immunocompromised), a dual vaccination (PCV13+PPV23) is recommended; (ii)among adults with increased risk (basically persons >65years-old and patients 15-64years with chronic pulmonary or heart disease, diabetes and/or alcoholism), a single vaccination with PPV23 is recommended (single dose in primo-vaccinated >65years; re-vaccination at 5-10years in those primo-vaccinated <65years-old); and (iii) in the rest of adults (risk normal/low) vaccination is not recommended.

  2. Meningococcal meningitis in sub-Saharan Africa: the case for mass and routine vaccination with available polysaccharide vaccines.

    PubMed Central

    Robbins, John B.; Schneerson, Rachel; Gotschlich, Emil C.; Mohammed, Idris; Nasidi, Abdulsalami; Chippaux, Jean-Philippe; Bernardino, Luis; Maiga, Moussa A.

    2003-01-01

    Endemic and epidemic group A meningococcal meningitis remains a major cause of morbidity and mortality in sub-Saharan Africa, despite the availability of the safe and inexpensive group A meningococcal polysaccharide vaccine, which is protective at all ages when administered as directed. Despite optimal therapy, meningococcal meningitis has a 10% fatality rate and at least 15% central nervous system damage. WHO's policy of epidemic containment prevents, at best, about 50% of cases and ignores endemic meningitis, which is estimated at 50,000 cases per year. The effectiveness of group A, C, W135, and Y capsular polysaccharides is the basis for recommending universal vaccination with group A meningococcal polysaccharide twice in infancy, followed by the four-valent vaccine in children aged two and six years. This could eliminate epidemic and endemic disease, prepare for the use of conjugates when they become available, and probably could have prevented the recent epidemics of groups A and W135 meningitis in Burkina Faso. PMID:14758435

  3. Next generation protein based Streptococcus pneumoniae vaccines.

    PubMed

    Pichichero, Michael E; Khan, M Nadeem; Xu, Qingfu

    2016-01-01

    All currently available Streptococcus pneumoniae (Spn) vaccines have limitations due to their capsular serotype composition. Both the 23-valent Spn polysaccharide vaccine (PPV) and 7, 10, or 13-valent Spn conjugate vaccines (PCV-7, 10, -13) are serotype-based vaccines and therefore they elicit only serotype-specific immunity. Emergence of replacement Spn strains expressing other serotypes has consistently occurred following introduction of capsular serotype based Spn vaccines. Furthermore, capsular polysaccharide vaccines are less effective in protection against non-bacteremic pneumonia and acute otitis media (AOM) than against invasive pneumococcal disease (IPD). These shortcomings of capsular polysaccharide-based Spn vaccines have created high interest in development of non-serotype specific protein-based vaccines that could be effective in preventing both IPD and non-IPD infections. This review discusses the progress to date on development of Spn protein vaccine candidates that are highly conserved by all Spn strains, are highly conserved, exhibit maximal antigenicity and minimal reactogenicity to replace or complement the current capsule-based vaccines. Key to development of a protein based Spn vaccine is an understanding of Spn pathogenesis. Based on pathogenesis, a protein-based Spn vaccine should include one or more ingredients that reduce NP colonization below a pathogenic inoculum. Elimination of all Spn colonization may not be achievable or even advisable. The level of expression of a target protein antigen during pathogenesis is another key to the success of protein based vaccines.. As with virtually all currently licensed vaccines, production of a serum antibody response in response to protein based vaccines is anticipated to provide protection from Spn infections. A significant advantage that protein vaccine formulations can offer over capsule based vaccination is their potential benefits associated with natural priming and boosting to all strains of

  4. Next generation protein based Streptococcus pneumoniae vaccines

    PubMed Central

    Pichichero, Michael E; Khan, M Nadeem; Xu, Qingfu

    2016-01-01

    All currently available Streptococcus pneumoniae (Spn) vaccines have limitations due to their capsular serotype composition. Both the 23-valent Spn polysaccharide vaccine (PPV) and 7, 10, or 13-valent Spn conjugate vaccines (PCV-7, 10, -13) are serotype-based vaccines and therefore they elicit only serotype-specific immunity. Emergence of replacement Spn strains expressing other serotypes has consistently occurred following introduction of capsular serotype based Spn vaccines. Furthermore, capsular polysaccharide vaccines are less effective in protection against non-bacteremic pneumonia and acute otitis media (AOM) than against invasive pneumococcal disease (IPD). These shortcomings of capsular polysaccharide-based Spn vaccines have created high interest in development of non-serotype specific protein-based vaccines that could be effective in preventing both IPD and non-IPD infections. This review discusses the progress to date on development of Spn protein vaccine candidates that are highly conserved by all Spn strains, are highly conserved, exhibit maximal antigenicity and minimal reactogenicity to replace or complement the current capsule-based vaccines. Key to development of a protein based Spn vaccine is an understanding of Spn pathogenesis. Based on pathogenesis, a protein-based Spn vaccine should include one or more ingredients that reduce NP colonization below a pathogenic inoculum. Elimination of all Spn colonization may not be achievable or even advisable. The level of expression of a target protein antigen during pathogenesis is another key to the success of protein based vaccines.. As with virtually all currently licensed vaccines, production of a serum antibody response in response to protein based vaccines is anticipated to provide protection from Spn infections. A significant advantage that protein vaccine formulations can offer over capsule based vaccination is their potential benefits associated with natural priming and boosting to all strains of

  5. Impaired serotype-specific immune function following pneumococcal vaccination in infants with prior carriage.

    PubMed

    Licciardi, Paul V; Russell, Fiona M; Balloch, Anne; Burton, Robert L; Nahm, Moon H; Gilbert, Gwendolyn; Tang, Mimi L K; Mulholland, Edward K

    2014-04-25

    The impact of prior nasopharyngeal carriage on serotype-specific IgG responses following immunization with pneumococcal conjugate vaccines (PCV) has recently been described. This report extends these findings to describe the attenuation of functional immune responses following 23-valent pneumococcal polysaccharide vaccination (PPS). We report the attenuation of immune responses following booster with the 23-valent pneumococcal polysaccharide vaccination (PPS) in infants with prior nasopharyngeal carriage of Streptococcus pneumoniae. Fijian infants who were part of a phase II randomized, controlled trial of reduced dose PCV7 schedules were the basis of this study. Pneumococcal carriage was determined at 6, 9 and 12 months of age, prior to PPS immunization. Serum samples collected at 18 weeks (post-PCV7), 12 months (pre-PPS), 12.5 months and 17 months (post-PPS) of age were assessed for serotype-specific IgG and opsonophagocytic responses. The most frequently carried serotypes were 6B (N=11), 19F (N=14) and 23F (N=23). Significantly lower serotype-specific IgG for 19F, 23F but not 6B post-PPS were detected in infants with homologous serotype carriage prior to PPS compared with non-carriers (N=230). However, OPA levels for 6B and 23F were lower in infants that carried these serotypes. Pneumococcal carriage with 19F or 23F at any time prior to PPS immunization in infants at 12 months of age who were previously primed with PCV resulted in serotype-specific hyporesponsiveness that persisted until 17 months of age. These results may have implications for the timing of infant vaccine schedules, particularly in high disease burden settings.

  6. The adjuvanticity of Ganoderma lucidum polysaccharide for Newcastle disease vaccine.

    PubMed

    Zhang, Ping; Ding, Ronglong; Jiang, Shanxiang; Ji, Liwei; Pan, Mingming; Liu, Li; Zhang, Wei; Gao, Xiuge; Huang, Wenjuan; Zhang, Guanjun; Peng, Lin; Ji, Hui

    2014-04-01

    The adjuvant activity of GLP was investigated in vitro and in vivo. In vitro experiment, the effects of GLP on chicken peripheral lymphocytes proliferation were compared by MTT assay. The results showed that GLP could significantly enhance lymphocytes proliferation singly or synergistically with ConA. The interferon-gamma (IFN-γ) mRNA levels of chicken peripheral lymphocytes stimulated by GLP synergistically with ConA were measured using fluorescent quantitative PCR. The results showed that GLP could promote interferon-γ mRNA levels in peripheral lymphocytes. In vivo experiment, 175 14-day-old chickens were randomly divided into 7 groups. The chickens except blank control (BC) group were vaccinated with Newcastle disease vaccine, repeated vaccination at 28 days old. At the same time of the first vaccination, the chickens in experimental groups were orally administrated with 5 different doses of GLP respectively, whereas vaccination control (VC) and BC groups were treated with physiological saline, once a day for three successive days. On Day 7, 14, 21 and 28 after the first vaccination, the peripheral lymphocytes proliferation and serum ND antibody titer were determined. The results showed that GLP could significantly promote lymphocyte proliferation and enhance serum antibody titer. The results indicated that GLP may be a novel immunomodulator.

  7. Effectiveness of natural and synthetic complexes of porin and O polysaccharide as vaccines against Brucella abortus in mice.

    PubMed Central

    Winter, A J; Rowe, G E; Duncan, J R; Eis, M J; Widom, J; Ganem, B; Morein, B

    1988-01-01

    A single vaccination of mice with a complex of porin and smooth lipopolysaccharide (porin-S-LPS) extracted from virulent Brucella abortus 2308 provided significant protection (P less than 0.01 to P less than 0.001) against challenge with the same strain, equivalent to that achieved by vaccination with living attenuated B. abortus 19. The porin-S-LPS vaccine given without adjuvant or in several adjuvants (trehalose dimycolate and muramyl dipeptide; the pluronic polymer L-121 and muramyl dipeptide; or complexed with Quil A in immunostimulating complexes) provided equivalent protection. In contrast, one vaccination with porin complexed with rough LPS (porin-R-LPS) from a rough mutant of strain 2308 provided no protection with any adjuvant tested. In one experiment, two inoculations with the porin-R-LPS resulted in a low level of protection, probably owing to priming of the animals for production of O-polysaccharide-specific antibodies. However, one vaccination with rough-strain porin covalently bound to purified O polysaccharide conferred protection equal to that obtained with natural complexes of porin-S-LPS or with living strain 19. A synthetic vaccine containing long chains of O polysaccharide was more effective than one prepared with short chains. Protective vaccines caused the formation of increased concentrations of circulating O-polysaccharide-specific antibodies, although there were individual exceptions to the quantitative association between O-polysaccharide-specific antibodies and protection. Antibodies specific for porin or R-LPS were found in negligible quantities in vaccinated mice. These results provide additional evidence that the O polysaccharide will constitute an essential component of an effective subcellular vaccine against B. abortus and that O-polysaccharide-specific antibodies play an important role in protective immunity in brucellosis. PMID:2844673

  8. Clinical evaluation of group A and group C meningococcal polysaccharide vaccines in infants.

    PubMed Central

    Gold, R; Lepow, M L; Goldschneider, I; Draper, T L; Gotschlich, E C

    1975-01-01

    Group A and group C meningoccal polysaccharide vaccines were evaluated in infants. No significant local or systemic reactions were observed with 908 doses of vaccine given to 396 infants between 3 and 12 mo of age. The antibody response varied with the age of the infant, vaccine dose, molecular weight of vaccine, prior immunization with vaccine, and prior exposure to naturally occurring cross-reactive antigens. Only 7% of 3-mo-old infants had detectable antibody responses to primary immunization with 5-200 mug of A vaccine, presumably because of suppressive effects of high concentrations of maternal anti-A. More than 90% of 7- and 12-mo-old infants responded to A vaccine, achieving geometric mean anti-A concentrations of 0.38 and 0.98 mug/ml, respectively. The dose-response curve was flat between 10 and 200 mug of A vaccine. Geometric mean anti-A concentrations of 2.51 and 4.00 mug/ml were induced in 7- and 12-mo-old infants by booster injections of A vaccine. Approximately 90% of 3-mo-old infants had detectable antibody responses to primary immunization with C vaccine. The 100-mug dose appeared to be optimal, resulting in geometric mean anti-C concentrations of 0.49, 1.55, and 2.64 mug/ml in 3-, 7-, and 12-mo-old infants, respectively. Significant booster responses were not observed with C vaccine. Indeed, except for the 10-mug dose, booster injections of C vaccine in 7- and 12-mo-old infants resulted in lower anti-C concentrations than did primary immunizations. PMID:1202084

  9. Factors Associated with Influenza Vaccination of Hospitalized Elderly Patients in Spain

    PubMed Central

    Domínguez, Àngela; Soldevila, Núria; Toledo, Diana; Godoy, Pere; Castilla, Jesús; Force, Lluís; Morales, María; Mayoral, José María; Egurrola, Mikel; Tamames, Sonia; Martín, Vicente; Astray, Jenaro

    2016-01-01

    Vaccination of the elderly is an important factor in limiting the impact of influenza in the community. The aim of this study was to investigate the factors associated with influenza vaccination coverage in hospitalized patients aged ≥65 years hospitalized due to causes unrelated to influenza in Spain. We carried out a cross-sectional study. Bivariate analysis was performed comparing vaccinated and unvaccinated patients, taking in to account sociodemographic variables and medical risk conditions. Multivariate analysis was performed using multilevel regression models. We included 1038 patients: 602 (58%) had received the influenza vaccine in the 2013–14 season. Three or more general practitioner visits (OR = 1.61; 95% CI 1.19–2.18); influenza vaccination in any of the 3 previous seasons (OR = 13.57; 95% CI 9.45–19.48); and 23-valent pneumococcal polysaccharide vaccination (OR = 1.97; 95% CI 1.38–2.80) were associated with receiving the influenza vaccine. Vaccination coverage of hospitalized elderly people is low in Spain and some predisposing characteristics influence vaccination coverage. Healthcare workers should take these characteristics into account and be encouraged to proactively propose influenza vaccination to all patients aged ≥65 years. PMID:26824383

  10. Factors Associated with Influenza Vaccination of Hospitalized Elderly Patients in Spain.

    PubMed

    Domínguez, Àngela; Soldevila, Núria; Toledo, Diana; Godoy, Pere; Castilla, Jesús; Force, Lluís; Morales, María; Mayoral, José María; Egurrola, Mikel; Tamames, Sonia; Martín, Vicente; Astray, Jenaro

    2016-01-01

    Vaccination of the elderly is an important factor in limiting the impact of influenza in the community. The aim of this study was to investigate the factors associated with influenza vaccination coverage in hospitalized patients aged ≥ 65 years hospitalized due to causes unrelated to influenza in Spain. We carried out a cross-sectional study. Bivariate analysis was performed comparing vaccinated and unvaccinated patients, taking in to account sociodemographic variables and medical risk conditions. Multivariate analysis was performed using multilevel regression models. We included 1038 patients: 602 (58%) had received the influenza vaccine in the 2013-14 season. Three or more general practitioner visits (OR = 1.61; 95% CI 1.19-2.18); influenza vaccination in any of the 3 previous seasons (OR = 13.57; 95% CI 9.45-19.48); and 23-valent pneumococcal polysaccharide vaccination (OR = 1.97; 95% CI 1.38-2.80) were associated with receiving the influenza vaccine. Vaccination coverage of hospitalized elderly people is low in Spain and some predisposing characteristics influence vaccination coverage. Healthcare workers should take these characteristics into account and be encouraged to proactively propose influenza vaccination to all patients aged ≥ 65 years.

  11. Preparation of pneumococcal capsular polysaccharide-protein conjugate vaccines utilizing new fragmentation and conjugation technologies.

    PubMed

    Pawlowski, A; Källenius, G; Svenson, S B

    2000-03-17

    There is a global urgent need for a new efficient and inexpensive vaccine to combat pneumococcal disease, which should also be affordable in developing countries. In view of this need a simple low-cost technique to prepare such a vaccine was developed. The preparation of serotype 14 and 23F pneumococcal capsular polysaccharide (PnPS)-protein conjugates to be included in a forthcoming multivalent PnPS conjugate vaccine is described. Commercial lots of PnPSs produced according to Good Manufacturing Practice from Streptococcus pneumoniae serotype 14 (PS14) and 23F (PS23F) were partially depolymerized by sonication or irradiation in an electron beam accelerator. The PnPS fragments were conjugated to tetanus toxoid (TT) using a recently developed conjugation chemistry. The application of these new simple, efficient and inexpensive fragmentation and conjugation technologies allowed the synthesis of several PnPS-protein conjugates containing PnPS fragments of preselected sizes and differing in the degree of substitution. The PS14TT and PS23FTT conjugate vaccine candidates were characterized chemically and their immunogenicity was evaluated in rabbits and mice. All PnPS conjugate vaccines, unlike the corresponding plain polysaccharides, produced high IgG titres in both animal species. The PS14TT conjugates tended to be more immunogenic than the PS23FTT conjugates. The immune response to the PS14TT conjugates, but not to the PS23FTT conjugates, was related to the size of the conjugated polysaccharide hapten. Both types of conjugates elicited strong booster effects upon secondary immunizations, resulting in high IgG1, IgG2a and IgG2b titres.

  12. Phase I clinical trial of O-Acetylated pectin conjugate, a plant polysaccharide based typhoid vaccine

    PubMed Central

    Szu, Shousun C.; Lin, Kimi F-Y; Hunt, Steven; Chu, Chiayung; Thinh, Nguyen Duc

    2014-01-01

    Background Typhoid fever remains an important cause of morbidity and mortality in the developing countries. Vi capsular polysaccharide conjugate vaccine demonstrated safety and efficacy in young children in high endemic regions. A novel typhoid conjugate vaccine based on plant polysaccharide pectin was studied in a phase I trial. Methods Fruit pectin, having the same carbohydrate backbone structure as Vi, was purified from citrus peel and used as the polysaccharide source to prepare a semi-synthetic typhoid conjugate vaccine. Pectin was chemically O-acetylated (OAcPec) to antigenically resemble Vi and conjugated to carrier protein rEPA, a recombinant exoprotein A from Pseudomonas aeruginosa. 25 healthy volunteers, 18–45 years old, were injected once with OAcPec-rEPA. Safety and IgG antibodies reactive with Vi and pectin were analyzed. Results No vaccine associated serious adverse reaction was reported. Six weeks after the injection of OAcPec-rEPA, 64% of the volunteers elicited >4 fold rise of anti-Vi IgG. At 26 weeks the level declined, but the difference between the levels at 6 and 26 weeks are not statistically significant. There is a direct correlation between the level of anti-Vi IgG before and after the injection (R2 = 0.96). The anti-Vi IgG can be absorbed by Vi, but not by pectin. There was no corresponding increase of anti-pectin after the injection, indicating the antibody response to OAcPec-rEPA was specific to Vi. There is no Vi-rEPA data in US adults for comparison of immune responses. The OAcPec-rEPA elicited significantly less IgG anti-Vi in US adults than those by Vi-rEPA in Vietnamese adults. Conclusion The O-acetylated pectin conjugate, a plant based typhoid vaccine, is safe and immunogenic in adult volunteers. PMID:24657719

  13. Pneumococcal vaccination among HIV-infected adult patients in the era of combination antiretroviral therapy

    PubMed Central

    Lee, Kuan-Yeh; Tsai, Mao-Song; Kuo, Kuang-Che; Tsai, Jen-Chih; Sun, Hsin-Yun; Cheng, Aristine C; Chang, Sui-Yuan; Lee, Chen-Hsiang; Hung, Chien-Ching

    2014-01-01

    HIV-infected patients remain at higher risk for pneumococcal disease than the general population despite immune reconstitution and suppression of HIV replication with combination antiretroviral therapy. Vaccination with 23-valent pneumococcal polysaccharide vaccine (PPV23) composed of T-cell-independent antigens has been recommended to reduce the risk of pneumococcal disease in HIV-infected adults. However, given the heterogeneity of study design, execution and subjects enrolled, studies examining serological responses to PPV23 yielded conflicting results and observational studies of clinical effectiveness only provided moderate evidence to support the routine use of PPV23 in HIV-infected adults. Pneumococcal conjugate vaccine (PCV), with conjugation of the capsular polysaccharide to a protein carrier, is more immunogenic than PPV23 and has been demonstrated to protect against pneumococcal disease in HIV-infected children and recurrent invasive pneumococcal disease in HIV-infected adolescents and adults. Guidelines have recently been revised to recommend that HIV-infected patients aged 19 y or older receive one dose of 13-valent pneumococcal conjugate vaccine (PCV13) followed by a booster vaccination with PPV23. In this paper, we review the studies using different vaccination strategies to improve immunogenicity among HIV-infected adult patients. PMID:25483681

  14. Efficacy trial of Vi polysaccharide vaccine against typhoid fever in south-western China.

    PubMed Central

    Yang, H. H.; Wu, C. G.; Xie, G. Z.; Gu, Q. W.; Wang, B. R.; Wang, L. Y.; Wang, H. F.; Ding, Z. S.; Yang, Y.; Tan, W. S.; Wang, W. Y.; Wang, X. C.; Qin, M.; Wang, J. H.; Tang, H. A.; Jiang, X. M.; Li, Y. H.; Wang, M. L.; Zhang, S. L.; Li, G. L.

    2001-01-01

    OBJECTIVE: To test the efficacy of locally produced Vi vaccine over a time period of longer than one year. METHODS: A double-blinded, randomized field trial was performed in Guangxi Zhuang Autonomous Region in south-western China, using 30 micrograms doses of locally produced Vi. Enrolled subjects were 3-50 years of age, although the majority (92%) were school-aged children, who have the highest rate of typhoid fever in this setting. A total of 131,271 people were systematically allocated a single dose of 30 micrograms of Vi polysaccharide or saline placebo. The study population was followed for 19 months, with passive surveillance conducted in the Ministry of Health and the Regional Health and Anti-epidemic Centre (HAEC). Clinically suspected cases of typhoid fever were confirmed by blood culture, or by serological reaction with O-antigen (Widal tests). FINDINGS: After 19 months, there were 23 culture-confirmed cases of typhoid fever in the placebo group versus 7 cases in the Vi group (Protective efficacy (PE) = 69%; 95% CI = 28%, 87%). Most of the isolates were from school-aged children: 22 cases in the placebo group versus 6 in the Vi group (PE = 72%; 95% CI = 32%, 82%). No serious post-injection reactions were observed. The locally produced Vi polysaccharide vaccine showed levels of protective efficacy similar to those for Vi vaccine produced in industrial countries. CONCLUSION: The slightly higher dose of vaccine did not seem to alter efficacy significantly in China. PMID:11477965

  15. Herpes zoster vaccine. Poorly effective in those who need it most.

    PubMed

    2012-12-01

    The results of a clinical trial suggest that zoster vaccination (Zostavax, Sanofi Pasteur MSD) of 1000 healthy persons aged 60 years or over prevents approximately one case of postherpetic neuralgia each year over the next 3 years. Vaccination is less effective in persons over 70 years of age. The results of another clinical trial suggest that vaccination of 1000 healthy persons aged 50 to 59 years prevents about 5 cases of herpes zoster over the following year. The impact on the frequency of postherpetic neuralgia is not known. The vaccine might not be protective in persons who subsequently become immunocompromised. In the trial in persons aged 50 years or older, 50% of vaccinees had mild local adverse effects. It should be noted that the protocol excluded immunocompromised patients, in whom the live vaccine virus could potentially cause clinically significant infection. In one study, the immune response to the vaccine was lower after simultaneous immunisation with a 23-valent pneumococcal polysaccharide vaccine. This live zoster vaccine is contraindicated in immunocompromised individuals, yet they are at highest risk of severe zoster. In practice, zoster vaccination is not sufficiently effective in the elderly to justify its widespread use.

  16. Cost-effectiveness analysis of pneumococcal conjugate vaccine 13-valent in older adults in Colombia

    PubMed Central

    2014-01-01

    Background Nowadays, there are two vaccination strategies in Colombia to prevent pneumococcal diseases in people over 50 years. Our aim is to estimate cost-effectiveness of pneumococcal conjugate vaccine 13-valent (PCV13) versus pneumococcal polysaccharide vaccine 23-valent (PPSV23) to prevent pneumococcal diseases and their related mortality in people over 50 years old in Colombia. Methods A Markov model was developed with national data, including pneumococcal serotypes distribution in Colombia between 2005 and 2010. Vaccination of a cohort was simulated and a five year time horizon was assumed. Analysis was done from a perspective of a third party payer. Direct costs were provided by a national insurance company; sensitive univariate and probabilistic analysis were done for epidemiological and clinical effectiveness parameters and costs. Results PCV13 avoids 3 560 deaths by pneumococcal infections versus PPSV23 and 4 255 deaths versus no vaccine. PCV13 prevents 79 633 cases by all-cause pneumonia versus PPSV23 and 81 468 cases versus no vaccine. Total costs (healthcare and vaccines costs) with PCV13 would be U.S. $ 97,587,113 cheaper than PPSV23 and it would save U.S. $ 145,196,578 versus no vaccine. Conclusion PCV13 would be a cost-saving strategy in the context of a mass vaccination program in Colombia to people over 50 years old because it would reduce burden of disease and specific mortality by pneumococcal diseases, besides, it saves money versus PPSV23. PMID:24679135

  17. Quantitation of serogroups in multivalent polysaccharide-based meningococcal vaccines: optimisation of hydrolysis conditions and chromatographic methods.

    PubMed

    Cook, Matthew C; Bliu, Alex; Kunkel, Jeremy P

    2013-08-12

    Quantitative determination of the individual polysaccharide components in multivalent meningococcal vaccines is an important step in manufacturing and regulatory control. Current methods are complicated due to the use of multiple chromatographic setups and/or other analytical techniques for the four meningococcal serogroup polysaccharides (A, C, Y, W135). In addition, different methods are sometimes used depending on whether or not the polysaccharide is conjugated to a carrier protein. In an effort to simplify such analyses, hydrolysis conditions were determined for the optimal yield of each characteristic saccharide from the respective repeating units. One condition was identified for mannosamine-6-phosphate from MenA, one for neuraminic acid from MenC, and one for both glucose and galactose from MenY and MenW135, respectively. These conditions, initially assessed for monovalent solutions, were then confirmed for a quadrivalent solution. The monosaccharide products were separated, identified and quantitated using a single HPAEC-PAD protocol, with a customised multi-stage linear gradient eluent profile and one column setup, for determination of all four serogroup components. Comparison to calibration curves constructed from sets of monosaccharide or hydrolysed polysaccharide standards allowed for the quantitation of each characteristic serogroup monosaccharide in polysaccharide and polysaccharide-conjugate vaccines. When required, molecular size separation using a non-cellulosic centrifugal filter device effectively removed all interfering saccharide excipient without loss of serogroup polysaccharides. These methods were used to analyse multiple lots of a number of different monovalent or multivalent real polysaccharide-based vaccine products, in liquid or lyophilised powder formulations, with or without excipients. The methods were demonstrated to be highly reproducible and very useful for the evaluation of antigen content and lot-to-lot consistency of manufacture

  18. Are the pneumococcal polysaccharide vaccines effective? Meta-analysis of the prospective trials

    PubMed Central

    Moore, R Andrew; Wiffen, Philip J; Lipsky, Benjamin A

    2000-01-01

    The objective was to review the evidence of effectiveness of the polyvalent polysaccharide pneumococcal vaccine from prospective properly randomised controlled trials comparing pneumococcal vaccines with placebo in subjects who are immunocompetent and those likely to have an impaired immune system. Databases searched included the Cochrane Library, (issue 2, 2000), MEDLINE (1966-August 2000), PubMed (to August 2000) and EMBASE ( to August 2000). Reference lists of reports and reviews were also searched. To be included in the analysis, a study had to have been a prospective randomised comparison of a polysaccharide pneumococcal vaccine (any valency) and to have a placebo or no treatment comparison group. Papers had to report important clinical outcomes, such as rates of pneumonia, pneumococcal pneumonia, lower respiratory tract infections, pneumonia deaths or bacteraemia. Serological outcomes were not sought. Thirteen randomised comparisons with over 45,000 subjects were identified in an extensive literature review. Eight studies had a quality score of 3 or more on a scale of 1 to 5. In three comparisons with 21,152 immunocompetent subjects (South African gold miners, New Guinea highlanders) pneumococcal vaccination was effective in reducing the incidence of all-cause pneumonia (relative risk 0.56, 95% confidence interval 0.47 to 0.66), pneumococcal pneumonia (0.16; 0.11 to 0.23), pneumonia deaths (0.70; 0.50 to 0.96) and bacteraemia (0.18; 0.09 to 0.34). In ten comparisons in over 24,000 people who were elderly or likely to have impaired immune systems, pneumococcal vaccination was without effect for any outcome. Present guidelines recommend pneumococcal vaccination for "high-risk" groups. There is no evidence from randomised trials that this is of any benefit. PMID:11038265

  19. [CONTEMPORARY CONCEPTION OF IMMUNE RESPONSE ACTIVATION MECHA- NISM BY CONJUGATED POLYSACCHARIDE VACCINES].

    PubMed

    Kolesnikov, A V; Kozyr, A V; Schemyakin, I G; Dyatlov, I A

    2015-01-01

    Vaccination remains the most effective method of control of spread of a whole range of infections of both viral and bacterial nature. Many bacterial pathogens (Streptococcus pneumoniae, Neisseria meningitidis and Haemophilus influenzae) carry polysaccharide capsule on the surface, that is one of the elements of protection from host organism immune system. At the same time, vaccination with bacteria exopolysaccharides (EPS) ensures infection neutralization. Effectiveness of such vaccine prophylaxis is limited by age of the vaccinated, intensity and duration of the immunity, development of secondary immune response. EPS conjugation with protein antigens was known for a long time to ensure activation of T-cell immunity against EPS and formation of secondary immune response. However, detailed studies of mechanism of immunity modulation by a protein partner as part of a glycoconjugate has not been carried out. T-lymphocyte activation was traditionally thought to occur exclusively due to peptide presentation, that are products of processing of protein component of the conjugate. Recently, information, accumulated in the field of natural carbohydrate, glycolipid and glycoprotein antigen presentation to T-cells, has generated interest in studying mechanisms of cell immunity activation by conjugated vaccines. Progress in this field, as well as development of novel chemical and biochemical, including combinative technologies of synthesis and study of these molecules, opens new opportunities for detailed understanding of mechanism of action for conjugated vaccines and creation of glycoconjugates with increased effectiveness of protective action.

  20. Long-term impact of pneumococcal polysaccharide vaccination on nasopharyngeal carriage in children previously vaccinated with various pneumococcal conjugate vaccine regimes.

    PubMed

    Boelsen, Laura K; Dunne, Eileen M; Lamb, Karen E; Bright, Kathryn; Cheung, Yin Bun; Tikoduadua, Lisi; Russell, Fiona M; Mulholland, E Kim; Licciardi, Paul V; Satzke, Catherine

    2015-10-13

    Previously, the Fiji Pneumococcal Project (FiPP) evaluated reduced dose immunization schedules that incorporated pneumococcal protein conjugate and/or polysaccharide vaccine (PCV7 and 23vPPV, respectively). Immune hyporesponsiveness was observed in children vaccinated with 23vPPV at 12 months of age compared with children who did not receive 23vPPV. Here we assess the long-term impact of 23vPPV vaccination on nasopharyngeal carriage rates and densities of Streptococcus pneumoniae, Haemophilus influenzae, Staphylococcus aureus and Moraxella catarrhalis. Nasopharyngeal swabs (n=194) were obtained from healthy children who participated in FiPP (now aged 5-7 years). S. pneumoniae were isolated and identified by standard culture-based methods, and serotyped using latex agglutination and the Quellung reaction. Carriage rates and densities of S. pneumoniae, H. influenzae, S. aureus and M. catarrhalis were determined using real-time quantitative PCR. There were no differences in the rate or density of S. pneumoniae, H. influenzae or M. catarrhalis carriage by PCV7 dose or 23vPPV vaccination in the vaccinated participants overall. However, differences were observed between the two main ethnic groups: Fijian children of Indian descent (Indo-Fijian) were less likely to carry S. pneumoniae, H. influenzae and M. catarrhalis, and there was evidence of a higher carriage rate of S. aureus compared with indigenous Fijian (iTaukei) children. Polysaccharide vaccination appeared to have effects that varied between ethnic groups, with 23vPPV vaccination associated with a higher carriage rate of S. aureus in iTaukei children, while there was a lower carriage rate of S. pneumoniae associated with 23vPPV vaccination in Indo-Fijian children. Overall, polysaccharide vaccination had no long-term impact on pneumococcal carriage, but may have impacted on S. aureus carriage and have varying effects in ethnic groups, suggesting current WHO vaccine schedule recommendations against the use of 23v

  1. A High-Throughput Size Exclusion Chromatography Method to Determine the Molecular Size Distribution of Meningococcal Polysaccharide Vaccine

    PubMed Central

    Khan, Imran; Rahman, K. M. Taufiqur; Siraj, S. M. Saad Us; Karim, Mahbubul; Muktadir, Abdul; Maheshwari, Arpan; Kabir, Md Azizul; Nahar, Zebun

    2016-01-01

    Molecular size distribution of meningococcal polysaccharide vaccine is a readily identifiable parameter that directly correlates with the immunogenicity. In this paper, we report a size exclusion chromatography method to determine the molecular size distribution and distribution coefficient value of meningococcal polysaccharide serogroups A, C, W, and Y in meningococcal polysaccharide (ACWY) vaccines. The analyses were performed on a XK16/70 column packed with sepharose CL-4B with six different batches of Ingovax® ACWY, a meningococcal polysaccharide vaccine produced by Incepta Vaccine Ltd., Bangladesh. A quantitative rocket immunoelectrophoresis assay was employed to determine the polysaccharide contents of each serogroup. The calculated distribution coefficient values of serogroups A, C, W, and Y were found to be 0.26 ± 0.16, 0.21 ± 0.11, 0.21 ± 0.11, and 0.14 ± 0.12, respectively, and met the requirements of British Pharmacopeia. The method was proved to be robust for determining the distribution coefficient values which is an obligatory requirement for vaccine lot release. PMID:27688770

  2. Brucellosis Vaccines: Assessment of Brucella melitensis Lipopolysaccharide Rough Mutants Defective in Core and O-Polysaccharide Synthesis and Export

    PubMed Central

    González, David; Grilló, María-Jesús; De Miguel, María-Jesús; Ali, Tara; Arce-Gorvel, Vilma; Delrue, Rose-May; Conde-Álvarez, Raquel; Muñoz, Pilar; López-Goñi, Ignacio; Iriarte, Maite; Marín, Clara-M.; Weintraub, Andrej; Widmalm, Göran; Zygmunt, Michel; Letesson, Jean-Jacques; Gorvel, Jean-Pierre; Blasco, José-María; Moriyón, Ignacio

    2008-01-01

    Background The brucellae are facultative intracellular bacteria that cause brucellosis, one of the major neglected zoonoses. In endemic areas, vaccination is the only effective way to control this disease. Brucella melitensis Rev 1 is a vaccine effective against the brucellosis of sheep and goat caused by B. melitensis, the commonest source of human infection. However, Rev 1 carries a smooth lipopolysaccharide with an O-polysaccharide that elicits antibodies interfering in serodiagnosis, a major problem in eradication campaigns. Because of this, rough Brucella mutants lacking the O-polysaccharide have been proposed as vaccines. Methodology/Principal Findings To examine the possibilities of rough vaccines, we screened B. melitensis for lipopolysaccharide genes and obtained mutants representing all main rough phenotypes with regard to core oligosaccharide and O-polysaccharide synthesis and export. Using the mouse model, mutants were classified into four attenuation patterns according to their multiplication and persistence in spleens at different doses. In macrophages, mutants belonging to three of these attenuation patterns reached the Brucella characteristic intracellular niche and multiplied intracellularly, suggesting that they could be suitable vaccine candidates. Virulence patterns, intracellular behavior and lipopolysaccharide defects roughly correlated with the degree of protection afforded by the mutants upon intraperitoneal vaccination of mice. However, when vaccination was applied by the subcutaneous route, only two mutants matched the protection obtained with Rev 1 albeit at doses one thousand fold higher than this reference vaccine. These mutants, which were blocked in O-polysaccharide export and accumulated internal O-polysaccharides, stimulated weak anti-smooth lipopolysaccharide antibodies. Conclusions/Significance The results demonstrate that no rough mutant is equal to Rev 1 in laboratory models and question the notion that rough vaccines are

  3. Conjugation of PEG-hexadecane markedly increases the immunogenicity of pneumococcal polysaccharide conjugate vaccine.

    PubMed

    Chang, Xin; Yu, Weili; Ji, Shaoyang; Shen, Lijuan; Tan, Aijuan; Hu, Tao

    2017-02-24

    Streptococcus pneumoniae is a serious Gram-positive pathogen that can lead to an invasive pneumococcal disease with high mortality rate. Pneumococcal capsular polysaccharide (PS) is a key virulence determinant and its immunogenicity can be increased by conjugation with a carrier protein. However, the PS-specific cellular and humoral immunity of pneumococcal conjugate vaccine needs further improvement. Hexadecane (HD) is an element of lipid that decorates the surface of nearly all microbial classes. Polyethylene glycol (PEG)-HD conjugate (PEG-HD) is soluble and can act as an adjuvant. In the present study, a novel pneumococcal polysaccharide conjugate vaccine was prepared by conjugation of tetanus toxoid (TT) portion of PS-TT conjugate (PS-TT) with PEG-HD. As compared with PS-TT, conjugation with PEG-HD led to an 8.0-fold increase in the PS-specific IgG titers. Conjugation with PEG-HD also gave rise to 34.9-, 3.6- and 7.7-fold increase in the IFN-γ, TNF-α and IL-5 levels, respectively. Thus, the conjugated PEG-HD has a stimulatory adjuvant activity to potentiate a robust humoral and cellular immunity. Our proposed conjugate was expected to act as an effective pneumococcal conjugate vaccine for prevention of S. pneumoniae infections.

  4. Vaccination with Astragalus and Ginseng Polysaccharides Improves Immune Response of Chickens against H5N1 Avian Influenza Virus

    PubMed Central

    Kallon, Sanpha; Yu, Xingang

    2016-01-01

    To determine the effect of astragalus and ginseng polysaccharides (APS, GPS) on immune response and improvement of H5N1 vaccine, 360-day-old broilers were randomly divided into 8 groups of 45 chicks, comprising APS groups (1–3); GPS groups (4–6); vaccine group (7); and blank control (8) (without polysaccharide and vaccine). From day 12 after hatch groups 1–3 were given APS and groups 4–6 with GPS both at 100, 200, and 400 (mg/kg), respectively. At day 15 after hatch, groups 1–7 were vaccinated with 0.3 mL H5N1 vaccine subcutaneously; daily weight gain (DWG) and serum Ig antibody (by HI-test) were measured on 3, 7, 14, and 28 days after vaccination. Serum antibody titers and expression of cytokines (IL-2, IL-10, I FN-γ, and TNF) were determined by ELISA and RT-PCR. Results revealed that all the polysaccharide groups were numerically increased in antibody levels and the expression of cytokines was significant (P < 0.05) in the APS and GPS groups compared to corresponding vaccine group and blank control. DWG was higher (P < 0.05) in 400 mg/kg APS groups than control groups. Thus oral supplements of GPS and APS have shown their potential in the improvement of immune response and could be used as adjuvant in a formulation of H5N1 vaccine. PMID:27597953

  5. Immune suppression induced by Vi capsular polysaccharide is overcome by Vi-DT conjugate vaccine.

    PubMed

    An, So Jung; Yoon, Yeon Kyung; Kothari, Sudeep; Kim, Deok Ryun; Kim, Jeong Ah; Kothari, Neha; Lee, Eugene; Park, Tai Hyun; Carbis, Rodney

    2012-02-01

    The influence pre-exposure of mice to Vi capsular polysaccharide, purified from Salmonella enterica Serovar Typhi, on the subsequent immune response induced by a Vi-diphtheria toxoid (Vi-DT) conjugate was evaluated. Vi induced low anti Vi IgG titers with the dominant subclass being IgG3. The Vi-DT conjugate induced high titers of anti Vi IgG with the dominant subclass being IgG1 but with considerable quantities of IgG2a, IgG2b and IgG3. Priming of mice with Vi suppressed the response to a subsequent dose of conjugate and the suppression was overcome by a second dose of conjugate. Priming with conjugate prevented suppression of the anti Vi response and subsequent dosing with Vi raised titers back to previous levels but did not boost to new higher levels. The anti DT IgG response to one dose of conjugate was relatively strong and protracted and continued to rise for 12 weeks, compared to the response to one dose of DT which was poor and peaked at two weeks. The prolonged anti DT response was most likely due to the slow release of DT from the conjugate lattice as it degrades within the mouse resulting in a continuous stimulation of the immune response. The presence of increasing amounts of un-conjugated Vi, up to 50%, administered with the conjugate resulted in increasingly higher levels of both anti Vi and anti DT. Larger amounts of un-conjugated Vi inhibited the anti Vi response. These findings have implications for vaccine quality and a limit for un-conjugated polysaccharide should not exceed 50% and from a vaccine program perspective if the results presented here translate to humans then a Vi conjugate, once it becomes available, should replace Vi polysaccharide vaccines.

  6. Therapeutic efficacy of a conjugate vaccine containing a peptide mimotope of cryptococcal capsular polysaccharide glucuronoxylomannan.

    PubMed

    Datta, Kausik; Lees, Andrew; Pirofski, Liise-anne

    2008-08-01

    Vaccination with P13, a peptide mimotope of the cryptococcal capsular polysaccharide glucuronoxylomannan (GXM), has been shown to confer protection against a subsequent lethal Cryptococcus neoformans challenge. In this study, we sought to investigate whether P13-based vaccines could be effective in an already-established infection. To address this question, we developed a systemic chronic cryptococcal infection model. We vaccinated chronically infected mice with P13-protein conjugates and monitored their survival. Compared to the controls, the conjugates prolonged the survival of chronically infected mice. The degree of protection was a function of the mouse strain (BALB/c or C57BL/6), the carrier protein (tetanus toxoid or diphtheria toxoid), and the route of infection (intraperitoneal or intravenous). Serum GXM levels were correlated with the day of death, but the correlation was driven by the carrier protein and mouse strain. The passive transfer of heat-treated sera from P13 conjugate-vaccinated mice conferred protection to naïve BALB/c mice, indicating that antibody immunity could contribute to protection. The measurement of peripheral blood cytokine (gamma interferon [IFN-gamma], interleukin-10 [IL-10], and IL-6) gene expression showed that P13 conjugate-vaccinated BALB/c and C57BL/6 mice mounted a strong Th2 (IL-10)-like response relative to the Th1 (IFN-gamma)-like response, with the degree depending on the mouse strain and carrier protein. Taken together, our data suggest that a vaccine could hold promise in the setting of chronic cryptococcosis, and that vaccine efficacy could depend on immunomodulation and augmentation of the natural immune response of the host.

  7. Development and validation of a molecular size distribution method for polysaccharide vaccines.

    PubMed

    Clément, G; Dierick, J-F; Lenfant, C; Giffroy, D

    2014-01-01

    Determination of the molecular size distribution of vaccine products by high performance size exclusion chromatography coupled to refractive index detection is important during the manufacturing process. Partial elution of high molecular weight compounds in the void volume of the chromatographic column is responsible for variation in the results obtained with a reference method using a TSK G5000PWXL chromatographic column. GlaxoSmithKline Vaccines has developed an alternative method relying on the selection of a different chromatographic column with a wider separation range and the generation of a dextran calibration curve to determine the optimal molecular weight cut-off values for all tested products. Validation of this method was performed according to The International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH). The new method detected product degradation with the same sensitivity as that observed for the reference method. All validation parameters were within the pre-specified range. Precision (relative standard deviation (RSD) of mean values) was < 5 per cent (intra-assay) and < 10 per cent (inter-assay). Sample recovery was > 70 per cent for all polysaccharide conjugates and for the Haemophilus influenzae type B final container vaccine. All results obtained for robustness met the acceptance criteria defined in the validation protocol (≤ 2 times (RSD) or ≤ 2 per cent difference between the modified and the reference parameter value if RSD = 0 per cent). The new method was shown to be a suitable quality control method for the release and stability follow-up of polysaccharide-containing vaccines. The new method gave comparable results to the reference method, but with less intra- and inter-assay variability.

  8. Comparison of safety and immunogenicity of a Vi polysaccharide typhoid vaccine with a whole-cell killed vaccine in Malaysian Air Force recruits.

    PubMed Central

    Panchanathan, V.; Kumar, S.; Yeap, W.; Devi, S.; Ismail, R.; Sarijan, S.; Sam, S. M.; Jusoh, Z.; Nordin, S.; Leboulleux, D.; Pang, T.

    2001-01-01

    OBJECTIVE: To carry out a comparative study of the safety and immunogenicity of Vi polysaccharide vaccine against whole-cell killed (WCK) typhoid vaccine. METHODS: The study was carried out on young adult recruits (aged 18-25 years) of the Malaysian Air Force. A total of 125 subjects received the Vi polysaccharide vaccine and 114 received the WCK vaccine. FINDINGS: The Vi vaccine was significantly less reactogenic than the WCK vaccine with regard to systemic and local reactions. Following administration of the Vi vaccine, seroconversion rates (defined as the percentage of subjects with a 4-fold rise of baseline antibody level) of 75.5% and 67% were observed at 2 weeks and 6 weeks, respectively, after immunization, compared with 25% and 31.3% among recipients of the WCK vaccine. Of the 110 Vi vaccinees with serological data, 21 (19%) had high, seroprotective, pre-immunization levels of anti-Vi antibodies (> or = 1 microgram/ml). The majority of subjects in this group came from a region in Malaysia which is known to have high typhoid endemicity. Interestingly, these antibody levels were boosted considerably following administration of vaccine at a level that was 5-fold higher than in subjects with low pre-immunization levels. In contrast, the seroconversion rates in those receiving the Vi vaccine were higher in subjects with low pre-immunization levels of anti-Vi antibodies (76-84%), compared to those with protective levels of > or = 1 microgram/ml prior to immunization (48-57%). CONCLUSIONS: The study reaffirms the safety and efficacy of the Vi polysaccharide vaccine and identifies a hitherto unrecognized advantage in its use, i.e. it is a potent immunogen that boosted considerably the protective antibody levels among a significant number of immunologically sensitized individuals living in typhoid-endemic regions. PMID:11584728

  9. Conjugation of β-glucan markedly increase the immunogencity of meningococcal group Y polysaccharide conjugate vaccine.

    PubMed

    Qiao, Weilin; Ji, Shaoyang; Zhao, Yubao; Hu, Tao

    2015-04-21

    Meningococcal disease is a fatal illness of sudden onset caused by Neisseria meningitides. Meningococcal capsular polysaccharide (CPS) is a major virulence factor that generally does not induce immunological memory. Conjugation with a carrier protein can significantly increase the immunogenicity of CPS and induce immunological memory. However, it is highly desired to optimize the CPS-specific immunogenicity of the conjugate vaccine. Although adjuvant has been widely used to improve the immunogenicity of antigens, co-administration and conjugation of adjuvant with the conjugate vaccine has rarely been investigated. As a stimulator of humoral and cellular immunity, β-glucan can activate macrophages and trigger intracellular processes to secrete cytokines initiating inflammatory reactions. In the present study, a conjugate vaccine (CPS-TT) was generated by conjugation of tetanus toxoid (TT) with meningococcal group Y CPS. CPS-TT was further conjugated with β-glucan to generate CPS-TT-G. Immunization with CPS-TT-G led to an 8.2-fold increase in the CPS-specific IgG titers as compared with CPS-TT. Presumably, conjugation of β-glucan ensured the two components to simultaneously reach the antigen presenting cells and stimulate the immune response. In contrast, co-administration of β-glucan suppressed the CPS-specific immunogenicity of CPS-TT. Thus, conjugation of β-glucan is an effective strategy to markedly improve the CPS-specific immunogenicity of the conjugate vaccine.

  10. Structural correlates of carrier protein recognition in tetanus toxoid-conjugated bacterial polysaccharide vaccines

    PubMed Central

    Lockyer, Kay; Gao, Fang; Derrick, Jeremy P.; Bolgiano, Barbara

    2015-01-01

    An analysis of structure-antibody recognition relationships in nine licenced polysaccharide-tetanus toxoid (TT) conjugate vaccines was performed. The panel of conjugates used included vaccine components to protect against disease caused by Haemophilus influenzae type b, Neisseria meningitidis groups A, C, W and Y and Streptococcus pneumoniae serotype 18C. Conformation and structural analysis included size exclusion chromatography with multi-angle light scattering to determine size, and intrinsic fluorescence spectroscopy and fluorescence quenching to evaluate the protein folding and exposure of Trp residues. A capture ELISA measured the recognition of TT epitopes in the conjugates, using four rat monoclonal antibodies: 2 localised to the HC domain, and 2 of which were holotoxoid conformation-dependent. The conjugates had a wide range of average molecular masses ranging from 1.8 × 106 g/mol to larger than 20 × 106 g/mol. The panel of conjugates were found to be well folded, and did not have spectral features typical of aggregated TT. A partial correlation was found between molecular mass and epitope recognition. Recognition of the epitopes either on the HC domain or the whole toxoid was not necessarily hampered by the size of the molecule. Correlation was also found between the accessibility of Trp side chains and polysaccharide loading, suggesting also that a higher level of conjugated PS does not necessarily interfere with toxoid accessibility. There were different levels of carrier protein Trp side-chain and epitope accessibility that were localised to the HC domain; these were related to the saccharide type, despite the conjugates being independently manufactured. These findings extend our understanding of the molecular basis for carrier protein recognition in TT conjugate vaccines. PMID:25640334

  11. Structural correlates of carrier protein recognition in tetanus toxoid-conjugated bacterial polysaccharide vaccines.

    PubMed

    Lockyer, Kay; Gao, Fang; Derrick, Jeremy P; Bolgiano, Barbara

    2015-03-10

    An analysis of structure-antibody recognition relationships in nine licenced polysaccharide-tetanus toxoid (TT) conjugate vaccines was performed. The panel of conjugates used included vaccine components to protect against disease caused by Haemophilus influenzae type b, Neisseria meningitidis groups A, C, W and Y and Streptococcus pneumoniae serotype 18C. Conformation and structural analysis included size exclusion chromatography with multi-angle light scattering to determine size, and intrinsic fluorescence spectroscopy and fluorescence quenching to evaluate the protein folding and exposure of Trp residues. A capture ELISA measured the recognition of TT epitopes in the conjugates, using four rat monoclonal antibodies: 2 localised to the HC domain, and 2 of which were holotoxoid conformation-dependent. The conjugates had a wide range of average molecular masses ranging from 1.8×10(6) g/mol to larger than 20×10(6) g/mol. The panel of conjugates were found to be well folded, and did not have spectral features typical of aggregated TT. A partial correlation was found between molecular mass and epitope recognition. Recognition of the epitopes either on the HC domain or the whole toxoid was not necessarily hampered by the size of the molecule. Correlation was also found between the accessibility of Trp side chains and polysaccharide loading, suggesting also that a higher level of conjugated PS does not necessarily interfere with toxoid accessibility. There were different levels of carrier protein Trp side-chain and epitope accessibility that were localised to the HC domain; these were related to the saccharide type, despite the conjugates being independently manufactured. These findings extend our understanding of the molecular basis for carrier protein recognition in TT conjugate vaccines.

  12. Protection against Streptococcus suis Serotype 2 Infection Using a Capsular Polysaccharide Glycoconjugate Vaccine

    PubMed Central

    Calzas, Cynthia; Shiao, Tze Chieh; Neubauer, Axel; Kempker, Jennifer; Roy, René; Gottschalk, Marcelo

    2016-01-01

    Streptococcus suis serotype 2 is an encapsulated bacterium and one of the most important bacterial pathogens in the porcine industry. Despite decades of research for an efficient vaccine, none is currently available. Based on the success achieved with other encapsulated pathogens, a glycoconjugate vaccine strategy was selected to elicit opsonizing anti-capsular polysaccharide (anti-CPS) IgG antibodies. In this work, glycoconjugate prototypes were prepared by coupling S. suis type 2 CPS to tetanus toxoid, and the immunological features of the postconjugation preparations were evaluated in vivo. In mice, experiments evaluating three different adjuvants showed that CpG oligodeoxyribonucleotide (ODN) induces very low levels of anti-CPS IgM antibodies, while the emulsifying adjuvants Stimune and TiterMax Gold both induced high levels of IgGs and IgM. Dose-response trials comparing free CPS with the conjugate vaccine showed that free CPS is nonimmunogenic independently of the dose used, while 25 μg of the conjugate preparation was optimal in inducing high levels of anti-CPS IgGs postboost. With an opsonophagocytosis assay using murine whole blood, sera from immunized mice showed functional activity. Finally, the conjugate vaccine showed immunogenicity and induced protection in a swine challenge model. When conjugated and administered with emulsifying adjuvants, S. suis type 2 CPS is able to induce potent IgM and isotype-switched IgGs in mice and pigs, yielding functional activity in vitro and protection against a lethal challenge in vivo, all features of a T cell-dependent response. This study represents a proof of concept for the potential of glycoconjugate vaccines in veterinary medicine applications against invasive bacterial infections. PMID:27113360

  13. Adjuvant effect of polysaccharide from fruits of Physalis alkekengi L. in DNA vaccine against systemic candidiasis.

    PubMed

    Yang, Huimin; Han, Shuying; Zhao, Danyang; Wang, Guiyun

    2014-08-30

    Adjuvant effect mediated by polysaccharide (PPSB) isolated from the fruits of Physalis alkekengi L. in DNA vaccine was evaluated in mice. Recombinant plasmid containing epitope C (LKVIRK) from heat shock protein 90 (HSP90) of Candida albicans (C. albican) was used as DNA vaccine (pD-HSP90C). The results indicated that PPSB significantly enhanced specific antibody titers IgG, IgG1, IgG2b, and concentration of IL-2 and IL-4 in sera of mice immunized with pD-HSP90C (p<0.05). More importantly, it was found that the mice immunized with pD-HSP90C/PPSB not only had fewer CFU (colony forming unites) in the kidneys than mice immunized with pD-HSP90C, but also a statistically significant higher survival rate over PBS-injected group (p<0.05) when the immunized mice were challenged with living C. albican cells. However, no statistically significant difference in survival rate was observed between pD-HSP90C-immunized group and PBS-injected group. Therefore, PPSB can be considered as a promising adjuvant eliciting both Th1 and Th2 responses to enhance the efficacy of DNA vaccines.

  14. Immune-Enhancing Effects of Taishan Pinus massoniana Pollen Polysaccharides on DNA Vaccine Expressing Bordetella avium ompA

    PubMed Central

    Zhu, Fujie; Liu, Xiao; Sun, Zhenhong; Yu, Cuilian; Liu, Liping; Yang, Shifa; Li, Bing; Wei, Kai; Zhu, Ruiliang

    2016-01-01

    Bordetella avium is the causative agent of bordetellosis, which remains to be the cause of severe losses in the turkey industry. Given the lack of vaccines that can provide good protection, developing a novel vaccine against B. avium infection is crucial. In this study, we constructed a eukaryotic expression plasmid, which expressed the outer membrane protein A (ompA) of B. avium, to prepare a B. avium recombinant ompA-DNA vaccine. Three concentrations (low, middle, and high) of Taishan Pinus massoniana pollen polysaccharides (TPPPS), a known immunomodulator, were used as adjuvants, and their immune conditioning effects on the developed DNA vaccine were examined. The pure ompA-DNA vaccine, Freund’s incomplete adjuvant ompA-DNA vaccine, and the empty plasmid served as the controls. The chickens in each group were separately inoculated with these vaccines three times at 1, 7, and 14 days old. Dynamic changes in antibody production, cytokine secretion, and lymphocyte count were then determined from 7 to 49 days after the first inoculation. Protective rates of the vaccines were also determined after the third inoculation. Results showed that the pure DNA vaccine obviously induced the production of antibodies, the secretion of cytokines, and the increase in CD4+ and CD8+ T lymphocyte counts in peripheral blood, as well as provided a protective rate of 50% to the B. avium-challenged chickens. The chickens inoculated with the TPPPS adjuvant ompA-DNA vaccine and Freund’s adjuvant ompA-DNA vaccine demonstrated higher levels of immune responses than those inoculated with pure ompA-DNA vaccine, whereas only the ompA-DNA vaccine with 200 mg/mL TPPPS completely protected the chickens against B. avium infection. These findings indicate that the B. avium ompA-DNA vaccine combined with TPPPS is a potentially effective B. avium vaccine. PMID:26870023

  15. Protecting the herd: the remarkable effectiveness of the bacterial meningitis polysaccharide-protein conjugate vaccines in altering transmission dynamics.

    PubMed

    Stephens, David S

    2011-01-01

    Interrupting human-to-human transmission of the agents (Neisseria meningitidis, Haemophilus influenzae, and Streptococcus pneumoniae) of bacterial meningitis by new capsular polysaccharide-protein conjugate vaccines (PPCVs) has proven to be a remarkable (and unanticipated) contributor to vaccine effectiveness. Herd immunity accounts for ∼50% of the protection by meningococcal serogroup C PPCVs, pneumococcal PPCV7, and H. influenzae b PPCVs. Nasopharyngeal carriage can be reduced ≥75% for vaccine serotypes; the decrease in carriage is correlated with disease reduction in unvaccinated individuals, and the impact of herd immunity lasts for years. Based on these data, models for using herd immunity in vaccine-based prevention strategies are underway for control of meningitis in sub-Saharan Africa. Although the immunologic basis of herd immunity and impact on microbial biology need more study, protecting the unvaccinated by altering pathogen transmission dynamics is a powerful effect of PPCVs and increasingly important in vaccine introduction, implementation, and evaluation strategies.

  16. A trial of 7-valent Pneumococcal Conjugate Vaccine in HIV-infected Adults

    PubMed Central

    French, Neil; Gordon, Stephen B; Mwalukomo, Thandie; White, Sarah A; Mwafulirwa, Gershom; Longwe, Herbert; Mwaiponya, Martin; Zijlstra, Eduard E; Molyneux, Malcolm E; Gilks, Charles F

    2010-01-01

    Background: Streptococcus pneumoniae is a leading and serious co-infection of HIV-infected adults, particularly in Africa. Prevention of disease by vaccination with the current 23-valent polysaccharide vaccine is sub-optimal. Protein conjugate vaccines offer a further option for protection but no data exist on their clinical efficacy in any adult population. Methods: We conducted a double-blind randomized placebo-controlled clinical efficacy trial of the seven-valent conjugate pneumococcal vaccine in predominantly HIV-infected Malawian adults who had recovered from documented invasive pneumococcal disease (IPD). Vaccine was given as a two dose schedule four weeks apart. The primary end-point was a further episode of IPD caused by a vaccine-serotype or serotype-6A (VST/6A) pneumococcus. Results: Between February 2003 and October 2007, 496 individuals (44% male, 88% HIV seropositive) were followed for 798 person years of observation. There were 67 IPD events in 52 individuals, all in the HIV infected sub-group. There were 24 VST/6A events (19 VST, five 6A) in 24 participants, 5 in vaccine and 19 in the placebo recipients, a vaccine efficacy of 74% (95% CI 30% - 90%). There were 73 deaths in the vaccine arm and 63 in the placebo arm, Hazard Ratio 1.18 (95% confidence intervals 0.84 -1.66). Compared to placebo, serious adverse events were significantly lower (3 vs 17, p = 0.002) and minor adverse events significantly higher (41 vs 13, p = 0.003 ) in vaccine recipients. Conclusions: The seven-valent pneumococcal conjugate vaccine protects HIV infected adults from recurrent IPD of vaccine serotype or serotype 6A. PMID:20200385

  17. Preclinical immunogenicity and functional activity studies of an A+W meningococcal outer membrane vesicle (OMV) vaccine and comparisons with existing meningococcal conjugate- and polysaccharide vaccines.

    PubMed

    Tunheim, G; Arnemo, M; Næss, L M; Fjeldheim, Å K; Nome, L; Bolstad, K; Aase, A; Mandiarote, A; González, H; González, D; García, L; Cardoso, D; Norheim, G; Rosenqvist, E

    2013-12-09

    Meningococci of serogroups A and W (MenA and MenW) are the main causes of epidemic bacterial meningitis outbreaks in sub-Saharan Africa. In this study we prepared a detergent extracted outer membrane vesicle (dOMV) vaccine from representative African MenA and MenW strains, and compared the immunogenicity of this vaccine with existing meningococcal conjugate and polysaccharide (PS) vaccines in mice. NMRI mice were immunized with preclinical batches of the A+W dOMV vaccine, or with commercially available vaccines; a MenA conjugate vaccine (MenAfriVac(®), Serum Institute of India), ACYW conjugate vaccine (Menveo(®), Novartis) or ACYW PS vaccine (Mencevax(®), GlaxoSmithKline). The mice received 2 doses of 1/10 or 1/50 of a human dose with a three week interval. Immune responses were tested in ELISA, serum bactericidal activity (SBA) and opsonophagocytic activity (OPA) assays. High levels of IgG antibodies against both A and W dOMV were detected in mice receiving the A+W dOMV vaccine. High SBA titers against both MenA and MenW vaccine strains were detected after only one dose of the A+W dOMV vaccine, and the titers were further increased after the second dose. The SBA and OPA titers in mice immunized with dOMV vaccine were significantly higher than in mice immunized with the ACYW-conjugate vaccine or the PS vaccine. Furthermore, the A+W dOMV vaccine was shown to induce SBA and OPA titers against MenA of the same magnitude as the titers induced by the A-conjugate vaccine. In conclusion, the A+W dOMV vaccine induced high levels of functional antibodies to both MenA and MenW strains, levels that were shown to be higher or equal to the levels induced by licensed meningococcal vaccines. Thus, an A+W dOMV vaccine could potentially serve as an alternative or a supplement to existing conjugate and PS vaccines in the African meningitis belt.

  18. Mutant Native Outer Membrane Vesicles Combined with a Serogroup A Polysaccharide Conjugate Vaccine for Prevention of Meningococcal Epidemics in Africa

    PubMed Central

    Pajon, Rolando; Fergus, Andrew M.; Granoff, Dan M.

    2013-01-01

    Background The meningococcal serogroup A (MenA) polysaccharide conjugate vaccine used in Sub-Saharan Africa does not prevent disease caused by MenW or MenX strains, which also cause epidemics in the region. We investigated the vaccine-potential of native outer membrane vesicles with over-expressed factor H-binding protein (NOMV-fHbp), which targeted antigens in African meningococcal strains, and was combined with a MenA polysaccharide conjugate vaccine. Methodology/Principal Findings The NOMV-fHbp vaccine was prepared from a mutant African MenW strain with PorA P1.5,2, attenuated endotoxin (ΔLpxL1), deleted capsular genes, and over-expressed fHbp in variant group 1. The NOMV-fHbp was adsorbed with Al(OH)3 and used to reconstitute a lyophilized MenA conjugate vaccine, which normally is reconstituted with liquid MenC, Y and W conjugates in a meningococcal quadrivalent conjugate vaccine (MCV4-CRM, Novartis). Mice immunized with the NOMV-fHbp vaccine alone developed serum bactericidal (human complement) activity against 13 of 15 African MenA strains tested; 10 of 10 African MenX strains, 7 of 7 African MenW strains, and 6 of 6 genetically diverse MenB strains with fHbp variant group 1 (including 1 strain from The Gambia). The combination NOMV-fHbp/MenA conjugate vaccine elicited high serum bactericidal titers against the two MenA strains tested that were resistant to bactericidal antibodies elicited by the NOMV-fHbp alone; the combination elicited higher titers against the MenA and MenW strains than those elicited by a control MCV4-CRM vaccine (P<0.05); and high titers against MenX and MenB strains. For most strains, the titers elicited by a control NOMV-fHbp knock out vaccine were <1∶10 except when the strain PorA matched the vaccine (titers >1∶000). Conclusion/Significance The NOMV-fHbp/MenA conjugate vaccine provided similar or higher coverage against MenA and MenW strains than a quadrivalent meningococcal conjugate vaccine, and extended protection against Men

  19. Immunological efficacy of pneumococcal vaccine strategies in HIV-infected adults: a randomized clinical trial.

    PubMed

    Sadlier, C; O'Dea, S; Bennett, K; Dunne, J; Conlon, N; Bergin, C

    2016-09-01

    The aim of this study was to compare the immunologic response to a prime-boost immunization strategy combining the 13-valent conjugate pneumococcal vaccine (PCV13) with the 23-valent polysaccharide pneumococcal vaccine (PPSV23) versus the PPSV23 alone in HIV-infected adults. HIV-infected adults were randomized to receive PCV13 at week 0 followed by PPSV23 at week 4 (n = 31, prime-boost group) or PPSV23 alone at week 4 (n = 33, PPSV23-alone group). Serotype specific IgG geometric mean concentration (GMC) and functional oposonophagocytic (OPA) geometric mean titer (GMT) were compared for 12 pneumococcal serotypes shared by both vaccines at week 8 and week 28. The prime-boost vaccine group were more likely to achieve a ≥2-fold increase in IgG GMC and a GMC >1 ug/ml at week 8 (odds ratio (OR) 2.00, 95% confidence interval (CI) 1.46-2.74, p < 0.01) and week 28 (OR 1.95, 95% CI 1.40-2.70, p < 0.01). Similarly, the prime-boost vaccine group were more likely to achieve a ≥4-fold increase in GMT at week 8 (OR 1.71, 95% CI 1.22-2.39, p < 0.01) and week 28 (OR 1.6, 95% CI 1.15-2.3, p < 0.01). This study adds to evidence supporting current pneumococcal vaccination recommendations combining the conjugate and polysaccharide pneumococcal vaccines in the United States and Europe for HIV-infected individuals.

  20. Open-Label Trial of Immunogenicity and Safety of a 13-Valent Pneumococcal Conjugate Vaccine in Adults ≥50 Years of Age in Mexico

    PubMed Central

    Juergens, Christine; Ruiz Palacios, Guillermo M.; Vazquez-Narvaez, Jorge; Enkerlin-Pauwells, Hermann Leo; Sundaraiyer, Vani; Pathirana, Sudam; Kalinina, Elena; Gruber, William C.; Scott, Daniel A.; Schmoele-Thoma, Beate

    2014-01-01

    This open-label multicenter clinical trial conducted in Mexico assessed the immunogenicity and safety of a 13-valent pneumococcal conjugate vaccine (PCV13) in adults ≥50 years of age not previously vaccinated with the 23-valent pneumococcal polysaccharide vaccine (PPSV23). The PCV13 elicited a robust immune response in this study population, as reflected by the magnitude of fold rises in functional antibody levels measured by serotype-specific opsonophagocytic activity (OPA) assays before and 1 month after vaccination. Although the prevaccination OPA geometric mean titers (GMTs) for the majority of the serotypes were significantly lower in the 50- to 64-year age group than those in the ≥65-year age group, the postvaccination immune responses were generally similar. The overall immune responses were higher for the majority of the serotypes in the Mexican study population than those in similar adult study populations who received the PCV13 in Europe and the United States. PCV13 was well tolerated, and there were no vaccine-related serious adverse events. In conclusion, PCV13 is safe and immunogenic when administered to adults ≥50 years of age in Mexico and has the potential to protect against vaccine-type pneumococcal disease. (This study has been registered at ClinicalTrials.gov under registration no. NCT01432262.) PMID:25499011

  1. Specific medicinal plant polysaccharides effectively enhance the potency of a DC-based vaccine against mouse mammary tumor metastasis.

    PubMed

    Chang, Wei Ting; Lai, Tzung Hsien; Chyan, Yau Jan; Yin, Shu Yi; Chen, Yung Hsiang; Wei, Wen Chi; Yang, Ning-Sun

    2015-01-01

    Dendritic cell (DC) vaccines are a newly emerging immunotherapeutic approach for the treatment and prevention of cancer, but major challenges still remain particularly with respect to clinical efficacy. Engineering and optimization of adjuvant formulations for DC-based vaccines is one strategy through which more efficacious treatments may be obtained. In this study, we developed a new ex vivo approach for DC vaccine preparation. We evaluated two highly purified mixed polysaccharide fractions from the root of Astragalus membranaceus and Codonopsis pilosulae, named Am and Cp, for their use in enhancing the efficiency of a DC-based cancer vaccine against metastasis of 4T1 mammary carcinoma in mice. Mixed lymphocyte reaction showed all Am-, Cp- and [Am+Cp]-treated DCs enhanced mouse CD4+ and CD8+ T-cell proliferation. [Am+Cp]-treated DCs exhibited the strongest anti-4T1 metastasis activity in test mice. Treatments with Am, Cp and [Am+Cp] also resulted in augmented expression of CD40, CD80 and CD86 markers in test DCs. Bioinformatics analysis of the cytokine array data from treated DCs identified that [Am+Cp] is efficacious in activation of specific immune functions via mediating the expression of cytokines/chemokines involved in the recruitment and differentiation of defined immune cells. Biochemical analysis revealed that Am and Cp are composed mainly of polysaccharides containing a high level (70-95%) glucose residues, but few or no (< 1%) mannose residues. In summary, our findings suggest that the specific plant polysaccharides Am and Cp extracted from traditional Chinese medicines can be effectively used instead of bacterial LPS as a potent adjuvant in the formulation of a DC-based vaccine for cancer immunotherapies.

  2. Specific Medicinal Plant Polysaccharides Effectively Enhance the Potency of a DC-Based Vaccine against Mouse Mammary Tumor Metastasis

    PubMed Central

    Chang, Wei Ting; Lai, Tzung Hsien; Chyan, Yau Jan; Yin, Shu Yi; Chen, Yung Hsiang; Wei, Wen Chi; Yang, Ning-Sun

    2015-01-01

    Dendritic cell (DC) vaccines are a newly emerging immunotherapeutic approach for the treatment and prevention of cancer, but major challenges still remain particularly with respect to clinical efficacy. Engineering and optimization of adjuvant formulations for DC-based vaccines is one strategy through which more efficacious treatments may be obtained. In this study, we developed a new ex vivo approach for DC vaccine preparation. We evaluated two highly purified mixed polysaccharide fractions from the root of Astragalus membranaceus and Codonopsis pilosulae, named Am and Cp, for their use in enhancing the efficiency of a DC-based cancer vaccine against metastasis of 4T1 mammary carcinoma in mice. Mixed lymphocyte reaction showed all Am-, Cp- and [Am+Cp]-treated DCs enhanced mouse CD4+ and CD8+ T-cell proliferation. [Am+Cp]-treated DCs exhibited the strongest anti-4T1 metastasis activity in test mice. Treatments with Am, Cp and [Am+Cp] also resulted in augmented expression of CD40, CD80 and CD86 markers in test DCs. Bioinformatics analysis of the cytokine array data from treated DCs identified that [Am+Cp] is efficacious in activation of specific immune functions via mediating the expression of cytokines/chemokines involved in the recruitment and differentiation of defined immune cells. Biochemical analysis revealed that Am and Cp are composed mainly of polysaccharides containing a high level (70–95%) glucose residues, but few or no (< 1%) mannose residues. In summary, our findings suggest that the specific plant polysaccharides Am and Cp extracted from traditional Chinese medicines can be effectively used instead of bacterial LPS as a potent adjuvant in the formulation of a DC-based vaccine for cancer immunotherapies. PMID:25825910

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

    PubMed

    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.

  4. Vaccines (immunizations) - overview

    MedlinePlus

    ... diphtheria, mumps, measles, pertussis (whooping cough), meningitis, and polio. Many of these infections can cause serious or ... MMR - vaccine Pneumococcal conjugate vaccine Pneumococcal polysaccharide ... (vaccine) Rotavirus vaccine Tdap vaccine Tetanus - vaccine

  5. Evaluation of the incidence of herpes zoster after concomitant administration of zoster vaccine and polysaccharide pneumococcal vaccine.

    PubMed

    Tseng, Hung Fu; Smith, Ning; Sy, Lina S; Jacobsen, Steven J

    2011-05-09

    In 2009, a revision to the zoster vaccine package insert was approved stating that the zoster vaccine and the pneumococcal vaccine should not be given concurrently because concomitant use resulted in reduced immunogenicity of the zoster vaccine. We conducted an observational study to evaluate if concomitant vaccination reduces the protective effect of the zoster vaccine. The study was conducted in Kaiser Permanente Southern California. Incidence of herpes zoster (HZ) after vaccination with a zoster vaccine in the population receiving both vaccines on the same day was compared to that in the population receiving a pneumococcal vaccine within one year to 30 days prior to zoster vaccine. Vaccinations and incident HZ cases were identified by electronic health records. The hazard ratio for incident HZ associated with concomitant vs. nonconcomitant vaccination was estimated using the Cox proportional hazard model. There were 56 incident HZ cases in the concomitant vaccination cohort and 58 in the nonconcomitant vaccination cohort, yielding a HZ incidence of 4.54 (95% confidence interval [CI], 3.43-5.89) and 4.51 (95% CI, 3.42-5.83) per 1000 person-years, respectively. The hazard ratio comparing the incidence rate of HZ in the two cohorts was 1.19 (95% CI, 0.81-1.74) in the adjusted analysis. In this study, we found no evidence of an increased risk of HZ in the population receiving zoster vaccine and pneumococcal vaccine concomitantly. The revision of the product information needs to be carefully assessed to avoid introducing barriers to patients and providers who are interested in these two important vaccines.

  6. Effects of Taishan Pinus massoniana pollen polysaccharide on immune response of rabbit haemorrhagic disease tissue inactivated vaccine and on production performance of Rex rabbits.

    PubMed

    Wei, Kai; Sun, Zhenhong; Yan, Zhengui; Tan, Yanling; Wang, Hui; Zhu, Xiaolin; Wang, Xinjian; Sheng, Pengcheng; Zhu, Ruiliang

    2011-03-21

    Varied doses of Taishan Pinus massoniana pollen polysaccharide (TPPPS) and Astragalus polysaccharide (APS) extracted by hot water extraction and ethanol precipitation method were added to the vaccine in order to prepare polysaccharide-rabbit haemorrhagic disease (RHD) tissue inactivated vaccine. The purpose was to study effects of TPPPS on immune response of RHD tissue inactivated vaccine and on production performance of Rex rabbits. Results showed that each index in groups I, II, III and IV was higher than that in group V, especially groups I, II and IV, the difference between which and group V was much more significant (P<0.05); each index in group I was extremely higher than that in group V (P<0.01); each index in group I was significantly higher than that in groups II, III (P<0.05), and generally no significant difference was observed between groups II and III. The overall level in group IV was slightly lower than that in group I. Each index in the polysaccharide groups reached its peak value later than that in the non-polysaccharide groups did. Results suggested that any dose of TPPPS can enhance immunologic function and production performance of rabbits, and the amount of 400mg per rabbit has the most obvious efficacy. Furthermore, it can extend the immune peak period of RHD tissue inactivated vaccine and the growing peak period of Rex rabbits. TPPPS has generally higher efficiency than APS.

  7. Nanoparticle and polysaccharide conjugate: a potential candidate vaccine to improve immunological stimuli.

    PubMed

    Devi, K Sanjana P; Sahoo, Banalata; Behera, Birendra; Maiti, Tapas K

    2015-01-01

    Active polysaccharides isolated from various fungal sources have been implicated to stimulate immune response against various pathogens as well as self anomalies such as cancer. Therefore, the nuanced approach presented in our work was to blend polysaccharides derived from Pleurotus ostreatus with biocompatible ferrite nanoparticles and thereafter investigate the enhanced immune functionality of the polysaccharide-nanoparticle composite. A Schiff base reductive amination reaction occurred between the aldehyde group of the polysaccharide and the amine group of the nanoparticles in the presence of a strong reducing agent such as sodium cyanoborohydride to form a stable amide bond between the two conjugating molecules. The multifaceted conjugate was characterized by physiochemical techniques such as electron microscopy, FTIR, VSM and DLS measurements. This particulate form of the polysaccharide showed a marked escalation in the production of free radicals such as reactive oxygen and nitrogen species in murine macrophages as compared to the soluble form. Animal based experiments demonstrated a reduction in tumor volume and augmentation in the proliferation of splenocytes in particulate or conjugated polysaccharide treated mice. Furthermore, molecular signaling studies showed a high upregulation in p-p38 and p-MEK molecules in particulate polysaccharide treated RAW264.7 cells suggesting a cellular downstream mechanistic regulation behind the immunostimulative response.

  8. Kinetics of antibody responses after primary immunization with meningococcal serogroup C conjugate vaccine or secondary immunization with either conjugate or polysaccharide vaccine in adults.

    PubMed

    de Voer, Richarda M; van der Klis, Fiona R M; Engels, Carla W A M; Schepp, Rutger M; van de Kassteele, Jan; Sanders, Elisabeth A M; Rijkers, Ger T; Berbers, Guy A M

    2009-11-23

    In the Netherlands the meningococcal serogroup C conjugate (MenCC) vaccine is administered as a single dose at 14 months. We evaluated the kinetics of isotype-specific antibodies in adults (n=21) after primary immunization with MenCC or secondary immunization with MenCC or plain MenC polysaccharide vaccine. Blood samples were collected prior to immunization and at 6 additional time points, from 3 to 25 days post-immunization. Secondary immunization resulted in 5-10-fold higher IgG titers compared to the primary immunization group, 25 days post-immunization. Prior to the secondary immunization, but 5 years after the first immunization, protective bactericidal antibodies and levels of MenC-specific IgG and IgM were still present. Furthermore, IgG antibodies present before secondary immunization were of higher avidity compared to antibodies produced one month after primary immunization. In addition, secondary immunization with nonconjugated MenC polysaccharide seemed to induce a higher IgG2 response compared to MenCC immunization. The kinetics of the observed secondary immune responses were not really faster than the observed primary responses. However, the rate of increase in antibodies seemed faster than the primary responses, representing a booster response. As the course of infection by Neisseria meningitidis can be very rapid, these data support the idea that sustainment of high antibody levels induced by MenCC are important for immediate protection.

  9. Immunogenicity differences of a 15-valent pneumococcal polysaccharide conjugate vaccine (PCV15) based on vaccine dose, route of immunization and mouse strain.

    PubMed

    Caro-Aguilar, Ivette; Indrawati, Lani; Kaufhold, Robin M; Gaunt, Christine; Zhang, Yuhua; Nawrocki, Denise K; Giovarelli, Cecilia; Winters, Michael A; Smith, William J; Heinrichs, Jon; Skinner, Julie M

    2017-02-07

    Pneumococcal disease continues to be a medical need even with very effective vaccines on the market. Globally, there are extensive research efforts to improve serotype coverage with novel vaccines; therefore, conducting preclinical studies in different animal models becomes essential. The work presented herein focuses on evaluating a 15-valent pneumococcal conjugate vaccine (PCV15) in mice. Initially we evaluated several doses of PCV15 in Balb/c mice. The optimal vaccine dose was determined to be 0.4μg per pneumococcal polysaccharide (PS) (0.8μg of 6B) for subsequent studies. This PS dose was chosen for PCV evaluation in mice based on antibody levels determined by multiplexed electrochemiluminescent (ECL) assays, T-cell responses following in vitro stimulation with CRM197 peptides and protection from pneumococcal challenge. We then selected four mouse strains for evaluation: Balb/c, C3H/HeN, CD1 and Swiss Webster (SW), immunized with PCV15 by either intraperitoneal (IP) or intramuscular (IM) routes. We assessed IgG responses by ECL assays and functional antibody activity by multiplexed opsonophagocytic assays (MOPA). Every mouse strain evaluated responded to all 15 serotypes contained in the vaccine. Mice tended to have lower responses to serotypes 6B, 23F and 33F. The IP route of immunization resulted in higher antibody titers for most serotypes in Balb/c, C3H and SW. CD1 mice tended to respond similarly for most serotypes, regardless of route of immunization. Similar trends were observed with the four mouse strains when evaluating functional antibody activity. Given the differences in antibody responses based on mouse strain and route of immunization, it is critical to evaluate pneumococcal vaccines in multiple animal models to determine the optimal formulation before moving to clinical trials.

  10. Humoral immune response of a pneumococcal conjugate vaccine: capsular polysaccharide serotype 14-Lysine modified PspA.

    PubMed

    Santamaria, Raquel; Goulart, Cibelly; Perciani, Catia T; Barazzone, Giovana C; Carvalho, Rimenys; Gonçalves, Viviane M; Leite, Luciana C C; Tanizaki, Martha M

    2011-11-03

    Polysaccharide-protein conjugates are so far the current antigens used for pneumococcal vaccines for children under 2 years of age. In this study, pneumococcal surface protein A (PspA) was used as a carrier protein for pneumococcal capsular polysaccharide serotype 14 as an alternative to broaden the vaccine coverage. PspA was modified by reductive amination with formaldehyde in order to improve the specificity of the reaction between protein and polysaccharide, inhibiting polymerization and the gel formation reaction. In the synthesis process, the currently used activator, 1-[3-(dimethylamine)propyl]-3-ethylcarbodiimide hydrochloride (EDAC) was substituted for 4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium chloride (DMT-MM). BALB/c mice were immunized with either the PS14-mPspA conjugate or the co-administered components in a three dose regimen and sera from the immunized animals were assayed for immunity induced against both antigens: PS14 and mPspA. Modification of more than 70% of lysine residues from PspA (mPspA) did not interfere in the immune response as evaluated by the anti-PspA titer and C3 complement deposition assay. Sera of mice immunized with conjugated PS14-mPspA showed similar IgG titers, avidity and isotype profile as compared to controls immunized with PspA or mPspA alone. The complement deposition was higher in the sera of mice immunized with the conjugate vaccine and the opsonophagocytic activity was similar for both sera. Conjugation improved the immune response against PS14. The anti PS14 IgG titer was higher in sera of mice immunized with the conjugate than with co-administered antigens and presented an increased avidity index, induction of a predominant IgG1 isotype and increased complement deposition on a bacteria with a surface serotype 14. These results strongly support the use of PspA as carrier in a conjugate vaccine where both components act as antigens.

  11. Protein-bound polysaccharide activates dendritic cells and enhances OVA-specific T cell response as vaccine adjuvant

    PubMed Central

    Engel, Abbi L.; Sun, Guan-Cheng; Gad, Ekram; Rastetter, Lauren R.; Strobe, Katie; Yang, Yi; Dang, Yushe; Disis, Mary L; Lu, Hailing

    2013-01-01

    Protein-bound polysaccharide-K (PSK) is a hot water extract from Trametes versicolor mushroom. It has been used traditionally in Asian countries for its immune stimulating and anti-cancer effects. We have recently found that PSK can activate toll-like receptor 2 (TLR2). TLR2 is highly expressed on dendritic cells (DC), so the currently study was undertaken to evaluate the effect of PSK on DC activation and the potential of using PSK as a vaccine adjuvant. In vitro experiments using mouse bone marrow-derived DC (BMDC) demonstrated that PSK induces DC maturation as shown by dose-dependent increase in the expression of CD80, CD86, MHCII, and CD40. PSK also induces the production of multiple inflammatory cytokines by DC, including IL-12, TNF-α, and IL-6, at both mRNA and protein levels. In vivo experiments using PSK as an adjuvant to OVAp323-339 vaccine showed that PSK as adjuvant leads to enlarged draining lymph nodes with higher number of activated DC. PSK also stimulates proliferation of OVA-specific T cells, and induces T cells that produce multiple cytokines, IFN-γ, IL-2, and TNF-α. Altogether, these results demonstrate the ability of PSK to activate DC in vitro and in vivo and the potential of using PSK as a novel vaccine adjuvant. PMID:23735481

  12. Safety and immunogenicity of CRM197-conjugated pneumococcal-meningococcal C combination vaccine (9vPnC-MnCC) whether given in two or three primary doses.

    PubMed

    Sigurdardottir, Sigurveig Th; Davidsdottir, Katrin; Arason, Vilhjalmur A; Jonsdottir, Olof; Laudat, France; Gruber, William C; Jonsdottir, Ingileif

    2008-08-05

    This randomized trial compares safety and immunogenicity when vaccinating infants with a pneumococcal-meningococcal conjugate vaccine in two doses vs. three doses. Infants (N=223) received 9vPnC-MnCC (CRM197-conjugated pneumococcal serotypes 1, 4, 5, 6B, 9V, 14, 18C, 19F, 23F and meningococcal C polysaccharides) either at 3 and 5 or 3, 4 and 5 months and a booster with either 9vPnC-MnCC or 23-valent pneumococcal-polysaccharide vaccine (23vPPS) and CRM197-MnCC, at 12 months. Safety was monitored and IgG measured at 3, 6, 12 and 13 months in all subjects and serum bactericidal activity (SBA) in half. The 9vPnC-MnCC vaccine was safe and induced significant IgG to all components. Three doses induced higher antibody GMCs (geometric mean concentrations) at 6 months to seven of nine pneumococcal serotypes. This was most significant for 6B and 23F (p<0.001), that also showed lower rate of responders>0.35 (6B, 23F) and >0.5 microg/mL (6B). Antibody GMCs remained lower following 9vPnC-MnCC booster in subjects primed with two doses although only significant for serotype 18C. Significant memory responses were observed 1 week after the 23vPPS toddler dose. MnCC-IgG GMC was lower after two doses, however with comparable SBA. This study shows that the 9vPnC-MnCC vaccine is safe and induces successful immunological memory, whether given in two or three primary doses.

  13. Clinical effectiveness of pneumococcal vaccination against acute myocardial infarction and stroke in people over 60 years: the CAPAMIS study, one-year follow-up

    PubMed Central

    2012-01-01

    Background Conflicting results have been recently reported evaluating the relationship between pneumococcal vaccination and the risk of thrombotic vascular events. This study assessed the clinical effectiveness of the 23-valent polysaccharide pneumococcal vaccine (PPV23) against acute myocardial infarction and ischaemic stroke in older adults. Methods Population-based prospective cohort study conducted from December 1, 2008 until November 30, 2009, including all individuals ≥ 60 years-old assigned to nine Primary Care Centres in Tarragona, Spain (N = 27,204 individuals). Primary outcomes were hospitalisation for acute myocardial infarction and/or ischaemic stroke. All cases were validated by checking clinical records. The association between pneumococcal vaccination and the risk of each outcome was evaluated by Multivariable Cox proportional-hazard models (adjusted by age, sex, influenza vaccine status, presence of comorbidities and cardiovascular risk factors). Results Cohort members were followed for a total of 26,444 person-years, of which 34% were for vaccinated subjects. Overall incidence rates (per 1000 person-years) were 4.9 for myocardial infarction and 4.6 for ischaemic stroke. In the multivariable analysis, vaccination was associated with a marginally significant 35% lower risk of stroke (hazard ratio [HR]: 0.65; 95% confidence interval [CI]: 0.42-0.99; p = 0.046). We found no evidence for an association between pneumococcal vaccination and reduced risk of myocardial infarction (HR: 0.83; 95% CI: 0.56-1.22; p = 0.347). Conclusions Our data supports a benefit of PPV23 against ischaemic stroke among the general population over 60 years, suggesting a possible protective role of pneumococcal vaccination against some acute thrombotic events. PMID:22436146

  14. Functional anti-polysaccharide IgG titres induced by unadjuvanted pneumococcal-conjugate vaccine when delivered by microprojection-based skin patch.

    PubMed

    Pearson, Frances E; Muller, David A; Roalfe, Lucy; Zancolli, Marta; Goldblatt, David; Kendall, Mark A F

    2015-11-27

    Adequate access to effective and affordable vaccines is essential for the prevention of mortality due to infectious disease. Pneumonia--a consequence of Streptococcus pneumoniae infection--is the world's leading cause of death in children aged under 5 years. The development of a needle-free, thermostable pneumococcal-conjugate vaccine (PCV) could revolutionise the field by reducing cold-chain and delivery constraints. Skin patches have been used to deliver a range of vaccines, with some inducing significantly higher vaccine-specific immunogenicity than needle-injected controls in pre-clinical models, though they have yet to be used to deliver a PCV. We dry-coated a licensed PCV onto a microprojection-based patch (the Nanopatch) and delivered it to mouse skin. We analysed resulting anti-polysaccharide IgG responses. With and without adjuvant, anti-polysaccharide IgG titres induced by Nanopatch immunisation were significantly higher than dose-matched intramuscular controls. These improved responses were primarily obtained against pneumococcal serotypes 4 and 14. Importantly, capsule-specific IgG correlated with functionality in an opsonophagocytic killing assay. We demonstrate enhanced anti-PCV immunogenicity when delivered by Nanopatch over intramuscular injection. As the first study of a PCV delivered by a skin vaccination technology, this report indicates the potential for reduced costs and greater global distribution of such a vaccine.

  15. Constitutive Expression of the Vi Polysaccharide Capsular Antigen in Attenuated Salmonella enterica Serovar Typhi Oral Vaccine Strain CVD 909

    PubMed Central

    Wang, Jin Yuan; Noriega, Fernando R.; Galen, James E.; Barry, Eileen; Levine, Myron M.

    2000-01-01

    Live oral Ty21a and parenteral Vi polysaccharide vaccines provide significant protection against typhoid fever, albeit by distinct immune mechanisms. Vi stimulates serum immunoglobulin G Vi antibodies, whereas Ty21a, which does not express Vi, elicits humoral and cell-mediated immune responses other than Vi antibodies. Protection may be enhanced if serum Vi antibody as well as cell-mediated and humoral responses can be stimulated. Disappointingly, several new attenuated Salmonella enterica serovar Typhi oral vaccines (e.g., CVD 908-htrA and Ty800) that elicit serum O and H antibody and cell-mediated responses following a single dose do not stimulate serum Vi antibody. Vi expression is regulated in response to environmental signals such as osmolarity by controlling the transcription of tviA in the viaB locus. To investigate if Vi antibodies can be stimulated if Vi expression is rendered constitutive, we replaced PtviA in serovar Typhi vaccine CVD 908-htrA with the constitutive promoter Ptac, resulting in CVD 909. CVD 909 expresses Vi even under high-osmolarity conditions and is less invasive for Henle 407 cells. In mice immunized with a single intranasal dose, CVD 909 was more immunogenic than CVD 908-htrA in eliciting serum Vi antibodies (geometric mean titer of 160 versus 49, P = 0.0007), whereas O antibody responses were virtually identical (geometric mean titer of 87 versus 80). In mice challenged intraperitoneally with wild-type serovar Typhi 4 weeks after a single intranasal immunization, the mortality of those immunized with CVD 909 (3 of 8) was significantly lower than that of control mice (10 of 10, P = 0.043) or mice given CVD 908-htrA (9 of 10, P = 0.0065). PMID:10899868

  16. Serological differentiation of Brucella-vaccinated and -infected domesticated animals by the agar gel immunodiffusion test using Brucella polysaccharide in mongolia.

    PubMed

    Erdenebaatar, Janchivdorj; Sugar, Sengee; Yondondorj, Agchbazar; Nagabayashi, Toshihiko; Syuto, Bunei; Watarai, Masahisa; Makino, Sou-Ichi; Shirahata, Toshikazu

    2002-09-01

    To investigate Brucella infection in cattle, sheep, goat, reindeer and yak in Mongolia, serological reactions of Brucella-infected and -vaccinated domestic animals were compared by the agar gel immunodiffusion (AGID) test with a polysaccharide (poly-B) of the B. Abortus strain S-19. The sensitivity and specificity were compared with conventional serological tests that are commonly used in Mongolia, such as the rose Bengal test, the tube agglutination test and the compliment fixation test. A total of 73.3, 100, 100, 95.8 and 61.9% of the sera from suspected cattle, yak, goat, sheep and reindeer, respectively, that were positive in the compliment fixation test, were also positive in the AGID test. Sera from vaccinated cattle, sheep and goat were positive over 90% by conventional tests 3 months after vaccination, but were negative by the AGID. These results suggest that the AGID test may be useful to differentiate infected and vaccinated animals in the field.

  17. Safety and immunogenicity of a meningococcal (Groups A, C, Y, W-135) polysaccharide diphtheria toxoid conjugate vaccine in healthy children aged 2 to 10 years in Chile.

    PubMed

    Lagos, Rosanna; Papa, Thomas; Muñoz, Alma; Ryall, Robert; Pina, Miriam; Bassily, Ehab

    2005-01-01

    Immune responses to meningococcal conjugate (Menactra; MCV-4) and plain polysaccharide (Menomune-A/C/Y/W-135; PSV-4) vaccines against serogroups A, C, Y, and W-135 were assessed in 220 of 1037 Chilean children aged 2 to 10 years participating in a comparative safety trial. Both vaccines were generally well tolerated. Geometric mean serum bactericidal antibody (SBA) titers 28 days postvaccination were comparable in both groups for all four serogroups. Seroconversion was evident in > 97% of MCV-4 and > 90% of PSV-4 vaccinees who tested seronegative at baseline. Menactra safely induced broad and robust immune responses against serogroups A, C, Y and W-135 in this population.

  18. Safety and Immunogenicity Testing of a Pilot Polysaccharide Vaccine Preparation to Pseudomonas aeruginosa.

    DTIC Science & Technology

    1979-09-01

    polysaccharides (PS) from P. aeru- ginosa in a plaque forming cell assay utilizing mouse spleen cells, and test- ing of PS preparations in other animal...in order to make a "hotter" antigen. b). P. aeruginosa grow well in media consisting only of phosphate, mag- nesium, ammonia , sulfate and a carbon...mice respond to IT-I PS in a typical dose - response fashion, generating a maximal response of 2854 IqM plaques/ spleen at a 1 ug/mouse dose (Table 2

  19. Safety and Immunogenicity Testing of a Pilot Polysaccharide Vaccine Preparation to Pseudomonas aeruginosa.

    DTIC Science & Technology

    1982-09-01

    residues similar to that produced by strains of S. 4 yeast . Although yeast extract is not a component of the media, this mannan appears to be part of...nization wTth this vaccine. We have also shown that passive transfer to mice of rabbit antibody made to the IT-l PS vaccine was effective in...abortus by hyerimmune rabbit immunoglobulin A. J. InuunoT r.7IM ’ 8. Onderdonk, A.B., R.B. Markham, D. Zaleznik, R.C. Cisneros, and D.L. Kasper. 1982

  20. Optimization and application of a multiplex bead-based assay to quantify serotype-specific IgG against Streptococcus pneumoniae polysaccharides: response to the booster vaccine after immunization with the pneumococcal 7-valent conjugate vaccine.

    PubMed

    Elberse, Karin E M; Tcherniaeva, Irina; Berbers, Guy A M; Schouls, Leo M

    2010-04-01

    We describe the optimization and application of a multiplex bead-based assay (Luminex) to quantify antibodies against polysaccharides of 13 pneumococcal serotypes. In the optimized multiplex immunoassay (MIA), intravenous immune globulin was introduced as an in-house reference serum, and nonspecific reacting antibodies were adsorbed with the commercial product pneumococcal C polysaccharides Multi. The antibody concentrations were assessed in 188 serum samples obtained pre- and post-booster vaccination at 11 months after administration of a primary series of the pneumococcal seven-valent conjugate vaccine (PCV-7) at 2, 3, and 4 months of age. The results of the MIA were compared with those of the ELISA for the serotypes included in the seven-valent conjugated polysaccharide vaccine and for a non-vaccine serotype, serotype 6A. The geometric mean concentrations of the antibodies determined by MIA were slightly higher than those determined by ELISA. The correlations between the assays were good, with R(2) values ranging from 0.84 to 0.91 for all serotypes except serotype 19F, for which R(2) was 0.70. The concentrations of antibody against serotype 6A increased after the administration of PCV-7 due to cross-reactivity with serotype 6B. The differences between the results obtained by ELISA and MIA suggest that the internationally established protective threshold of 0.35 microg/ml should be reevaluated for use in the MIA and may need to be amended separately for each serotype.

  1. Physico-chemical properties of Salmonella typhi Vi polysaccharide-diphtheria toxoid conjugate vaccines affect immunogenicity.

    PubMed

    An, So Jung; Yoon, Yeon Kyung; Kothari, Sudeep; Kothari, Neha; Kim, Jeong Ah; Lee, Eugene; Kim, Deok Ryun; Park, Tai Hyun; Smith, Greg W; Carbis, Rodney

    2011-10-13

    In this study it was demonstrated that the immunogenicity of Vi polysaccharide-diphtheria toxoid conjugates was related to the physical and chemical structure of the conjugate. Conjugates were prepared in two steps, firstly binding adipic acid dihydrazide (ADH) spacer molecules to diphtheria toxoid (DT) carrier protein then secondly binding varying amounts of this derivatized DT to a fixed amount of Vi capsular polysaccharide purified from Salmonella enterica Serovar Typhi. As the amount of DT bound to the Vi increased the size of the conjugate increased but also the degree of cross-linking increased. The immunogenicity of the conjugates was tested in mice and measured by ELISA for anti Vi and anti DT IgG responses, and the results revealed a trend that as the amount of DT bound to the Vi increased the anti Vi responses increased. This study establishes a correlation between physico-chemical characteristics of the conjugate and the magnitude of the anti Vi and anti DT responses.

  2. Education does pay off: pneumococcal vaccine screening and administration in hospitalized adult patients with pneumonia.

    PubMed

    Kruspe, Rachel; Lillis, Rebecca; Daberkow, Dayton W; Blais, Christopher M; Wilbright, Wayne; Gupta, Shaminder; Gould, Cynthia A; Sun, Tony; Martinez, Jorge A; deBoisblanc, Ben; Ladabaum, Uri; Sanders, Charles V; Lopez, Fred A

    2003-01-01

    Streptococcus pneumoniae-associated infections are an important cause of hospitalization and mortality in high-risk and elderly patients. Even in the setting of appropriate therapy, the case fatality rate of invasive pneumococcal disease in the elderly may approach 40%. Since approximately 40,000 people die annually from pneumococcal-associated disease, it represents a substantial target for vaccine-preventable, bacterial fatalities. The 23-valent pneumococcal polysaccharide vaccine has proven consistently effective in preventing invasive pneumococcal disease. Despite its endorsement by numerous specialty societies, the pneumococcal vaccine is underutilized in the inpatient setting. In a recent report of quality indicators for Medicare beneficiaries, the percentage of Medicare beneficiaries in Louisiana admitted with pneumonia who were screened or received the pneumococcal vaccination prior to discharge was only 4%, the lowest percentage in the United States. The Louisiana State University-New Orleans Internal Medicine Department and its house staff embarked upon a retrospective study to determine its baseline pneumococcal vaccination or screening rates for all patients with pneumonia on its inpatient services at the The Medical Center of Louisiana in New Orleans from July 2000 through June 2001. From July 2001 through June 2002 an intensive educational intervention concentrating on the indications and benefits of pneumococcal vaccination was directed toward the Louisiana State University Internal Medicine house staff assigned to the inpatient service. Retrospective analysis for pneumococcal vaccine screening and administration of charts of all patients with pneumonia on the LSU Medicine service from July 2001 through June 2002 was performed in order to determine the effects of the intervention. Data from the pre-educational intervention period revealed a baseline pneumococcal vaccine screening or administration rate of 11% for all patients with pneumonia on the

  3. Antibody response to a seven-valent pneumococcal conjugated vaccine in patients with ataxia-telangiectasia.

    PubMed

    Sanal, Ozden; Ersoy, Fugen; Tezcan, Ilhan; Metin, Ayse; Turul, Tuba; Gariboglu, Semra; Yel, Leman

    2004-07-01

    Immunodeficiency is a characteristic feature of ataxia-telangiectasia (A-T). Humoral immunodeficiency generally consists of hypogammaglobulinemia and impaired antibody response to bacterial and viral antigens. We previously observed defective antibody response to 23-valent pneumococcal polysaccharide vaccine (PPV) in 96% of 29 patients with A-T. In this study, we investigated the antibody response to a seven-valent pneumococcal conjugate vaccine, PCV7, in 14 patients with A-T. IgG antibody levels to four pneumococcal serotypes, 6B, 14, 19F, 23F, which were included in PCV7, were measured by ELISA in pre- and postimmunization serum samples. Antibody titers against each individual Streptococcus pneumoniae serotype was considered to be positive when serotype specific pneumococcal antibody titer was higher than 10% (>10 U/mL) of the reference plasma pool level. However, when the fold increase (FI) in postimmunization antibody titer was less than two, the subject was determined to be unresponsive to the given serotype. The values were compared with the results obtained in age- and ethnic-matched children after one dose of PPV. Only two patients produced antibodies to one serotype each; one to serotype 19 with a fold increase of <2, and the other to serotype 23F with a fold increase of 5.7 based on the above criteria, although the differences between pre- and postvaccine antibody titers for serotypes 14, 19, and 23 appeared to be statistically significant. In conclusion, A-T patients failed to respond to one dose of PCV7 vaccine. Two or more doses of conjugated vaccine may be required to recruit the help of T lymphocytes in A-T patients.

  4. Synthetic peptides representing T-cell epitopes act as carriers in pneumococcal polysaccharide conjugate vaccines.

    PubMed Central

    de Velasco, E A; Merkus, D; Anderton, S; Verheul, A F; Lizzio, E F; Van der Zee, R; Van Eden, W; Hoffman, T; Verhoef, J; Snippe, H

    1995-01-01

    Improvement of antibody responses to polysaccharides through their linkage to proteins is thought to be mediated by protein-specific T helper (Th) cells. To investigate whether the carrier protein of a conjugate could be substituted by a Th epitope, Streptococcus pneumoniae type 17F polysaccharide (PS) was bromoacetylated and coupled to different peptides via their carboxy-terminal cysteines. Two peptides, one from the mycobacterial 65-kDa heat shock protein (hsp65) and the other from influenza virus hemagglutinin, are well-known Th epitopes. Two other peptides were selected from the pneumolysin sequence by Th epitope prediction methods; one of them was synthesized with cysteine either at the carboxy or the amino terminus. Three conjugates consistently elicited in mice anti-PS immunoglobulin M (IgM) and IgG responses that were not observed upon immunization with derivatized PS without peptide. The same conjugates induced no anti-PS antibody responses in athymic (nu/nu) mice, whereas clear responses were elicited in euthymic (nu/+) controls, demonstrating the thymus-dependent character of these conjugates. Only the three conjugates inducing anti-PS responses were capable of eliciting antipeptide antibodies. One of the immunogenic conjugates was studied in more detail. It induced significant protection and an anti-PS IgG response comprising all subclasses. On the basis of these results and proliferation studies with peptide and conjugate-primed cells, it is concluded that linkage of Th epitopes to PS in the right orientation enhances its immunogenicity in a thymus-dependent manner. Future possibilities for using peptides as carriers for inducing antibody responses to poorly immunogenic saccharide antigens are discussed. PMID:7532630

  5. Rationale and design of the CAPAMIS study: Effectiveness of pneumococcal vaccination against community-acquired pneumonia, acute myocardial infarction and stroke

    PubMed Central

    2010-01-01

    Background The 23-valent polysaccharide pneumococcal vaccine (PPV-23) is recommended for elderly and high-risk people, although its effectiveness is controversial. Some studies have reported an increasing risk of acute vascular events among patients with pneumonia, and a recent case-control study has reported a reduction in the risk of myocardial infarction among patients vaccinated with PPV-23. Given that animal experiments have shown that pneumococcal vaccination reduces the extent of atherosclerotic lesions, it has been hypothesized that PPV-23 could protect against acute vascular events by an indirect effect preventing pneumonia or by a direct effect on oxidized low-density lipoproteins. The main objective of this study is to evaluate the clinical effectiveness of PPV-23 in reducing the risk of pneumonia and acute vascular events (related or nonrelated with prior pneumonia) in the general population over 60 years. Methods/Design Cohort study including 27,000 individuals 60 years or older assigned to nine Primary Care Centers in the region of Tarragona, Spain. According to the reception of PPV-23 before the start of the study, the study population will be divided into vaccinated and nonvaccinated groups, which will be followed during a consecutive 30-month period. Primary Care and Hospitals discharge databases will initially be used to identify study events (community-acquired pneumonia, hospitalisation for acute myocardial infarction and stroke), but all cases will be further validated by checking clinical records. Multivariable Cox regression analyses estimating hazard ratios (adjusted for age, sex and comorbidities) will be used to estimate vaccine effectiveness. Discussion The results of the study will contribute to clarify the controversial effect of the PPV-23 in preventing community-acquired pneumonia and they will be critical in determining the posible role of pneumococcal vaccination in cardiovascular prevention. PMID:20085658

  6. MyD88-dependent pro-inflammatory activity in Vi polysaccharide vaccine against typhoid promotes Ab switching to IgG.

    PubMed

    Garg, Rohini; Akhade, Ajay Suresh; Yadav, Jitender; Qadri, Ayub

    2015-10-01

    Vi capsular polysaccharide is currently in use as a vaccine against human typhoid caused by Salmonella Typhi. The vaccine efficacy correlates with IgG anti-Vi Abs. We have recently reported that Vi can generate inflammatory responses through activation of the TLR2/TLR1 complex. In the present study, we show that immunization with Vi produces IgM as well as IgG Abs in wild type mice. This ability is not compromised in mice deficient in T cells. However, immunization of mice lacking the TLR adaptor protein, MyD88, with Vi elicits only IgM Abs. These results suggest that MyD88-dependent pro-inflammatory ability of the Vi vaccine might be vital in generating IgG Abs with this T-independent Ag.

  7. Biologic properties and vaccine potential of the staphylococcal poly-N-acetyl glucosamine surface polysaccharide.

    PubMed

    Maira-Litran, Tomas; Kropec, Andrea; Goldmann, Donald; Pier, Gerald B

    2004-02-17

    Staphylococci have become the most common causes of nosocomial bacterial infections, and this fact, along with increasing problems associated with antimicrobial resistance, spurs the need for finding immunotherapeutic alternatives to prevent and possibly treat these infections. Most virulent, clinical isolates of both coagulase-negative staphylococci (CoNS) and Staphylococcus aureus carry the ica locus which encodes proteins that synthesize a polymer of beta-1-6 linked N-acetyl glucosamine residues (PNAG). Animal studies have shown purified PNAG can elicit protective immunity against both CoNS and S. aureus, suggesting its potential as a broadly protective vaccine for many clinically important strains of staphylococci.

  8. [Pneumococcal vaccines. New conjugate vaccines for adults].

    PubMed

    Campins Martí, Magda

    2015-11-01

    Pneumococcal infections are a significant cause of morbidity and mortality, and are one of the 10 leading causes of death worldwide. Children under 2 years have a higher incidence rate, followed by adults over 64 years. The main risk group are individuals with immunodeficiency, and those with anatomical or functional asplenia, but can also affect immunocompetent persons with certain chronic diseases. Significant progress has been made in the last 10 years in the prevention of these infections. Until a few years ago, only the 23-valent non-conjugate pneumococcal vaccine was available. Its results were controversial in terms of efficacy and effectiveness, and with serious limitations on the type of immune response induced. The current possibility of using the 13-valent conjugate vaccine in adults has led to greater expectations in improving the prevention of pneumococcal disease in these age groups.

  9. Immune Responses to the O-Specific Polysaccharide Antigen in Children Who Received a Killed Oral Cholera Vaccine Compared to Responses following Natural Cholera Infection in Bangladesh

    PubMed Central

    Uddin, Taher; Xu, Peng; Aktar, Amena; Johnson, Russell A.; Rahman, Mohammad Arif; Alam, Mohammad Murshid; Bufano, Meagan Kelly; Eckhoff, Grace; Wu-Freeman, Ying; Yu, Yanan; Sultana, Tania; Khanam, Farhana; Saha, Amit; Chowdhury, Fahima; Khan, Ashraf I.; Charles, Richelle C.; LaRocque, Regina C.; Harris, Jason B.; Calderwood, Stephen B.; Kováč, Pavol; Qadri, Firdausi; Ryan, Edward T.

    2013-01-01

    Current oral cholera vaccines induce lower levels of protective efficacy and shorter durations of protection in young children than in adults. Immunity against cholera is serogroup specific, and immune responses to Vibrio cholerae lipopolysaccharide (LPS), the antigen that mediates serogroup-specific responses, are associated with protection against disease. Despite this, responses against V. cholerae O-specific polysaccharide (OSP), a key component of the LPS responsible for specificity, have not been characterized in children. Here, we report a comparison of polysaccharide antibody responses in children from a region in Bangladesh where cholera is endemic, including infants (6 to 23 months, n = 15), young children (24 to 59 months, n = 14), and older children (5 to 15 years, n = 23) who received two doses of a killed oral cholera vaccine 14 days apart. We found that infants and young children receiving the vaccine did not mount an IgG, IgA, or IgM antibody response to V. cholerae OSP or LPS, whereas older children showed significant responses. In comparison to the vaccinees, young children with wild-type V. cholerae O1 Ogawa infection did mount significant antibody responses against OSP and LPS. We also demonstrated that OSP responses correlated with age in vaccinees, but not in cholera patients, reflecting the ability of even young children with wild-type cholera to develop OSP responses. These differences might contribute to the lower efficacy of protection rendered by vaccination than by wild-type disease in young children and suggest that efforts to improve lipopolysaccharide-specific responses might be critical for achieving optimal cholera vaccine efficacy in this younger age group. PMID:23515016

  10. A Staphylococcus aureus capsular polysaccharide (CP) vaccine and CP-specific antibodies protect mice against bacterial challenge.

    PubMed Central

    Fattom, A I; Sarwar, J; Ortiz, A; Naso, R

    1996-01-01

    The efficacy of capsular polysaccharide (CP)-specific antibodies elicited by active immunization with vaccines composed of Staphylococcus aureus types 5 and 8 CP linked to Pseudomonas aeruginosa exoprotein A or with immune immunoglobulin G (I-IgG) obtained from vaccinated plasma donors was tested in lethal and sublethal bacterial mouse challenge models. A dose of 2 x 10(5) CFU of S. aureus type 5 CP per mouse administered intraperitoneally (i.p.) with 5% hog mucin was found to cause 80 to 100% mortality in BALB/c mice within 2 to 5 days. Mice passively immunized i.p. 24 h earlier or subcutaneously 48 h earlier with 0.5 ml of I-IgG showed significantly higher average survival rates than animals receiving standard IgG or saline (P < 0.01) following the bacterial challenge. Animals actively immunized with the monovalent type 5 CP-P. aeruginosa exoprotein A conjugate showed a survival rate of 73% compared with 13% in phosphate-buffered saline-immunized animals. The prechallenge geometric mean titer of type 5 CP antibodies in animals that died was significantly (P < 0.05) lower than that of animals which survived the challenge (95.7 versus 223.6 micrograms/ml, respectively). The IgG was further evaluated in mice challenged i.p. with a sublethal dose of 5 x 10(4) CFU per mouse. Serial blood counts were performed on surviving animals at 6, 12, 24, and 48 h. Surviving animals were sacrificed at 72 h, and bacterial counts were performed on their kidneys, livers, and peritoneal lavage fluids. Animals receiving I-IgG had lower bacterial counts in blood samples and lower bacterial densities in kidneys, livers, and peritoneal lavage samples than mice immunized with standard IgG (P < 0.05). These data suggest that S. aureus type 5 CP antibodies induced by active immunization or administered by passive immunization confer protection against S. aureus infections. PMID:8613375

  11. The adjuvant effects of high-molecule-weight polysaccharides purified from Antrodia cinnamomea on dendritic cell function and DNA vaccines.

    PubMed

    Lin, Chi-Chen; Pan, I-Hong; Li, Yi-Rong; Pan, Yi-Gen; Lin, Ming-Kuem; Lu, Yi-Huang; Wu, Hsin-Chieh; Chu, Ching-Liang

    2015-01-01

    The biological activity of the edible basidiomycete Antrodia cinnamomea (AC) has been studied extensively. Many effects, such as anti-cancer, anti-inflammatory, and antioxidant activities, have been reported from either crude extracts or compounds isolated from AC. However, research addressing the function of AC in enhancing immunity is rare. The aim of the present study is to investigate the active components and the mechanism involved in the immunostimulatory effect of AC. We found that polysaccharides (PS) in the water extract of AC played a major role in dendritic cell (DC) activation, which is a critical leukocyte in initiating immune responses. We further size purified and identified that the high-molecular weight PS fraction (greater than 100 kDa) exhibited the activating effect. The AC high-molecular weight PSs (AC hmwPSs) promoted pro-inflammatory cytokine production by DCs and the maturation of DCs. In addition, DC-induced antigen-specific T cell activation and Th1 differentiation were increased by AC hmwPSs. In studying the molecular mechanism, we confirmed the activation of the MAPK and NF-κB pathways in DCs after AC hmwPSs treatment. Furthermore, we demonstrated that TLR2 and TLR4 are required for the stimulatory activity of AC hmwPSs on DCs. In a mouse tumor model, we demonstrated that AC hmwPSs enhanced the anti-tumor efficacy of the HER-2/neu DNA vaccine by facilitating specific Th1 responses. Thus, we conclude that hmwPSs are the major components of AC that stimulate DCs via the TLR2/TLR4 and NF-κB/MAPK signaling pathways. The AC hmwPSs have potential to be applied as adjuvants.

  12. The Adjuvant Effects of High-Molecule-Weight Polysaccharides Purified from Antrodia cinnamomea on Dendritic Cell Function and DNA Vaccines

    PubMed Central

    Lin, Chi-Chen; Pan, I-Hong; Li, Yi-Rong; Pan, Yi-Gen; Lin, Ming-Kuem; Lu, Yi-Huang; Wu, Hsin-Chieh; Chu, Ching-Liang

    2015-01-01

    The biological activity of the edible basidiomycete Antrodia cinnamomea (AC) has been studied extensively. Many effects, such as anti-cancer, anti-inflammatory, and antioxidant activities, have been reported from either crude extracts or compounds isolated from AC. However, research addressing the function of AC in enhancing immunity is rare. The aim of the present study is to investigate the active components and the mechanism involved in the immunostimulatory effect of AC. We found that polysaccharides (PS) in the water extract of AC played a major role in dendritic cell (DC) activation, which is a critical leukocyte in initiating immune responses. We further size purified and identified that the high-molecular weight PS fraction (greater than 100 kDa) exhibited the activating effect. The AC high-molecular weight PSs (AC hmwPSs) promoted pro-inflammatory cytokine production by DCs and the maturation of DCs. In addition, DC-induced antigen-specific T cell activation and Th1 differentiation were increased by AC hmwPSs. In studying the molecular mechanism, we confirmed the activation of the MAPK and NF-κB pathways in DCs after AC hmwPSs treatment. Furthermore, we demonstrated that TLR2 and TLR4 are required for the stimulatory activity of AC hmwPSs on DCs. In a mouse tumor model, we demonstrated that AC hmwPSs enhanced the anti-tumor efficacy of the HER-2/neu DNA vaccine by facilitating specific Th1 responses. Thus, we conclude that hmwPSs are the major components of AC that stimulate DCs via the TLR2/TLR4 and NF-κB/MAPK signaling pathways. The AC hmwPSs have potential to be applied as adjuvants. PMID:25723174

  13. Advax™, a polysaccharide adjuvant derived from delta inulin, provides improved influenza vaccine protection through broad-based enhancement of adaptive immune responses

    PubMed Central

    Honda-Okubo, Yoshikazu; Saade, Fadi; Petrovsky, Nikolai

    2012-01-01

    Advax™ adjuvant is derived from inulin, a natural plant-derived polysaccharide that when crystallized in the delta polymorphic form, becomes immunologically active. This study was performed to assess the ability of Advax™ adjuvant to enhance influenza vaccine immunogenicity and protection. Mice were immunized with influenza vaccine alone or combined with Advax™ adjuvant. Immuno-phenotyping of the anti-influenza response was performed including antibody isotypes, B-cell ELISPOT, CD4 and CD8 T-cell proliferation, influenza-stimulated cytokine secretion, DTH skin tests and challenge with live influenza virus. Advax™ adjuvant increased neutralizing antibody and memory B-cell responses to influenza. It similarly enhanced CD4 and CD8 T-cell proliferation and increased influenza-stimulated IL-2, IFN-γ, IL-5, IL-6, and GM-CSF responses. This translated into enhanced protection against mortality and morbidity in mice. Advax™ adjuvant provided significant antigen dose-sparing compared to influenza antigen alone. Protection could be transferred from mice that had received Advax™-adjuvanted vaccine to naïve mice by immune serum. Enhanced humoral and T-cell responses induced by Advax™-formulated vaccine were sustained 12 months post-immunization. Advax™ adjuvant had low reactogenicity and no adverse events were identified. This suggests Advax™ adjuvant could be a useful influenza vaccine adjuvant. PMID:22728225

  14. Aging promotes B-1b cell responses to native, but not protein-conjugated, pneumococcal polysaccharides: implications for vaccine protection in older adults.

    PubMed

    Haas, Karen M; Blevins, Maria W; High, Kevin P; Pang, Bing; Swords, W Edward; Yammani, Rama D

    2014-01-01

    The efficacy of different vaccines in protecting elderly individuals against Streptococcus pneumoniae infections is not clear. In the current study, aged mice (22-25 months old) exhibited significantly increased susceptibility to respiratory infection with serotype 3 S. pneumoniae relative to younger adult mice, regardless of whether mice were naive or immunized with native pneumococcal polysaccharide (PPS; Pneumovax23) or protein-PPS conjugate (Prevnar-13) vaccines. Nonetheless, Pneumovax-immunized aged mice developed limited bacteremia following respiratory challenge and exhibited significantly increased survival following systemic challenge relative to Prevnar-immune aged mice and young mice that had received either vaccine. This was explained by >10-fold increases in PPS-specific immunoglobulin G (IgG) levels in Pneumovax-immunized aged mice relative to other groups. Remarkably, PPS3-specific B-cell expansion, IgG switching, plasmablast differentiation, and spleen and bone marrow antibody-secreting cell frequencies were 10-fold higher in aged mice following Pneumovax immunization relative to young mice, due to significantly increased B-1b cell participation. In summary, this study highlights (1) the need to devise strategies to enhance respiratory immunity in aged populations, (2) the diverse responses young and aged populations generate to Pneumovax vs Prevnar vaccines, and (3) the potential value of exploiting B-1b cell responses in aged individuals for increased vaccine efficacy.

  15. Rough mutants defective in core and O-polysaccharide synthesis and export induce antibodies reacting in an indirect ELISA with smooth lipopolysaccharide and are less effective than Rev 1 vaccine against Brucella melitensis infection of sheep.

    PubMed

    Barrio, María B; Grilló, María J; Muñoz, Pilar M; Jacques, Isabelle; González, David; de Miguel, María J; Marín, Clara M; Barberán, Montserrat; Letesson, Jean-J; Gorvel, Jean-P; Moriyón, Ignacio; Blasco, José M; Zygmunt, Michel S

    2009-03-10

    Classical brucellosis vaccines induce antibodies to the O-polysaccharide section of the lipopolysaccharide that interfere in serodiagnosis. Brucella rough (R) mutants lack the O-polysaccharide but their usefulness as vaccines is controversial. Here, Brucella melitensis R mutants in all main lipopolysaccharide biosynthetic pathways were evaluated in sheep in comparison with the reference B. melitensis Rev 1 vaccine. In a first experiment, these mutants were tested for ability to induce anti-O-polysaccharide antibodies, persistence and spread through target organs, and innocuousness. Using the data obtained and those of genetic studies, three candidates were selected and tested for efficacy as vaccines against a challenge infecting 100% of unvaccinated ewes. Protection by R vaccines was 54% or less whereas Rev 1 afforded 100% protection. One-third of R mutant vaccinated ewes became positive in an enzyme-linked immunosorbent assay with smooth lipopolysaccharide due to the core epitopes remaining in the mutated lipopolysaccharide. We conclude that R vaccines interfere in lipopolysaccharide immunosorbent assays and are less effective than Rev 1 against B. melitensis infection of sheep.

  16. Antibody and Plasmablast Response to 13-Valent Pneumococcal Conjugate Vaccine in Chronic Lymphocytic Leukemia Patients – Preliminary Report

    PubMed Central

    Pasiarski, Marcin; Rolinski, Jacek; Grywalska, Ewelina; Stelmach-Goldys, Agnieszka; Korona-Glowniak, Izabela; Gozdz, Stanislaw; Hus, Iwona; Malm, Anna

    2014-01-01

    Background Chronic lymphocytic leukemia (CLL) leads to significant immune system dysfunction. The predominant clinical presentation in 50% of patients involves recurrent, often severe, infections. Infections are also the most common (60–80%) cause of deaths in CLL patients. The scope of infections varies with the clinical stage of the disease. Treatment-naive patients typically present with respiratory tract infections caused by encapsulated bacteria Streptococcus pneumoniae and Haemophilus influenzae. Since 2012, the 13-valent pneumococcal conjugate vaccine (PCV13) has been recommended in the United States and some EU countries for pneumococcal infection prevention in patients with CLL (besides the long-standing standard, 23-valent pneumococcal polysaccharide vaccine, PPV23). The aim of this study was to compare the immune response to PCV13 in 24 previously untreated CLL patients and healthy subjects. Methods Both groups were evaluated for: the levels of specific pneumococcal antibodies, the levels of IgG and IgG subclasses and selected peripheral blood lymphocyte subpopulations including the frequency of plasmablasts before and after immunization. Results Adequate response to vaccination, defined as an at least two-fold increase in specific pneumococcal antibody titers versus pre-vaccination baseline titers, was found in 58.3% of CLL patients and 100% of healthy subjects. Both the CLL group and the control group demonstrated a statistically significant increase in the IgG2 subclass levels following vaccination (P = 0.0301). After vaccination, the frequency of plasmablasts was significantly lower (P<0.0001) in CLL patients in comparison to that in controls. Patients who responded to vaccination had lower clinical stage of CLL as well as higher total IgG, and IgG2 subclass levels. No significant vaccine-related side effects were observed. Conclusions PCV13 vaccination in CLL patients is safe and induces an effective immune response in a considerable

  17. Group B Streptococcus Capsular Polysaccharide-Cholera Toxin B Subunit Conjugate Vaccines Prepared by Different Methods for Intranasal Immunization

    PubMed Central

    Shen, Xuzhuang; Lagergård, Teresa; Yang, Yonghong; Lindblad, Marianne; Fredriksson, Margareta; Holmgren, Jan

    2001-01-01

    Group B Streptococcus (GBS) type III capsular polysaccharide (CPS III) was conjugated to recombinant cholera toxin B subunit (rCTB) using three different methods which employed (i) cystamine and N-succinimidyl-3-(2-pyridyldithio)propionate (SPDP), (ii) carbodiimide with adipic acid dihydrazide (ADH) as a spacer, or (iii) reductive amination (RA). The CPS III-rCTB conjugates were divided into large- and small-molecular-weight (Mr) fractions, and the immunogenicities of the different preparations after intranasal (i.n.) immunization were studied in mice. Both large- and small-Mr conjugates of CPS III-rCTBRA or CPS III-rCTBADH induced high, almost comparable levels of CPS-specific immunoglobulin G (IgG) in serum, lungs, and vagina that were generally superior to those obtained with CPS III-rCTBSPDP conjugates or a CPS III and rCTB mixture. However, the smaller-Mr conjugates of CPS III-rCTBRA or CPS III-rCTBADH in most cases elicited a lower anti-CPS IgA immune response than the large-Mr conjugates, and the highest anti-CPS IgA titers in both tissues and serum were obtained with the large-Mr CPS III-rCTBRA conjugate. Serum IgG anti-CPS titers induced by the CPS III-rCTBRA conjugate had high levels of specific IgG1, IgG2a, IgG2b, and IgG3 antibodies. Based on the effectiveness of RA for coupling CPS III to rCTB, RA was also tested for conjugating GBS CPS Ia with rCTB. As for the CPS III-rCTB conjugates, the immunogenicity of CPS Ia was greatly increased by conjugation to rCTB. Intranasal immunization with a combination of CPS Ia-rCTB and CPS III-rCTB conjugates was shown to induce anti-CPS Ia and III immune responses in serum and lungs that were fully comparable with the responses to immunization with the monovalent CPS Ia-rCTB or CPS III-rCTB conjugates. These results suggest that the GBS CPS III-rCTB and CPS Ia-rCTB conjugates prepared by the RA method may be used in bivalent and possibly also in multivalent mucosal GBS conjugate vaccines. PMID:11119518

  18. Salmonella enterica Serovar Enteritidis Core O Polysaccharide Conjugated to H:g,m Flagellin as a Candidate Vaccine for Protection against Invasive Infection with S. Enteritidis▿†

    PubMed Central

    Simon, Raphael; Tennant, Sharon M.; Wang, Jin Y.; Schmidlein, Patrick J.; Lees, Andrew; Ernst, Robert K.; Pasetti, Marcela F.; Galen, James E.; Levine, Myron M.

    2011-01-01

    Nontyphoidal Salmonella enterica serovars Enteritidis and Typhimurium are a common cause of gastroenteritis but also cause invasive infections and enteric fever in certain hosts (young children in sub-Saharan Africa, the elderly, and immunocompromised individuals). Salmonella O polysaccharides (OPS) and flagellar proteins are virulence factors and protective antigens. The surface polysaccharides of Salmonella are poorly immunogenic and do not confer immunologic memory, limitations overcome by covalently attaching them to carrier proteins. We conjugated core polysaccharide-OPS (COPS) of Salmonella Enteritidis lipopolysaccharide (LPS) to flagellin protein from the homologous strain. COPS and flagellin were purified from a genetically attenuated (ΔguaBA) “reagent strain” (derived from an isolate from a patient with clinical bacteremia) engineered for increased flagellin production (ΔclpPX). Conjugates were constructed by linking flagellin monomers or polymers at random COPS hydroxyls with various polysaccharide/protein ratios by 1-cyano-4-dimethylaminopyridinium tetrafluoroborate (CDAP) or at the 3-deoxy-d-manno-octulosonic acid (KDO) terminus by thioether chemistry. Mice immunized on days 0, 28, and 56 with COPS-flagellin conjugates mounted higher anti-LPS IgG levels than mice receiving unconjugated COPS and exhibited high antiflagellin IgG; anti-LPS and antiflagellin IgG levels increased following booster doses. Antibodies generated by COPS-flagellin conjugates mediated opsonophagocytosis of S. Enteritidis cells into mouse macrophages. Mice immunized with flagellin alone, COPS-CRM197, or COPS-flagellin conjugates were significantly protected from lethal challenge with wild-type S. Enteritidis (80 to 100% vaccine efficacy). PMID:21807909

  19. Mixture of polysaccharide and nucleic acid extracted from Bacillus Calmette-Guerin (BCG) enhances immune response of infectious bursal disease virus vaccine in chickens.

    PubMed

    Wang, X B; Liu, Z J; Lv, Y J; Long, Y; Bao, E D

    2016-05-12

    In this study, the immune response induced by a mixture of polysaccharide and nucleic acid extracted from Bacillus Calmette-Guerin (BCG) was evaluated in chickens inoculated with infectious bursal disease virus (IBDV) vaccine. After the mixture was injected intramuscularly at a dose of 0.075, 0.15 or 0.3 mg·kg(-1)·day(-1) for 3 days, the 14-day-old chickens were inoculated with the attenuated IBDV vaccine via intranasal and ocular routes. The relative weight of bursa of Fabricius (BF) and thymus, the serum IBD antibody titer, the CD4+/CD8+ ratio, and the concentrations of IFN-γ, IL-2 and IL-6 in peripheral blood were investigated on days 5, 15 and 25. The IBD antibody titer in BCG-treated groups was higher than in the negative control and only IBD-vaccinated chickens, indicating that the mixture of BCG can significantly enhance chicken humoral response. CD4+/CD8+ and the secretions of IFN-γ, IL-2 and IL-6 were also clearly increased compared with that in the negative control and IBD-vaccinated chickens, indicating that the mixture can also enhance the cell-mediated immune response. The results also showed that the relative weights of BF and thymus increased after chickens were inoculated with BCG, indicating that the BCG mixture can clearly enhance the immunity of IBD-vaccine and can be expected to be viewed as a candidate for a new type of immune adjuvant.

  20. Pneumococcal Polysaccharide Vaccine

    MedlinePlus

    ... the United States.Treatment of pneumococcal infections with penicillin and other drugs used to be more effective. ... get another dose. Anyone who has a severe allergy to any component of PPSV should not receive ...

  1. The Adjuvant Activity of Epimedium Polysaccharide-Propolis Flavone Liposome on Enhancing Immune Responses to Inactivated Porcine Circovirus Vaccine in Mice

    PubMed Central

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

    2015-01-01

    Objectives. The adjuvant activity of Epimedium polysaccharide-propolis flavone liposome (EPL) was investigated in vitro and in vivo. Methods. In vitro, the effects of EPL at different concentrations on splenic lymphocytes proliferation and mRNA expression of IFN-γ and IL-6 were determined. In vivo, the adjuvant activities of EPL, EP, and mineral oil were compared in BALB/c mice through vaccination with inactivated porcine circovirus type 2 (PCV2) vaccine. Results. In vitro, EPL promoted lymphocytes proliferation and increased the mRNA expression of IFN-γ and IL-6, and the effect was significantly better than EP at all concentrations. In vivo, EPL significantly promoted the lymphocytes proliferation and the secretion of cytokines and improved the killing activity of NK cells, PCV2-specific antibody titers, and the proportion of T-cell subgroups. The effects of EPL were significantly better than EP and oil adjuvant at most time points. Conclusion. EPL could significantly improve both PCV2-specific cellular and humoral immune responses, and its medium dose had the best efficacy. Therefore, EPL would be exploited in an effective immune adjuvant for inactivated PCV2 vaccine. PMID:26612996

  2. Evaluation of a Brucella melitensis mutant deficient in O-polysaccharide export system ATP-binding protein as a rough vaccine candidate.

    PubMed

    Wang, Zhen; Niu, Jian Rui; Wang, Xiao Lei; Wu, Tong Lei; Cheng, Jie; Lu, Lin; Wu, Qing Min

    2014-08-01

    Rough Brucella mutants have been sought as vaccine candidates that do not interfere with the conventional serological diagnosis of brucellosis. In this study, a rough mutant of Brucella melitensis was generated by the disruption of the wzt gene, which encodes the O-polysaccharide (O-PS) export system ATP-binding protein. In vivo, the mutant 16MΔwzt was attenuated and conferred a level of protection against B. melitensis 16M challenge similar to that conferred by the vaccine strain B. melitensis M5 in mice. In pregnant sheep, the mutant 16MΔwzt did not induce abortion. In vitro, 16MΔwzt was more susceptible to polymyxin B and complement-mediated killing than B. melitensis 16M was. Most importantly, although 16MΔwzt had a rough phenotype, it was able to synthesize O-PS and did not induce detectable specific antibodies in sheep. These results suggested that 16MΔwzt deserved to further systematic evaluation as a vaccine for target animal hosts due to its promising features.

  3. Antibody Persistence at 1 and 4 Years Following a Single Dose of MenAfriVac or Quadrivalent Polysaccharide Vaccine in Healthy Subjects Aged 2–29 Years

    PubMed Central

    Diallo, Aldiouma; Sow, Samba O.; Idoko, Olubukola T.; Hirve, Siddhivinayak; Findlow, Helen; Preziosi, Marie-Pierre; Elie, Cheryl; Kulkarni, Prasad S.; Parulekar, Varsha; Diarra, Bou; Cheick Haidara, Fadima; Diallo, Fatoumata; Tapia, Milagritos; Akinsola, Adebayo K.; Adegbola, Richard A.; Bavdekar, Ashish; Juvekar, Sanjay; Chaumont, Julie; Martellet, Lionel; Marchetti, Elisa; LaForce, Marc F.; Plikaytis, Brian D.; Enwere, Godwin C.; Tang, Yuxiao; Borrow, Ray; Carlone, George; Viviani, Simonetta

    2015-01-01

    Background. Mass vaccination campaigns of the population aged 1–29 years with 1 dose of group A meningococcal (MenA) conjugate vaccine (PsA-TT, MenAfriVac) in African meningitis belt countries has resulted in the near-disappearance of MenA. The vaccine was tested in clinical trials in Africa and in India and found to be safe and highly immunogenic compared with the group A component of the licensed quadrivalent polysaccharide vaccine (PsACWY). Antibody persistence in Africa and in India was investigated. Methods. A total of 900 subjects aged 2–29 years were followed up for 4 years in Senegal, Mali, and The Gambia (study A). A total of 340 subjects aged 2–10 years were followed up for 1 year in India (study B). In study A, subjects were randomized in a 2:1 ratio, and in study B a 1:1 ratio to receive either PsA-TT or PsACWY. Immunogenicity was evaluated by measuring MenA serum bactericidal antibody (SBA) with rabbit complement and by a group A–specific immunoglobulin G (IgG) enzyme-linked immunosorbent assay. Results. In both studies, substantial SBA decay was observed at 6 months postvaccination in both vaccine groups, although more marked in the PsACWY group. At 1 year and 4 years (only for study A) postvaccination, SBA titers were relatively sustained in the PsA-TT group, whereas a slight increasing trend, more pronounced among the youngest, was observed in the participants aged <18 years in the PsACWY groups. The SBA titers were significantly higher in the PsA-TT group than in the PsACWY group at any time point, and the majority of subjects in the PsA-TT group had SBA titers ≥128 and group A–specific IgG concentrations ≥2 µg/mL at any point in time in both the African and Indian study populations. Conclusions. Four years after vaccination with a single dose of PsA-TT vaccine in Africa, most subjects are considered protected from MenA disease. Clinical Trials Registration. PsA-TT-003 (ISRCTN87739946); PsA-TT-003a (ISRCTN46335400). PMID

  4. Comparison of dual influenza and pneumococcal polysaccharide vaccination with influenza vaccination alone for preventing pneumonia and reducing mortality among the elderly: A meta-analysis

    PubMed Central

    Zhang, Yan-Yang; Tang, Xue-Feng; Du, Chang-Hui; Wang, Bin-Bing; Bi, Zhen-Wang; Dong, Bi-Rong

    2016-01-01

    ABSTRACT The purpose of this study was to perform a meta-analysis comparing the effectiveness of influenza vaccination alone versus influenza plus pneumococcal dual vaccination for the prevention of pneumonia and mortality in adults ≥ 65 years of age. Medline, Cochrane, CENTRAL, EMBASE, and Google Scholar databases were searched. Inclusion criteria were: 1) Randomized controlled trials (RCTs), 2-arm prospective studies, or retrospective cohort studies; 2) Patients were ≥ 65 years of age with or without chronic respiratory disease; 3) Patients received the influenza vaccine alone or dual pneumococcal and influenza vaccination; 4) Results included incidence of recurrent respiratory tract infections, length of hospital stay, and overall mortality rate. The outcomes were pneumonia and all-cause mortality rates. Of 142 studies identified in the database searches, 6 were ultimately included in the systematic review, and 5 were included in meta-analysis. The number of patients that received the influenza vaccination alone ranged from 211 to 29,346 (total = 53,107), and the number that received influenza+pneumococcal vaccination ranged from 246 to 72,107 (total = 102,068). Influenza+pneumococcal vaccination was associated with a significantly lower pneumonia rate than influenza vaccination alone (relative risk [RR] = 0.835, 95% confidence interval [CI]: 0.718–0.971, P = 0.019), and with a significantly lower all-cause mortality rate than influenza vaccination alone (relative risk [RR] = 0.771, 95% confidence interval [CI]: 0.707–0.842, P = 0.001). In conclusion, the results of this study support concomitant pneumococcal and influenza vaccination of the elderly as a dual vaccination strategy is associated with lower pneumonia and all-cause mortality rates. PMID:27629584

  5. Water-soluble polysaccharide isolated with alkali from the stem of Physalis alkekengi L.: structural characterization and immunologic enhancement in DNA vaccine.

    PubMed

    Yang, Jingjing; Yang, Fan; Yang, Huimin; Wang, Guiyun

    2015-05-05

    A water-soluble polysaccharide (WSPA) was isolated with alkali and purified from the mature stem of Physalis alkekengi L. WSPA (Mw=31kDa) was an acid heteropolysaccharide, which consisted of Rha, Ara, Xyl, Gal, Glc and GalA in ratio of 1.0:2.5:0.8:2.7:4.4:1.4. The results from structural analysis indicated backbone and branches of WSPA were composed of (1→3)-linked Glc, (1→3)-linked Gal, (1→2)-linked Xyl, (1→2)-linked Ara, and (1→2)-linked Rha residues. However, GalA was distributed only in the backbone of WSPA. All branches of WSPA were at O-2 of (1→6)-linked Gal and terminated with Glc. More importantly, it was found that WSPA significantly enhanced specific antibody IgG response with higher titers of IgG1 as well as IgG2b (p<0.05) in mice immunized with DNA vaccine. Therefore, WSPA can be considered as a potential adjuvant candidate in DNA vaccine.

  6. Vaccinations

    MedlinePlus

    ... vaccinated? For many years, a set of annual vaccinations was considered normal and necessary for dogs and ... to protect for a full year. Consequently, one vaccination schedule will not work well for all pets. ...

  7. Preparation, characterization, and immunological properties in mice of Escherichia coli O157 O-specific polysaccharide-protein conjugate vaccines.

    PubMed Central

    Konadu, E; Robbins, J B; Shiloach, J; Bryla, D A; Szu, S C

    1994-01-01

    Escherichia coli O157 causes severe enteritis and the extraintestinal complication of hemolytic-uremic syndrome, with their highest incidence occurring in children. We postulated that serum immunoglobulin G (IgG) antibodies to the O-specific polysaccharide of lipopolysaccharide (LPS) may confer protective immunity to enteric pathogens by inducing bactericidal reactions against the ingested organisms in the jejunum (J. B. Robbins, C. Chu, and R. Schneerson, Clin. Infect. Dis. 15:346-361, 1992; S. C. Szu, R. Gupta, and J. B. Robbins, p. 381-394, in I. K. Wachsmuth, P. A. Blake, and O. Olsvik, ed., Vibrio cholerae, 1994). Because polysaccharide-protein conjugates induce serum IgG antibodies in infants, we bound the O-specific polysaccharide of E. coli O157 to proteins. E. coli O157 LPS, treated with acetic acid or hydrazine, was derivatized with adipic acid dihydrazide and bound to proteins by carbodiimide-mediated condensation. Conjugates of these adipic hydrazide derivative were prepared with bovine serum albumin, formalin-treated exotoxin C of Clostridium welchii (Pig Bel toxoid), or Pseudomonas aeruginosa recombinant exoprotein A. The conjugates had low levels of endotoxin and elicited serum antibodies with bactericidal activity to the O157 LPS. The largest increase in LPS antibodies was of the IgG class. Clinical evaluation of E. coli O157-toxoid conjugates is planned. Images PMID:7927787

  8. Randomized Controlled Study of the Safety and Immunogenicity of Pneumococcal Vaccine Formulations Containing PhtD and Detoxified Pneumolysin with Alum or Adjuvant System AS02V in Elderly Adults

    PubMed Central

    Nilsson, Anna C.; Caubet, Magalie; Pascal, Thierry G.; Van Belle, Pascale; Poolman, Jan T.; Vandepapelière, Pierre G.; Verlant, Vincent; Vink, Peter E.

    2014-01-01

    Six vaccine formulations containing AS02V or alum (aluminum phosphate [AlPO4]) adjuvant with pneumococcal proteins, pneumococcal histidine triad D (PhtD), and/or detoxified pneumolysin (dPly), either as a polysaccharide carrier in an 8-valent pneumococcal conjugate vaccine (8PCV) or as free (unconjugated) proteins, were evaluated in adults -65 to 85 years of age. In this phase I observer-blind study, 167 healthy subjects were randomized to receive two doses (days 0 and 60) of 10 or 30 μg PhtD-dPly plus AS02V or alum, 8PCV plus AS02V or alum, or one dose (day 0) of 23-valent polysaccharide pneumococcal vaccine (23PPV) as a control (placebo on day 60). The safety, reactogenicity, and antibody-specific responses to these vaccines were evaluated. No vaccine-related serious adverse events were reported. The incidences of solicited local and specific general (fatigue and myalgia) symptoms tended to be higher in the AS02V groups than in other groups. Anti-PhtD and anti-Ply antibody responses were observed in all groups except the control group. One month post-dose 2, the anti-PhtD and anti-Ply antibody geometric mean concentrations tended to be higher with AS02V than with alum, higher with a dose of 30 μg than with 10 μg for PhtD-dPly and higher with 30-μg PhtD-dPly formulations than with conjugated PhtD and dPly (8PCV) formulations. Functional antibody responses, measured by an opsonophagocytic activity assay, tended to be higher with 8PCV than with 23PPV. In conclusion, vaccine formulations containing free or conjugated PhtD and dPly had acceptable reactogenicity and safety profiles in elderly adults. Immune responses were enhanced with an AS02V-adjuvanted formulation containing free 30-μg PhtD-dPly compared to those with alum adjuvant and conjugated proteins. (This study has been registered at ClinicalTrials.gov under registration no. NCT00756067.) PMID:24599529

  9. Randomized controlled study of the safety and immunogenicity of pneumococcal vaccine formulations containing PhtD and detoxified pneumolysin with alum or adjuvant system AS02V in elderly adults.

    PubMed

    Pauksens, Karlis; Nilsson, Anna C; Caubet, Magalie; Pascal, Thierry G; Van Belle, Pascale; Poolman, Jan T; Vandepapelière, Pierre G; Verlant, Vincent; Vink, Peter E

    2014-05-01

    Six vaccine formulations containing AS02V or alum (aluminum phosphate [AlPO4]) adjuvant with pneumococcal proteins, pneumococcal histidine triad D (PhtD), and/or detoxified pneumolysin (dPly), either as a polysaccharide carrier in an 8-valent pneumococcal conjugate vaccine (8PCV) or as free (unconjugated) proteins, were evaluated in adults -65 to 85 years of age. In this phase I observer-blind study, 167 healthy subjects were randomized to receive two doses (days 0 and 60) of 10 or 30 μg PhtD-dPly plus AS02V or alum, 8PCV plus AS02V or alum, or one dose (day 0) of 23-valent polysaccharide pneumococcal vaccine (23PPV) as a control (placebo on day 60). The safety, reactogenicity, and antibody-specific responses to these vaccines were evaluated. No vaccine-related serious adverse events were reported. The incidences of solicited local and specific general (fatigue and myalgia) symptoms tended to be higher in the AS02V groups than in other groups. Anti-PhtD and anti-Ply antibody responses were observed in all groups except the control group. One month post-dose 2, the anti-PhtD and anti-Ply antibody geometric mean concentrations tended to be higher with AS02V than with alum, higher with a dose of 30 μg than with 10 μg for PhtD-dPly and higher with 30-μg PhtD-dPly formulations than with conjugated PhtD and dPly (8PCV) formulations. Functional antibody responses, measured by an opsonophagocytic activity assay, tended to be higher with 8PCV than with 23PPV. In conclusion, vaccine formulations containing free or conjugated PhtD and dPly had acceptable reactogenicity and safety profiles in elderly adults. Immune responses were enhanced with an AS02V-adjuvanted formulation containing free 30-μg PhtD-dPly compared to those with alum adjuvant and conjugated proteins. (This study has been registered at ClinicalTrials.gov under registration no. NCT00756067.).

  10. Increased Invasive Pneumococcal Disease, North East England, UK

    PubMed Central

    Houseman, Catherine; Hughes, Gareth J.; Chapman, Kaye E.; Wilson, Deborah

    2017-01-01

    Since April 2014, invasive pneumococcal disease incidence has increased substantially across North East England, United Kingdom, reversing the decline that followed the 2006 introduction of pneumococcal conjugate vaccines. Significant increases occurred in 23-valent polysaccharide vaccine serotypes and nonvaccine serotypes. Trends in other regions and long-term effects of multivalent vaccines require further investigation. PMID:27983490

  11. American Academy of Pediatrics. Committee on Infectious Diseases. Technical report: prevention of pneumococcal infections, including the use of pneumococcal conjugate and polysaccharide vaccines and antibiotic prophylaxis.

    PubMed

    Overturf, G D

    2000-08-01

    Pneumococcal infections are the most common invasive bacterial infections in children in the United States. The incidence of invasive pneumococcal infections peaks in children younger than 2 years, reaching rates of 228/100,000 in children 6 to 12 months old. Children with functional or anatomic asplenia (including sickle cell disease [SCD]) and children with human immunodeficiency virus infection have pneumococcal infection rates 20- to 100-fold higher than those of healthy children during the first 5 years of life. Others at high risk of pneumococcal infections include children with congenital immunodeficiency; chronic cardiopulmonary disease; children receiving immunosuppressive chemotherapy; children with immunosuppressive neoplastic diseases; children with chronic renal insufficiency, including nephrotic syndrome; children with diabetes; and children with cerebrospinal fluid leaks. Children of Native American (American Indian and Alaska Native) or African American descent also have higher rates of invasive pneumococcal disease. Outbreaks of pneumococcal infection have occurred with increased frequency in children attending out-of-home care. Among these children, nasopharyngeal colonization rates of 60% have been observed, along with pneumococci resistant to multiple antibiotics. The administration of antibiotics to children involved in outbreaks of pneumococcal disease has had an inconsistent effect on nasopharyngeal carriage. In contrast, continuous penicillin prophylaxis in children younger than 5 years with SCD has been successful in reducing rates of pneumococcal disease by 84%. Pneumococcal polysaccharide vaccines have been recommended since 1985 for children older than 2 years who are at high risk of invasive disease, but these vaccines were not recommended for younger children and infants because of poor antibody response before 2 years of age. In contrast, pneumococcal conjugate vaccines (Prevnar) induce proposed protective antibody responses (>.15

  12. Epitope specificity of rabbit immunoglobulin G (IgG) elicited by pneumococcal type 23F synthetic oligosaccharide- and native polysaccharide-protein conjugate vaccines: comparison with human anti-polysaccharide 23F IgG.

    PubMed Central

    Alonso de Velasco, E; Verheul, A F; van Steijn, A M; Dekker, H A; Feldman, R G; Fernández, I M; Kamerling, J P; Vliegenthart, J F; Verhoef, J; Snippe, H

    1994-01-01

    Streptococcus pneumoniae type 23F capsular polysaccharide (PS23F) consitss of a repeating glycerol-phosphorylated branched tetrasaccharide. The immunogenicities of the following related antigens were investigated: (i) a synthetic trisaccharide comprising the backbone of one repeating unit, (ii) a synthetic tetrasaccharide comprising the complete repeating unit, and (iii) native PS23F (all three conjugated to keyhole limpet hemocyanin [KLH]) and (iv) formalin-killed S. pneumoniae 23F. All antigens except the trisaccharide-KLH conjugate induced relatively high anti-PS23F antibody levels in rabbits. The epitope specificity of such antibodies was then studied by means of an inhibition immunoassay. The alpha(1-->2)-linked L-rhamnose branch was shown to be immunodominant for immunoglobulin G (IgG) induced by tetrasaccharide-KLH, PS23F-KLH, and killed S. pneumoniae 23F: in most sera L-rhamnose totally inhibited the binding of IgG to PS23F. Thus, there appears to be no major difference in epitope specificity between IgG induced by tetrasaccharide-KLH and that induced by antigens containing the polymeric form of PS23F. Human anti-PS23F IgG (either vaccine induced or naturally acquired) had a different epitope specificity: none of the inhibitors used, including L-rhamnose and tetrasaccharide-KLH, exhibited substantial inhibition. These observations suggest that the epitope recognized by human IgG on PS23F is larger than the epitope recognized by rabbit IgG. Both human and rabbit antisera efficiently opsonized type 23F pneumococci, as measured in a phagocytosis assay using human polymorphonuclear leukocytes. PMID:7509318

  13. Vaccines

    MedlinePlus Videos and Cool Tools

    Vaccinations are injections of antigens into the body. Once the antigens enter the blood, they circulate along ... suppressor T cells stop the attack. After a vaccination, the body will have a memory of an ...

  14. Antibody Persistence and Immunologic Memory after Sequential Pneumococcal Conjugate and Polysaccharide Vaccination in HIV-Infected Children on Highly Active Antiretroviral Therapy

    PubMed Central

    Abzug, Mark J.; Song, Lin Ye; Levin, Myron J.; Nachman, Sharon A.; Borkowsky, William; Pelton, Stephen I.

    2013-01-01

    Background The capacity of pneumococcal vaccination to confer memory in HIV-infected children is critical for durable protection. Methods HIV-infected children 2–<19 years administered two doses of pneumococcal conjugate vaccine (PCV7) and one dose of polysaccharide vaccine (PPV) on HAART were randomized four-five years later to receive a PCV7 or PPV booster. Total and high avidity antibodies to serotypes 1 (PPV) and 6B and 14 (PCV7 and PPV) were determined by ELISA. Memory was defined as persistence of ≥0.5 mcg/mL of serotype-specific antibody on day 0 or change from <0.5 mcg/mL to ≥0.5 mcg/mL between day 0 and week 1, or, ≥4-fold antibody rise between day 0 and week 1. Results Prior to boosting, four to five years after the previous PCV7-PCV7-PPV series, geometric mean concentrations (GMCs) were 0.46 mcg/mL (serotype 1), 1.31 mcg/mL (serotype 6B), and 1.47 mcg/mL (serotype 14), with concentrations ≥0.5 mcg/mL in 41% (serotype 1) to 82% (serotypes 6B and 14). Memory based on antibody concentration ≥0.5 mcg/mL before or 1 week after boosting with PCV7 or PPV was demonstrated in 42–61% for serotype 1 and 87–94% for serotypes 6B and 14, with lower rates based on day 0 to week 1 ≥4-fold antibody rise (serotype 1, 3–13%; serotype 6B, 13–31%; serotype 14, 29–53%). Antibody concentrations post-boosting were greater following PCV7 than PPV for serotypes 6B and 14. Ratios of highly avid to total antibody pre- and post-boosting were 0.5–0.8. Predictors of memory included higher CD4% (nadir before HAART and at P1024 and P1061s entry), CD19% (at P1024 and P1061s entry), and antibody response after the PCV7-PCV7-PPV primary series and lower viral load (at P1024 and P1061s entry) and age. Conclusions Protective antibody concentrations, high avidity, and booster responses to PCV7 or PPV indicative of memory were present four-five years after PCV7-PCV7-PPV in HIV-infected children on HAART. PMID:23954381

  15. Vaccinating welders against pneumonia

    PubMed Central

    Palmer, Keith T; Cosgrove, Martin P

    2013-01-01

    Background In 2011 the Department of Health in England recommended that welders should each receive a single dose of the 23-valent pneumococcal vaccine (PPV23). This review assesses the evidence behind the advice and its practical implications. Method The review was informed by a systematic search in Medline, which related pneumonia to welding and/or exposure to metal fume, and was supplemented using the personal libraries of the authors. Findings There is consistent evidence that welders die more often of pneumonia, especially lobar pneumonia, are hospitalised more often with lobar and pneumococcal pneumonia, and more often develop invasive pneumococcal disease (IPD). It is estimated that one case of IPD may be prevented over a 10-year period by vaccinating 588 welders against pneumococcal infection. Conclusions A good case exists that employers should offer PPV23 vaccination to welders and other employees exposed to metal fume. Additionally, reasonable measures must be taken to minimise exposure to welding fume and welders should be encouraged not to smoke. PMID:22764269

  16. Worldwide Haemophilus influenzae Type b Disease at the Beginning of the 21st Century: Global Analysis of the Disease Burden 25 Years after the Use of the Polysaccharide Vaccine and a Decade after the Advent of Conjugates

    PubMed Central

    Peltola, Heikki

    2000-01-01

    Vaccination against Haemophilus influenzae type b (Hib) diseases began a quarter of a century ago with a polysaccharide vaccine; this vaccine was followed by four different conjugates 10 years later. In this review, the burden of global Hib disease is quantified following this 25-year period of vaccine availability to determine the potential impact of conjugate vaccines. This task was accomplished by analysis of data available in 10 languages in 75 geographical regions of over 50 countries. All severe Hib diseases, not only meningitis, were characterized, and special attention was paid to the most vulnerable age group, i.e., children aged 0 to 4 years. Prior to vaccination, the weighted worldwide incidence of meningitis in patients younger than 5 years was 57/100,000, and for all Hib diseases except nonbacteremic pneumonia, it was 71/100,000, indicating 357,000 and 445,000 cases per year, respectively. At least 108,500 of these children died. For all age groups combined, there were 486,000 cases of Hib disease, excluding pneumonia, with 114,200 deaths and probably an equal number of sequelae per annum. If the figures for nonbacteremic pneumonia are included, a conservative estimate is that over 2.2 million cases of infection and 520,000 deaths from Hib disease occurred worldwide, but the true numbers might have been greater. Despite these large numbers and availability of safe and efficacious vaccines, only 38,000 cases annually are prevented—a meager 8% or less than a 2% reduction in cases, depending on whether nonbacteremic pneumonia is included in the calculations. Although vaccination has had great success in some affluent countries, the current level of activity has had a very small impact globally. The use of conjugates, preferably with a reduced number of doses and in combination with other vaccines or perhaps in fractional doses, should be extended to less privileged countries, where most Hib disease occurs. PMID:10756001

  17. Antigen processing of glycoconjugate vaccines; the polysaccharide portion of the pneumococcal CRM(197) conjugate vaccine co-localizes with MHC II on the antigen processing cell surface.

    PubMed

    Lai, Zengzu; Schreiber, John R

    2009-05-21

    Pneumococcal (Pn) polysaccharides (PS) are T-independent (TI) antigens and do not induce immunological memory or antibodies in infants. Conjugation of PnPS to the carrier protein CRM(197) induces PS-specific antibody in infants, and memory similar to T-dependent (Td) antigens. Conjugates have improved immunogenicity via antigen processing and presentation of carrier protein with MHC II and recruitment of T cell help, but the fate of the PS attached to the carrier is unknown. To determine the location of the PS component of PnPS-CRM(197) in the APC, we separately labeled PS and protein and tracked their location. The PS of types 14-CRM(197) and 19F-CRM(197) was specifically labeled by Alexa Fluor 594 hydrazide (red). The CRM(197) was separately labeled red in a reaction that did not label PS. Labeled antigens were incubated with APC which were fixed, permeabilized and incubated with anti-MHC II antibody labeled green by Alexa Fluor 488, followed by confocal microscopy. Labeled CRM(197) was presented on APC surface and co-localized with MHC II (yellow). Labeled unconjugated 14 or 19F PS did not go to the APC surface, but PS labeled 14-CRM(197) and 19F-CRM(197) was internalized and co-localized with MHC II. Monoclonal antibody to type 14 PS bound to intracellular type 14 PS and PS-CRM(197). Brefeldin A and chloroquine blocked both CRM(197) and PS labeled 14-CRM(197) and 19F-CRM(197) from co-localizing with MHC II. These data suggest that the PS component of the CRM(197) glycoconjugate enters the endosome, travels with CRM(197) peptides to the APC surface and co-localizes with MHC II.

  18. Pneumococcal Conjugated Vaccine Reduces the High Mortality for Community-Acquired Pneumonia in the Elderly: an Italian Regional Experience

    PubMed Central

    Gallo, Tolinda; Furlan, Patrizia; Romor, Pierantonio; Bertoncello, Chiara; Buja, Alessandra; Baldovin, Tatjana

    2016-01-01

    Background Community-acquired pneumonia (CAP) is an important cause of illness and death worldwide, particularly among the elderly. Previous studies on the factors associated with mortality in patients hospitalized for CAP revealed a direct association between the type of microorganism involved, the characteristics of the patient and mortality. Vaccination status against pneumococcal disease was not considered. We conducted a retrospective analysis on the mortality rates after a first hospitalization for CAP in north-east Italy with a view to examining especially the role of anti-pneumococcal vaccination as a factor associated with pneumonia-related mortality at one year. Method Between 2012–2013, patients aged 65+ hospitalized with a primary diagnosis of CAP, identified based on International Classification of Diseases, Ninth Revision, Clinical Modification codes 481–486, were enrolled in the study only once. Patients were divided into three groups by pneumococcal vaccination status: 1) 13-valent pneumococcal conjugate vaccine (PCV13) prior to their hospitalization; 2) 23-valent pneumococcal polysaccharide vaccine (PPV23) within 5 years before hospitalization and 3) unvaccinated or PPV23 more than 5 years prior to admission. Gender, age, length of hospital stay and influenza vaccination were considered. Comorbidities were ascertained by means of a properly coded diagnosis. Every patient was followed up for 1 year and the outcome investigated was mortality for any cause and for pneumonia. Results A total of 4,030 patient were included in the study; mean age at the time of admission to hospital was 84.3±7.7; 50.9% were female. 74.2% of subjects had at least one comorbidity; 73.7% has been vaccinated against influenza. Regard to pneumococcal vaccine, 80.4% of patients were not vaccinated, 14.5% vaccinated with PPV23 and 5.1% with PCV13. The 1-year survival rates after hospitalization for pneumonia were 83.6%, 85.9% and 89.3% in the unvaccinated, PPV23 and PCV13

  19. Comparison of the immunogenicity and safety of polysaccharide and protein-conjugated pneumococcal vaccines among the elderly aged 80 years or older in Japan: an open-labeled randomized study.

    PubMed

    Namkoong, Ho; Funatsu, Yohei; Oishi, Kazunori; Akeda, Yukihiro; Hiraoka, Rika; Takeshita, Kei; Asami, Takahiro; Yagi, Kazuma; Kimizuka, Yoshifumi; Ishii, Makoto; Tasaka, Sadatomo; Suzuki, Yukio; Iwata, Satoshi; Betsuyaku, Tomoko; Hasegawa, Naoki

    2015-01-03

    An open-labeled randomized study was conducted to compare the immunogenicity and safety of polysaccharide (PPV23) or protein-conjugated pneumococcal vaccine (PCV7) among the elderly aged 80 years or older. A total of 105 nursing home residents were enrolled in this study. We analyzed the geometric mean concentration (GMC) of serotype-specific immunoglobulin G (IgG) and the geometric mean titer (GMT) of the opsonization index (OI) for serotypes 4, 6B, 9V, 14, 18C, 19F, and 23F. The GMCs of serotype-specific IgG and the GMTs of the OI significantly increased one month after vaccination in both groups for all seven serotypes evaluated. In the PCV7 group, study subjects with serotypes 4, 9V, 18C, and 23F exhibited statistically significant elevations in both serotype-specific IgGs and OIs compared to those of the PPV23 group. Both vaccines were tolerated without any severe adverse events, and no differences in systemic adverse events were observed between the two groups, although adverse reactions such as redness and localized swelling were more common in the PCV7 group. Our data demonstrated that the GMCs of serotype-specific IgG and the GMTs of the OI were higher in the PCV7 group compared to those in the PPV23 group. Our study also confirmed the safety of both the PCV7 and PPV23 vaccines in elderly people aged 80 years or older.

  20. Antibiofilm polysaccharides

    PubMed Central

    Rendueles, Olaya; Kaplan, Jeffrey B.; Ghigo, Jean-Marc

    2012-01-01

    Summary Bacterial extracellular polysaccharides have been shown to mediate many of the cell-to cell and cell-to-surface interactions that are required for the formation, cohesion and stabilization of bacterial biofilms. However, recent studies have identified several bacterial polysaccharides that inhibit biofilm formation by a wide-spectrum of bacteria and fungi both in vitro and in vivo. This review discusses the composition, modes of action, and potential biological roles of antibiofilm polysaccharides recently identified in bacteria and eukaria. Some of these molecules may have technological applications as antibiofilm agents in industry and medicine. PMID:22730907

  1. Preparation, Immunogenicity, and Protective Efficacy, in a Murine Model, of a Conjugate Vaccine Composed of the Polysaccharide Moiety of the Lipopolysaccharide of Vibrio cholerae O139 Bound to Tetanus Toxoid

    PubMed Central

    Boutonnier, Alain; Villeneuve, Sylvain; Nato, Farida; Dassy, Bruno; Fournier, Jean-Michel

    2001-01-01

    The epidemic and pandemic potential of Vibrio cholerae O139 is such that a vaccine against this newly emerged serogroup of V. cholerae is required. A conjugate made of the polysaccharide moiety (O-specific polysaccharide plus core) of the lipopolysaccharide (LPS) of V. cholerae O139 (pmLPS) was prepared by derivatization of the pmLPS with adipic acid dihydrazide and coupling to tetanus toxoid (TT) by carbodiimide-mediated condensation. The immunologic properties of the conjugate were tested using BALB/c mice injected subcutaneously three times at 2 weeks interval and then a fourth time 4 weeks later. Mice were bled 7 days after each injection and then once each month for the following 6 months. LPS and TT antibody levels were determined by enzyme-linked immunosorbent assay using immunoplates coated with either O139 LPS or TT. Both pmLPS and pmLPS-TT conjugate elicited low levels of immunoglobulin M (IgM), peaking 5 weeks after the first immunization. The conjugate elicited high levels of IgG antibodies, peaking 3 months after the first immunization and declining slowly during the following 5 months. TT alone, or as a component of conjugate, induced mostly IgG antibodies. Antibodies elicited by the conjugate recognized both capsular polysaccharide and LPS from V. cholerae O139 and were vibriocidal. They were also protective in the neonatal mouse model of cholera infection. The conjugation of the O139 pmLPS, therefore, enhanced its immunogenicity and conferred T-dependent properties to this polysaccharide. PMID:11292781

  2. Antibacterials: A sweet vaccine

    NASA Astrophysics Data System (ADS)

    Bundle, David

    2016-03-01

    Vaccination with a synthetic glycoconjugate, in combination with the administration of an inhibitor that blocks capsular polysaccharide synthesis in bacteria, could offer an alternative route to combat bacterial infections.

  3. [Pneumococcal disease and its prevention. The heptavalent pneumococcal conjugate vaccine].

    PubMed

    de Arístegui Fernández, J; Corretger Rauet, J M; García Martín, F; Hernández-Sampelayo, T; Moraga Llop, F A; Rodrigo Gonzalo De Liria, C; Ruiz Contreras, J

    2002-01-01

    Pneumococcal disease is a major cause of morbidity, hospitalization and mortality. Two age groups show a greater incidence and severity of the disease: children under the age of 5 years (mainly during the first 2 years of life) and adults aged more than 65 years. The heptavalent pneumococcal conjugate vaccine, which was commercialized in Spain in June 2001, is efficacious in children aged less than 2 years and, unlike the non-conjugate 23-valent vaccine, it induces immunological memory. In Spain the heptavalent vaccine covers 80 % of serotypes causing pneumococcal invasive disease and acute otitis media in children aged 2-59 months. The heptavalent vaccine has been shown to be immunogenic, efficacious and safe. It has proven efficacy in the prevention of invasive disease caused by the seven vaccine serotypes. In addition, it significantly decreases pneumonia and also prevent acute otitis media. The vaccine is preferably indicated in children aged less than 2 years; children aged 2-5 years may also benefit from the vaccine but those in risk groups should be prioritized. Greater knowledge of the epidemiology of pneumococcal disease and the efficiency of this vaccine in Spain will determine whether it should be included in the immunization schedule.

  4. Fungal polysaccharides.

    PubMed

    San-Blas, G; Suzuki, S; Hearn, V; Pinel, C; Kobayashi, H; Mendez, C; Niño, G; Nishikawa, A; San-Blas, F; Shibata, N

    1994-01-01

    Fungal polysaccharides are cell wall components which may act as antigens or as structural substrates. As antigens, the role of mannans in Saccharomyces cerevisiae and Candida albicans, and of glycoproteins in Aspergillus fumigatus are discussed. Analyses on beta-glucan synthetase in Paracoccidioides brasiliensis and the inhibitory effect of Hansenula mrakii killer toxin on beta-glucan biosynthesis are also considered.

  5. 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

    PubMed Central

    Eckhoff, Grace; Charles, Richelle C.; Alam, Mohammad Murshid; Sultana, Tania; Rashu, Md. Rasheduzzaman; Berger, Amanda; Gonzalez-Escobedo, Geoffrey; Mandlik, Anjali; Bhuiyan, Taufiqur Rahman; Leung, Daniel T.; LaRocque, Regina C.; Harris, Jason B.; Calderwood, Stephen B.; Qadri, Firdausi; Vann, W. F.; Kováč, Pavol; Ryan, Edward T.

    2015-01-01

    Background 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). Methodology 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. Principle Findings 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. Conclusion 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. PMID:26154421

  6. Protein carriers of conjugate vaccines

    PubMed Central

    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

  7. Vibrio cholerae O139 Conjugate Vaccines: Synthesis and Immunogenicity of V. cholerae O139 Capsular Polysaccharide Conjugates with Recombinant Diphtheria Toxin Mutant in Mice

    PubMed Central

    Kossaczka, Zuzana; Shiloach, Joseph; Johnson, Virginia; Taylor, David N.; Finkelstein, Richard A.; Robbins, John B.; Szu, Shousun C.

    2000-01-01

    Epidemiologic and experimental data provide evidence that a critical level of serum immunoglobulin G (IgG) antibodies to the surface polysaccharide of Vibrio cholerae O1 (lipopolysaccharide) and of Vibrio cholerae O139 (capsular polysaccharide [CPS]) is associated with immunity to the homologous pathogen. The immunogenicity of polysaccharides, especially in infants, may be enhanced by their covalent attachment to proteins (conjugates). Two synthetic schemes, involving 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (EDC) and 1-cyano-4-dimethylaminopyridinium tetrafluoroborate (CDAP) as activating agents, were adapted to prepare four conjugates of V. cholerae O139 CPS with the recombinant diphtheria toxin mutant, CRMH21G. Adipic acid dihydrazide was used as a linker. When injected subcutaneously into young outbred mice by a clinically relevant dose and schedule, these conjugates elicited serum CPS antibodies of the IgG and IgM classes with vibriocidal activity to strains of capsulated V. cholerae O139. Treatment of these sera with 2-mercaptoethanol (2-ME) reduced, but did not eliminate, their vibriocidal activity. These results indicate that the conjugates elicited IgG with vibriocidal activity. Conjugates also elicited high levels of serum diphtheria toxin IgG. Convalescent sera from 20 cholera patients infected with V. cholerae O139 had vibriocidal titers ranging from 100 to 3,200: absorption with the CPS reduced the vibriocidal titer of all sera to ≤50. Treatment with 2-ME reduced the titers of 17 of 20 patients to ≤50. These data show that, like infection with V. cholerae O1, infection with V. cholerae O139 induces vibriocidal antibodies specific to the surface polysaccharide of this bacterium (CPS) that are mostly of IgM class. Based on these data, clinical trials with the V. cholerae O139 CPS conjugates with recombinant diphtheria toxin are planned. PMID:10948122

  8. Polysaccharide Degradation

    NASA Astrophysics Data System (ADS)

    Stone, Bruce A.; Svensson, Birte; Collins, Michelle E.; Rastall, Robert A.

    An overview of current and potential enzymes used to degrade polysaccharides is presented. Such depolymerases are comprised of glycoside hydrolases, glycosyl transferases, phosphorylases and lyases, and their classification, active sites and action patterns are discussed. Additionally, the mechanisms that these enzymes use to cleave glycosidic linkages is reviewed as are inhibitors of depolymerase activity; reagents which react with amino acid residues, glycoside derivatives, transition state inhibitors and proteinaceous inhibitors. The characterization of various enzymes of microbial, animal or plant origin has led to their widespread use in the production of important oligosaccharides which can be incorporated into food stuffs. Sources of polysaccharides of particular interest in this chapter are those from plants and include inulin, dextran, xylan and pectin, as their hydrolysis products are purported to be functional foods in the context of gastrointestinal health. An alternative use of degraded polysaccharides is in the treatment of disease. The possibility exists to treat bacterial exopolysaccharide with lyases from bacteriophage to produce oligosaccharides exhibiting bioactive sequences. Although this area is currently in its infancy the knowledge is available to investigate further.

  9. Immunizations: vaccinations in general.

    PubMed

    Wiley, Catherine C

    2015-06-01

    The childhood immunization schedule is complex and nuanced. Although serious adverse reactions to immunizations are uncommon, clinicians must be well-versed in these reactions as well as the contraindications and precautions to each vaccine. • Conjugate vaccine technology links polysaccharide antigens to carrier proteins, triggering T-cell-dependent immunity to polysaccharides, thereby strengthening immune memory. • On the basis of some research evidence and consensus, live vaccines are generally contraindicated in immunocompromised patients and in pregnancy. Most live vaccines can be administered to household contacts of immunocompromised patients. • On the basis of some research and consensus, modified administration of meningococcal, pneumococcal, and less commonly, other vaccines may be indicated to protect immunocompromised patients. • On the basis of disease epidemiology and consensus, international travelers should be up-to-date with all routine immunizations; depending on destination, additional vaccines or immune globulin may be required.

  10. Vaccine potential of poly-1-6 beta-D-N-succinylglucosamine, an immunoprotective surface polysaccharide of Staphylococcus aureus and Staphylococcus epidermidis.

    PubMed

    Mckenney, D; Pouliot, K; Wang, Y; Murthy, V; Ulrich, M; Döring, G; Lee, J C; Goldmann, D A; Pier, G B

    2000-09-29

    Staphylococcus aureus and S. epidermidis are among the most common causes of nosocomial infection, and S. aureus is also of major concern to human health due to its occurrence in community-acquired infections. These staphylococcal species are also major pathogens for domesticated animals. We have previously identified poly-N-succinyl beta-1-6 glucosamine (PNSG) as the chemical form of the S. epidermidis capsular polysaccharide/adhesin (PS/A) which mediates adherence of coagulase-negative staphylococci (CoNS) to biomaterials, serves as the capsule for strains of CoNS that express PS/A, and is a target for protective antibodies. We have recently found that PNSG is made by S. aureus as well, where it is an environmentally regulated, in vivo-expressed surface polysaccharide and similarly serves as a target for protective immunity. Only a minority of fresh human clinical isolates of S. aureus elaborate PNSG in vitro but most could be induced to do so under specific in vitro growth conditions. However, by immunofluorescence microscopy, S. aureus cells in infected human sputa and lung elaborated PNSG. The ica genes, previously shown to encode proteins in CoNS that synthesize PNSG, were found by PCR in all S. aureus strains examined, and immunogenic and protective PNSG could be isolated from S. aureus. Active and passive immunization of mice with PNSG protected them against metastatic kidney infections after intravenous inoculation with eight phenotypically PNSG-negative S. aureus. Isolates recovered from kidneys expressed PNSG, but expression was lost with in vitro culture. Strong antibody responses to PNSG were elicited in S. aureus infected mice, and a PNSG-capsule was observed by electron microscopy on isolates directly plated from infected kidneys. PNSG represents a previously unidentified surface polysaccharide of S. aureus that is elaborated during human and animal infection and is a prominent target for protective antibodies.

  11. Vaccination status of people living with HIV/AIDS in outpatient care in Fortaleza, Ceará, Brazil.

    PubMed

    Cunha, Gilmara Holanda da; Galvão, Marli Teresinha Gimeniz; Medeiros, Camila Martins de; Rocha, Ryvanne Paulino; Lima, Maria Amanda Correia; Fechine, Francisco Vagnaldo

    2016-01-01

    Antiretroviral therapy has increased the survival of patients with HIV/AIDS, thus necessitating health promotion practice with immunization. Vaccines are critical components for protecting people living with HIV/AIDS (PLWHA). The purpose of study was to analyze the vaccination status of PLWHA in outpatient care in Fortaleza, Ceará, Brazil. Cross-sectional study performed from June 2014 to June 2015. The screening was done with patients in antiretroviral therapy, 420 patients underwent screening, but only 99 met the inclusion criteria. Data were collected for interviews using forms to characterize sociodemographic, clinical and vaccination situations. Only 14 patients had complete vaccination schedules. The most used vaccines were hepatitis B, influenza vaccine and 23-valent pneumococcal. There was no difference between men and women regarding the proportion of PLWHA with full vaccination schedule or between sex, skin color, marital status, sexual orientation, religion or occupational status. There was no difference between having or not having a complete vaccination schedule and age, years of education, family income or number of hospitalizations. CD4+ T-cells count of patients with incomplete immunization was lower than patients with complete immunization. Health education strategies can be done individually or in groups to explain the importance of vaccination and to remind about doses to be administered. Most patients did not have proper adherence to vaccination schedules, especially due to lack of guidance. Results implied that education in health is important for vaccination adhesion, knowledge of adverse events and continuation of schemes.

  12. Progress toward developing a carbohydrate-conjugate vaccine against Clostridium difficile ribotype 027: synthesis of the cell-surface polysaccharide PS-I repeating unit.

    PubMed

    Martin, Christopher E; Weishaupt, Markus W; Seeberger, Peter H

    2011-10-07

    Clostridium difficile strain ribotype 027 is a hypervirulent pathogen that is responsible for recent, severe outbreaks of serious nosocomial infections. As a foundation for the development of a preventative carbohydrate-based vaccine, we have synthesized a pentasaccharide cell wall repeating unit from PS-I unique to this strain, by the linear assembly of four monosaccharide building blocks.

  13. Immunogenicity and safety of a pentavalent acellular pertussis combined vaccine including diphtheria, tetanus, inactivated poliovirus and conjugated Haemophilus Influenzae type b polysaccharide for primary vaccination at 2, 3, 4 or 3, 4, 5 months of age in infants in China.

    PubMed

    Li, Rong Cheng; Li, Feng Xiang; Li, Yan Ping; Hou, Qi Ming; Li, Chang Gui; Li, Ya Nan; Chen, Fu Sheng; Hu, Xue Zhong; Su, Wen Bin; Zhang, Shu Min; Fang, Han Hua; Ye, Qiang; Zeng, Tian De; Liu, Tao Xuan; Li, Xiu Bi; Huang, Yun Neng; Deng, Man Ling; Zhang, Yan Ping; Ortiz, Esteban

    2011-02-24

    The aim was to demonstrate the immunogenicity and safety of a DTaP-IPV//PRP-T combined vaccine (Pentaxim(®)) compared to individual vaccines in infants in the People's Republic of China. Infants (N=792) were randomly assigned to receive DTaP-IPV//PRP-T at 2, 3 and 4 months of age (Group A) or 3, 4 and 5 months of age (Group B), or DTaP (Wuhan Institute of Biological Products), PRP-T (Act-Hib(®)) and IPV (Imovax(®) Polio) at 3, 4 and 5 months of age (Group C). Antibody titers were measured pre- and 1 month after the third vaccination; non-inferiority analyses were performed for seroprotection/seroconversion (SP/SC) rates. Safety was assessed 1 month after the primary series. SP/SC rates for the DTaP-IPV//PRP-T vaccine were high and non-inferior to the controls. Reactogenicity was low for each group and no hypotonic hyporesponsive episode or seizure was reported. In conclusion, the DTaP-IPV//PRP-T vaccine was highly immunogenic, non-inferior to the commercially available control vaccines and had a good safety profile for both primary administration schedules.

  14. Working Group on quality, safety and efficacy of typhoid Vi capsular polysaccharide conjugate, vaccines, Jeju, Republic of Korea, 5-7 September 2012.

    PubMed

    Jones, Chris; Lee, Chung Keel; Ahn, Chiyoung; Shin, Jinho; Knezevic, Ivana

    2013-09-23

    Typhoid fever is a gastrointestinal disease transmitted through the ingestion of contaminated water or food. The bacterium, Salmonella enterica subspecies enterica serovar Typhi is an important cause of illness and death in many poor countries where access to safe water and basic sanitation is limited. Humans are the only natural host and reservoir of S. Typhi. Typhoid fever causes around 21 million cases and at least 200,000 deaths per year. Currently, several groups are developing typhoid conjugate vaccines that are expected to be safe and effective in infancy or early childhood. The World Health Organization convened a meeting, in collaboration with the Korea Food and Drug Administration, with experts group in September 2012 to develop guidelines for regulatory evaluation of the quality, safety and efficacy of typhoid conjugate vaccines. This report summarizes collective views on scientific and technical issues that need to be considered in the guidelines.

  15. Typhoid fever vaccination strategies.

    PubMed

    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.

  16. Enzymatic Modifications of Polysaccharides

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Polysaccharides are often modified chemically in order to improve its properties or to impart specific characteristics. Indeed quite a few commercial products are based on modified polysaccharides. In this talk, I shall describe a new set of modified polysaccharides based on enzymatic reactions. ...

  17. Continuing effectiveness of serogroup A meningococcal conjugate vaccine, Chad, 2013.

    PubMed

    Gamougam, Kadidja; Daugla, Doumagoum M; Toralta, Jacques; Ngadoua, Cyriaque; Fermon, Florence; Page, Anne-Laure; Djingarey, Mamoudou H; Caugant, Dominique A; Manigart, Olivier; Trotter, Caroline L; Stuart, James M; Greenwood, Brian M

    2015-01-01

    In 2011, vaccination with a serogroup A meningococcal polysaccharide conjugate vaccine was implemented in 3 of 23 regions in Chad. Cases of meningitis declined dramatically in vaccinated areas, but an epidemic continued in the rest of Chad. In 2012, the remaining Chad population was vaccinated, and the epidemic was halted.

  18. New and Improved Vaccines Against Meningococcal Disease

    DTIC Science & Technology

    1990-01-01

    associated with group B meningococcal disease and their use for rapid vaccine development. Antonie Leeuwenhoek J Microbiol 1987; 53:395. 37. Gotschlich EC...Brandt B, Moran EE, Ray J. Safety and antigenicity studies of a polyvalent meningococcal protein-polysaccharide vaccine. Antonie Leeuwenhoek J Microbiol...2b and 15 antigens in complex with mixed A,CY, and W135 polysaccharides. Antonie Leeuwenhoek I Microbiol 1985; 52:239. 91. Frasch CE, Zahradnik JM

  19. Method for producing capsular polysaccharides

    NASA Technical Reports Server (NTRS)

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

    1994-01-01

    Structurally altered capsular polysaccharides are produced by mutant bacteria. These polysaccharides are isolated by selecting a wild type bacterial strain and a phage producing degradative enzymes that have substrate specificity for the capsular polysaccharides produced by the wild type bacteria. Phage-resistant mutants producing capsular polysaccharides are selected and the structurally altered capsular polysaccharide is isolated therefrom.

  20. Chemical Modification of Polysaccharides

    PubMed Central

    Cumpstey, Ian

    2013-01-01

    This review covers methods for modifying the structures of polysaccharides. The introduction of hydrophobic, acidic, basic, or other functionality into polysaccharide structures can alter the properties of materials based on these substances. The development of chemical methods to achieve this aim is an ongoing area of research that is expected to become more important as the emphasis on using renewable starting materials and sustainable processes increases in the future. The methods covered in this review include ester and ether formation using saccharide oxygen nucleophiles, including enzymatic reactions and aspects of regioselectivity; the introduction of heteroatomic nucleophiles into polysaccharide chains; the oxidation of polysaccharides, including oxidative glycol cleavage, chemical oxidation of primary alcohols to carboxylic acids, and enzymatic oxidation of primary alcohols to aldehydes; reactions of uronic-acid-based polysaccharides; nucleophilic reactions of the amines of chitosan; and the formation of unsaturated polysaccharide derivatives. PMID:24151557

  1. The diversity of Klebsiella pneumoniae surface polysaccharides

    PubMed Central

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

    2016-01-01

    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. PMID:28348868

  2. [Pneumococcal vaccine: protection of adults and reduction of antibiotic resistence by vaccination of children with a conjugated vaccine].

    PubMed

    Pletz, Mathias W

    2011-06-01

    Pneumococcal infections (pneumonia, otitis media, sinusitis, meningitis) are common and usually involve toddlers, immunocompromised and the elderly. Main reservoir of pneumococci is the nasopharyngeal zone of healthy carriers, especially of toddlers. Currently, two types of pneumococcal vaccines are in clinical use, which induce production of antibodies against capsular polysaccharides. The older vaccine consists of pure capsular polysaccharides. It induces a limited immunity, because polysaccharides are poor antigens that stimulate mainly B-cells. In children under two years of age this vaccine is not used, because it does not induce a sufficient immunologic response, presumably because of the immaturity of their immune system. In 2000, a vaccination program with a novel pneumococcal vaccine was launched in the USA. This vaccine contains capsular polysaccharides, that are conjugated with a highly immunogenic protein. It induces both a T cell and B cell response that results in specific humoral and mucosal immunity. U.S. data demonstrate, that serotypes covered by the conjugated vaccine can be reduced in the whole population by vaccination of children being the main reservoir of pneumococci. This so called ,,herd protection" results in a decrease in invasive pneumococcal diseases in vaccinees and non-vaccinees as well as in a reduction of antibiotic resistance rates by reducing resistant pneumococcal cones.

  3. Factors contributing to the immunogenicity of meningococcal conjugate vaccines

    PubMed Central

    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

  4. Recombinant expression of Streptococcus pneumoniae capsular polysaccharides in Escherichia coli

    PubMed Central

    Kay, Emily J.; Yates, Laura E.; Terra, Vanessa S.; Cuccui, Jon; Wren, Brendan W.

    2016-01-01

    Currently, Streptococcus pneumoniae is responsible for over 14 million cases of pneumonia worldwide annually, and over 1 million deaths, the majority of them children. The major determinant for pathogenesis is a polysaccharide capsule that is variable and is used to distinguish strains based on their serotype. The capsule forms the basis of the pneumococcal polysaccharide vaccine (PPV23) that contains purified capsular polysaccharide from 23 serotypes, and the pneumococcal conjugate vaccine (PCV13), containing 13 common serotypes conjugated to CRM197 (mutant diphtheria toxin). Purified capsule from S. pneumoniae is required for pneumococcal conjugate vaccine production, and costs can be prohibitively high, limiting accessibility of the vaccine in low-income countries. In this study, we demonstrate the recombinant expression of the capsule-encoding locus from four different serotypes of S. pneumoniae within Escherichia coli. Furthermore, we attempt to identify the minimum set of genes necessary to reliably and efficiently express these capsules heterologously. These E. coli strains could be used to produce a supply of S. pneumoniae serotype-specific capsules without the need to culture pathogenic bacteria. Additionally, these strains could be applied to synthetic glycobiological applications: recombinant vaccine production using E. coli outer membrane vesicles or coupling to proteins using protein glycan coupling technology. PMID:27110302

  5. HPV vaccine

    MedlinePlus

    Vaccine - HPV; Immunization - HPV; Gardasil; HPV2; HPV4; Vaccine to prevent cervical cancer; Genital warts - HPV vaccine; Cervical dysplasia - HPV vaccine; Cervical cancer - HPV vaccine; Cancer of the cervix - HPV vaccine; Abnormal ...

  6. Vaccines against typhoid fever.

    PubMed

    Guzman, Carlos A; Borsutzky, Stefan; Griot-Wenk, Monika; Metcalfe, Ian C; Pearman, Jon; Collioud, Andre; Favre, Didier; Dietrich, Guido

    2006-05-01

    Because of high infectivity and significant disease burden, typhoid fever constitutes a major global health problem. Implementation of adequate food handling practices and establishment of safe water supplies are the cornerstone for the development of an effective prevention program. However, vaccination against typhoid fever remains an essential tool for the effective management of this disease. Currently, there are two well tolerated and effective licensed vaccines. One is based on defined subunit virulence (Vi) polysaccharide antigen and can be administered either intramuscularly or subcutaneously and the other is based on the use of live attenuated bacteria for oral administration. The advantages and disadvantages of the various approaches taken in the development of a vaccine against typhoid fever are discussed, along with the potential for future vaccine candidates.

  7. A Novel ICOS-Independent, but CD28- and SAP-Dependent, Pathway of T Cell-Dependent, Polysaccharide-Specific Humoral Immunity in Response to Intact Streptococcus pneumoniae versus Pneumococcal Conjugate Vaccine

    DTIC Science & Technology

    2008-01-01

    PPS14) and the phosphorylcholine determinant (PC) of the cell wall C-polysaccharide (C-PS, teichoic acid). The protein- and PS-specific IgG responses...hydroxy-3-nitrophenyl)acetyl; PC, phosphorylcholine determi- nant of teichoic or lipoteichoic acid; Pn, intact Streptococcus pneumoniae; PPS14, capsular

  8. Uronic polysaccharide degrading enzymes.

    PubMed

    Garron, Marie-Line; Cygler, Miroslaw

    2014-10-01

    In the past several years progress has been made in the field of structure and function of polysaccharide lyases (PLs). The number of classified polysaccharide lyase families has increased to 23 and more detailed analysis has allowed the identification of more closely related subfamilies, leading to stronger correlation between each subfamily and a unique substrate. The number of as yet unclassified polysaccharide lyases has also increased and we expect that sequencing projects will allow many of these unclassified sequences to emerge as new families. The progress in structural analysis of PLs has led to having at least one representative structure for each of the families and for two unclassified enzymes. The newly determined structures have folds observed previously in other PL families and their catalytic mechanisms follow either metal-assisted or Tyr/His mechanisms characteristic for other PL enzymes. Comparison of PLs with glycoside hydrolases (GHs) shows several folds common to both classes but only for the β-helix fold is there strong indication of divergent evolution from a common ancestor. Analysis of bacterial genomes identified gene clusters containing multiple polysaccharide cleaving enzymes, the Polysaccharides Utilization Loci (PULs), and their gene complement suggests that they are organized to process completely a specific polysaccharide.

  9. Vaccine process technology.

    PubMed

    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

  10. Technical Development of a New Meningococcal Conjugate Vaccine

    PubMed Central

    Frasch, Carl E.; Kapre, Subhash V.; Lee, Che-Hung; Préaud, Jean-Marie

    2015-01-01

    Background. Group A Neisseria meningitidis has been a major cause of bacterial meningitis in the sub-Saharan region of Africa in the meningitis belt. Neisseria meningitidis is an encapsulated pathogen, and antibodies against the capsular polysaccharide are protective. Polysaccharide–protein conjugate vaccines have proven to be highly effective against several different encapsulated bacterial pathogens. Purified polysaccharide vaccines have been used to control group A meningococcal (MenA) epidemics with minimal success. Methods. A monovalent MenA polysaccharide–tetanus toxoid conjugate was therefore developed. This vaccine was developed by scientists working with the Meningitis Vaccine Project, a partnership between PATH and the World Health Organization. Results. A high-efficiency conjugation method was developed in the Laboratory of Bacterial Polysaccharides in the Center for Biologics Evaluation and Research and transferred to the Serum Institute of India, Ltd, which then developed methods for purification of the group A polysaccharide and used its tetanus toxoid as the carrier protein to produce the now-licensed, highly effective MenAfriVac conjugate vaccine. Conclusions. Although many years of application of meningococcal polysaccharide vaccines have had minimal success in preventing meningococcal epidemics in the meningitis belt of Africa, our collaborative efforts to develop a MenA conjugate vaccine yielded a safe and highly effective vaccine. PMID:26553667

  11. Influenza and Pneumococcal Vaccinations for Patients With Chronic Obstructive Pulmonary Disease (COPD)

    PubMed Central

    Sehatzadeh, S

    2012-01-01

    nasopharynx of healthy children and adults. Pneumococcus can be transmitted from person to person during close contact. The bacteria can cause illnesses such as otitis media and sinusitis, and may become more aggressive and affect other areas of the body such as the lungs, brain, joints, and blood stream. More severe infections caused by pneumococcus are pneumonia, bacterial sepsis, meningitis, peritonitis, arthritis, osteomyelitis, and in rare cases, endocarditis and pericarditis. People with impaired immune systems are susceptible to pneumococcal infection. Young children, elderly people, patients with underlying medical conditions including chronic lung or heart disease, human immunodeficiency virus (HIV) infection, sickle cell disease, and people who have undergone a splenectomy are at a higher risk for acquiring pneumococcal pneumonia. Technology Influenza and Pneumococcal Vaccines Trivalent Influenza Vaccines in Canada In Canada, 5 trivalent influenza vaccines are currently authorized for use by injection. Four of these are formulated for intramuscular use and the fifth product (Intanza®) is formulated for intradermal use. The 4 vaccines for intramuscular use are: Fluviral (GlaxoSmithKline), split virus, inactivated vaccine, for use in adults and children ≥ 6 months; Vaxigrip (Sanofi Pasteur), split virus inactivated vaccine, for use in adults and children ≥ 6 months; Agriflu (Novartis), surface antigen inactivated vaccine, for use in adults and children ≥ 6 months; and Influvac (Abbott), surface antigen inactivated vaccine, for use in persons ≥ 18 years of age. FluMist is a live attenuated virus in the form of an intranasal spray for persons aged 2 to 59 years. Immunization with current available influenza vaccines is not recommended for infants less than 6 months of age. Pneumococcal Vaccine Pneumococcal polysaccharide vaccines were developed more than 50 years ago and have progressed from 2-valent vaccines to the current 23-valent vaccines to prevent

  12. [Pneumococcal vaccination: conjugated vaccine induces herd immunity and reduces antibiotic resistance].

    PubMed

    Pletz, M W; Maus, U; Hohlfeld, J M; Lode, H; Welte, T

    2008-02-01

    Pneumococcal infections (pneumonia, otitis media, sinusitis, meningitis) are common and usually involve toddlers and the elderly. Currently, two pneumococcal vaccines are in clinical use. The older vaccine consists of pure capsular polysaccharides from 23 pneumococcal serotypes and induces only a limited B-cell response because polysaccharides are poor antigens that stimulate mainly B-cells. In 2000, a vaccination program with a novel 7-valent pneumococcal conjugate vaccine was launched in the U.S. The conjugation of capsular polysaccharides with a highly immunogenic diphtheria toxoid protein induces both a T cell and B cell response that results in specific humoral and mucosal immunity. Since children are the main reservoir of pneumococci, the 7-valent conjugate vaccine seems to eradicate the respective pneumococcal serotypes within the population, as demonstrated by recent US data. Pronounced herd immunity resulted in a decrease in invasive pneumococcal diseases in vaccinees and non-vaccinees as well as in a reduction of antibiotic resistance rates. However, recent data suggest a replacement of vaccine-serotypes by non-vaccine serotypes, which conquer the ecological niche created by the vaccine. In order to encounter this problem a 13-valent conjugated vaccine is currently under development.

  13. Marine Polysaccharides in Microencapsulation and Application to Aquaculture: “From Sea to Sea”

    PubMed Central

    Borgogna, Massimiliano; Bellich, Barbara; Cesàro, Attilio

    2011-01-01

    This review’s main objective is to discuss some physico-chemical features of polysaccharides as intrinsic determinants for the supramolecular structures that can efficiently provide encapsulation of drugs and other biological entities. Thus, the general characteristics of some basic polysaccharides are outlined in terms of their conformational, dynamic and thermodynamic properties. The analysis of some polysaccharide gelling properties is also provided, including the peculiarity of the charged polysaccharides. Then, the way the basic physical chemistry of polymer self-assembly is made in practice through the laboratory methods is highlighted. A description of the several literature procedures used to influence molecular interactions into the macroscopic goal of the encapsulation is given with an attempt at classification. Finally, a practical case study of specific interest, the use of marine polysaccharide matrices for encapsulation of vaccines in aquaculture, is reported. PMID:22363241

  14. Marine polysaccharides in microencapsulation and application to aquaculture: "from sea to sea".

    PubMed

    Borgogna, Massimiliano; Bellich, Barbara; Cesàro, Attilio

    2011-12-01

    This review's main objective is to discuss some physico-chemical features of polysaccharides as intrinsic determinants for the supramolecular structures that can efficiently provide encapsulation of drugs and other biological entities. Thus, the general characteristics of some basic polysaccharides are outlined in terms of their conformational, dynamic and thermodynamic properties. The analysis of some polysaccharide gelling properties is also provided, including the peculiarity of the charged polysaccharides. Then, the way the basic physical chemistry of polymer self-assembly is made in practice through the laboratory methods is highlighted. A description of the several literature procedures used to influence molecular interactions into the macroscopic goal of the encapsulation is given with an attempt at classification. Finally, a practical case study of specific interest, the use of marine polysaccharide matrices for encapsulation of vaccines in aquaculture, is reported.

  15. Immunochemical characterization of polysaccharide antigens from six clinical strains of Enterococci

    PubMed Central

    Hsu, Carolyn T; Ganong, Amanda L; Reinap, Barbara; Mourelatos, Zafiria; Huebner, Johannes; Wang, Julia Y

    2006-01-01

    Background Enterococci have become major nosocomial pathogens due to their intrinsic and acquired resistance to a broad spectrum of antibiotics. Their increasing drug resistance prompts us to search for prominent antigens to develop vaccines against enterococci. Given the success of polysaccharide-based vaccines against various bacterial pathogens, we isolated and characterized the immunochemical properties of polysaccharide antigens from five strains of Enterococcus faecalis and one strain of vancomycin-resistant E. faecium. Results We cultured large batches of each strain, isolated sufficient quantities of polysaccharides, analyzed their chemical structures, and compared their antigenic specificity. Three classes of polysaccharides were isolated from each strain, including a polyglucan, a teichoic acid, and a heteroglycan composed of rhamnose, glucose, galactose, mannosamine, and glucosamine. The polyglucans from all six strains are identical and appear to be dextran. Yields of the teichoic acids were generally low. The most abundant polysaccharides are the heteroglycans. The six heteroglycans are structurally different as evidenced by NMR spectroscopy. They also differ in their antigenic specificities as revealed by competitive ELISA. The heteroglycans are not immunogenic by themselves but conjugation to protein carriers significantly enhanced their ability to induce antibodies. Conclusion The six clinical strains of enterococci express abundant, strain-specific cell-surface heteroglycans. These polysaccharides may provide a molecular basis for serological typing of enterococcal strains and antigens for the development of vaccines against multi-drug resistant enterococci. PMID:16836754

  16. Immunological evaluation of meningococcal group C polysaccharide-tetanus toxoid conjugate in mice.

    PubMed Central

    Beuvery, E C; van Delft, R W; Miedema, F; Kanhai, V; Nagel, J

    1983-01-01

    Neisseria meningitidis group C polysaccharide-tetanus toxoid conjugate was prepared to obtain the polysaccharide component in a thymus-dependent form and to preserve the immunogenic properties of the tetanus toxoid component. Biochemical and immunochemical analyses of this conjugate revealed that (i) it was composed of equal amounts of polysaccharide and protein; (ii) the antigenic activity of the polysaccharide component was greatly reduced; (iii) it contained about 10% free polysaccharide; (iv) the composition was not homogeneous; and (v) only 5% of the tetanus toxoid component was present at the surface of the conjugate molecules. In this study, the influence of these characteristics on the antibody response to both components in mice was investigated. The dose-response relationship, the persistence of antibodies, a possible antigenic competition, and the specificities of the antibodies induced were also studied. Our data suggest that the conjugate behaves as a pronounced thymus-dependent antigen, that the tetanus toxoid component is more immunogenic at lower dosages (0.8 and 20 ng) than equivalent doses of tetanus vaccine, that the presence of free polysaccharide does not influence the induction of antibodies to polysaccharide by the conjugate, and that no antibodies to new structures in the conjugate are induced. These characteristics favor the application of this conjugate as a vaccine for human use. PMID:6409811

  17. [Conjugate vaccines against bacterial infections: typhoid fever].

    PubMed

    Paniagua, J; García, J A; López, C R; González, C R; Isibasi, A; Kumate, J

    1992-01-01

    Capsular polysaccharides have been studied as possible vaccines against infectious diseases. However, they are capable to induce only short-run protection because of their T-independent properties and they would not be protective against infection in high-risk populations. The alternative to face this problem is to develop methods to join covalently the polysaccharide and proteins to both increase the immunogenicity of and to confer the property of T-dependence to this antigen. In order to obtain a conjugate vaccine against typhoid fever, in our laboratory we have tried to synthesize a conjugate immunogen between the Vi antigen and porins from Salmonella typhi.

  18. NMR line-fitting quantification of polysaccharide N-acylurea-based modification in glycoconjugates of Salmonella Typhi Vi polysaccharide.

    PubMed

    Garrido, Raine; Soubal, Jean Pierre; Torres, Leonid; Ramírez, Ubel; Vérez, Vicente

    2017-01-14

    The polysaccharides modification via carbodiimide reaction is one of the most applied methods for obtaining conjugated vaccines against Salmonella enterica. However, N-acylurea carbodiimide adduct generated in the process is a critical impurity in carbohydrate-based vaccines. A quantitative NMR method was developed for assessing the N-acylurea carbodiimide adduct impurity. The procedure was based on line-fitting facilities for processing the NMR signals on complex spectra. The method showed good linearity, accuracy and precision under inter-operator variation (relative standard deviation <5%). Copyright © 2017 John Wiley & Sons, Ltd.

  19. Designer vaccines to prevent infections due to group B Streptococcus.

    PubMed

    Kasper, D L

    1995-10-01

    Group B streptococci (GBS) are the major cause of serious infections in neonates and an important cause of infection in adults, particularly peripartum women and patients with diabetes mellitus and malignancy. Immunity to GBS in neonates is associated with naturally acquired maternal antibodies to the type-specific capsular polysaccharides of these organisms. IgG class antibodies directed to these polysaccharides are passed transplacentally and protect the child from invasive GBS disease. Phase I and II clinical trials showed that the purified polysaccharides had limited immunogenicity. However, vaccine responders passed functional IgG class antibodies to their children. A glycoconjugate vaccine has been designed so that the type-specific polysaccharides are covalently linked to a carrier protein. This secondary amine linkage is between aldehyde groups created on the eighth carbon of a selected number of periodate-oxidized sialic acid residues of the polysaccharide and epsilon-amino groups on lysine residues of tetanus toxoid. Careful epitope mapping studies had demonstrated that modification by controlled periodate oxidation could be accomplished and that an important conformational epitope on the polysaccharide would be preserved. Preclinical testing of the glycoconjugate vaccines in animal models of GBS disease demonstrated the immunogenicity and protective efficacy of the vaccine-induced antibodies. Phase I clinical testing of the glycoconjugate vaccine is in progress, and the early results appear promising.

  20. [Pneumococcal surface protein A and new approaches for pneumococcal vaccine development].

    PubMed

    Vorob'ev, D S; Semenova, I B

    2011-01-01

    The problem of pneumococcal infections is pressing for the whole world. Existing vaccines based only on pneumococci polysaccharide antigens or polysaccharide antigens and diphtherial anatoxin are not capable of protecting from all serotypes of the microorganism. Reasonability of creation of pneumococcal vaccine based on surface proteins of Streptococcus pneumoniae is discussed in the literature. One of such key pneumococcal proteins is pneumococcal surface protein A (PSPA), because it is detected in all the S. pneumoniae strains, has cross activity and switches B-cell immune response to T-cell. Currently the development of conjugated vaccine based on surface proteins and capsule polysaccharides of pneumococcus seems promising.

  1. HPV Vaccine

    MedlinePlus

    ... Surgery? A Week of Healthy Breakfasts Shyness HPV Vaccine KidsHealth > For Teens > HPV Vaccine Print A A ... starting at age 9. continue How Does the Vaccine Work? The HPV vaccine is approved for people ...

  2. HPV Vaccine

    MedlinePlus

    ... Surgery? A Week of Healthy Breakfasts Shyness HPV Vaccine KidsHealth > For Teens > HPV Vaccine A A A ... starting at age 9. continue How Does the Vaccine Work? The HPV vaccine is approved for people ...

  3. Carbohydrate-based Clostridium difficile vaccines.

    PubMed

    Monteiro, Mario A; Ma, Zuchao; Bertolo, Lisa; Jiao, Yuening; Arroyo, Luis; Hodgins, Douglas; Mallozzi, Michael; Vedantam, Gayatri; Sagermann, Martin; Sundsmo, John; Chow, Herbert

    2013-04-01

    Clostridium difficile is responsible for thousands of deaths each year and a vaccine would be welcomed, especially one that would disrupt bacterial maintenance, colonization and persistence in carriers and convalescent patients. Structural explorations at the University of Guelph (ON, Canada) discovered that C. difficile may express three phosphorylated polysaccharides, named PSI, PSII and PSIII; this review captures our recent efforts to create vaccines based on these glycans, especially PSII, the common antigen that has precipitated immediate attention. The authors describe the design and immunogenicity of vaccines composed of raw polysaccharides and conjugates thereof. So far, it has been observed that anti-PSII antibodies can be raised in farm animals, mice and hamster models; humans and horses carry anti-PSII IgA and IgG antibodies from natural exposure to C. difficile, respectively; phosphate is an indispensable immunogenic epitope and vaccine-induced PSII antibodies recognize PSII on C. difficile outer surface.

  4. CAPSULAR POLYSACCHARIDE OF AZOTOBACTER AGILIS.

    PubMed

    COHEN, G H; JOHNSTONE, D B

    1964-12-01

    Cohen, Gary H. (University of Vermont, Burlington), and Donald B. Johnstone. Capsular polysaccharide of Azotobacter agilis. J. Bacteriol. 88:1695-1699. 1964.-Capsular polysaccharide from Azotobacter agilis strain 132 was recovered from washed cells by alkaline digestion. The polysaccharide was purified by centrifugation, repeated alcohol precipitation, Sevag deproteinization, and treatment with ribonuclease and charcoal-cellulose. Methods of isolation and purification appeared to provide a polymer showing no evidence of heterogeneity when examined by chemical and physical methods. Colorimetric, paper chromatographic, and enzymatic analyses on both intact and acid-hydrolyzed polysaccharide indicated that the polymer contained galactose and rhamnose at a molar ratio of approximately 1.0:0.7. A sialic acid-like component was also present in the polysaccharide. The study shows significant differences in the chemical composition of the extra-cellular polysaccharide of A. agilis and that of A. vinelandii. This adds further biochemical evidence for the right of these species to independent status.

  5. Tailoring the strategies to specific shortages: pneumococcal conjugate vaccine.

    PubMed

    Peter, Georges

    2006-03-01

    Less than 1 year after recommendations for the routine vaccination of infants with the newly licensed 7-valent polysaccharide-protein conjugate pneumococcal vaccine were issued in February 2000, shortages of the 7-valent polysaccharide-protein conjugate pneumococcal vaccine supply began to occur. A national shortage developed in 2001, involving both the public and private sectors, and it resulted in temporary recommendations to conserve vaccine supply for infants and young children at the highest risk for invasive disease. Multiple factors contributed to this vaccine shortage, including demand that exceeded the expectations of the manufacturer and the need for compliance with the Good Manufacturing Practice of the US Food and Drug Administration. Of the possible strategies that might have averted this shortage, establishment of a vaccine stockpile is the most likely solution. However, establishing a stockpile for a newly licensed vaccine, such as 7-valent polysaccharide-protein conjugate pneumococcal vaccine, presents unique challenges. Improved communication with physicians and parents regarding changes in vaccine schedules also will promote better adherence to recommended changes and conservation of limited vaccine supplies during a shortage.

  6. Antimicrobial susceptibility of Streptococcus pneumoniae isolates from vaccinated and non-vaccinated patients with a clinically confirmed diagnosis of community-acquired pneumonia in Belgium.

    PubMed

    Lismond, Ann; Carbonnelle, Sylviane; Verhaegen, Jan; Schatt, Patricia; De Bel, Annelies; Jordens, Paul; Jacobs, Frédérique; Dediste, Anne; Verschuren, Frank; Huang, Te-Din; Tulkens, Paul M; Glupczynski, Youri; Van Bambeke, Françoise

    2012-03-01

    We assessed the in vitro susceptibility of Streptococcus pneumoniae isolates from patients with confirmed community-acquired pneumonia (CAP) to β-lactams, macrolides and fluoroquinolones and the association of non-susceptibility and resistance with serotypes/serogroups (STs/SGs), patient's risk factors and vaccination status. Samples (blood or lower respiratory tract) were obtained in 2007-2009 from 249 patients (from seven hospitals in Belgium) with a clinical and radiological diagnosis of CAP [median age 61 years (11.6% aged <5 years); 85% without previous antibiotic therapy; 86% adults with level II Niederman's severity score]. MIC determination (EUCAST breakpoints) showed for: (i) amoxicillin, 6% non-susceptible; cefuroxime (oral), 6.8% resistant; (ii) macrolides: 24.9% erythromycin-resistant [93.5% erm(B)-positive] but 98.4% telithromycin-susceptible; and (iii) levofloxacin and moxifloxacin, all susceptible. Amongst SGs: ST14, all resistant to macrolides and most intermediate to β-lactams; SG19 (>94% ST19A), 73.5% resistant to macrolides and 18-21% intermediate to β-lactams; and SG6, 33% resistant to clarithromycin. Apparent vaccine failures: 3/17 for 7-valent vaccine (children; ST6B, 23F); 16/29 for 23-valent vaccine (adults ST3, 7F, 12F, 14, 19A, 22F, 23F, 33F). Isolates from nursing home residents, hospitalised patients and patients with non-respiratory co-morbidities showed increased MICs for amoxicillin, all β-lactams, and β-lactams and macrolides, respectively. Regarding antibiotic susceptibilities: (i) amoxicillin is still useful for empirical therapy but with a high daily dose; (ii) cefuroxime axetil and macrolides (but not telithromycin) are inappropriate for empirical therapy; and (iii) moxifloxacin and levofloxacin are the next 'best empirical choice' (no resistant isolates) but levofloxacin will require 500 mg twice-daily dosing for effective coverage.

  7. Evaluation of some selected vaccines and other biological products irradiated by gamma rays, electron beams and X-rays

    NASA Astrophysics Data System (ADS)

    May, J. C.; Rey, L.; Lee, Chi-Jen

    2002-03-01

    Molecular sizing potency results are presented for irradiated samples of one lot of Haemophilus b conjugate vaccine, pneumococcal polysaccharide type 6B and typhoid vi polysaccharide vaccine. The samples were irradiated (25 kGy) by gamma rays, electron beams and X-rays. IgG and IgM antibody response in mice test results (ELISA) are given for the Hib conjugate vaccine irradiated at 0°C or frozen in liquid nitrogen.

  8. Novel nanoparticle vaccines for Listeriosis

    PubMed Central

    Calderon-Gonzalez, Ricardo; Marradi, Marco; Garcia, Isabel; Petrovsky, Nikolai; Alvarez-Dominguez, Carmen

    2015-01-01

    In recent years, nanomedicine has transformed many areas of traditional medicine, and enabled fresh insights into the prevention of previously difficult to treat diseases. An example of the transformative power of nanomedicine is a recent nano-vaccine against listeriosis, a serious bacterial infection affecting not only pregnant women and their neonates, but also immune-compromised patients with neoplastic or chronic autoimmune diseases. There is a major unmet need for an effective and safe vaccine against listeriosis, with the challenge that an effective vaccine needs to generate protective T cell immunity, a hitherto difficult to achieve objective. Now utilizing a gold nanoparticle antigen delivery approach together with a novel polysaccharide nanoparticulate adjuvant, an effective T-cell vaccine has been developed that provides robust protection in animal models of listeriosis, raising the hope that one day this nanovaccine technology may protect immune-compromised humans against this serious opportunistic infection. PMID:26252360

  9. Vaccine hesitancy

    PubMed Central

    Dubé, Eve; Laberge, Caroline; Guay, Maryse; Bramadat, Paul; Roy, Réal; Bettinger, Julie A.

    2013-01-01

    Despite being recognized as one of the most successful public health measures, vaccination is perceived as unsafe and unnecessary by a growing number of individuals. Lack of confidence in vaccines is now considered a threat to the success of vaccination programs. Vaccine hesitancy is believed to be responsible for decreasing vaccine coverage and an increasing risk of vaccine-preventable disease outbreaks and epidemics. This review provides an overview of the phenomenon of vaccine hesitancy. First, we will characterize vaccine hesitancy and suggest the possible causes of the apparent increase in vaccine hesitancy in the developed world. Then we will look at determinants of individual decision-making about vaccination. PMID:23584253

  10. [Research and development strategies, examples among new vaccines].

    PubMed

    Denis, F; Ploy, M-C

    2009-05-01

    Classical methods are still providing new vaccines, but molecular biology and genetic engineering have enabled new approaches to development. Changes in vaccinology have involved the isolation, presentation and administration of vaccinal antigens or attenuated vaccinal strains. New methods of vaccine delivery other than injection will be used (e.g. mucosal administration) and new vectors or adjuvants will be added to vaccines in order to stimulate specific responses. New vaccines can also be obtained by using viral-like particles (VLP of papillomavirus), conjugate polysaccharides (N. meningitidis, S. pneumoniae) or the reassortment of segmented genomes (rotavirus, influenza). Here, we analyze the different steps of a vaccine's life using concrete cases of two new vaccines against papillomavirus and rotavirus. Vaccination has a promising future.

  11. Microneedle patches for vaccine delivery

    PubMed Central

    Suh, Hyemee; Shin, Juhyung

    2014-01-01

    In today's medical industry, the range of vaccines that exist for administration in humans represents an eclectic variety of forms and immunologic mechanisms. Namely, these are the live attenuated viruses, inactivated viruses, subunit proteins, and virus-like particles for treating virus-caused diseases, as well as the bacterial-based polysaccharide, protein, and conjugated vaccines. Currently, a new approach to vaccination is being investigated with the concept of DNA vaccines. As an alternative delivery route to enhance the vaccination efficacy, microneedles have been devised to target the rich network of immunologic antigen-presenting cells in the dermis and epidermis layers under the skin. Numerous studies have outlined the parameters of microneedle delivery of a wide range of vaccines, revealing comparable or higher immunogenicity to conventional intramuscular routes, overall level of stability, and dose-sparing advantages. Furthermore, recent mechanism studies have begun to successfully elucidate the biological mechanisms behind microneedle vaccination. This paper describes the current status of microneedle vaccine research. PMID:24427762

  12. Iodine-Catalyzed Polysaccharide Esterification

    Technology Transfer Automated Retrieval System (TEKTRAN)

    A review is provided of the recent reports to use iodine-catalyzed esterification reaction to produce esters from polysaccharides. The process entails reaction of the polysaccharide with an acid anhydride in the presence of a catalytic level of iodine, and in the absence of additional solvents. T...

  13. Polysaccharides of the red algae.

    PubMed

    Usov, Anatolii I

    2011-01-01

    Red algae (Rhodophyta) are known as the source of unique sulfated galactans, such as agar, agarose, and carrageenans. The wide practical uses of these polysaccharides are based on their ability to form strong gels in aqueous solutions. Gelling polysaccharides usually have molecules built up of repeating disaccharide units with a regular distribution of sulfate groups, but most of the red algal species contain more complex galactans devoid of gelling ability because of various deviations from the regular structure. Moreover, several red algae may contain sulfated mannans or neutral xylans instead of sulfated galactans as the main structural polysaccharides. This chapter is devoted to a description of the structural diversity of polysaccharides found in the red algae, with special emphasis on the methods of structural analysis of sulfated galactans. In addition to the structural information, some data on the possible use of red algal polysaccharides as biologically active polymers or as taxonomic markers are briefly discussed.

  14. [Travelers' vaccines].

    PubMed

    Ouchi, Kazunobu

    2011-09-01

    The number of Japanese oversea travelers has gradually increased year by year, however they usually pay less attention to the poor physical condition at the voyage place. Many oversea travelers caught vaccine preventable diseases in developing countries. The Vaccine Guideline for Oversea Travelers 2010 published by Japanese Society of Travel Health will be helpful for spreading the knowledge of travelers' vaccine and vaccine preventable diseases in developing countries. Many travelers' vaccines have not licensed in Japan. I hope these travelers' vaccines, such as typhoid vaccine, meningococcal vaccine, cholera vaccine and so on will be licensed in the near future.

  15. Why were polysaccharides necessary?

    PubMed

    Tolstoguzov, Vladimir

    2004-12-01

    The main idea of this paper is that the primordial soup may be modelled by food systems whose structure-property relationship is based on non-specific interactions between denatured biopolymers. According to the proposed hypothesis, polysaccharides were the first biopolymers that decreased concentration of salts in the primordial soup, 'compatibilised' and drove the joint evolution of proto-biopolymers. Synthesis of macromolecules within the polysaccharide-rich medium could have resulted in phase separation of the primordial soup and concentration of the polypeptides and nucleic acids in the dispersed phase particles. The concentration of proto-biopolymer mixtures favoured their cross-linking in hybrid supermacromolecules of conjugates. The cross-linking of proto-biopolymers could occur by hydrophobic, electrostatic interactions, H-bonds due to freezing aqueous mixed biopolymer dispersions and/or by covalent bonds due to the Maillard reaction. Cross-linking could have increased the local concentration of chemically different proto-biopolymers, fixed their relative positions and made their interactions reproducible. Attractive-repulsive interactions between cross-linked proto-biopolymer chains could develop pairing of the monomer units, improved chemical stability (against hydrolysis) and led to their mutual catalytic activity and coding. Conjugates could probably evolve to the first self-reproduced entities and then to specialized cellular organelles. Phase separation of the primordial soup with concentration of conjugates in the dispersed particles has probably resulted in proto-cells.

  16. Why Were Polysaccharides Necessary?

    NASA Astrophysics Data System (ADS)

    Tolstoguzov, Vladimir

    2004-12-01

    The main idea of this paper is that the primordial soup may be modelled by food systems whose structure-property relationship is based on non-specific interactions between denatured biopolymers. According to the proposed hypothesis, polysaccharides were the first biopolymers that decreased concentration of salts in the primordial soup, `compatibilised' and drove the joint evolution of proto-biopolymers. Synthesis of macromolecules within the polysaccharide-rich medium could have resulted in phase separation of the primordial soup and concentration of the polypeptides and nucleic acids in the dispersed phase particles. The concentration of proto-biopolymer mixtures favoured their cross-linking in hybrid supermacromolecules of conjugates. The cross-linking of proto-biopolymers could occur by hydrophobic, electrostatic interactions, H-bonds due to freezing aqueous mixed biopolymer dispersions and/or by covalent bonds due to the Maillard reaction. Cross-linking could have increased the local concentration of chemically different proto-biopolymers, fixed their relative positions and made their interactions reproducible. Attractive-repulsive interactions between cross-linked proto-biopolymer chains could develop pairing of the monomer units, improved chemical stability (against hydrolysis) and led to their mutual catalytic activity and coding. Conjugates could probably evolve to the first self-reproduced entities and then to specialized cellular organelles. Phase separation of the primordial soup with concentration of conjugates in the dispersed particles has probably resulted in proto-cells.

  17. Polysaccharides and bacterial plugging

    SciTech Connect

    Fogler, H.S.

    1991-11-01

    Before any successful application of Microbial Enhanced Oil Recovery process can be realized, an understanding of the cells' transport and retentive mechanisms in porous media is needed. Cell transport differs from particle transport in their ability to produce polysaccharides, which are used by cells to adhere to surfaces. Cell injection experiments have been conducted using Leuconostoc cells to illustrate the importance of cellular polysaccharide production as a transport mechanism that hinders cell movement and plugs porous media. Kinetic studies of the Leuconostoc cells, carried out to further understand the plugging rates of porous media, have shown that the cells' growth rates are approximately equal when provided with monosaccharide (glucose and fructose) or sucrose. The only difference in cell metabolism is the production of dextran when sucrose is supplied as a carbon source. Experimentally it has also been shown that the cells' growth rate is weakly dependent upon the sucrose concentration in the media, and strongly dependent upon the concentration of yeast extract. The synthesis of cellular dextran has been found to lag behind cell generation, thus indicating that the cells need to reach maturity before they are capable of expressing the detransucrase enzyme and synthesizing insoluble dextran. Dextran yields were found to be dependent upon the sucrose concentration in the media. 10 refs., 9 figs., 9 tabs.

  18. Polysaccharides from Extremophilic Microorganisms

    NASA Astrophysics Data System (ADS)

    Nicolaus, B.; Moriello, V. Schiano; Lama, L.; Poli, A.; Gambacorta, A.

    2004-02-01

    Several marine thermophilic strains were analyzed for exopolysaccharide production. The screening process revealed that a significant number of thermophilic microorganisms were able to produce biopolymers, and some of them also revealed interesting chemical compositions. We have identified four new polysaccharides from thermophilic marine bacteria, with complex primary structures and with different repetitive units: a galacto-mannane type from strain number 4004 and mannane type for the other strains. The thermophilic Bacillus thermantarcticus produces two exocellular polysaccharides (EPS 1, EPS 2) that give the colonies a typical mucous character. The exopolysaccharide fraction was produced with all substrates assayed, although a higher yield 400 mg liter-1 was obtained with mannose as carbon and energy source. NMR spectra confirmed that EPS 1 was a heteropolysaccharide of which the repeating unit was constituted by four different α-D-mannoses and three different β-D-glucoses. It seems to be close to some xantan polymers. EPS 2 was a mannan. Four different α-D-mannoses were found as the repeating unit. Production and chemical studies of biopolymers produced by halophilic archaea, Haloarcula species were also reported.

  19. The molecular basis of polysaccharide cleavage by lytic polysaccharide monooxygenases

    PubMed Central

    Frandsen, Kristian E. H.; Simmons, Thomas J.; Dupree, Paul; Poulsen, Jens-Christian N.; Hemsworth, Glyn R.; Ciano, Luisa; Johnston, Esther M.; Tovborg, Morten; Johansen, Katja S.; von Freiesleben, Pernille; Marmuse, Laurence; Fort, Sébastien; Cottaz, Sylvain; Driguez, Hugues; Henrissat, Bernard; Lenfant, Nicolas; Tuna, Floriana; Baldansuren, Amgalanbaatar; Davies, Gideon J.; Leggio, Leila Lo; Walton, Paul H.

    2016-01-01

    Lytic polysaccharide monooxygenases (LPMOs) are copper-containing enzymes which oxidatively break down recalcitrant polysaccharides such as cellulose and chitin. Since their discovery LPMOs have become integral factors in the industrial utilization of biomass, especially in the sustainable generation of cellulosic bioethanol. We report here the first structural determination of an LPMO–oligosaccharide complex, yielding detailed insights into the mechanism of action of these enzymes. Using a combination of structure and electron paramagnetic resonance spectroscopy, we reveal the means by which LPMOs interact with saccharide substrates. We further uncover electronic and structural features of the enzyme active site, showing how LPMOs orchestrate the reaction of oxygen with polysaccharide chains. PMID:26928935

  20. Meningococcal Disease in US Military Personnel Before and after Adoption of Conjugate Vaccine

    DTIC Science & Technology

    2015-02-01

    after Adoption of Conjugate Vaccine Michael P. Broderick, Christopher Phillips, Dennis Faix Author affiliation: Naval Health Research Center, San Diego... vaccines , the first of which was developed by the US Army (1–5). In 1985, the quadrivalent polysaccharide vaccine (MPSV-4) was implemented as the...military standard. It was replaced during 2006–2008 by the quadrivalent conjugate vaccine (MCV-4). Every person en- tering US military service is required

  1. HPAEC-PAD method for the analysis of alkaline hydrolyzates of Haemophilus influenzae type b capsular polysaccharide.

    PubMed

    de Haan, Alex; van der Put, Robert M F; Beurret, Michel

    2013-09-01

    A gradient method has been devised for the rapid analysis of alkaline hydrolyzates of Haemophilus influenzae type b (Hib) capsular polysaccharide-based vaccines by high-performance anion exchange chromatography with pulsed amperometric detection (HPAEC-PAD). As compared with published procedures, peak shape and sensitivity were significantly improved with this approach, analysis time was short and there was little interference from impurities. The limits of detection and quantification were established with a purified reference polysaccharide. We propose this method as a practical alternative for the analysis of minute amounts of Hib polysaccharide, which can be lower than with the conventional approaches.

  2. Developmental toxicity testing of vaccines.

    PubMed

    Barrow, Paul C; Allais, Linda

    2013-01-01

    Preventative and therapeutic vaccines are increasingly used during pregnancy and present special considerations for developmental toxicity testing. The various components of the vaccine formulation (i.e., protein or polysaccharide antigen, adjuvants, and excipients) need to be assessed for direct effects on the developing conceptus. In addition, possible adverse influences of the induced antibodies on fetal and/or postnatal development need to be evaluated. A guidance document on the preclinical testing of preventative and therapeutic vaccines for developmental toxicity was issued by the FDA in 2006. Preclinical studies are designed to assess possible influences of vaccines on pre- and postnatal development. The choice of model animal for these experiments is influenced by species differences in the timing and extent of the transfer of the induced maternal antibodies to the fetus. The cross-placental transport of maternal immunoglobulins generally only occurs in late gestation and tends to be greater in humans and monkeys than in non-primate species. For many vaccines, the rabbit shows a greater rate of prenatal transfer of the induced antibodies than rodents. For biotechnology-derived vaccines that are not immunogenic in lower species, nonhuman primates may be the only appropriate models. It may be advisable to test new adjuvants using the ICH study designs for conventional pharmaceuticals in addition to the developmental toxicity study with the final vaccine formulation.

  3. Leptospirosis vaccines

    PubMed Central

    Wang, Zhijun; Jin, Li; Węgrzyn, Alicja

    2007-01-01

    Leptospirosis is a serious infection disease caused by pathogenic strains of the Leptospira spirochetes, which affects not only humans but also animals. It has long been expected to find an effective vaccine to prevent leptospirosis through immunization of high risk humans or animals. Although some leptospirosis vaccines have been obtained, the vaccination is relatively unsuccessful in clinical application despite decades of research and millions of dollars spent. In this review, the recent advancements of recombinant outer membrane protein (OMP) vaccines, lipopolysaccharide (LPS) vaccines, inactivated vaccines, attenuated vaccines and DNA vaccines against leptospirosis are reviewed. A comparison of these vaccines may lead to development of new potential methods to combat leptospirosis and facilitate the leptospirosis vaccine research. Moreover, a vaccine ontology database was built for the scientists working on the leptospirosis vaccines as a starting tool. PMID:18072968

  4. Comparison of radioimmunoassay and enzyme-linked immunosorbent assay in measurement of antibodies to Neisseria meningitidis group A capsular polysaccharide.

    PubMed Central

    Beuvery, E C; Kayhty, M H; Leussink, A B; Kanhai, V

    1984-01-01

    Antibodies to meningococcal group A polysaccharide were determined by radioimmunoassay (RIA) and enzyme-linked immunosorbent assay (ELISA) in serum samples from 16 adults vaccinated with bivalent meningococcal group A and C polysaccharide vaccine. The specific antibody levels in the serum samples were expressed as micrograms of antibody protein per milliliter of serum. For RIA the polysaccharide was radiolabeled extrinsically with 125I. Both native polysaccharide and polysaccharide labeled with 127I were used in ELISA. Because these antigens gave similar results, it can be concluded that the introduction of tyramine and iodine by the labeling procedure did not alter the antigenic activity of the polysaccharide. The reproducibility of RIA was clearly better than that of ELISA. The antibody levels detected by the methods were equal, which means that ELISA can be used satisfactorily to measure antibodies to meningococcal group A polysaccharide quantitatively. Some discrepant results were found due to an underestimation of immunoglobulin M antibodies in ELISA. This was shown by a correlation test in which a weakly significant negative correlation was found between the immunoglobulin M antibody level/immunoglobulin G antibody level ratio and the RIA antibody level/ELISA antibody level ratio. PMID:6436314

  5. Vaccines and recommendations for their use in inflammatory bowel disease

    PubMed Central

    Sánchez-Tembleque, María Dolores; Corella, Carmen; Pérez-Calle, Jose L

    2013-01-01

    The patient with inflammatory bowel disease will be predisposed to numerous infections due their immune status. It is therefore important to understand the immune and serologic status at diagnosis and to put the patient into an adapted vaccination program. This program would be applied differently according to two patient groups: the immunocompromised and the non-immunocom-promised. In general, the first group would avoid the use of live-virus vaccines, and in all cases, inflammatory bowel disease treatment would take precedence over vaccine risk. It is important to individualize vaccination schedules according to the type of patient, the treatment used and the disease pattern.In addition, patient with inflammatory bowel disease should be considered for the following vaccines: varicella vaccine, human papilloma virus, influenza, pneumococcal polysaccharide vaccine and hepatitis B vaccine. PMID:23538680

  6. Vaccine Hesitancy.

    PubMed

    Jacobson, Robert M; St Sauver, Jennifer L; Finney Rutten, Lila J

    2015-11-01

    Vaccine refusal received a lot of press with the 2015 Disneyland measles outbreak, but vaccine refusal is only a fraction of a much larger problem of vaccine delay and hesitancy. Opposition to vaccination dates back to the 1800 s, Edward Jenner, and the first vaccine ever. It has never gone away despite the public's growing scientific sophistication. A variety of factors contribute to modern vaccine hesitancy, including the layperson's heuristic thinking when it comes to balancing risks and benefits as well as a number of other features of vaccination, including falling victim to its own success. Vaccine hesitancy is pervasive, affecting a quarter to a third of US parents. Clinicians report that they routinely receive requests to delay vaccines and that they routinely acquiesce. Vaccine rates vary by state and locale and by specific vaccine, and vaccine hesitancy results in personal risk and in the failure to achieve or sustain herd immunity to protect others who have contraindications to the vaccine or fail to generate immunity to the vaccine. Clinicians should adopt a variety of practices to combat vaccine hesitancy, including a variety of population health management approaches that go beyond the usual call to educate patients, clinicians, and the public. Strategies include using every visit to vaccinate, the creation of standing orders or nursing protocols to provide vaccination without clinical encounters, and adopting the practice of stating clear recommendations. Up-to-date, trusted resources exist to support clinicians' efforts in adopting these approaches to reduce vaccine hesitancy and its impact.

  7. Improvement in the purification process of the capsular polysaccharide from Haemophilus influenzae type b by using tangential ultrafiltration and diafiltration.

    PubMed

    Albani, Silvia Maria Ferreira; da Silva, Mateus Ribeiro; Takagi, Mickie; Cabrera-Crespo, Joaquin

    2012-08-01

    Capsular polysaccharide produced by Haemophilus influenzae b (Hib) is the main virulent agent and used as the antigen in the vaccine formulation. In this study, an improved process of polysaccharide purification was established based on tangential flow ultrafiltration using detergents (cocamidopropyl betaine and sodium deoxycholate), two selective ethanol precipitations steps, and extensive enzymatic hydrolysis as strategy. The relative purity (RP) related to protein and nucleic acids were 122~263 and 294~480, respectively, and compatible with the specifications established by the World Health Organization for Hib vaccine, RP≥100. These results make this process simple, cheaper, efficient, environmentally friendly, and prone to be scaled up.

  8. [Cholera update and vaccination problems].

    PubMed

    Fournier, J M; Villeneuve, S

    1998-01-01

    Cholera remains an important public health problem. The long-term control of cholera depends on good personal hygiene, uncontaminated water supply and appropriate sewage disposal. However, the improvement of hygiene is distant goal for many countries. Thus the availability of an effective cholera vaccine is important for the prevention of cholera in these countries. Research on new cholera vaccines has mainly focused on oral formulations that stimulate the mucosal secretory immune system. Two oral cholera vaccines were experimented on large scale in human. The first vaccine, containing inactivated bacterial cells and B-subunit of cholera toxin, has been tested in Bangladesh from 1985 to 1989. This vaccine, according to WHO, may prove useful in the stable phase of refugee/displaced person crises, especially when given preventively. The second vaccine is a live attenuated vaccine containing the genetically manipulated Vibrio cholerae O1 strain CVD 103-HgR. Despite its efficacy in adult volunteers, results of a large-scale field trial carried-out in Indonesia for 4 years have shown a surprisingly low protection. Moreover, one of the safety concerns associated with live cholera vaccine is a possible horizontal gene transfer and recombination event leading to reversion to virulence. A new vaccine development program for cholera is based upon the hypothesis that immunoglobulins G directed to the O-specific polysaccharide of Vibrio cholerae O1 could confer protective immunity to cholera by inactivating the inoculum on intestinal mucosal surface. This program may lead to the development of cholera conjugate vaccines to elicit protection in infants.

  9. A threading receptor for polysaccharides

    NASA Astrophysics Data System (ADS)

    Mooibroek, Tiddo J.; Casas-Solvas, Juan M.; Harniman, Robert L.; Renney, Charles M.; Carter, Tom S.; Crump, Matthew P.; Davis, Anthony P.

    2016-01-01

    Cellulose, chitin and related polysaccharides are key renewable sources of organic molecules and materials. However, poor solubility tends to hamper their exploitation. Synthetic receptors could aid dissolution provided they are capable of cooperative action, for example by multiple threading on a single polysaccharide molecule. Here we report a synthetic receptor designed to form threaded complexes (polypseudorotaxanes) with these natural polymers. The receptor binds fragments of the polysaccharides in aqueous solution with high affinities (Ka up to 19,000 M-1), and is shown—by nuclear Overhauser effect spectroscopy—to adopt the threading geometry. Evidence from induced circular dichroism and atomic force microscopy implies that the receptor also forms polypseudorotaxanes with cellulose and its polycationic analogue chitosan. The results hold promise for polysaccharide solubilization under mild conditions, as well as for new approaches to the design of biologically active molecules.

  10. Development and evaluation of a novel vaccine against prevalent invasive multi-drug resistant strains of Streptococcus pneumoniae

    PubMed Central

    Bahy, Rehab H.; Hamouda, Hayam M.; Shahat, Amal S.; Amin, Magdy A.

    2016-01-01

    Streptococcus pneumoniae is a pathogen that causes serious invasive infections, such as septicemia, meningitis and pneumonia in addition to mild upper respiratory tract infections. Protection from pneumococcal diseases is thought to be mediated mainly by serotype-specific antibodies to capsular antigens. Pneumococcal conjugate vaccine consists of sugars (polysaccharides) from the capsule of the bacterium S. pneumoniae that are conjugated to a carrier protein. Three pneumococcal conjugated vaccines, each directed against a group of serotypes, are registered in Egypt; however, local vaccine production is required to cover the most prevalent serotypes. In this work, capsular polysaccharide from the most current and prevalent serotypes in Egypt were extracted, purified and conjugated to bovine serum albumin (BSA). The polysaccharide protein conjugate was purified through ultrafiltration technique and molecular size distribution was compared to an available vaccine. The immunogenicity of the prepared vaccine was examined via two methods: First, by measuring the levels of the elicited antibodies in the sera of the vaccinated mice; second, by challenging the vaccinated groups of mice with approximately 107 CFU of each specific serotype and determining the degree of protection the developled vaccine offers. Our results show that the developed conjugated capsular polysaccharide vaccine is highly immunogenic and protective in mice. This finding illustrates the importance of tracking the most recent and predominant peneumococcal serotypes to generate effective vaccines, instead of using expensive imported vaccines with large number of serotypes which might not be even present in the community. PMID:27917323

  11. 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

    NASA Astrophysics Data System (ADS)

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

    2004-09-01

    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.

  12. Edible vaccines.

    PubMed

    Meloen, R H; Hamilton, W D; Casal, J I; Dalsgaard, K; Langeveld, J P

    1998-01-01

    The ultimate vaccine is an oral vaccine which given once protects against a multitude of diseases. Furthermore this ultimate vaccine needs to be very stable and inexpensive to produce. Probably this latter condition can be met only if the vaccines are produced in plants. Such vaccines are called 'edible vaccines'. Edible vaccines can be produced in plants in many ways. Using recombinant plantvirus, CPMV, it was shown that plants can produce massive amounts of chimaeric virus particles which protect after a single injection the target animal against disease. The final step, oral administration, is being addressed at present. Preliminary experiments by others suggest that this step may be solved sooner than expected.

  13. Preparation of polysaccharides from wax gourd.

    PubMed

    Huang, Gangliang; Tan, Jiantao; Tan, Xianchun; Peng, Daquan

    2011-08-01

    Preparation of polysaccharides from the wax gourd was studied. The crude polysaccharides were extracted by ethanol precipitation, and deproteinized by the hydrochloric acid method. The deproteinized polysaccharides were separated by column chromatography to obtain the pure polysaccharides. The pure polysaccharides have a β-D-pyranosidic bond, and their molecular weight distribution is about 22,500. It was indicated that the final product had much more purity by IR spectrum analysis, UV absorption spectrum analysis, and phenol-sulfuric acid method, respectively. It was proved that wax gourd polysaccharides were composed of rhamnose, xylose, arabinose, mannose, glucose, and galactose by thin layer chromatography.

  14. Biochemical And Genetic Modification Of Polysaccharides

    NASA Technical Reports Server (NTRS)

    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.

  15. Edible vaccines.

    PubMed

    Artnzen, C J

    1997-01-01

    Vaccines were the result of trial and error research until molecular biology and genetic engineering made possible the creation of of many new and improved vaccines. New vaccines need to be inexpensive, easily administered, and capable of being stored and transported without refrigeration; without these characteristics, developing countries find it difficult to adopt vaccination as the central strategy for preventing their most devastating diseases. The authors describe a promising approach to inexpensive and effective vaccines: producing them in plants we commonly consume.

  16. Genomics of immune response to typhoid and cholera vaccines.

    PubMed

    Majumder, Partha P

    2015-06-19

    Considerable variation in antibody response (AR) was observed among recipients of an injectable typhoid vaccine and an oral cholera vaccine. We sought to find whether polymorphisms in genes of the immune system, both innate and adaptive, were associated with the observed variation in response. For both vaccines, we were able to discover and validate several polymorphisms that were significantly associated with immune response. For the typhoid vaccines, these polymorphisms were on genes that belonged to pathways of polysaccharide recognition, signal transduction, inhibition of T-cell proliferation, pro-inflammatory signalling and eventual production of antimicrobial peptides. For the cholera vaccine, the pathways included epithelial barrier integrity, intestinal homeostasis and leucocyte recruitment. Even though traditional wisdom indicates that both vaccines should act as T-cell-independent antigens, our findings reveal that the vaccines induce AR using different pathways.

  17. Vaccine safety.

    PubMed

    Jacobson, Robert M

    2003-11-01

    Rates of reported adverse events are remarkably low. VAERS identifies an adverse event rate approximating 11.4 reports per 100,000 vaccine doses. Approximately 15% of these reports represent SAEs, but less than 2% involve death; in most cases, reviews have shown no causal relation between the events and the vaccine. Across the spectrum of vaccines in use (including those directed against influenza and hepatitis B virus), many claims of adverse events regarding vaccines represent typical reactions to vaccinations. These reactions can be thought of as foreign-body reactions and predominate among the inactivated vaccines. In controlled studies, the adverse event rates that occur with vaccination resemble those that occur with placebo injections. Typical reactions associated with live viral and bacterial vaccines, such as MMR and varicella vaccines, may resemble attenuated forms of the disease for which the vaccine is directed. Other claims against vaccines represent chance-coincidence or misunderstood data; further studies of claims have vindicated the overall safety of the vaccines in most cases. Two documented safety concerns with vaccines, however, have demonstrated that vaccines (like other biologics and pharmacologic) can result in harm (eg, rotavirus and OPV vaccines). The denouement with these vaccines indicates the broad postmarketing data collection and evaluation that extends efforts made with prelicensure study to balance the benefits from vaccination with the risk for harm. Overall, measures including prelicensure study and postlicensure surveillance, such as VAERS, the Vaccine Safety Datalink Project, and the Clinical Immunization Safety Assessment Centers, have resulted in an exceptional safety profile for the vaccines in use.

  18. Priming for immunologic memory in adults by meningococcal group C conjugate vaccination.

    PubMed

    Vu, David M; de Boer, Alberdina W; Danzig, Lisa; Santos, George; Canty, Bridget; Flores, Betty M; Granoff, Dan M

    2006-06-01

    Meningococcal group C polysaccharide-protein conjugate vaccines (MCV) prime infants and children for memory anticapsular responses upon subsequent exposure to unconjugated polysaccharide. The objective of this study was to determine whether MCV primes vaccine-naïve adults and adults previously vaccinated with meningococcal polysaccharide vaccine (MPSV) for memory antibody responses. Meningococcal vaccine-naïve adults were randomized to receive either MCV (MCV/naïve group) (n = 35) or pneumococcal conjugate vaccine (PCV) (PCV/naïve group) (n = 34). Participants with a history of receiving MPSV were given MCV (MCV/MPSV group) (n = 26). All subjects were challenged 10 months later with one-fifth of the usual dose of MPSV (10 mug of each polysaccharide). Sera were obtained before the conjugate vaccination and before and 7 days after the MPSV challenge and assayed for immunoglobulin G (IgG) anticapsular antibody concentrations and bactericidal titers. The MCV/naïve group had 7- to 10-fold-higher serum IgG and bactericidal responses after the MPSV challenge than the PCV/naïve group (P < 0.001). The increases (n-fold) in anticapsular antibody concentrations in the MCV/naïve group were greatest in subjects with antibody concentrations of 2 microg/ml before the challenge; P < 0.0001). Only 3 of 11 MCV-vaccinated subjects who had received MPSV before enrollment and who had antibody concentrations of polysaccharide challenge showed more-than-twofold increases in anticapsular antibody concentration or bactericidal titer after the challenge. MCV vaccination of meningococcal vaccine-naïve adults primes for robust memory antibody responses. There was no evidence of induction of memory by MCV in adults previously vaccinated with MPSV.

  19. Pneumococcal vaccination--current situation and perspectives.

    PubMed

    Madar, R; Strakova, J; Baska, T; Kavcova, E; Straka, S

    2005-01-01

    The authors carried out a survey in outpatient and hospitalised patients with risk factors for invasive pneumococcal disease in a tertiary-care medical faculty affiliated hospital. Data were collected by individual interviews and verified against the medical records of all addressed patients. The authors also attempted to discover the attitude of general practitioners (GPs) from 2 Slovak districts towards the pneumococcal vaccine by means of an anonymous questionnaire. Out of the total of 154 addressed patients, 128 (83.1%) had at least one risk factor for acquiring invasive pneumococcal disease. However, only 8 (6.3%) of them had ever been administered pneumococcal vaccine. Out of 34 hospitalised patients with at least one risk factor 82.4 % had not received any pneumococcal vaccination in the past. When subdivided according to age and risk factors (chronic respiratory, cardiovascular, uropoetic, metabolic, immunne system disorders, asplenia), vaccination coverage in all groups was very low, ranging between --9.3%. In an anonymous questionnaire 74 (94.9%) out of 77 surveyed GPs referred to a lack of information on the polysaccharide pneumococcal vaccine and 22 (28.2%) expressed their general distrust towards vaccination of any kind. The main role in increasing the disturbingly low pneumococcal vaccination coverage lies in the hands of medical professionals, especially GPs who should inform their patients about the possibility of a free vaccine and who should make an effort to explain to their patients the benefit of pneumococcal vaccination. (Tab. 4, Reft 9.)

  20. Vaccines against stimulants: cocaine and MA.

    PubMed

    Kosten, Thomas; Domingo, Coreen; Orson, Frank; Kinsey, Berma

    2014-02-01

    While the worldwide prevalence of cocaine use remains significant, medications, or small molecule approaches, to treat drug addictions have met with limited success. Anti-addiction vaccines, on the other hand, have demonstrated great potential for treating drug abuse using a distinctly different mechanism of eliciting an antibody response that blocks the pharmacological effects of drugs. We provide a review of vaccine-based approaches to treating stimulant addictions; specifically and cocaine addictions. This selective review article focuses on the one cocaine vaccine that has been into clinical trials and presents new data related to pre-clinical development of a methamphetamine (MA) vaccine. We also review the mechanism of action for vaccine induced antibodies to abused drugs, which involves kinetic slowing of brain entry as well as simple blocking properties. We present pre-clinical innovations for MA vaccines including hapten design, linkage to carrier proteins and new adjuvants beyond alum. We provide some new information on hapten structures and linkers and variations in protein carriers. We consider a carrier, outer membrance polysaccharide coat protein (OMPC), that provides some self-adjuvant through lipopolysaccharide components and provide new results with a monophosopholipid adjuvant for the more standard carrier proteins with cocaine and MA. The review then covers the clinical trials with the cocaine vaccine TA-CD. The clinical prospects for advances in this field over the next few years include a multi-site cocaine vaccine clinical trial to be reported in 2013 and phase 1 clinical trials of a MA vaccine in 2014.

  1. Dismantling the Taboo against Vaccines in Pregnancy.

    PubMed

    de Martino, Maurizio

    2016-06-07

    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.

  2. Dismantling the Taboo against Vaccines in Pregnancy

    PubMed Central

    de Martino, Maurizio

    2016-01-01

    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. PMID:27338346

  3. Rotavirus vaccines

    PubMed Central

    Yen, Catherine; Tate, Jacqueline E; Hyde, Terri B; Cortese, Margaret M; Lopman, Benjamin A; Jiang, Baoming; Glass, Roger I; Parashar, Umesh D

    2016-01-01

    Rotavirus is the leading cause of severe diarrhea among children <5 years worldwide. Currently licensed rotavirus vaccines have been efficacious and effective, with many countries reporting substantial declines in diarrheal and rotavirus-specific morbidity and mortality. However, the full public health impact of these vaccines has not been realized. Most countries, including those with the highest disease burden, have not yet introduced rotavirus vaccines into their national immunization programs. Research activities that may help inform vaccine introduction decisions include (1) establishing effectiveness, impact, and safety for rotavirus vaccines in low-income settings; (2) identifying potential strategies to improve performance of oral rotavirus vaccines in developing countries, such as zinc supplementation; and (3) pursuing alternate approaches to oral vaccines, such as parenteral immunization. Policy- and program-level barriers, such as financial implications of new vaccine introductions, should be addressed to ensure that countries are able to make informed decisions regarding rotavirus vaccine introduction. PMID:24755452

  4. DENGUE VACCINES.

    PubMed

    Thisyakorn, Usa; Thisyakorn, Chule

    2015-01-01

    The uniqueness of the dengue viruses (DENVs) and the spectrum of disease resulting from infection have made dengue vaccine development difficult. Several vaccine candidates are currently being evaluated in clinical studies. The candidate currently at the most advanced clinical development stage, a live-attenuated tetravalent vaccine based on the chimeric yellow fever-dengue virus (CYD-TDV), has progressed to Phase 3 efficacy studies. Several other live-attenuated vaccines, as well as subunit, DNA, and purified inactivated vaccine candidates are at earlier stages of clinical development. Additional technological approaches, such as virus-vectored and Virus-Like Particles (VLP)-based vaccines are under evaluation in preclinical studies.

  5. Effect of vaccination with carrier protein on response to meningococcal C conjugate vaccines and value of different immunoassays as predictors of protection.

    PubMed

    Burrage, Moya; Robinson, Andrew; Borrow, Ray; Andrews, Nick; Southern, Joanna; Findlow, Jamie; Martin, Sarah; Thornton, Carol; Goldblatt, David; Corbel, Michael; Sesardic, Dorothea; Cartwight, Keith; Richmond, Peter; Miller, Elizabeth

    2002-09-01

    In order to plan for the wide-scale introduction of meningococcal C conjugate (MCC) vaccine for United Kingdom children up to 18 years old, phase II trials were undertaken to investigate whether there was any interaction between MCC vaccines conjugated to tetanus toxoid (TT) or a derivative of diphtheria toxin (CRM(197)) and diphtheria-tetanus vaccines given for boosting at school entry or leaving. Children (n = 1,766) received a diphtheria-tetanus booster either 1 month before, 1 month after, or concurrently with one of three MCC vaccines conjugated to CRM(197) or TT. All of the MCC vaccines induced high antibody responses to the serogroup C polysaccharide that were indicative of protection. The immune response to the MCC-TT vaccine was reduced as a result of prior immunization with a tetanus-containing vaccine, but antibody levels were still well above the lower threshold for protection. Prior or simultaneous administration of a diphtheria-containing vaccine did not affect the response to MCC-CRM(197) vaccines. The immune responses to the carrier proteins were similar to those induced by a comparable dose of diphtheria or tetanus vaccine. The results also demonstrate that, for these conjugate vaccines in these age groups, both standard enzyme-linked immunosorbent assays and those that measure high-avidity antibodies to meningococcal C polysaccharide correlated equally well with assays that measure serum bactericidal antibodies, the established serological correlate of protection for MCC vaccines.

  6. Rheologically interesting polysaccharides from yeasts

    NASA Technical Reports Server (NTRS)

    Petersen, G. R.; Nelson, G. A.; Cathey, C. A.; Fuller, G. G.

    1989-01-01

    We have examined the relationships between primary, secondary, and tertiary structures of polysaccharides exhibiting the rheological property of friction (drag) reduction in turbulent flows. We found an example of an exopolysaccharide from the yeast Cryptococcus laurentii that possessed high molecular weight but exhibited lower than expected drag reducing activity. Earlier correlations by Hoyt showing that beta 1 --> 3, beta 2 --> 4, and alpha 1 --> 3 linkages in polysaccharides favored drag reduction were expanded to include correlations to secondary structure. The effect of sidechains in a series of gellan gums was shown to be related to sidechain length and position. Disruption of secondary structure in drag reducing polysaccharides reduced drag reducing activity for some but not all exopolysaccharides. The polymer from C. laurentii was shown to be more stable than xanthan gum and other exopolysaccharides under the most vigorous of denaturing conditions. We also showed a direct relationship between extensional viscosity measurements and the drag reducing coefficient for four exopolysaccharides.

  7. Vaccine Safety

    MedlinePlus

    ... FAQs about Vaccine Safety Research Publications HDM Reports ISO Scientific Agenda Ensuring Safety History Understanding Side Effects ... Datalink Publications Emergency Preparedness Vaccine Safety Partners About ISO File Formats Help: How do I view different ...

  8. Polysaccharide-Modified Synthetic Polymeric Biomaterials

    PubMed Central

    Baldwin, Aaron D.; Kiick, Kristi L.

    2010-01-01

    This review presents an overview of polysaccharide-conjugated synthetic polymers and their use in tissue-engineered scaffolds and drug-delivery applications. This topic will be divided into four categories: (1) polymeric materials modified with non-mammalian polysaccharides such as alginate, chitin, and dextran; (2) polymers modified with mammalian polysaccharides such as hyaluronan, chondroitin sulfate, and heparin; (3) multi-polysaccharide-derivatized polymer conjugate systems; and (4) polymers containing polysaccharide-mimetic molecules. Each section will discuss relevant conjugation techniques, analysis, and the impact of these materials as micelles, particles, or hydrogels used in in-vitro and in-vivo biomaterial applications. PMID:20091875

  9. Vaccination against typhoid fever: present status.

    PubMed Central

    Ivanoff, B.; Levine, M. M.; Lambert, P. H.

    1994-01-01

    Typhoid fever remains an underestimated important health problem in many developing countries, causing more than 600,000 deaths annually in the world. Because of the reactogenicity of the parenteral, killed whole-cell vaccine, research has been oriented towards vaccination orally using live organisms and purified antigen. Live vaccine Ty21a, given by the oral route, has been extensively tested in several studies in developing countries. Its liquid formulation was the most effective, providing more than 60% protection after 7 years of follow-up. A Vi polysaccharide vaccine has been elaborated and provided more than 65% protection; after 3 years of follow-up the Vi antibody level was still at a high level. These two vaccines are therefore candidates for use in public health control programmes. Before such use, however, they need further evaluation for safety and protective efficacy when administered to the EPI-targeted age groups. The question of whether typhoid fever vaccines interfere with the response to simultaneously administered measles vaccine must also be studied. New live vaccines, given by the oral route in one dose, have been constructed through genetic engineering. The first results are promising, but they must be improved before use in a large-scale study. These strains could be used as live vector to deliver foreign antigens to the intestinal mucosa. PMID:7867143

  10. Immunomodulatory and Anti-IBDV Activities of the Polysaccharide AEX from Coccomyxa gloeobotrydiformis

    PubMed Central

    Guo, Qiang; Shao, Qiang; Xu, Wenping; Rui, Lei; Sumi, Ryo; Eguchi, Fumio; Li, Zandong

    2017-01-01

    A number of polysaccharides have been reported to show immunomodulatory and antiviral activities against various animal viruses. AEX is a polysaccharide extracted from the green algae, Coccomyxa gloeobotrydiformis. The aim of this study was to examine the function of AEX in regulating the immune response in chickens and its capacity to inhibit the infectious bursal disease virus (IBDV), to gain an understanding of its immunomodulatory and antiviral ability. Here, preliminary immunological tests in vitro showed that the polysaccharide AEX can activate the chicken peripheral blood molecular cells’ (PBMCs) response by inducing the production of cytokines and NO, promote extracellular antigen presentation but negatively regulate intracellular antigen presentation in chicken splenic lymphocytes, and promote the proliferation of splenic lymphocytes and DT40 cells. An antiviral analysis showed that AEX repressed IBDV replication by the deactivation of viral particles or by interfering with adsorption in vitro and reduced the IBDV viral titer in the chicken bursa of Fabricius. Finally, in this study, when AEX was used as an adjuvant for the IBDV vaccine, specific anti-IBDV antibody (IgY, IgM, and IgA) titers were significantly decreased. These results indicate that the polysaccharide AEX may be a potential alternative approach for anti-IBDV therapy and an immunomodulator for the poultry industry. However, more experimentation is needed to find suitable conditions for it to be used as an adjuvant for the IBDV vaccine. PMID:28208594

  11. Polysaccharides templates for assembly of nanosilver.

    PubMed

    Emam, Hossam E; Ahmed, Hanan B

    2016-01-01

    Polysaccharides are particularly attractive in biomedical applications due to its biodegradability and biocompatibility. In addition to its ecofriendly effects and easy processing into different hydrogel shapes, made polysaccharides used on a large scale as suitable media for preparation of silver nanoparticles (AgNPs). In spite of, most of polysaccharides are water insoluble, but it has shown to be quite efficient capping agents and/or nanoreactor matrices for production of AgNPs. Several methods have been developed to get the benefit of multi-functionality for polysaccharides' macromolecules in preparation of AgNPs. Therefore, recently, preparation of nanosilver using different polysaccharides have been the focus of an exponentially increasing number of works devoted to develop nanocomposites by blending AgNPs with different polysaccharides matrices. The current review represents a wide survey for the published studies which interested in using of polysaccharides in nanosilver preparations.

  12. Effect of the Polysaccharide Extract from the Edible Mushroom Pleurotus ostreatus against Infectious Bursal Disease Virus

    PubMed Central

    Selegean, Mircea; Putz, Mihai V.; Rugea, Tatiana

    2009-01-01

    The polysaccharide-containing extracellular fractions (EFs) of the edible mushroom Pleurotus ostreatus have immunomodulating effects. Being aware of these therapeutic effects of mushroom extracts, we have investigated the synergistic relations between these extracts and BIAVAC and BIAROMVAC vaccines. These vaccines target the stimulation of the immune system in commercial poultry, which are extremely vulnerable in the first days of their lives. By administrating EF with polysaccharides from P. ostreatus to unvaccinated broilers we have noticed slow stimulation of maternal antibodies against infectious bursal disease (IBD) starting from four weeks post hatching. For the broilers vaccinated with BIAVAC and BIAROMVAC vaccines a low to almost complete lack of IBD maternal antibodies has been recorded. By adding 5% and 15% EF in the water intake, as compared to the reaction of the immune system in the previous experiment, the level of IBD antibodies was increased. This has led us to believe that by using this combination of BIAVAC and BIAROMVAC vaccine and EF from P. ostreatus we can obtain good results in stimulating the production of IBD antibodies in the period of the chicken first days of life, which are critical to broilers’ survival. This can be rationalized by the newly proposed reactivity biological activity (ReBiAc) principles by examining the parabolic relationship between EF administration and recorded biological activity. PMID:20111675

  13. Effect of the polysaccharide extract from the edible mushroom Pleurotus ostreatus against infectious bursal disease virus.

    PubMed

    Selegean, Mircea; Putz, Mihai V; Rugea, Tatiana

    2009-08-18

    The polysaccharide-containing extracellular fractions (EFs) of the edible mushroom Pleurotus ostreatus have immunomodulating effects. Being aware of these therapeutic effects of mushroom extracts, we have investigated the synergistic relations between these extracts and BIAVAC and BIAROMVAC vaccines. These vaccines target the stimulation of the immune system in commercial poultry, which are extremely vulnerable in the first days of their lives. By administrating EF with polysaccharides from P. ostreatus to unvaccinated broilers we have noticed slow stimulation of maternal antibodies against infectious bursal disease (IBD) starting from four weeks post hatching. For the broilers vaccinated with BIAVAC and BIAROMVAC vaccines a low to almost complete lack of IBD maternal antibodies has been recorded. By adding 5% and 15% EF in the water intake, as compared to the reaction of the immune system in the previous experiment, the level of IBD antibodies was increased. This has led us to believe that by using this combination of BIAVAC and BIAROMVAC vaccine and EF from P. ostreatus we can obtain good results in stimulating the production of IBD antibodies in the period of the chicken first days of life, which are critical to broilers' survival. This can be rationalized by the newly proposed reactivity biological activity (ReBiAc) principles by examining the parabolic relationship between EF administration and recorded biological activity.

  14. Edible vaccines.

    PubMed Central

    Artnzen, C J

    1997-01-01

    Vaccines were the result of trial and error research until molecular biology and genetic engineering made possible the creation of of many new and improved vaccines. New vaccines need to be inexpensive, easily administered, and capable of being stored and transported without refrigeration; without these characteristics, developing countries find it difficult to adopt vaccination as the central strategy for preventing their most devastating diseases. The authors describe a promising approach to inexpensive and effective vaccines: producing them in plants we commonly consume. Images p190-a p191-a p193-a p196-a PMID:9182305

  15. DNA vaccines

    NASA Astrophysics Data System (ADS)

    Gregersen, Jens-Peter

    2001-12-01

    Immunization by genes encoding immunogens, rather than with the immunogen itself, has opened up new possibilities for vaccine research and development and offers chances for new applications and indications for future vaccines. The underlying mechanisms of antigen processing, immune presentation and regulation of immune responses raise high expectations for new and more effective prophylactic or therapeutic vaccines, particularly for vaccines against chronic or persistent infectious diseases and tumors. Our current knowledge and experience of DNA vaccination is summarized and critically reviewed with particular attention to basic immunological mechanisms, the construction of plasmids, screening for protective immunogens to be encoded by these plasmids, modes of application, pharmacokinetics, safety and immunotoxicological aspects. DNA vaccines have the potential to accelerate the research phase of new vaccines and to improve the chances of success, since finding new immunogens with the desired properties is at least technically less demanding than for conventional vaccines. However, on the way to innovative vaccine products, several hurdles have to be overcome. The efficacy of DNA vaccines in humans appears to be much less than indicated by early studies in mice. Open questions remain concerning the persistence and distribution of inoculated plasmid DNA in vivo, its potential to express antigens inappropriately, or the potentially deleterious ability to insert genes into the host cell's genome. Furthermore, the possibility of inducing immunotolerance or autoimmune diseases also needs to be investigated more thoroughly, in order to arrive at a well-founded consensus, which justifies the widespread application of DNA vaccines in a healthy population.

  16. [Antiviral vaccines].

    PubMed

    Girard, M

    1999-01-01

    Vaccination has been successful in controlling numerous diseases in man and animals. Smallpox has been eradicated and poliomyelitis is on the verge of being eradicated. The traditional immunization arsenal includes vaccines using live, attenuated, and inactivated organisms. DNA recombinant technology has added two new types of vaccines, i.e. subunit vaccines based on purified antigens produced by genetic engineering in bacterial, yeast, or animal-cell cultures and live recombinant vaccines based on attenuated bacterial or viral vectors. Currently the best known examples of these new vaccines are those using poxvirus vectors (vaccinia virus, canarypox virus, or fowlpox virus) but new vectors are under development. Another application for genetic engineering in the field of vaccinology is the development of DNA vaccines using naked plasmid DNA. This technique has achieved remarkable results in small rodents but its efficacy, safety, and feasibility in man has yet to be demonstrated. Numerous studies are now under way to improve the process. In the field of synthetic vaccines, lipopeptides have shown promise for induction of cell immune response. Development of vaccines for administration by the oral or nasal route may one day revolutionize vaccination techniques. However, effective vaccines against hepatitis C and HIV have stalled in the face of the complexity and pathophysiology of these diseases. These are the greatest challenges confronting scientists at the dawn of the new millennium.

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

    PubMed Central

    2012-01-01

    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 via the web

  18. The Evolution of the Meningitis Vaccine Project

    PubMed Central

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

    2015-01-01

    Background. 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. Methods. 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. Results. 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. Conclusions. 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. PMID:26553666

  19. Safety of immunization during pregnancy: a review of the evidence of selected inactivated and live attenuated vaccines.

    PubMed

    Keller-Stanislawski, Brigitte; Englund, Janet A; Kang, Gagandeep; Mangtani, Punam; Neuzil, Kathleen; Nohynek, Hanna; Pless, Robert; Lambach, Philipp; Zuber, Patrick

    2014-12-12

    Vaccine-preventable infectious diseases are responsible for significant maternal, neonatal, and young infant morbidity and mortality. While there is emerging scientific evidence, as well as theoretical considerations, indicating that certain vaccines are safe for pregnant women and fetuses, policy formulation is challenging because of perceived potential risks to the fetus. This report presents an overview of available evidence on pregnant women vaccination safety monitoring in pregnant women, from both published literature and ongoing surveillance programs. Safety data were reviewed for vaccines against diseases which increase morbidity in pregnant women, their fetus or infant as well as vaccines which are used in mass vaccination campaigns against diseases. They include inactivated seasonal and pandemic influenza, mono- and combined meningococcal polysaccharide and conjugated vaccines, tetanus toxoid and acellular pertussis combination vaccines, as well as monovalent or combined rubella, oral poliomyelitis virus and yellow fever vaccines. No evidence of adverse pregnancy outcomes has been identified from immunization of pregnant women with these vaccines.

  20. Structurally altered capsular polysaccharides produced by mutant bacteria

    NASA Technical Reports Server (NTRS)

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

    1995-01-01

    Structurally altered capsular polysaccharides are produced by mutant bacteria. These polysaccharides are isolated by selecting a wild type bacterial strain and a phage producing degradative enzymes that have substrate specificity for the capsular polysaccharides produced by the wild type bacteria. Phage-resistant mutants producing capsular polysaccharides are selected and the structurally altered capsular polysaccharide is isolated therefrom.

  1. Hepatitis Vaccines

    PubMed Central

    Ogholikhan, Sina; Schwarz, Kathleen B.

    2016-01-01

    Viral hepatitis is a serious health problem all over the world. However, the reduction of the morbidity and mortality due to vaccinations against hepatitis A and hepatitis B has been a major component in the overall reduction in vaccine preventable diseases. We will discuss the epidemiology, vaccine development, and post-vaccination effects of the hepatitis A and B virus. In addition, we discuss attempts to provide hepatitis D vaccine for the 350 million individuals infected with hepatitis B globally. Given the lack of a hepatitis C vaccine, the many challenges facing the production of a hepatitis C vaccine will be shown, along with current and former vaccination trials. As there is no current FDA-approved hepatitis E vaccine, we will present vaccination data that is available in the rest of the world. Finally, we will discuss the existing challenges and questions facing future endeavors for each of the hepatitis viruses, with efforts continuing to focus on dramatically reducing the morbidity and mortality associated with these serious infections of the liver. PMID:26978406

  2. Pneumococcal polysaccharide vaccine - what you need to know

    MedlinePlus

    ... the Unites States. Treatment of pneumococcal infections with penicillin and other drugs used to be more effective. ... get another dose. Anyone who has a severe allergy to any component of PPSV should not receive ...

  3. Pneumococcal Polysaccharide Vaccine: What You Need to Know

    MedlinePlus

    ... Unite d States. Treatment of pneumococcal infections with penicillin and other drugs used to be more effective. ... get another dose. • Anyone who has a severe allergy to any component of PPSV should not receive ...

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

    PubMed Central

    Wiertsema, Selma P.; Corscadden, Karli J.; Mateus, Tulia; Mullaney, Gemma L.; Zhang, Guicheng; Richmond, Peter C.; Thornton, Ruth B.

    2016-01-01

    ABSTRACT 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 < 0.05). The production of functional antipneumococcal antibodies in 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. PMID:28031178

  5. Vaccine Adverse Events

    MedlinePlus

    ... Vaccines, Blood & Biologics Animal & Veterinary Cosmetics Tobacco Products Vaccines, Blood & Biologics Home Vaccines, Blood & Biologics Safety & Availability ( ... Center for Biologics Evaluation & Research Vaccine Adverse Events Vaccine Adverse Events Share Tweet Linkedin Pin it More ...

  6. Vaccines.gov

    MedlinePlus

    ... Statements Vaccine Approvals Features: News & Video Free Resources Vaccines are safe, effective, and save lives. Find answers ... by science, on vaccine safety. Are your child’s vaccines up to date? Getting all recommended vaccines on ...

  7. Marine Polysaccharides in Pharmaceutical Applications: An Overview

    PubMed Central

    Laurienzo, Paola

    2010-01-01

    The enormous variety of polysaccharides that can be extracted from marine plants and animal organisms or produced by marine bacteria means that the field of marine polysaccharides is constantly evolving. Recent advances in biological techniques allow high levels of polysaccharides of interest to be produced in vitro. Biotechnology is a powerful tool to obtain polysaccharides from a variety of micro-organisms, by controlling the growth conditions in a bioreactor while tailoring the production of biologically active compounds. Following an overview of the current knowledge on marine polysaccharides, with special attention to potential pharmaceutical applications and to more recent progress on the discovering of new polysaccharides with biological appealing characteristics, this review will focus on possible strategies for chemical or physical modification aimed to tailor the final properties of interest. PMID:20948899

  8. Phase 3 trial evaluating the immunogenicity, safety, and tolerability of manufacturing scale 13-valent pneumococcal conjugate vaccine.

    PubMed

    Gadzinowski, Janusz; Albrecht, Piotr; Hasiec, Barbara; Konior, Ryszard; Dziduch, Jerzy; Witor, Anita; Mellelieu, Tracey; Tansey, Susan P; Jones, Thomas; Sarkozy, Denise; Emini, Emilio A; Gruber, William C; Scott, Daniel A

    2011-04-05

    13-valent pneumococcal conjugate vaccine (PCV13) includes polysaccharide conjugates from six pneumococcal serotypes in addition to those in the licensed 7-valent vaccine, thereby offering expanded protection against pneumococcal disease. The phase 3 trial reported here was conducted per a regulatory requirement to evaluate the immunogenicity, safety, and tolerability of two lots of the final PCV13 formulation that differed with respect to production scale but not the manufacturing process. The anti-pneumococcal polysaccharide immunogenicity and safety/tolerability were found to be similar between the two PCV13 vaccine lots.

  9. [HPV vaccination].

    PubMed

    Stronski Huwiler, Susanne; Spaar, Anne

    2016-01-01

    Human Papilloma Viruses are associated with genital carcinoma (of the cervix, anus, vulva, vagina and the penis) as well as with non-genital carcinoma (oropharyngeal carcinoma) and genital warts. In Switzerland two highly efficient and safe vaccines are available. The safety of these vaccines has been repeatedly subject of controversial discussions, however so far post marketing surveillance has always been able to confirm the safety. In Switzerland girls and young women have been offered the HPV vaccination within cantonal programmes since 2008. 2015 the recommendation for the HPV-vaccination for boys and young men was issued, and starting July 1, 2016 they as well will be offered vaccination free of charge within the cantonal programmes. This article discusses the burden of disease, efficacy and safety of the vaccines and presents facts which are important for vaccinating these young people. Specifically, aspects of the decisional capacity of adolescents to consent to the vaccination are presented. Finally, the future perspective with a focus on a new vaccine with an enlarged spectrum of HPV-types is discussed.

  10. Polysaccharide-based nanocomposites and their applications

    PubMed Central

    Zheng, Yingying; Monty, Jonathan; Linhardt, Robert J.

    2014-01-01

    Polysaccharide nanocomposites have become increasingly important materials over the past decade. Polysaccharides offer a green alternative to synthetic polymers in the preparation of soft nanomaterials. They have also been used in composites with hard nanomaterials, such as metal nanoparticles and carbon-based nanomaterials. This mini review describes methods for polysaccharide nanocomposite preparation and reviews the various types and diverse applications for these novel materials. PMID:25498200

  11. Advances on Bioactive Polysaccharides from Medicinal Plants.

    PubMed

    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.

  12. Clinical effectiveness of pneumococcal vaccine. Meta-analysis.

    PubMed Central

    Hutchison, B. G.; Oxman, A. D.; Shannon, H. S.; Lloyd, S.; Altmayer, C. A.; Thomas, K.

    1999-01-01

    OBJECTIVE: To determine the clinical effectiveness of pneumococcal vaccine. DATA SOURCES: Computerized searches of MEDLINE, EMBASE, and SCISEARCH databases were performed, reference lists of retrieved articles were reviewed, and first authors of published studies were contacted. STUDY SELECTION: Studies of use of pneumococcal vaccines in adults were included if the study design was a randomized or quasi-randomized controlled trial and at least one of the following clinical outcomes was reported: vaccine-type systemic pneumococcal infection, systemic pneumococcal infection, vaccine-type pneumococcal pneumonia, pneumococcal pneumonia, non-vaccine-type pneumococcal pneumonia. SYNTHESIS: Study quality was assessed and descriptive information concerning the study populations, interventions, and outcome measurements was extracted for 13 trials involving more than 65,000 patients. Estimates of vaccine efficacy, based on a meta-analysis of randomized and quasi-randomized trials, were determined for clinical outcomes. CONCLUSIONS: Vaccination with pneumococcal polysaccharide vaccine can be expected to reduce the risk of systemic infection due to pneumococcal types included in the vaccine by 83% and systemic infection due to all pneumococci by 73%. We found no evidence that the vaccine was less efficacious for the elderly, institutionalized people, or those with chronic disease. PMID:10540698

  13. Activity of glycated chitosan and other adjuvants to PDT vaccines

    NASA Astrophysics Data System (ADS)

    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.

  14. Promises and pitfalls of live attenuated pneumococcal vaccines.

    PubMed

    Rosch, Jason W

    2014-01-01

    The pneumococcus is a remarkably adaptable pathogen whose disease manifestations range from mucosal surface infections such as acute otitis media and pneumonia to invasive infections such as sepsis and meningitis. Currently approved vaccines target the polysaccharide capsule, of which there are over 90 distinct serotypes, leading to rapid serotype replacement in vaccinated populations. Substantial progress has been made in the development of a universal pneumococcal vaccine, with efforts focused on broadly conserved and protective protein antigens. An area attracting considerable attention is the potential application of live attenuated vaccines to confer serotype-independent protection against mucosal and systemic infection. On the basis of recent work to understand the mucosal and systemic responses to nasal administration of pneumococci and to develop novel attenuation strategies, the prospect of a practical and protective live vaccine remains promising.

  15. Bioactive polysaccharides and gut microbiome (abstract)

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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...

  16. Polysaccharide Based Hydrogels for Biomedical Applications

    NASA Astrophysics Data System (ADS)

    Leone, Gemma; Barbucci, Rolando

    Polysaccharide based hydrogels for their physico-chemical and biological properties can be used as scaffolds for soft tissue regneration and as vehicles for drug controlled release. For both these applications, Hyaluronan shows optimal characteristics even though its quick enzymatic degradability makes this natural polysaccharide unsuitable for applications which require prolonged presence in the human organism.

  17. Solution NMR spectroscopy of food polysaccharides

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Many polysaccharides are allowed for direct food use, where they serve a number of useful functions. In addition to possibly being a source of calories, a food polysaccharide may be a dietary fiber, bulking agent, crystallization inhibitor, thickener, encapsulant, gelling agent, foam and emulsion s...

  18. Indirect Effects of Pneumococcal Conjugate Vaccines in National Immunization Programs for Children on Adult Pneumococcal Disease

    PubMed Central

    2016-01-01

    The pneumococcal conjugate vaccine (PCV) was developed to overcome the limitations of the pneumococcal polysaccharide vaccine, which produces poor immunogenicity in infants younger than 2 years. As many countries have included PCVs in national immunization programs for children, the incidence of invasive pneumococcal disease caused by vaccine type Streptococcus pneumoniae has declined markedly, not only among the vaccinated pediatric population, but also among unvaccinated adults. In this review, we present a concise overview of the indirect effects of mass pediatric PCV immunization on unvaccinated adults. PMID:28032483

  19. Polysaccharides in colon-specific drug delivery.

    PubMed

    Sinha, V R; Kumria, R

    2001-08-14

    Natural polysaccharides are now extensively used for the development of solid dosage forms for delivery of drug to the colon. The rationale for the development of a polysaccharide based delivery system for colon is the presence of large amounts of polysaccharidases in the human colon as the colon is inhabited by a large number and variety of bacteria which secrete many enzymes e.g. beta-D-glucosidase, beta-D-galactosidase, amylase, pectinase, xylanase, beta-D-xylosidase, dextranase, etc. Various major approaches utilizing polysaccharides for colon-specific delivery are fermentable coating of the drug core, embedding of the drug in biodegradable matrix, formulation of drug-saccharide conjugate (prodrugs). A large number of polysaccharides have already been studied for their potential as colon-specific drug carrier systems, such as chitosan, pectin, chondroitin sulphate, cyclodextrin, dextrans, guar gum, inulin, amylose and locust bean gum. Recent efforts and approaches exploiting these polysaccharides in colon-specific drug delivery are discussed.

  20. Unexplored possibilities of all-polysaccharide composites.

    PubMed

    Simkovic, Ivan

    2013-06-20

    Composites made solely from polysaccharides are mostly ecological because they can degrade without leaving behind ecologically harmful residues, in contrast to composites which contain synthetic polymers. Herein, the following groups of all-polysaccharide composites (APCs) are discussed: an all-cellulose group that includes cotton composites, cellulose combined with other polysaccharides, as well as those based on chitin/chitosan, heparin, hyaluronan, xylan, glucomannan, pectin, xyloglucan, arabinan, starch, carrageenan, alginate, galactan as one of the components in combination with other polysaccharides. They can be used in medical, paper, food, packing, textile, electronic, mechanical engineering and other applications. The composites were tested for absorptivity, biodegradability, crystallinity, rheology, and mechanical, optical, separation, gelling, pasting, film-forming, adhesive, antimicrobial properties, as well as water vapor permeability, water repellency, dye uptake, and fire-retardancy. Except for food applications, composites based on more than two types of polysaccharides have rarely been used and many possible combinations remain unexplored.

  1. Synthesis of part structures of Cryptococcus neoformans serotype C capsular polysaccharide.

    PubMed

    Guazzelli, Lorenzo; McCabe, Orla; Oscarson, Stefan

    2016-10-04

    Cryptococcus neoformans is a fungal pathogen that can cause life-threatening infections in immunocompromised patients. The development of a vaccine based on the capsular polysaccharide of C. neoformans is still an open challenge due to the heterogeneity of the capsular polysaccharide and the difficulty of identifying protective epitopes. Therefore, construction of structurally defined part structures of the C. neoformans GXM capsule is in great demand. Herein is presented the synthesis of a 3-O-naphthalenylmethyl protected trisaccharide thioglycoside building block which is present in C. neoformans serotype C polysaccharide. Its property as a donor in a glycosylation reaction with a model acceptor has been evaluated together with its behaviour as an acceptor following removal of the temporary protecting group. The heavily branched hexasaccharide was obtained in good yields and excellent α-selectivity. The frame shifted octasaccharide structural triad motif for serotype C was also prepared following the same building block strategy. For the first time this structural motif, which is the most substituted amongst the four C. neoformans serotypes, was prepared. Three synthesized C. neoformans serotype C fragments of varying size, from penta-up to octasaccharide, were deprotected and will be included in unique glycoarrays to further investigate the possibility to develop a synthetic vaccine against this pathogen.

  2. Evolution of the capsular operon of Streptococcus iniae in response to vaccination.

    PubMed

    Millard, Candice M; Baiano, Justice C F; Chan, Candy; Yuen, Benedict; Aviles, Fabian; Landos, Matt; Chong, Roger S M; Benedict, Suresh; Barnes, Andrew C

    2012-12-01

    Streptococcus iniae causes severe septicemia and meningitis in farmed fish and is also occasionally zoonotic. Vaccination against S. iniae is problematic, with frequent breakdown of protection in vaccinated fish. The major protective antigens in S. iniae are the polysaccharides of the capsule, which are essential for virulence. Capsular biosynthesis is driven and regulated by a 21-kb operon comprising up to 20 genes. In a long-term study, we have sequenced the capsular operon of strains that have been used in autogenous vaccines across Australia and compared it with the capsular operon sequences of strains subsequently isolated from infected vaccinated fish. Intriguingly, strains isolated from vaccinated fish that subsequently become infected have coding mutations that are confined to a limited number of genes in the cps operon, with the remainder of the genes in the operon remaining stable. Mutations in strains in diseased vaccinated fish occur in key genes in the capsular operon that are associated with polysaccharide configuration (cpsG) and with regulation of biosynthesis (cpsD and cpsE). This, along with high ratios of nonsynonymous to synonymous mutations within the cps genes, suggests that immune response directed predominantly against capsular polysaccharide may be driving evolution in a very specific set of genes in the operon. From these data, it may be possible to design a simple polyvalent vaccine with a greater operational life span than the current monovalent killed bacterins.

  3. Evolution of the Capsular Operon of Streptococcus iniae in Response to Vaccination

    PubMed Central

    Millard, Candice M.; Baiano, Justice C. F.; Chan, Candy; Yuen, Benedict; Aviles, Fabian; Landos, Matt; Chong, Roger S. M.; Benedict, Suresh

    2012-01-01

    Streptococcus iniae causes severe septicemia and meningitis in farmed fish and is also occasionally zoonotic. Vaccination against S. iniae is problematic, with frequent breakdown of protection in vaccinated fish. The major protective antigens in S. iniae are the polysaccharides of the capsule, which are essential for virulence. Capsular biosynthesis is driven and regulated by a 21-kb operon comprising up to 20 genes. In a long-term study, we have sequenced the capsular operon of strains that have been used in autogenous vaccines across Australia and compared it with the capsular operon sequences of strains subsequently isolated from infected vaccinated fish. Intriguingly, strains isolated from vaccinated fish that subsequently become infected have coding mutations that are confined to a limited number of genes in the cps operon, with the remainder of the genes in the operon remaining stable. Mutations in strains in diseased vaccinated fish occur in key genes in the capsular operon that are associated with polysaccharide configuration (cpsG) and with regulation of biosynthesis (cpsD and cpsE). This, along with high ratios of nonsynonymous to synonymous mutations within the cps genes, suggests that immune response directed predominantly against capsular polysaccharide may be driving evolution in a very specific set of genes in the operon. From these data, it may be possible to design a simple polyvalent vaccine with a greater operational life span than the current monovalent killed bacterins. PMID:23001668

  4. [Somatic antigens of the Brucella genus. The structure of the O-specific polysaccharide chain of Brucella melitensis lipopolysaccharide].

    PubMed

    L'vov, V L; Malikov, V E; Shashkov, A S; Dranovskaia, E A; Dmitriev, B A

    1985-07-01

    The phenol-phase soluble antigenic lipopolysaccharide was isolated from Brucella melitensis, strain 565, by the routine phenol/water procedure followed by chromatography on Sepharose 4B. After mild acid hydrolysis and chromatography on Sephadex G-50, the lipopolysaccharide yielded a linear O-specific polysaccharide built up from 1,2-linked 4,6-dideoxy-4-formamido-alpha-D-mannopyranosyl units. The structure of the polysaccharide was deduced mainly from the nuclear magnetic resonance and methylation analyses. The phenol-soluble lipopolysaccharide, isolated from commercial vaccine strain B. abortus 19-BA, on mild hydrolysis afforded material, 13C and 1H-NMR spectra of which were identical to those of the O-specific polysaccharide from B. melitensis 565.

  5. Experimental design to optimize an Haemophilus influenzae type b conjugate vaccine made with hydrazide-derivatized tetanus toxoid.

    PubMed

    Laferriere, Craig; Ravenscroft, Neil; Wilson, Seanette; Combrink, Jill; Gordon, Lizelle; Petre, Jean

    2011-10-01

    The introduction of type b Haemophilus influenzae conjugate vaccines into routine vaccination schedules has significantly reduced the burden of this disease; however, widespread use in developing countries is constrained by vaccine costs, and there is a need for a simple and high-yielding manufacturing process. The vaccine is composed of purified capsular polysaccharide conjugated to an immunogenic carrier protein. To improve the yield and rate of the reductive amination conjugation reaction used to make this vaccine, some of the carboxyl groups of the carrier protein, tetanus toxoid, were modified to hydrazides, which are more reactive than the ε -amine of lysine. Other reaction parameters, including the ratio of the reactants, the size of the polysaccharide, the temperature and the salt concentration, were also investigated. Experimental design was used to minimize the number of experiments required to optimize all these parameters to obtain conjugate in high yield with target characteristics. It was found that increasing the reactant ratio and decreasing the size of the polysaccharide increased the polysaccharide:protein mass ratio in the product. Temperature and salt concentration did not improve this ratio. These results are consistent with a diffusion controlled rate limiting step in the conjugation reaction. Excessive modification of tetanus toxoid with hydrazide was correlated with reduced yield and lower free polysaccharide. This was attributed to a greater tendency for precipitation, possibly due to changes in the isoelectric point. Experimental design and multiple regression helped identify key parameters to control and thereby optimize this conjugation reaction.

  6. Agglutination by anti-capsular polysaccharide antibody is associated with protection against experimental human pneumococcal carriage

    PubMed Central

    Reiné, J; Zangari, T; Owugha, JT; Pennington, SH; Gritzfeld, JF; Wright, AD; Collins, AM; van Selm, S; de Jonge, MI; Gordon, SB; Weiser, JN; Ferreira, DM

    2016-01-01

    The ability of pneumococcal conjugate vaccine (PCV) to decrease transmission by blocking the acquisition of colonization has been attributed to herd immunity. We describe the role of mucosal IgG to capsular polysaccharide (CPS) in mediating protection from carriage, translating our findings from a murine model to humans. We used a flow-cytometric assay to quantify antibody-mediated agglutination demonstrating that hyperimmune sera generated against an unencapsulated mutant was poorly agglutinating. Passive immunization with this antiserum was ineffective to block acquisition of colonization compared to agglutinating antisera raised against the encapsulated parent strain. In the human challenge model samples were collected from PCV and control vaccinated adults. In PCV-vaccinated subjects IgG levels to CPS were increased in serum and nasal wash (NW). IgG to the inoculated strain CPS dropped in NW samples after inoculation suggesting its sequestration by colonizing pneumococci. In post-vaccination NW samples pneumococci were heavily agglutinated compared to pre-vaccination samples in subjects protected against carriage. Our results indicate that pneumococcal agglutination mediated by CPS specific antibodies is a key mechanism of protection against acquisition of carriage. Capsule may be the only vaccine target that can elicit strong agglutinating antibody responses, leading to protection against carriage acquisition and generation of herd immunity. PMID:27579859

  7. Novel strategies for development of next-generation glycoconjugate vaccines.

    PubMed

    Avci, Fikri Y

    2013-01-01

    Most bacterial pathogens are decorated with surface glycans called capsular polysaccharides (CPSs). Each CPS has a unique structure that is distinctively recognized by our immune cells. These polysaccharides are important vaccine candidates given that they are located on the surface of pathogens, are easily accessible by the immune system, and often result in formation of protective antibodies. To induce CPS specific adaptive immune response (i.e., T cell-mediated B cell response), CPSs are conjugated with carrier proteins, and the conjugation products are called glycoconjugate vaccines. Immunization with glycoconjugate vaccines has had significant health benefits in controlling infections caused by Haemophilus influenzae, Streptococcus pneumoniae and Neisseria meningitidis. However, owing to insufficient understanding of their immune activation mechanisms, glycoconjugate vaccines have been designed and synthesized empirically. In recent years, we have witnessed important advancements in the glycoconjugate vaccine field: the discovery of the mechanism of action for glycoconjugate vaccines, a novel in vivo conjugation strategy, and progress in the use of novel carriers. These studies will be reviewed in detail herein.

  8. Novel Solutions for Vaccines and Diagnostics To Combat Brucellosis

    PubMed Central

    2017-01-01

    Brucellosis is diagnosed by detection of antibodies in the blood of animals and humans that are specific for two carbohydrate antigens, termed A and M, which are present concurrently in a single cell wall O-polysaccharide. Animal brucellosis vaccines contain these antigenic determinants, and consequently infected and vaccinated animals cannot be differentiated as both groups produce A and M specific antibodies. We hypothesized that chemical synthesis of a pure A vaccine would offer unique identification of infected animals by a synthetic M diagnostic antigen that would not react with antibodies generated by this vaccine. Two forms of the A antigen, a hexasaccharide and a heptasaccharide conjugated to tetanus toxoid via reducing and nonreducing terminal sugars, were synthesized and used as lead vaccine candidates. Mouse antibody profiles to these immunogens showed that to avoid reaction with diagnostic M antigen it was essential to maximize the induction of anti-A antibodies that bind internal oligosaccharide sequences and minimize production of antibodies directed toward the terminal nonreducing monosaccharide. This objective was achieved by conjugation of Brucella O-polysaccharide to tetanus toxoid via its periodate oxidized terminal nonreducing monosaccharide, thereby destroying terminal epitopes and focusing the antibody response on internal A epitopes. This establishes the method to resolve the decades-long challenge of how to create effective brucellosis vaccines without compromising diagnosis of infected animals. PMID:28386600

  9. Typhoid Vaccine

    MedlinePlus

    ... serious disease. It is caused by bacteria called Salmonella Typhi. Typhoid causes a high fever, fatigue, weakness, stomach ... a typhoid carrier. Laboratory workers who work with Salmonella Typhi bacteria. Inactivated typhoid vaccine (shot)One dose provides ...

  10. Typhoid Vaccine

    MedlinePlus

    ... serious disease. It is caused by bacteria called Salmonella Typhi. Typhoid causes a high fever, fatigue, weakness, ... a typhoid carrier. • Laboratory workers who work with Salmonella Typhi bacteria. Inactivated typhoid vaccine (shot) • One dose ...

  11. Ear Infection and Vaccines

    MedlinePlus

    ... an ENT Doctor Near You Ear Infection and Vaccines Ear Infection and Vaccines Patient Health Information News ... or may need reinsertion over time. What about vaccines? A vaccine is a preparation administered to stimulate ...

  12. Adults Need Vaccines, Too!

    MedlinePlus

    ... turn JavaScript on. Feature: Adult Vaccinations Adults Need Vaccines, Too! Past Issues / Summer 2015 Table of Contents ... of the millions of adults not receiving the vaccines you need? What vaccines do you need? All ...

  13. Smallpox Vaccine Overview

    MedlinePlus

    ... Facebook Tweet Share Compartir SMALLPOX FACT SHEET The Smallpox Vaccine The smallpox vaccine helps the body develop ... disease or may modify the severity of disease. Smallpox Vaccine Safety The smallpox vaccine is the best ...

  14. Influenza Vaccine, Live Intranasal

    MedlinePlus

    ... the recombinant influenza vaccine (RIV). The nasal spray flu vaccine (live attenuated influenza vaccine or LAIV) should NOT ... to your doctor or pharmacist about the best flu vaccine option for you or your family.

  15. The Differential Impact of Coadministered Vaccines, Geographic Region, Vaccine Product and Other Covariates on Pneumococcal Conjugate Vaccine Immunogenicity

    PubMed Central

    2014-01-01

    Background: Antipneumococcal capsular polysaccharide antibody concentrations are used as predictors of vaccine efficacy against vaccine serotype (ST) pneumococcal disease among infants. While pneumococcal conjugate vaccines (PCV) are recommended globally, factors associated with optimal PCV immune response are not well described. We aimed to systematically assess local setting factors, beyond dosing schedule, which may affect PCV antibody levels. Methods: We conducted a literature review of PCV immunogenicity, abstracting data from published reports, unpublished sources, and conference abstracts from 1994 to 2010 (and ad hoc 2011 reports). Studies included in this analysis evaluated ≥ 2 primary doses of PCV before 6 months of age in non–high-risk populations, used 7-valent or higher PCV products (excluding Aventis-Pasteur and Merck products) and provided information on geometric mean concentration (GMC) for STs 1, 5, 6B, 14, 19F or 23F. Using random effects meta-regression, we assessed the impact of geographic region, coadministered vaccines and PCV product on postprimary GMC, adjusting for dosing schedule and ELISA laboratory method. Results: Of 12,980 citations reviewed, we identified 103 vaccine study arms for this analysis. Children in studies from Asia, Africa and Latin America had significantly higher GMC responses compared with those in studies from Europe and North America. Coadministration with acellular pertussis DTP compared with whole-cell DTP had no effect on PCV immunogenicity except for ST14, where GMCs were higher when coadministered with acellular pertussis DTP. Vaccine product, number of PCV doses, dosing interval, age at first dose and ELISA laboratory method also affected the GMC. Conclusions: PCV immunogenicity is associated with geographic region and vaccine product; however, the associations and magnitude varied by ST. Consideration of these factors is essential when comparing PCV immunogenicity results between groups and should be

  16. Enzymatic method for improving the injectability of polysaccharides

    DOEpatents

    Griffith, William L.; Compere, Alicia L.; Holleman, James W.

    1982-01-01

    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.

  17. Staphylococcus aureus vaccines: Deviating from the carol

    PubMed Central

    2016-01-01

    Staphylococcus aureus, a commensal of the human nasopharynx and skin, also causes invasive disease, most frequently skin and soft tissue infections. Invasive disease caused by drug-resistant strains, designated MRSA (methicillin-resistant S. aureus), is associated with failure of antibiotic therapy and elevated mortality. Here we review polysaccharide-conjugate and subunit vaccines that were designed to prevent S. aureus infection in patients at risk of bacteremia or surgical wound infection but failed to reach their clinical endpoints. We also discuss vaccines with ongoing trials for combinations of polysaccharide-conjugates and subunits. S. aureus colonization and invasive disease are not associated with the development of protective immune responses, which is attributable to a large spectrum of immune evasion factors. Two evasive strategies, assembly of protective fibrin shields via coagulases and protein A–mediated B cell superantigen activity, are discussed as possible vaccine targets. Although correlates for protective immunity are not yet known, opsonophagocytic killing of staphylococci by phagocytic cells offers opportunities to establish such criteria. PMID:27526714

  18. Novel adjuvant Alum-TLR7 significantly potentiates immune response to glycoconjugate vaccines

    PubMed Central

    Buonsanti, Cecilia; Balocchi, Cristiana; Harfouche, Carole; Corrente, Federica; Galli Stampino, Luisa; Mancini, Francesca; Tontini, Marta; Malyala, Padma; Bufali, Simone; Baudner, Barbara; De Gregorio, Ennio; Valiante, Nicholas M.; O’Hagan, Derek T.; Rappuoli, Rino; D’Oro, Ugo

    2016-01-01

    Although glycoconjugate vaccines are generally very efficacious, there is still a need to improve their efficacy, especially in eliciting a strong primary antibody response. We have recently described a new type of vaccine adjuvant based on a TLR7 agonist adsorbed to alum (Alum-TLR7), which is highly efficacious at enhancing immunogenicity of protein based vaccines. Since no adjuvant has been shown to potentiate the immune response to glycoconjugate vaccines in humans, we investigated if Alum-TLR7 is able to improve immunogenicity of this class of vaccines. We found that in a mouse model Alum-TLR7 greatly improved potency of a CRM197-MenC vaccine increasing anti-MenC antibody titers and serum bactericidal activity (SBA) against MenC compared to alum adjuvanted vaccine, especially with a low dose of antigen and already after a single immunization. Alum-TLR7 also drives antibody response towards Th1 isotypes. This adjuvant was also able to increase immunogenicity of all polysaccharides of a multicomponent glycoconjugate vaccine CRM197-MenACWY. Furthermore, we found that Alum-TLR7 increases anti-polysaccharide immune response even in the presence of a prior immune response against the carrier protein. Finally, we demonstrate that Alum-TLR7 adjuvant effect requires a functional TLR7. Taken together, our data support the use of Alum-TLR7 as adjuvant for glycoconjugate vaccines. PMID:27439378

  19. Vacuum Ultraviolet Action Spectroscopy of Polysaccharides

    NASA Astrophysics Data System (ADS)

    Enjalbert, Quentin; Brunet, Claire; Vernier, Arnaud; Allouche, Abdul-Rahman; Antoine, Rodolphe; Dugourd, Philippe; Lemoine, Jérôme; Giuliani, Alexandre; Nahon, Laurent

    2013-08-01

    We studied the optical properties of gas-phase polysaccharides (maltose, maltotetraose, and maltohexaose) ions by action spectroscopy using the coupling between a quadrupole ion trap and a vacuum ultraviolet (VUV) beamline at the SOLEIL synchrotron radiation facility (France) in the 7 to 18 eV range. The spectra provide unique benchmarks for evaluation of theoretical data on electronic transitions of model carbohydrates in the VUV range. The effects of the nature of the charge held by polysaccharide ions on the relaxation processes were also explored. Finally the effect of isomerization of polysaccharides (with melezitose and raffinose) on their photofragmentation with VUV photons is presented.

  20. Human vaccines & immunotherapeutics: news.

    PubMed

    Riedmann, Eva M

    2013-10-01

    Infant rotavirus vaccination provides for herd immunity Nonreplicating sporozoite vaccine protects humans against malaria Personalized brain cancer vaccine enters phase 2 trial Novel implantable therapeutic cancer vaccine to be tested in humans Clostridium difficile vaccine candidate successful in phase 1 CDC reports strong uptake of HPV vaccine in boys Whooping cough outbreak in Texas.

  1. HIV Infection and Adult Vaccination

    MedlinePlus

    ... conjugate vaccine series which protects against meningococcal disease Hepatitis B vaccine series to protect against hepatitis B HPV vaccine ... conjugate vaccine series which protects against meningococcal disease Hepatitis B vaccine series to protect against hepatitis B HPV vaccine ...

  2. Characteristics of a new meningococcal serogroup B vaccine, bivalent rLP2086 (MenB-FHbp; Trumenba®).

    PubMed

    Gandhi, Ashesh; Balmer, Paul; York, Laura J

    2016-08-01

    Neisseria meningitidis is a common cause of bacterial meningitis, often leading to permanent sequelae or death. N. meningitidis is classified into serogroups based on the composition of the bacterial capsular polysaccharide; the 6 major disease-causing serogroups are designated A, B, C, W, X, and Y. Four of the 6 disease-causing serogroups (A, C, Y, and W) can be effectively prevented with available quadrivalent capsular polysaccharide protein conjugate vaccines; however, capsular polysaccharide conjugate vaccines are not effective against meningococcal serogroup B (MnB). There is no vaccine available for serogroup X. The public health need for an effective serogroup B vaccine is evident, as MnB is the most common cause of meningococcal disease in the United States and is responsible for almost half of all cases in persons aged 17 to 22 years. In fact, serogroup B meningococci were responsible for the recent meningococcal disease outbreaks on college campuses. However, development of a suitable serogroup B vaccine has been challenging, as serogroup B polysaccharide-based vaccines were found to be poorly immunogenic. Vaccine development for MnB focused on identifying potential outer membrane protein targets that elicit broadly protective immune responses across strains from the vast number of proteins that exist on the bacterial surface. Human factor H binding protein (fHBP; also known as LP2086), a conserved surface-exposed bacterial lipoprotein, was identified as a promising vaccine candidate. Two recombinant protein-based serogroup B vaccines that contain fHBP have been successfully developed and licensed in the United States under an accelerated approval process: bivalent rLP2086 (MenB-FHbp; Trumenba®) and 4CMenB (MenB-4 C; Bexsero®). This review will focus on bivalent rLP2086 only, including vaccine components, mechanism of action, and potential coverage across serogroup B strains in the United States.

  3. Hib Vaccines: Past, Present, and Future Perspectives

    PubMed Central

    Zarei, Adi Essam; Almehdar, Hussein A.; Redwan, Elrashdy M.

    2016-01-01

    Haemophilus influenzae type b (Hib) causes many severe diseases, including epiglottitis, pneumonia, sepsis, and meningitis. In developed countries, the annual incidence of meningitis caused by bacteria is approximately 5–10 cases per population of 100,000. The Hib conjugate vaccine is considered protective and safe. Adjuvants, molecules that can enhance and/or regulate the fundamental immunogenicity of an antigen, comprise a wide range of diverse compounds. While earlier developments of adjuvants created effective products, there is still a need to create new generations, rationally designed based on recent discoveries in immunology, mainly in innate immunity. Many factors may play a role in the immunogenicity of Hib conjugate vaccines, such as the polysaccharides and proteins carrier used in vaccine construction, as well as the method of conjugation. A Hib conjugate vaccine has been constructed via chemical synthesis of a Hib saccharide antigen. Two models of carbohydrate-protein conjugate have been established, the single ended model (terminal amination-single method) and cross-linked lattice matrix (dual amination method). Increased knowledge in the fields of immunology, molecular biology, glycobiology, glycoimmunology, and the biology of infectious microorganisms has led to a dramatic increase in vaccine efficacy. PMID:26904695

  4. Prevention of pneumococcal disease through vaccination.

    PubMed

    Gentile, Angela; Bazán, Virginia

    2011-09-14

    The Millennium Development Goals (MDGs), adopted by world leaders in the year 2000 with an aim to accomplish them by 2015, provide concrete benchmarks for tackling extreme poverty in its many dimensions. One aim is to reduce by two thirds the mortality rate among children <5 years of age. The deaths of nearly 3 million children under 5 each year worldwide can be attributed to diarrhea and pneumonia. Pneumonia, one form of pneumococcal disease, causes almost 1 in 5 deaths of children under 5 worldwide-more than 1.6 million children each year. Pneumococcal disease is preventable by vaccination; because antibiotic resistance is a growing problem worldwide, there is a great need to promote effective pneumococcal vaccines. Vaccines differ from other types of drugs, because they are administered to healthy individuals. Therefore, a good safety profile is required, there is a large governmental regulatory role, and low efficacy is unacceptable. Other important considerations are as follows: vaccines are often used in infants, are typically given in multiple doses, the manufacturing is a larger part of cost, requires high regulatory and quality control burden and minimization of costs. From a biological standpoint, the induction of vaccine-mediated protection is a complex procedure. Long-term protection typically requires the persistence of anti-microbial antibodies and/or the generation of immune memory cells capable of rapid and effective reactivation after microbial re-exposure. Appreciation of the predominant role of B cells in the efficacy of current vaccines should not minimize the importance of generating a T cell response, as this is essential for the induction of high affinity antibodies and immune memory. Pneumococcal capsular polysaccharides typically elicit B cell responses in a T-independent manner. Because of this, capsular polysaccharides are poorly immunogenic in children below 2 years of age and will generate an IgM isotype-based primary response with only

  5. Cancer vaccines.

    PubMed

    Butterfield, Lisa H

    2015-04-22

    Cancer vaccines are designed to promote tumor specific immune responses, particularly cytotoxic CD8 positive T cells that are specific to tumor antigens. The earliest vaccines, which were developed in 1994-95, tested non-mutated, shared tumor associated antigens that had been shown to be immunogenic and capable of inducing clinical responses in a minority of people with late stage cancer. Technological developments in the past few years have enabled the investigation of vaccines that target mutated antigens that are patient specific. Several platforms for cancer vaccination are being tested, including peptides, proteins, antigen presenting cells, tumor cells, and viral vectors. Standard of care treatments, such as surgery and ablation, chemotherapy, and radiotherapy, can also induce antitumor immunity, thereby having cancer vaccine effects. The monitoring of patients' immune responses at baseline and after standard of care treatment is shedding light on immune biomarkers. Combination therapies are being tested in clinical trials and are likely to be the best approach to improving patient outcomes.

  6. Nanoparticle vaccines.

    PubMed

    Zhao, Liang; Seth, Arjun; Wibowo, Nani; Zhao, Chun-Xia; Mitter, Neena; Yu, Chengzhong; Middelberg, Anton P J

    2014-01-09

    Nanotechnology increasingly plays a significant role in vaccine development. As vaccine development orientates toward less immunogenic "minimalist" compositions, formulations that boost antigen effectiveness are increasingly needed. The use of nanoparticles in vaccine formulations allows not only improved antigen stability and immunogenicity, but also targeted delivery and slow release. A number of nanoparticle vaccines varying in composition, size, shape, and surface properties have been approved for human use and the number of candidates is increasing. However, challenges remain due to a lack of fundamental understanding regarding the in vivo behavior of nanoparticles, which can operate as either a delivery system to enhance antigen processing and/or as an immunostimulant adjuvant to activate or enhance immunity. This review provides a broad overview of recent advances in prophylactic nanovaccinology. Types of nanoparticles used are outlined and their interaction with immune cells and the biosystem are discussed. Increased knowledge and fundamental understanding of nanoparticle mechanism of action in both immunostimulatory and delivery modes, and better understanding of in vivo biodistribution and fate, are urgently required, and will accelerate the rational design of nanoparticle-containing vaccines.

  7. Polysaccharide-based Nanoparticles for Gene Delivery.

    PubMed

    Huh, Myung Sook; Lee, Eun Jung; Koo, Heebeom; Yhee, Ji Young; Oh, Keun Sang; Son, Sohee; Lee, Sojin; Kim, Sun Hwa; Kwon, Ick Chan; Kim, Kwangmeyung

    2017-04-01

    Nanoparticles based on nanotechnology and biotechnology have emerged as efficient carriers for various biopharmaceutical agents including proteins and genes. In particular, polysaccharides have attracted interest of many researchers in the drug delivery field due to their advantages such as biocompatibility, biodegradability, low toxicity, and ease of modification. A number of polysaccharides including chitosan, hyaluronic acid, and dextran, and their derivatives have been widely used as polymeric backbones for the formation of nanoparticles, which can be provided as valuable gene delivery carriers. In this review, we introduce the chemical and physical natures of different polysaccharides particularly used in biomedical applications, and then discuss recent progress in the development of polysaccharide-based nanoparticles for gene delivery.

  8. Brazilian meningococcal C conjugate vaccine: Scaling up studies.

    PubMed

    Bastos, Renata Chagas; de Souza, Iaralice Medeiros; da Silva, Milton Neto; Silva, Flavia de Paiva; Figueira, Elza Scott; Leal, Maria de Lurdes; Jessouroun, Ellen; da Silva, José Godinho; Medronho, Ricardo de Andrade; da Silveira, Ivna Alana Freitas Brasileiro

    2015-08-20

    Several outbreaks caused by Neisseria meningitidis group C have been occurred in different regions of Brazil. A conjugate vaccine for Neisseria meningitidis was produced by chemical linkage between periodate-oxidized meningococcal C polysaccharide and hydrazide-activated monomeric tetanus toxoid via a modified reductive amination conjugation method. Vaccine safety and immunogenicity tested in Phase I and II trials showed satisfactory results. Before starting Phase III trials, vaccine production was scaled up to obtain industrial lots under Good Manufacture Practices (GMP). Comparative analysis between data obtained from industrial and pilot scales of the meningococcal C conjugate bulk showed similar execution times in the scaling up production process without significant losses or alterations in the quality attributes of purified compounds. In conclusion, scale up was considered satisfactory and the Brazilian meningococcal conjugate vaccine production aiming to perform Phase III trials is feasible.

  9. Response to conjugate pneumococcal and Haemophilus influenzae type b vaccines in asplenic patients.

    PubMed

    Meerveld-Eggink, A; de Weerdt, O; van Velzen-Blad, H; Biesma, D H; Rijkers, G T

    2011-01-17

    We determined the immunogenicity of conjugated Haemophilus influenzae type b and pneumococcal vaccines by quantitative analysis of the antibody response in asplenic patients. To that end, we vaccinated 92 patients with a conjugated Hib vaccine and 54 received two doses of conjugated pneumococcal vaccine (PCV7), followed at six months by a plain polysaccharide pneumococcal vaccine (PPV23). Antibody concentrations were measured before and three weeks after vaccination. After one dose of pneumococcal conjugate vaccine, 46% of the patients reached the antibody threshold of ≥ 1.0 μg/mL for all 7 tested vaccine serotypes. This percentage rose to 54% after the second dose of PCV7 and did not increase further after PPV23. Over 90% of patients had antibody concentrations ≥ 1.0 μg/mL for at least 5 out of the 7 conjugated pneumococcal serotypes after 2 doses of PCV7. For serotypes, included in the PPV23 vaccine only, 25% (PPS3)-100% (PPS19A) of the patients reached antibody concentrations ≥ 1.0 μg/mL after one dose of PPV23. For Hib, 97% of the patients reached the threshold concentration of ≥ 1.0 μg/mL after one dose of vaccine. It can be concluded that the majority of asplenic patients had a sufficient response to conjugated vaccines against Streptococcus pneumoniae and Hib, reflected by a ≥ 1.0 μg/mL antibody response. Inclusion of conjugated pneumococcal polysaccharide vaccines might be of additional value in the vaccination schedule for asplenic patients because of their high immunogenicity.

  10. [Chemoprophylaxis and vaccine for prevention of bacterial meningitis in children].

    PubMed

    Bourrillon, Antoine; Bingen, Edouard

    2004-05-15

    Given the devastating nature of Neisseria meningitidis disease and emergence of resistant strains prevention through chemoprophylaxis and meningococcal vaccine remains the best approach to control this serious infection. Chemoprophylaxis may limited strictly to the contact subjects. Polysaccharide meningococcal serogroups A, C, Y and W135 should be given less than 10 days to patients with prolonged contact with the index case. Meningococcal C conjugate vaccine constitutes an additional advantage in the prevention of meningococcal meningitis in children < 2 years. High Haemophilus serotype B coverage level led to near-disappearance of H. influenzae serotype b meningitis but chemoprophylaxis remains indicated.

  11. Mucosal vaccines

    PubMed Central

    Nizard, Mevyn; Diniz, Mariana O; Roussel, Helene; Tran, Thi; Ferreira, Luis CS; Badoual, Cecile; Tartour, Eric

    2014-01-01

    The mucosal immune system displays several adaptations reflecting the exposure to the external environment. The efficient induction of mucosal immune responses also requires specific approaches, such as the use of appropriate administration routes and specific adjuvants and/or delivery systems. In contrast to vaccines delivered via parenteral routes, experimental, and clinical evidences demonstrated that mucosal vaccines can efficiently induce local immune responses to pathogens or tumors located at mucosal sites as well as systemic response. At least in part, such features can be explained by the compartmentalization of mucosal B and T cell populations that play important roles in the modulation of local immune responses. In the present review, we discuss molecular and cellular features of the mucosal immune system as well as novel immunization approaches that may lead to the development of innovative and efficient vaccines targeting pathogens and tumors at different mucosal sites. PMID:25424921

  12. DTaP-IPV-Hep B-Hib vaccine (Hexaxim®) : a review of its use in primary and booster vaccination.

    PubMed

    McCormack, Paul L

    2013-02-01

    Hexaxim(®) (DTaP-IPV-Hep B-Hib) is a new, thiomersal-free, fully liquid, hexavalent combination pediatric vaccine containing diphtheria and tetanus toxoids, acellular pertussis, inactivated poliovirus, recombinant hepatitis B virus surface antigen produced in the yeast Hansenula polymorpha, and Haemophilus influenzae type b polysaccharide (polyribosylribitol phosphate) conjugated to tetanus toxoid. It is currently registered in markets outside of the EU for primary vaccination of infants from 6 weeks of age and for booster vaccination up to 24 months of age. In randomized controlled trials, primary vaccination of infants with Hexaxim(®) using various immunization schedules was highly immunogenic for all vaccine component antigens regardless of the administration schedule, producing high levels of seroprotection or seroconversion for each antigen. Hexaxim(®) was as immunogenic as the comparator DTwP- or DTaP-based vaccines in these studies. The serological responses were generally sustained at high levels over a follow-up of ≈1 year, and booster vaccination at 15-18 months further enhanced the immune response. Hexaxim(®) was less reactogenic than a DTwP-based combination vaccine, and displayed a tolerability profile similar to those of the comparator DTaP-based combination vaccines. Thus, Hexaxim(®) provides effective seroprotection or seroconversion against six major childhood diseases simultaneously, both as primary and booster vaccination, and offers the benefits and convenience of a fully liquid, ready-to-use vaccine.

  13. Monoclonal antibodies against plant cell wall polysaccharides

    SciTech Connect

    Hahn, M.G.; Bucheli, E.; Darvill, A.; Albersheim, P. )

    1989-04-01

    Monoclonal antibodies (McAbs) are useful tools to probe the structure of plant cell wall polysaccharides and to localize these polysaccharides in plant cells and tissues. Murine McAbs were generated against the pectic polysaccharide, rhamnogalacturonan I (RG-I), isolated from suspension-cultured sycamore cells. The McAbs that were obtained were grouped into three classes based upon their reactivities with a variety of plant polysaccharides and membrane glycoproteins. Eleven McAbs (Class I) recognize epitope(s) that appear to be immunodominant and are found in RG-I from sycamore and maize, citrus pectin, polygalacturonic acid, and membrane glycoproteins from suspension-cultured cells of sycamore, maize, tobacco, parsley, and soybean. A second group of five McAbs (Class II) recognize epitope(s) present in sycamore RG-I, but do not bind to any of the other polysaccharides or glycoproteins recognized by Class I. Lastly, one McAb (Class III) reacts with sycamore RG-I, sycamore and tamarind xyloglucan, and sycamore and rice glucuronoarabinoxylan, but does not bind to maize RG-I, polygalacturonic acid or the plant membrane glycoproteins recognized by Class I. McAbs in Classes II and III are likely to be useful in studies of the structure, biosynthesis and localization of plant cell wall polysaccharides.

  14. Vaccines against invasive Salmonella disease: current status and future directions.

    PubMed

    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.

  15. Development of a thermostable microneedle patch for influenza vaccination.

    PubMed

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

    2015-02-01

    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 4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid (HEPES) buffer salts stabilized influenza vaccine, surfactants had little effect during drying, drying temperature had weak effects on vaccine stability, and drying on polydimethylsiloxane (PDMS) led to increased stability compared with 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 6 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.

  16. Meningococcal disease: risk for international travellers and vaccine strategies.

    PubMed

    Wilder-Smith, Annelies

    2008-07-01

    International travel and migration facilitate the rapid intercontinental spread of meningococcal disease. Serogroup A and, less so serogroup C, have been responsible for epidemics in the past (mainly in Africa). In recent years, W135 has emerged (first in Saudi Arabia, then in West Africa) as a serogroup that requires attention. Serogroups X and Y are infrequent, but associated with slowly rising trends. There are significant variations in the incidence of meningococcal disease and the distribution of serogroups responsible for meningococcal disease, both geographically and with time. Vaccine strategies need to address this variation, and broad coverage against all serogroups for which vaccines are currently available should be offered to travellers. Tetravalent polysaccharide meningococcal vaccines are limited by their poor immunogenicity in small infants and by the lack of long-term protection. In contrast, the novel tetravalent conjugate vaccine that is currently only available in North America is immunogenic in young infants, induces long-term protection and reduces nasopharyngeal carriage. The tetravalent conjugate meningococcal vaccine will be a leap forward in the control of meningococcal epidemics in affected countries. It will also boost the uptake of meningococcal vaccines in travellers because the duration of protection is longer and it eliminates the problem of immune hyporesponsiveness of serogroup C with repeated dosing. Current vaccine recommendations are to vaccinate all Hajj pilgrims, all travellers to areas with current outbreaks, travellers to the SubSaharan meningitis belt, and individuals with certain medical conditions.

  17. Modelling the impact of vaccination on curtailing Haemophilus influenzae serotype 'a'.

    PubMed

    Konini, Angjelina; Moghadas, Seyed M

    2015-12-21

    Haemophilus influenzae serotype a (Hia) is a human-restricted bacterial pathogen transmitted via direct contacts with an infectious individual. Currently, there is no vaccine available for prevention of Hia, and the disease is treated with antibiotics upon diagnosis. With ongoing efforts for the development of an anti-Hia protein-polysaccharide conjugated vaccine, we sought to investigate the effect of vaccination on curtailing Hia infection. We present the first stochastic model of Hia transmission and control dynamics, and parameterize it using available estimates in the literature. Since both naturally acquired and vaccine-induced immunity wane with time, model simulations show three important results. First, vaccination of only newborns cannot eliminate the pathogen from the population, even when a booster program is implemented with a high coverage. Second, achieving and maintaining a sufficiently high level of herd immunity for pathogen elimination requires vaccination of susceptible individuals in addition to a high vaccination coverage of newborns. Third, for a low vaccination rate of susceptible individuals, a high coverage of booster dose may be needed to raise the level of herd immunity for Hia eradication. Our findings highlight the importance of vaccination and timely boosting of the individual׳s immunity within the expected duration of vaccine-induced protection against Hia. When an anti-Hia vaccine becomes available, enhanced surveillance of Hia incidence and herd immunity could help determine vaccination rates and timelines for booster doses necessary to eliminate Hia from affected populations.

  18. Typhoid vaccine introduction: An evidence-based pilot implementation project in Nepal and Pakistan.

    PubMed

    Khan, M Imran; Pach, Alfred; Khan, Ghulam Mustafa; Bajracharya, Deepak; Sahastrabuddhe, Sushant; Bhutta, Waqaas; Tahir, Rehman; Soofi, Sajid; Thapa, Chandra B; Joshi, Nilesh; Puri, Mahesh K; Shrestha, Parisha; Upreti, Shyam Raj; Clemens, John D; Bhutta, Zulfiqar; Ochiai, R Leon

    2015-06-19

    The World Health Organization (WHO) in 2008 recommended the use of currently licensed typhoid vaccines using a high risk or targeted approach. The epidemiology of disease and the vaccine characteristics make school-based vaccination most feasible in reducing typhoid disease burden in many settings. To assess feasibility of school-based typhoid vaccination, two districts in Kathmandu, Nepal and two towns in Karachi, Pakistan were selected for pilot program. Vaccination campaigns were conducted through the departments of health and in partnerships with not-for-profit organizations. In total 257,015 doses of Vi polysaccharide vaccine were given to students in grades 1-10 of participating schools. The vaccination coverage ranged from 39 percent (38,389/99,503) in Gulshan town in Karachi, to 81 percent (62,615/77,341) in Bhaktapur in Kathmandu valley. No serious adverse event was reported post vaccination. The coverage increased for vaccination of the second district in Pakistan as well as in Nepal. There was an initial concern of vaccine safety. However, as the campaign progressed, parents were more comfortable with vaccinating their children in schools. Supported and conducted by departments of health in Pakistan and Nepal, a school-based typhoid vaccination was found to be safe and feasible.

  19. Enhancement of HIV-1 DNA vaccine immunogenicity by BCG-PSN, a novel adjuvant.

    PubMed

    Sun, Jing; Hou, Jue; Li, Dingfeng; Liu, Yong; Hu, Ningzhu; Hao, Yanling; Fu, Jingjing; Hu, Yunzhang; Shao, Yiming

    2013-01-07

    Although the importance of DNA vaccines, especially as a priming immunization has been well established in numerous HIV vaccine studies, the immunogenictiy of DNA vaccines is generally moderate. Novel adjuvant is in urgent need for improving the immunogenicity of DNA vaccine. Polysaccharide and nucleic acid fraction extracted by hot phenol method from Mycobacterium bovis bacillus Calmette-Guérin, known as BCG-PSN, is a widely used immunomodulatory product in China clinical practice. In this study, we evaluated whether the BCG-PSN could serve as a novel adjuvant of DNA vaccine to trigger better cellular and humoral immune responses against the HIV-1 Env antigen in Balb/C mouse model. The BCG-PSN was mixed with 10 μg or 100 μg of pDRVI1.0gp145 (HIV-1 CN54 gp145 gene) DNA vaccine and intramuscularly immunized two or three times. We found that BCG-PSN could significantly improve the immunogenicity of DNA vaccine when co-administered with DNA vaccine. Further, at the same vaccination schedule, BCG-PSN co-immunization with 10 μg DNA vaccine could elicit cellular and humoral immune responses which were comparable to that induced by 100 μg DNA vaccine alone. Moreover, our results demonstrate that BCG-PSN can activate TLR signaling pathways and induce Th1-type cytokines secretion. These findings suggest that BCG-PSN can serve as a novel and effective adjuvant for DNA vaccination.

  20. [Retrospective assessment of laboratory surveillance for invasive Streptococcus pneumoniae isolates from adults of the Metropolitan Region (Chile): 2000-2006].

    PubMed

    Maldonado, Aurora; Seoane, Mabel; San Martín, Oriana; Hormazábal, Juan C; Lagos, Rosanna

    2007-12-01

    This study assessed the performance of the national norm for laboratory surveillance of invasive Streptococcus pneumoniae in adults of the Metropolitan Region (Chile). Material and Methods. We reviewed all notifications of isolates from patients > 15 years of age received by the Institute of Public Health of Chile during the period 2000-2006, submitted by health care facilities of the study region. We also reviewed the original records of sterile fluid cultures, in 14 public adult hospitals. Results. We found documentation of 1429 invasive S. pneumoniae isolates recovered from adult patients, including 1095 reported and 334 not-reported isolates. A 33% under-reporting rate was estimated for the 14 hospitals where local laboratory records were inspected. Age and clinical diagnosis were omitted in 23% and 78% of the notifications, respectively. Among 303 isolates from patients > 65 years of age that were investigated with Quellung reaction, 235 (78%) had capsular serotypes represented in the 23-valent polysaccharide vaccine. Conclusions. The Ministry of Health of Chile announced implementation of 23-valent vaccine immunization program for the elderly. In the perspective of future evaluations of the impact of this intervention, the results of this study indicate the need of reinforcing adherence and improving the quality of notifications of invasive S. pneumoniae.

  1. Development of Vaccines to Prevent Wound Infectious Due to Anaerobic Bacteria.

    DTIC Science & Technology

    1985-10-11

    factorily. The bottled vaccine was shown to contain 1:9100 thimerosal which is used as a preservative. Sterility testing was performed and the lot was...from strain 23745 (American Type Culture Collection). Other than the salt used for reconsti- tution and thimerosal , the polysaccharide is a pure

  2. Purification and characterization of a Shigella conjugate vaccine, produced by glycoengineering Escherichia coli.

    PubMed

    Ravenscroft, Neil; Haeuptle, Micha A; Kowarik, Michael; Fernandez, Fabiana S; Carranza, Paula; Brunner, Andreas; Steffen, Michael; Wetter, Michael; Keller, Sacha; Ruch, Corina; Wacker, Michael

    2016-01-01

    Shigellosis remains a major cause of diarrheal disease in developing countries and causes substantial morbidity and mortality in children. Glycoconjugate vaccines consisting of bacterial surface polysaccharides conjugated to carrier proteins are the most effective vaccines for controlling invasive bacterial infections. Nevertheless, the development of a multivalent conjugate vaccine to prevent Shigellosis has been hampered by the complex manufacturing process as the surface polysaccharide for each strain requires extraction, hydrolysis, chemical activation and conjugation to a carrier protein. The use of an innovative biosynthetic Escherichia coli glycosylation system substantially simplifies the production of glycoconjugates. Herein, the Shigella dysenteriae type 1 (Sd1) O-polysaccharide is expressed and its functional assembly on an E. coli glycosyl carrier lipid is demonstrated by HPLC analysis and mass spectrometry. The polysaccharide is enzymatically conjugated to specific asparagine residues of the carrier protein by co-expression of the PglB oligosaccharyltransferase and the carrier protein exotoxin A (EPA) from Pseudomonas aeruginosa. The extraction and purification of the Shigella glycoconjugate (Sd1-EPA) and its detailed characterization by the use of physicochemical methods including NMR and mass spectrometry is described. The report shows for the first time that bioconjugation provides a newly developed and improved approach to produce an Sd1 glycoconjugate that can be characterized using state-of-the-art techniques. In addition, this generic process together with the analytical methods is ideally suited for the production of additional Shigella serotypes, allowing the development of a multivalent Shigella vaccine.

  3. Immunogenicity and efficacy of Cryptococcus neoformans capsular polysaccharide glucuronoxylomannan peptide mimotope-protein conjugates in human immunoglobulin transgenic mice.

    PubMed

    Maitta, Robert W; Datta, Kausik; Lees, Andrew; Belouski, Shelley Sims; Pirofski, Liise-anne

    2004-01-01

    Peptide mimotopes of capsular polysaccharides have been proposed as antigens for vaccines against encapsulated pathogens. In this study, we determined the antibody response to and efficacy of P13, a peptide mimetic of the Cryptococcus neoformans capsular polysaccharide glucuronoxylomannan (GXM), in mice that produce human antibodies. P13 was conjugated to tetanus toxoid (TT) or diphtheria toxoid (DT) and administered subcutaneously in Alhydrogel with or without CpG to mice transgenic for human immunoglobulin loci (XenoMouse mice) and expressing either immunoglobulin G2 (IgG2) (G2 mice) or IgG4 (G4 mice). Mice were vaccinated and revaccinated two or three times. The serum antibody responses of the mice to GXM and P13 and antibody idiotype expression were analyzed by an enzyme-linked immunosorbent assay. The results showed that both P13-TT and P13-DT were antigenic, inducing a mimetic response to P13 in both G2 and G4 mice, and immunogenic, inducing a mimotope response including VH3 (idiotype)-positive antibodies to GXM in G2 but not G4 mice. CpG led to higher titers of IgG to P13 and GXM in P13-TT-vaccinated G2 mice. C. neoformans challenge of P13-protein conjugate-vaccinated and control G2 mice induced anamnestic IgG- and VH3-positive responses to GXM and was associated with a significantly decreased risk of death and a prolongation of survival in P13-DT-vaccinated mice compared to phosphate-buffered saline-treated or protein carrier-vaccinated mice. These findings reveal that P13 elicited a human antibody response with VH3 expression in human immunoglobulin transgenic mice that has been observed for human antibodies to GXM and support the concept that peptide mimotope-based vaccines may hold promise for the treatment of C. neoformans infections.

  4. Immune Interference After Sequential Alphavirus Vaccine Vaccinations

    DTIC Science & Technology

    2009-01-01

    REPORT DATE 11 MAR 2009 2. REPORT TYPE N/A 3. DATES COVERED - 4. TITLE AND SUBTITLE Immune interference after sequential alphavirus ...of administration of investigational alphavirus vaccines on neutralizing antibody response. Volunteers who received the inactivated eastern and...vaccine strategy among those receiving multiple alphavirus vaccines and those developing next generation vaccines for these threats. 15. SUBJECT TERMS

  5. TLR9-adjuvanted pneumococcal conjugate vaccine induces antibody-independent memory responses in HIV-infected adults.

    PubMed

    Offersen, Rasmus; Melchjorsen, Jesper; Paludan, Søren R; Østergaard, Lars; Tolstrup, Martin; Søgaard, Ole S

    2012-08-01

    HIV-patients have excess of pneumococcal infection. We immunized 40 HIV-patients twice with pneumococcal conjugate vaccine (Prevnar, Pfizer) +/- a TLR9 agonist (CPG 7909). Peripheral blood mononuclear cells were stimulated with pneumococcal polysaccharides and cytokine concentrations measured. The CPG 7909 adjuvant group had significantly higher relative cytokine responses than the placebo group for IL-1β, IL-2R, IL-6, IFN-γ and MIP-β, which, did not correlate with IgG antibody responses. These findings suggests that CPG 7909 as adjuvant to pneumococcal conjugate vaccine induces cellular memory to pneumococcal polysaccharides in HIV-patients, independently of the humoral response.

  6. Hydrolytic stability of pneumococcal group 6 (type 6A and 6B) capsular polysaccharides.

    PubMed

    Zon, G; Szu, S C; Egan, W; Robbins, J D; Robbins, J B

    1982-07-01

    that the hydrolytic stability of the type 6B antigen would favor its use in the polyvalent pneumococcal vaccine rather than the cross-reactive, but comparatively unstable, type 6A polysaccharide, if all other factors are equal.

  7. Hydrolytic stability of pneumococcal group 6 (type 6A and 6B) capsular polysaccharides.

    PubMed Central

    Zon, G; Szu, S C; Egan, W; Robbins, J D; Robbins, J B

    1982-01-01

    that the hydrolytic stability of the type 6B antigen would favor its use in the polyvalent pneumococcal vaccine rather than the cross-reactive, but comparatively unstable, type 6A polysaccharide, if all other factors are equal. Images PMID:7107011

  8. Polysaccharide intercellular adhesin in biofilm: structural and regulatory aspects

    PubMed Central

    Arciola, Carla Renata; Campoccia, Davide; Ravaioli, Stefano; Montanaro, Lucio

    2015-01-01

    Staphylococcus aureus and Staphylococcus epidermidis are the leading etiologic agents of implant-related infections. Biofilm formation is the main pathogenetic mechanism leading to the chronicity and irreducibility of infections. The extracellular polymeric substances of staphylococcal biofilms are the polysaccharide intercellular adhesin (PIA), extracellular-DNA, proteins, and amyloid fibrils. PIA is a poly-β(1-6)-N-acetylglucosamine (PNAG), partially deacetylated, positively charged, whose synthesis is mediated by the icaADBC locus. DNA sequences homologous to ica locus are present in many coagulase-negative staphylococcal species, among which S. lugdunensis, however, produces a biofilm prevalently consisting of proteins. The product of icaA is an N-acetylglucosaminyltransferase that synthetizes PIA oligomers from UDP-N-acetylglucosamine. The product of icaD gives optimal efficiency to IcaA. The product of icaC is involved in the externalization of the nascent polysaccharide. The product of icaB is an N-deacetylase responsible for the partial deacetylation of PIA. The expression of ica locus is affected by environmental conditions. In S. aureus and S. epidermidis ica-independent alternative mechanisms of biofilm production have been described. S. epidermidis and S. aureus undergo to a phase variation for the biofilm production that has been ascribed, in turn, to the transposition of an insertion sequence in the icaC gene or to the expansion/contraction of a tandem repeat naturally harbored within icaC. A role is played by the quorum sensing system, which negatively regulates biofilm formation, favoring the dispersal phase that disseminates bacteria to new infection sites. Interfering with the QS system is a much debated strategy to combat biofilm-related infections. In the search of vaccines against staphylococcal infections deacetylated PNAG retained on the surface of S. aureus favors opsonophagocytosis and is a potential candidate for immune-protection. PMID

  9. In vivo anti-radiation activities of the Ulva pertusa polysaccharides and polysaccharide-iron(III) complex.

    PubMed

    Shi, Jinming; Cheng, Cuilin; Zhao, Haitian; Jing, Jing; Gong, Ning; Lu, Weihong

    2013-09-01

    Polysaccharides with different molecular weights were extracted from Ulva pertusa and fractionated by ultrafiltration. Iron(III) complex of the low molecular-weight U. pertusa polysaccharides were synthesized. Atomic absorption spectrum showed that the iron content of iron(III)-polysaccharide complex was 27.4%. The comparison between U. pertusa polysaccharides and their iron(III) complex showed that iron chelating altered the structural characteristics of the polysaccharides. The bioactivity analysis showed that polysaccharide with low molecular weight was more effective than polysaccharide with high molecular weight in protecting mice from radiation induced damages on bone marrow cells and immune system. Results also proved that the anti-radiation and anti-oxidative activity of iron(III) complex of low molecular-weight polysaccharides were not less than that of low molecular-weight polysaccharides.

  10. Replicating vaccines

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Early work on fish immunology and disease resistance demonstrated fish (like animals and humans) that survived infection were typically resistant to re-infection with the same pathogen. The concepts of resistance upon reinfection lead to the research and development of replicating (live) vaccines in...

  11. AIDS Vaccines.

    ERIC Educational Resources Information Center

    Matthews, Thomas J.; Bolognesi, Dani P.

    1988-01-01

    Reveals that success of discovering vaccines is far from being assured although several candidates are being tested. States that the devious nature of the virus, the lack of a good animal model for the disease, and the difficulties of clinical trials inhibit the efforts of researchers. (RT)

  12. Polio Vaccine

    MedlinePlus

    ... workers who might handle polio virus, and healthcare workers treating patients who could have polio. These higher-risk adults may need 1 to 3 doses of IPV, depending on how many doses they have had in the past.There are no known risks to getting IPV at the same time as other vaccines.

  13. Rotavirus Vaccine

    MedlinePlus

    ... including a severe allergy to latex. Babies with "severe combined immunodeficiency" (SCID) should not get rotavirus vaccine. Babies who have had a type of bowel blockage called "intussusception" should not get ... with moderate or severe diarrhea or vomiting. Check with your doctor if ...

  14. Malaria vaccine.

    PubMed

    1994-05-01

    Some have argued that the vaccine against malaria developed by Manuel Pattaroyo, a Colombian scientist, is being tested prematurely in humans and that it is unlikely to be successful. While the Pattaroyo vaccine has been shown to confer protection against the relatively mild malaria found in Colombia, doubts exist over whether it will be effective in Africa. Encouraging first results, however, are emerging from field tests in Tanzania. The vaccine triggered a strong new immune response, even in individuals previously exposed to malaria. Additional steps must be taken to establish its impact upon mortality and morbidity. Five major trials are underway around the world. The creator estimates that the first ever effective malaria vaccine could be available for widespread use within five years and he has no intention of securing a patent for the discovery. In another development, malaria specialists from 35 African countries convened at an international workshop in Zimbabwe to compare notes. Participants disparaged financial outlays for the fight against malaria equivalent to 2% of total AIDS funding as insufficient; noted intercountry differences in prevention, diagnosis, and treatment; and found information exchange between anglophone and francophone doctors to be generally poor.

  15. Valuing vaccination

    PubMed Central

    Bärnighausen, Till; Bloom, David E.; Cafiero-Fonseca, Elizabeth T.; O’Brien, Jennifer Carroll

    2014-01-01

    Vaccination has led to remarkable health gains over the last century. However, large coverage gaps remain, which will require significant financial resources and political will to address. In recent years, a compelling line of inquiry has established the economic benefits of health, at both the individual and aggregate levels. Most existing economic evaluations of particular health interventions fail to account for this new research, leading to potentially sizable undervaluation of those interventions. In line with this new research, we set forth a framework for conceptualizing the full benefits of vaccination, including avoided medical care costs, outcome-related productivity gains, behavior-related productivity gains, community health externalities, community economic externalities, and the value of risk reduction and pure health gains. We also review literature highlighting the magnitude of these sources of benefit for different vaccinations. Finally, we outline the steps that need to be taken to implement a broad-approach economic evaluation and discuss the implications of this work for research, policy, and resource allocation for vaccine development and delivery. PMID:25136129

  16. Nanotoxoid Vaccines

    PubMed Central

    Hu, Che-Ming J.; Zhang, Liangfang

    2014-01-01

    To improve innate defense against diseases, vaccine formulations are routinely administered to mount immune responses against disease-causing organisms or their associated toxins. These formulations are typically prepared with weakened forms of microbes, their surface proteins, or their virulence factors, which can train the immune system to recognize and neutralize similar infectious threats in later exposures. Owing to many unique properties of nanoparticles in enhancing vaccine potency, nanoscale carriers are drawing increasing interest as a platform for developing safer and more effective vaccine formulations. Notably, a nanoparticle-based strategy was recently demonstrated to safely deliver intact, non-denatured protein toxins to mount a potent anti-toxin immune response. A biomimetic nanoparticle cloaked in biological membranes was used to sequester membrane-active toxins. Upon interaction with the nanoparticles, the toxins become retrained and lose their toxicity as they are precluded from interacting with cellular targets. The resulting particle/toxin complex adopts a nanoparticulate morphology that facilitates the toxins’ intracellular delivery. This sequestration approach has immense immunological implications owing to its ability in enabling structurally preserved toxins for immune processing. This technique offers opportunities in novel toxoid vaccine designs that promise more effective anti-toxin immune responses and contrasts the existing paradigm in toxoid preparation, in which toxins are antigenically altered to ensure virulence removal. The potent nanotoxoid formulations provide a viable anti-virulence measure in combating microbial infections that involve membrane-damaging toxins, including methicillin-resistant Staphylococcus aureus (MRSA) and Group A streptococcal infections. PMID:25285152

  17. Vexing Vaccines

    ERIC Educational Resources Information Center

    Bowman, Darcia Harris

    2004-01-01

    Schools play a key role in ensuring that children are being immunized against diseases, but conflicting research is making enforcement difficult. This article discusses a growing trend of vaccine avoidance and the endless supply of conflicting information and research about immunization safety. Despite the controversy, many people appear to accept…

  18. Mycoplasma polysaccharide protects against complement

    PubMed Central

    Bolland, Jeffrey R.; Simmons, Warren L.; Daubenspeck, James M.

    2012-01-01

    Although they lack a cell wall, mycoplasmas do possess a glycocalyx. The interactions between the glycocalyx, mycoplasmal surface proteins and host complement were explored using the murine pathogen Mycoplasma pulmonis as a model. It was previously shown that the length of the tandem repeat region of the surface lipoprotein Vsa is associated with susceptibility to complement-mediated killing. Cells producing a long Vsa containing about 40 repeats are resistant to complement, whereas strains that produce a short Vsa of five or fewer repeats are susceptible. We show here that the length of the Vsa protein modulates the affinity of the M. pulmonis EPS-I polysaccharide for the mycoplasma cell surface, with more EPS-I being associated with mycoplasmas producing a short Vsa protein. An examination of mutants that lack EPS-I revealed that planktonic mycoplasmas were highly susceptible to complement killing even when the Vsa protein was long, demonstrating that both EPS-I and Vsa length contribute to resistance. In contrast, the mycoplasmas were resistant to complement even in the absence of EPS-I when the cells were encased in a biofilm. PMID:22504437

  19. Viscoelastic properties of levan polysaccharides

    NASA Astrophysics Data System (ADS)

    Noll, Kenneth; Rende, Deniz; Ozisik, Rahmi; Toksoy-Oner, Ebru

    2014-03-01

    Levan is a naturally occurring polysaccharide that is composed of β-D-fructofuranose units with β(2-6) linkages between fructose rings. It is synthesized by the action of a secreted levansucrase (EC 2.4.1.10) that converts sucrose into the levan externally (exopolysaccharide). Levan is a homopolysaccharide that is non-toxic, water soluble,, and has anti-tumor activity and low immunological response. Therefore, levan presents great potential to be used as a novel functional biopolymer in foods, feeds, cosmetics, pharmaceutical and chemical industries. Despite these favorable properties, levan has a moderately low mechanical properties and poor film forming capability. In the current study, the agglomeration behavior of levan in water and in saline solutions was investigated at 298 and 310 K by dynamic light scattering and transmission electron microscopy (TEM). The viscoelastic properties of neat and oxidized levan films were studied via nanoindentation experiments in the quasi-static and dynamic modes The material is partially based upon work supported by NSF under Grant Nos. 1200270 and 1003574, and TUBITAK 111M232.

  20. EXTRACELLULAR POLYSACCHARIDES OF AZOTOBACTER VINELANDII1

    PubMed Central

    Cohen, Gary H.; Johnstone, Donald B.

    1964-01-01

    Cohen, Gary H. (University of Vermont, Burlington), and Donald B. Johnstone. Extracellular polysaccharides of Azotobacter vinelandii. J. Bacteriol. 88:329–338. 1964.—Extracellular polysaccharides synthetized by Azotobacter vinelandii strains 155, 102, and 3A were shown to be carboxylic acid heteropolysaccharides of apparent high molecular weight. Cells were grown in a nitrogen-free, mineral broth medium with 2% sucrose. Extracellular slime was recovered by centrifugation and purified by repeated alcohol precipitation and Sevag deproteinization. Capsular polysaccharide was recovered from washed cells by mild alkaline digestion. Methods of isolation and purification appeared to provide polysaccharide showing no evidence of heterogeneity when examined by chemical and physical methods. Infrared analysis of purified slime from the three strains suggested fundamental structural similarities. Colorimetric, paper chromatographic, and enzymatic analyses on both intact and acid-hydrolyzed slime polysaccharide indicated that the polymers contained in common galacturonic acid, [α] d-glucose, and rhamnose at a ratio of approximately 43:2:1, as well as a hexuronic acid lactone, probably mannurono-lactone. However, as shown by chemical and infrared analysis, minor differences did exist; namely, slime from strain 155 and 102 contained o-acetyl groups, whereas slime from strain 3A contained none. A sialic acid-like component (1.5% of dry weight of the polysaccharide, calculated as N-acetyl neuraminic acid), was found only in the slime of strain 155. Capsular polysaccharide composition closely resembled that for slime. It is of interest that the major slime components were identical whether the energy source provided for the cells was sucrose, glucose, fructose, or ethanol. PMID:14203348

  1. Vaccine chronicle in Japan.

    PubMed

    Nakayama, Tetsuo

    2013-10-01

    The concept of immunization was started in Japan in 1849 when Jenner's cowpox vaccine seed was introduced, and the current immunization law was stipulated in 1948. There have been two turning points for amendments to the immunization law: the compensation remedy for vaccine-associated adverse events in 1976, and the concept of private vaccination in 1994. In 1992, the regional Court of Tokyo, not the Supreme Court, decided the governmental responsibility on vaccine-associated adverse events, which caused the stagnation of vaccine development. In 2010, many universal vaccines became available as the recommended vaccines, but several vaccines, including mumps, zoster, hepatitis B, and rota vaccines, are still voluntary vaccines, not universal routine applications. In this report, immunization strategies and vaccine development are reviewed for each vaccine item and future vaccine concerns are discussed.

  2. Varicella (Chickenpox) Vaccine

    MedlinePlus

    ProQuad® (as a combination product containing Measles Vaccine, Mumps Vaccine, Rubella Vaccine, Varicella Vaccine) ... up to about 1 person in 5) and measles-like rash (about 1 person in 20) than MMR and varicella vaccines given separately. Moderate Problems:Seizure (jerking or staring) ...

  3. A bivalent vaccine to protect against Streptococcus pneumoniae and Salmonella typhi.

    PubMed

    Lu, Ying-Jie; Zhang, Fan; Sayeed, Sabina; Thompson, Claudette M; Szu, Shousun; Anderson, Porter W; Malley, Richard

    2012-05-14

    Pneumococcal and Salmonella typhi infections are two major diseases for children in developing countries. For typhoid fever, licensed Vi polysaccharide vaccines are ineffective in children <2-year old. While investigational Vi conjugate vaccines have been shown effective in clinical trials, they are currently only available to restricted areas. Pneumococcal capsular polysaccharide conjugate vaccines are highly effective in children, but suffer from some limitations including cost and limited serotype coverage. We have previously shown that a fusion conjugate vaccine, consisting of pneumococcal fusion protein PsaA and pneumolysoid (PdT) conjugated to a polysaccharide, results in enhanced antibody and CD4+ Th17 cell responses as well as protection against pneumococcal colonization and disease in mice. Here we applied this approach to develop a bivalent vaccine against pneumococcus and S. typhi. Two species-conserved pneumococcal antigens (SP1572 or SP2070) were fused to the nonhemolytic pneumolysoid PdT. SP1572-PdT was then conjugated to Vi polysaccharide and SP2070-PdT was conjugated to the pneumococcal cell wall polysaccharide (CWPS; also conserved). Mice immunized with this bivalent conjugate were protected against pneumococcal colonization and sepsis challenges, and made anti-Vi antibody concentrations higher by 40-fold compared to mice that received equimolar mixtures of the antigens. An enhanced killing of Vi-bearing Salmonellae in vitro was demonstrated from plasma of mice that received the fusion conjugate but not the mixture of antigens. Our results support further evaluation of this bivalent immunogen for the prevention of pneumococcal colonization and disease, and of typhoid fever.

  4. Biochemical properties of polysaccharides from black pepper.

    PubMed

    Chun, Hyug; Shin, Dong Hoon; Hong, Bum Shik; Cho, Won Dai; Cho, Hong Yon; Yang, Han Chul

    2002-09-01

    The purified polysaccharides from Piper nigrum were prepared as follows: a hot water extract of pepper seeds was fractionated by ultrafiltration with a 5-kDa-membrane cartridge. A fraction with 5 kDa or bigger molecules was successively purified by open column chromatography on DEAE-Toyopearl 650C and Bio-gel P-60 with each active fraction, resulting in PN-Ib and PN-IIa, purified anti-complementary polysaccharides. None of the anti-complementary activity of any polysaccharide was changed by pronase digestion or polymyxin B treatment, but they were decreased by periodate oxidation. Analysis of component sugar and molecular mass determination of the anti-complementary polysaccharides indicated that PN-Ib with an average molecular mass of 21 kDa contained 88.5% glucose and other negligible minor monosaccharides, while PN-IIa showed a different monosaccharide composition, which contained a significant proportion of galactose, arabinose, galacturonic acid and rhamnose. The molar ratio of galactose and arabinose of PN-IIa (48 kDa) was 1.93:1. PN-1 did not react with beta-glucosyl Yariv reagent, however, PN-IIa did react, which indicated that PN-IIa might be an arabinogalactan. Based upon these results, the usefulness of purified anti-complementary polysaccharides from Piper nigrum is suggested as a supplement for immune enhancement.

  5. Immune interference after sequential alphavirus vaccine vaccinations.

    PubMed

    Pittman, Phillip R; Liu, Ching-Tong; Cannon, Timothy L; Mangiafico, Joseph A; Gibbs, Paul H

    2009-08-06

    We compared the effect of order of administration of investigational alphavirus vaccines on neutralizing antibody response. Volunteers who received the inactivated eastern and western equine encephalitis (EEE and WEE) vaccines before live attenuated Venezuelan (VEE) vaccine had significantly lower rates of antibody response than those receiving VEE vaccine before EEE and WEE vaccines (66.7% vs. 80.6%; p=0.026). The odds of having a VEE antibody non-response among those initially receiving EEE and WEE vaccines, adjusted for gender, were significant (odds ratio [OR]=2.20; 95% CI=1.2-4.1 [p=0.0145]) as were the odds of non-response among females adjusted for group (OR=1.81; 95% CI=1.2-2.7 [p=0.0037]). Antibody interference and gender effect have major implications for vaccine strategy among those receiving multiple alphavirus vaccines and those developing next generation vaccines for these threats.

  6. Neisseria meningitidis serogroup A capsular polysaccharide acetyltransferase, methods and compositions

    DOEpatents

    Stephens, David S [Stone Mountain, GA; Gudlavalleti, Seshu K [Kensington, MD; Tzeng, Yih-Ling [Atlanta, GA; Datta, Anup K [San Diego, CA; Carlson, Russell W [Athens, GA

    2011-02-08

    Provided are methods for recombinant production of an O-acetyltransferase and methods for acetylating capsular polysaccharides, especially those of a Serogroup A Neisseria meningitidis using the recombinant O-acetyltransferase, and immunogenic compositions comprising the acetylated capsular polysaccharide.

  7. Immobilized phosphorylase for synthesis of polysaccharides from glucose

    NASA Technical Reports Server (NTRS)

    Marshall, D. L.

    1972-01-01

    Continuous processes for enzymatic production of carbohydrates from glucose are discussed. Key reactant in process is identified as phosphorylase which catalyzes reversible formation or degradation of polysaccharide. Chemical compounds and reactions to synthesize polysaccharides are analyzed.

  8. Unveiling Unexpected Immune Activities Induced by Your Pneumococcal Vaccine

    PubMed Central

    Hurwitz, Julia L.

    2016-01-01

    ABSTRACT In modern-day vaccine design, a good pneumococcal capsular polysaccharide vaccine is measured by its ability to induce opsonic antibodies. These antibodies label bacteria for phagocytosis by neutrophils and thereby overcome the capsule’s barrier function. Doyle and Pirofski have raised a serious challenge to the current paradigm by describing anti-capsular antibodies that are highly protective but nonopsonic [C.R. Doyle and L. Pirofski, mBio 7(1):e02260-15, 2016, doi:10.1128/mBio.02260-15]. In fact, some functions are not related to neutrophils or phagocytosis at all. An increased awareness of these activities is critical not only for accurate comparisons of vaccine candidates but also for improvements in vaccination outcomes in settings of neutropenia. When vaccine developers select a single gatekeeper assay (e.g., an opsonophagocytic assay for bacteria or a neutralization assay for viruses), promising vaccine candidates may be missed. Doyle and Pirofski stress that multiple functions, not just one, should be investigated to enhance discovery of antibody mechanisms and to best assess vaccine-induced correlates of immune protection. PMID:26908576

  9. Ice nucleation activity of polysaccharides

    NASA Astrophysics Data System (ADS)

    Bichler, Magdalena; Felgitsch, Laura; Haeusler, Thomas; Seidl-Seiboth, Verena; Grothe, Hinrich

    2015-04-01

    Heterogeneous ice nucleation is an important process in the atmosphere. It shows direct impact on our climate by triggering ice cloud formation and therefore it has much influence on the radiation balance of our planet (Lohmann et al. 2002; Mishchenko et al. 1996). The process itself is not completely understood so far and many questions remain open. Different substances have been found to exhibit ice nucleation activity (INA). Due to their vast differences in chemistry and morphology it is difficult to predict what substance will make good ice nuclei and which will not. Hence simple model substances must be found and be tested regarding INA. Our work aims at gaining to a deeper understanding of heterogeneous ice nucleation. We intend to find some reference standards with defined chemistry, which may explain the mechanisms of heterogeneous ice nucleation. A particular focus lies on biological carbohydrates in regards to their INA. Biological carbohydrates are widely distributed in all kingdoms of life. Mostly they are specific for certain organisms and have well defined purposes, e.g. structural polysaccharides like chitin (in fungi and insects) and pectin (in plants), which has also water-binding properties. Since they are widely distributed throughout our biosphere and mostly safe to use for nutrition purposes, they are well studied and easily accessible, rendering them ideal candidates as proxies. In our experiments we examined various carbohydrates, like the already mentioned chitin and pectin, as well as their chemical modifications. Lohmann U.; A Glaciation Indirect Aerosol Effect Caused by Soot Aerosols; J. Geoph. Res.; Vol. 24 No.4; pp 11-1 - 11-4; 2002 Mishchenko M.I., Rossow W.B., Macke A., Lacis A. A.; Sensitivity of Cirrus Cloud Albedo, Bidirectional Reflectance and Optical Thickness Retrieval Accuracy to Ice Particle Shape, J. Geoph. Res.; Vol. 101, No D12; pp. 16,973 - 16,985; 1996

  10. Human Papillomavirus (HPV) Vaccines

    MedlinePlus

    ... Directory Cancer Prevention Overview Research Human Papillomavirus (HPV) Vaccines On This Page What are human papillomaviruses? Which ... infections? Can HPV infections be prevented? What HPV vaccines are available? Who should get the HPV vaccines? ...

  11. Meningococcal Vaccine (For Parents)

    MedlinePlus

    ... to 2-Year-Old Your Child's Immunizations: Meningococcal Vaccines KidsHealth > For Parents > Your Child's Immunizations: Meningococcal Vaccines ... or her parents, and the doctor. Why the Vaccines Are Recommended Meningococcal disease is caused by a ...

  12. Your Baby's First Vaccines

    MedlinePlus

    ... Link Vaccines & Immunizations Immunization Schedules Your Child's First Vaccines Format: Select one PDF [335 KB] RTF [260 ... child will get one or more of these vaccines today: DTaP Hib Hepatitis B Polio PCV13 Why ...

  13. Vaccines Stop Illness

    MedlinePlus

    Skip Navigation Bar Home Current Issue Past Issues Vaccines Stop Illness Past Issues / Spring 2008 Table of ... meningitis won't infect, cripple, or kill children. Vaccine Safety In light of recent questions about vaccine ...

  14. Vaccines and Thimerosal

    MedlinePlus

    ... this? Submit What's this? Submit Button Thimerosal in Vaccines Recommend on Facebook Tweet Share Compartir Thimerosal is ... harm. Thimerosal prevents the growth of bacteria in vaccines. Thimerosal is added to vials of vaccine that ...

  15. Childhood Vaccine Schedule

    MedlinePlus

    ... Navigation Bar Home Current Issue Past Issues Childhood Vaccine Schedule Past Issues / Spring 2008 Table of Contents ... please turn Javascript on. When to Vaccinate What Vaccine Why Birth (or any age if not previously ...

  16. Meningococcal Vaccine (For Parents)

    MedlinePlus

    ... Your 1- to 2-Year-Old Your Child's Immunizations: Meningococcal Vaccines KidsHealth > For Parents > Your Child's Immunizations: ... who are at increased risk for meningococcal disease. Immunization Schedule Vaccination with meningococcal conjugate vaccine is recommended: ...

  17. Human Papillomavirus (HPV) Vaccine

    MedlinePlus

    Why get vaccinated?HPV vaccine prevents infection with human papillomavirus (HPV) types that are associated with cause ... at http://www.cdc.gov/hpv. HPV Vaccine (Human Papillomavirus) Information Statement. U.S. Department of Health and ...

  18. Vaccinations during Pregnancy

    MedlinePlus

    ... get is safe. Make sure your vaccinations are up to date before you get pregnant. What is a vaccination? ... are recommended before pregnancy? It’s best to be up to date on all your routine adult vaccinations before you ...

  19. Vaccine-Preventable Disease Photos

    MedlinePlus

    Home | About | A-Z | Contact | Follow Vaccine Information You Need VACCINE BASICS Evaluating Online Health Information FAQs How Vaccines Work Importance of Vaccines Paying for Vaccines State Immunization Programs ...

  20. Depolymerization of sulfated polysaccharides under hydrothermal conditions.

    PubMed

    Morimoto, Minoru; Takatori, Masaki; Hayashi, Tetsuya; Mori, Daiki; Takashima, Osamu; Yoshida, Shinichi; Sato, Kimihiko; Kawamoto, Hitoshi; Tamura, Jun-ichi; Izawa, Hironori; Ifuku, Shinsuke; Saimoto, Hiroyuki

    2014-01-30

    Fucoidan and chondroitin sulfate, which are well known sulfated polysaccharides, were depolymerized under hydrothermal conditions (120-180°C, 5-60min) as a method for the preparation of sulfated polysaccharides with controlled molecular weights. Fucoidan was easily depolymerized, and the change of the molecular weight values depended on the reaction temperature and time. The degree of sulfation and IR spectra of the depolymerized fucoidan did not change compared with those of untreated fucoidan at reaction temperatures below 140°C. However, fucoidan was partially degraded during depolymerization above 160°C. Nearly the same depolymerization was observed for chondroitin sulfate. These results indicate that hydrothermal treatment is applicable for the depolymerization of sulfated polysaccharides, and that low molecular weight products without desulfation and deformation of the initial glycan structures can be obtained under mild hydrothermal conditions.

  1. Learning from microbial strategies for polysaccharide degradation.

    PubMed

    Hemsworth, Glyn R; Déjean, Guillaume; Davies, Gideon J; Brumer, Harry

    2016-02-01

    Complex carbohydrates are ubiquitous in all kingdoms of life. As major components of the plant cell wall they constitute both a rich renewable carbon source for biotechnological transformation into fuels, chemicals and materials, and also form an important energy source as part of a healthy human diet. In both contexts, there has been significant, sustained interest in understanding how microbes transform these substrates. Classical perspectives of microbial polysaccharide degradation are currently being augmented by recent advances in the discovery of lytic polysaccharide monooxygenases (LPMOs) and polysaccharide utilization loci (PULs). Fundamental discoveries in carbohydrate enzymology are both advancing biological understanding, as well as informing applications in industrial biomass conversion and modulation of the human gut microbiota to mediate health benefits.

  2. Influence of polysaccharides on wine protein aggregation.

    PubMed

    Jaeckels, Nadine; Meier, Miriam; Dietrich, Helmut; Will, Frank; Decker, Heinz; Fronk, Petra

    2016-06-01

    Polysaccharides are the major high-molecular weight components of wines. In contrast, proteins occur only in small amounts in wine, but contribute to haze formation. The detailed mechanism of aggregation of these proteins, especially in combination with other wine components, remains unclear. This study demonstrates the different aggregation behavior between a buffer and a model wine system by dynamic light scattering. Arabinogalactan-protein, for example, shows an increased aggregation in the model wine system, while in the buffer system a reducing effect is observed. Thus, we could show the importance to examine the behavior of wine additives under conditions close to reality, instead of simpler buffer systems. Additional experiments on melting points of wine proteins reveal that only some isoforms of thaumatin-like proteins and chitinases are involved in haze formation. We can confirm interactions between polysaccharides and proteins, but none of these polysaccharides is able to prevent haze in wine.

  3. Cellular immunity to Bacteroides fragilis capsular polysaccharide

    PubMed Central

    1982-01-01

    The polysaccharide capsule of Bacteroides fragilis has been shown to be important in the virulence of the organism. The capsular polysaccharide (CP) of B. fragilis has been extensively purified. Using a murine model of intraabdominal abscess formation, we have been able to demonstrate cellular immunity to the capsular polysaccharide of B. fragilis. Immunization of C57BL/10J mice with the CP over 5 wk prevents abscess formation when the mice are challenged with B. fragilis intraperitoneally. This immunity can be transferred to naive mice with spleen cells from immune animals. The immune cells bear Thy-1.2 and Ly- 2.2 antigens. The immune response has been shown to be antigen specific, but not H-2 restricted. The possibility that these immune cells are suppressor T cells is discussed. The experimental system presented provides a model for the examination of the cellular interactions responsible for abscess formation and the cellular response to bacterial pathogens. PMID:6174672

  4. Subviral Particle as Vaccine and Vaccine Platform

    PubMed Central

    Tan, Ming; Jiang, Xi

    2014-01-01

    Recombinant subvirual particles retain similar antigenic features of their authentic viral capsids and thus have been applied as nonreplicating subunit vaccines against viral infection and illness. Additionally, the self-assembled, polyvalent subviral particles are excellent platforms to display foreign antigens for immune enhancement for vaccine development. These subviral particle-based vaccines are noninfectious and thus safer than the conventional live attenuated and inactivated vaccines. While several VLP vaccines are available in the markets, numerous others, including dual vaccines against more than one pathogen, are under clinical or preclinical development. This article provides an update of these efforts. PMID:24662314

  5. [Vaccination against mouse pox].

    PubMed

    Mahnel, H

    1985-01-01

    Attenuated MVA-strain of vaccinia virus has been efficient in the control of enzootic mousepox and in prophylactic vaccination. The virus has been used as a live vaccine for prophylactic and emergency vaccinations as well as for sanitation of populations. More than 100 000 vaccinations were carried out safely. Even after suspension of the obligatory vaccination of humans against smallpox the MVA-vaccine can be employed without risk and danger.

  6. Engineered human vaccines

    SciTech Connect

    Sandhu, J.S. . Div. of Immunology and Neurobiology)

    1994-01-01

    The limitations of human vaccines in use at present and the design requirements for a new generation of human vaccines are discussed. The progress in engineering of human vaccines for bacteria, viruses, parasites, and cancer is reviewed, and the data from human studies with the engineered vaccines are discussed, especially for cancer and AIDS vaccines. The final section of the review deals with the possible future developments in the field of engineered human vaccines and the requirement for effective new human adjuvants.

  7. Human Vaccines & Immunotherapeutics

    PubMed Central

    Riedmann, Eva M

    2014-01-01

    Measles vaccination: Targeted and non-targeted benefits CDC reports: 2-dose regimen of chickenpox vaccine is a success Positive preliminary results from the CAPiTA study Seasonal flu vaccine associate with reduced stroke risk HPV vaccine shown to halve cervical abnormalities Global prize for mobile mast vaccine storage project Developmental pathway of potent HIV-neutralizing antibodies Burkholderia vaccine: US Dep of Defense collaborates with Bavarian Nordic

  8. [Component analysis on polysaccharides in exocarp of Ginkgo biloba].

    PubMed

    Song, G; Xu, A; Chen, H; Wang, X

    1997-09-01

    This paper reports the content and component analysis on polysaccharides in exocarp of Ginkgo biloba. The results show that the content of total saccharides is 89.7%; content of polysaccharides is 84.6%; content of reductic saccharides is 5.1%; the polysaccharides are composed of glucose, fructose, galactose and rhamnose.

  9. Development of an opsonin inhibition assay for evaluation of complex polysaccharide protective epitopes.

    PubMed

    McNeely, Tessie; Luo, Shengyuan; Manger, Walt; Herber, Wayne; Schofield, Tim; Tan, Charles; Newman, Kathy; Sadoff, Jerald; Donnelly, John; Cross, Alan

    2006-03-10

    The induction of opsonic antibodies directed against capsular polysaccharides (Ps) is an important mechanism by which immunization protects against the development of invasive pneumococcal (Pn) infection. In preparing Pn vaccines, it is necessary to compare different manufacturing lots of capsular Ps, or to compare oligosaccharides used for conjugate vaccines with native capsular Ps, in order to insure that important epitopes of the Ps are maintained. We have developed an opsonic-antibody inhibition assay (OIA) to compare the functional epitopes of different capsular Ps preparations in vitro. Components of the OIA are primary neutrophils, rabbit complement (C'), and type-specific antibody (Ab). After conditions for optimal opsonic killing were determined for each Pn serotype, anti-Pn Ab was pre-incubated with different dilutions of purified capsular Ps, then added to the OIA mix. Plotting the % bacteria killed versus Ps concentration (log transformed) yielded a linear curve that was used to quantify the concentration of capsular Ps which inhibited the bacteria killing by 50% (IC50). The IC50 was determined for 8 Pn Ps types. These ranged between 6 ng/ml for type 6B and 1268 ng/ml for type 23F. Importantly OIA curves were statistically identical for two different manufacturing lots of capsular Ps for the 8 Pn Ps types. We conclude that differences among capsular Ps used for Pn vaccines could be detected with an OIA assay and these differences may predict the ability of Ps preparations to induce functionally active antibody when formulated into vaccines.

  10. Biosynthesis of Conjugate Vaccines Using an O-Linked Glycosylation System

    PubMed Central

    Pan, Chao; Sun, Peng; Liu, Bo; Liang, Haoyu; Peng, Zhehui; Dong, Yan; Wang, Dongshu; Liu, Xiankai; Wang, Bin

    2016-01-01

    ABSTRACT  Conjugate vaccines are known to be one of the most effective and safest types of vaccines against bacterial pathogens. Previously, vaccine biosynthesis has been performed by using N-linked glycosylation systems. However, the structural specificity of these systems for sugar substrates has hindered their application. Here, we report a novel protein glycosylation system (O-linked glycosylation via Neisseria meningitidis) that can transfer virtually any glycan to produce a conjugate vaccine. We successfully established this system in Shigella spp., avoiding the construction of an expression vector for polysaccharide synthesis. We further found that different protein substrates can be glycosylated using this system and that the O-linked glycosylation system can also effectively function in other Gram-negative bacteria, including some strains whose polysaccharide structure was not suitable for conjugation using the N-linked glycosylation system. The results from a series of animal experiments show that the conjugate vaccine produced by this O-linked glycosylation system offered a potentially protective antibody response. Furthermore, we elucidated and optimized the recognition motif, named MOOR, for the O-glycosyltransferase PglL. Finally, we demonstrated that the fusion of other peptides recognized by major histocompatibility complex class II around MOOR had no adverse effects on substrate glycosylation, suggesting that this optimized system will be useful for future vaccine development. Our results expand the glycoengineering toolbox and provide a simpler and more robust strategy for producing bioconjugate vaccines against a variety of pathogens. PMID:27118590

  11. Hepatitis B Vaccine

    MedlinePlus

    ... a combination product containing Haemophilus influenzae type b, Hepatitis B Vaccine) ... combination product containing Diphtheria, Tetanus Toxoids, Acellular Pertussis, Hepatitis B, Polio Vaccine)

  12. HPAEC-PAD quantification of Haemophilus influenzae type b polysaccharide in upstream and downstream samples.

    PubMed

    van der Put, Robert M F; de Haan, Alex; van den IJssel, Jan G M; Hamidi, Ahd; Beurret, Michel

    2015-11-27

    Due to the rapidly increasing introduction of Haemophilus influenzae type b (Hib) and other conjugate vaccines worldwide during the last decade, reliable and robust analytical methods are needed for the quantitative monitoring of intermediate samples generated during fermentation (upstream processing, USP) and purification (downstream processing, DSP) of polysaccharide vaccine components. This study describes the quantitative characterization of in-process control (IPC) samples generated during the fermentation and purification of the capsular polysaccharide (CPS), polyribosyl-ribitol-phosphate (PRP), derived from Hib. Reliable quantitative methods are necessary for all stages of production; otherwise accurate process monitoring and validation is not possible. Prior to the availability of high performance anion exchange chromatography methods, this polysaccharide was predominantly quantified either with immunochemical methods, or with the colorimetric orcinol method, which shows interference from fermentation medium components and reagents used during purification. Next to an improved high performance anion exchange chromatography-pulsed amperometric detection (HPAEC-PAD) method, using a modified gradient elution, both the orcinol assay and high performance size exclusion chromatography (HPSEC) analyses were evaluated. For DSP samples, it was found that the correlation between the results obtained by HPAEC-PAD specific quantification of the PRP monomeric repeat unit released by alkaline hydrolysis, and those from the orcinol method was high (R(2)=0.8762), and that it was lower between HPAEC-PAD and HPSEC results. Additionally, HPSEC analysis of USP samples yielded surprisingly comparable results to those obtained by HPAEC-PAD. In the early part of the fermentation, medium components interfered with the different types of analysis, but quantitative HPSEC data could still be obtained, although lacking the specificity of the HPAEC-PAD method. Thus, the HPAEC

  13. Capsular Polysaccharide Expression in Commensal Streptococcus Species: Genetic and Antigenic Similarities to Streptococcus pneumoniae

    PubMed Central

    Skov Sørensen, Uffe B.; Yao, Kaihu; Yang, Yonghong; Tettelin, Hervé

    2016-01-01

    ABSTRACT 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 production distinguishes S. pneumoniae from closely related commensals of the mitis group streptococci. Based on antigenic and genetic analyses of 187 mitis group streptococci, including 90 recognized serotypes of S. pneumoniae, we demonstrated capsule production by the Wzy/Wzx pathway in 74% of 66 S. mitis strains and in virtually all tested strains of S. oralis (subspecies oralis, dentisani, and tigurinus) and S. infantis. Additional analyses of genomes of S. cristatus, S. parasanguinis, S. australis, S. sanguinis, S. gordonii, S. anginosus, S. intermedius, and S. constellatus revealed complete capsular biosynthesis (cps) loci in all strains tested. Truncated cps loci were detected in three strains of S. pseudopneumoniae, in 26% of S. mitis strains, and in a single S. oralis strain. The level of sequence identities of cps locus genes confirmed that the structural polymorphism of capsular polysaccharides in S. 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. pneumoniae raises concerns about potential misidentifications in addition to important questions concerning the consequences for vaccination and host-parasite relationships both for the commensals and for the pathogen. PMID:27935839

  14. Solution conformation and flexibility of capsular polysaccharides from Neisseria meningitidis and glycoconjugates with the tetanus toxoid protein

    NASA Astrophysics Data System (ADS)

    Abdelhameed, Ali Saber; Morris, Gordon A.; Almutairi, Fahad; Adams, Gary G.; Duvivier, Pierre; Conrath, Karel; Harding, Stephen E.

    2016-10-01

    The structural integrity of meningococcal native, micro-fluidized and activated capsular polysaccharides and their glycoconjugates – in the form most relevant to their potential use as vaccines (dilute solution) - have been investigated with respect to their homogeneity, conformation and flexibility. Sedimentation velocity analysis showed that the polysaccharide size distributions were generally bimodal with some evidence for higher molar mass forms at higher concentration. Weight average molar masses Mw where lower for activated polysaccharides. Conjugation with tetanus toxoid protein however greatly increased the molar mass and polydispersity of the final conjugates. Glycoconjugates had an approximately unimodal log-normal but broad and large molar mass profiles, confirmed by sedimentation equilibrium “SEDFIT MSTAR” analysis. Conformation analysis using HYDFIT (which globally combines sedimentation and viscosity data), “Conformation Zoning” and Wales-van Holde approaches showed a high degree of flexibility – at least as great as the unconjugated polysaccharides, and very different from the tetanus toxoid (TT) protein used for the conjugation. As with the recently published finding for Hib-TT complexes, it is the carbohydrate component that dictates the solution behaviour of these glycoconjugates, although the lower intrinsic viscosities suggest some degree of compaction of the carbohydrate chains around the protein.

  15. Solution conformation and flexibility of capsular polysaccharides from Neisseria meningitidis and glycoconjugates with the tetanus toxoid protein

    PubMed Central

    Abdelhameed, Ali Saber; Morris, Gordon A.; Almutairi, Fahad; Adams, Gary G.; Duvivier, Pierre; Conrath, Karel; Harding, Stephen E.

    2016-01-01

    The structural integrity of meningococcal native, micro-fluidized and activated capsular polysaccharides and their glycoconjugates – in the form most relevant to their potential use as vaccines (dilute solution) - have been investigated with respect to their homogeneity, conformation and flexibility. Sedimentation velocity analysis showed that the polysaccharide size distributions were generally bimodal with some evidence for higher molar mass forms at higher concentration. Weight average molar masses Mw where lower for activated polysaccharides. Conjugation with tetanus toxoid protein however greatly increased the molar mass and polydispersity of the final conjugates. Glycoconjugates had an approximately unimodal log-normal but broad and large molar mass profiles, confirmed by sedimentation equilibrium “SEDFIT MSTAR” analysis. Conformation analysis using HYDFIT (which globally combines sedimentation and viscosity data), “Conformation Zoning” and Wales-van Holde approaches showed a high degree of flexibility – at least as great as the unconjugated polysaccharides, and very different from the tetanus toxoid (TT) protein used for the conjugation. As with the recently published finding for Hib-TT complexes, it is the carbohydrate component that dictates the solution behaviour of these glycoconjugates, although the lower intrinsic viscosities suggest some degree of compaction of the carbohydrate chains around the protein. PMID:27782149

  16. Use of immuno assays during the development of a Hemophilus influenzae type b vaccine for technology transfer to emerging vaccine manufacturers.

    PubMed

    Hamidi, Ahd; Kreeftenberg, Hans

    2014-01-01

    Quality control of Hemophilus Influenzae type b (Hib) conjugate vaccines is mainly dependent on physicochemical methods. Overcoming sample matrix interference when using physicochemical tests is very challenging, these tests are therefore only used to test purified samples of polysaccharide, protein, bulk conjugate, and final product. For successful development of a Hib conjugate vaccine, several ELISA (enzyme-linked immunosorbent assay) methods were needed as an additional tool to enable testing of in process (IP) samples. In this paper, three of the ELISA's that have been very valuable during the process development, implementation and scaling up are highlighted. The PRP-ELISA, was a very efficient tool in testing in process (IP) samples generated during the development of the cultivation and purification process of the Hib-polysaccharide. The antigenicity ELISA, was used to confirm the covalent linkage of PRP and TTd in the conjugate. The anti-PRP IgG ELISA was developed as part of the immunogenicity test, used to demonstrate the ability of the Hib conjugate vaccine to elicit a T-cell dependent immune response in mice. ELISA methods are relatively cheap and easy to implement and therefore very useful during the development of polysaccharide conjugate vaccines.

  17. Use of immuno assays during the development of a Hemophilus influenzae type b vaccine for technology transfer to emerging vaccine manufacturers

    PubMed Central

    Hamidi, Ahd; Kreeftenberg, Hans

    2014-01-01

    Quality control of Hemophilus Influenzae type b (Hib) conjugate vaccines is mainly dependent on physicochemical methods. Overcoming sample matrix interference when using physicochemical tests is very challenging, these tests are therefore only used to test purified samples of polysaccharide, protein, bulk conjugate, and final product. For successful development of a Hib conjugate vaccine, several ELISA (enzyme-linked immunosorbent assay) methods were needed as an additional tool to enable testing of in process (IP) samples. In this paper, three of the ELISA's that have been very valuable during the process development, implementation and scaling up are highlighted. The PRP-ELISA, was a very efficient tool in testing in process (IP) samples generated during the development of the cultivation and purification process of the Hib-polysaccharide. The antigenicity ELISA, was used to confirm the covalent linkage of PRP and TTd in the conjugate. The anti-PRP IgG ELISA was developed as part of the immunogenicity test, used to demonstrate the ability of the Hib conjugate vaccine to elicit a T-cell dependent immune response in mice. ELISA methods are relatively cheap and easy to implement and therefore very useful during the development of polysaccharide conjugate vaccines. PMID:25483494

  18. Approach to the Discovery, Development, and Evaluation of a Novel Neisseria meningitidis Serogroup B Vaccine.

    PubMed

    Green, Luke R; Eiden, Joseph; Hao, Li; Jones, Tom; Perez, John; McNeil, Lisa K; Jansen, Kathrin U; Anderson, Annaliesa S

    2016-01-01

    In this chapter, we describe a research and development pathway to identify and demonstrate the efficacy of a Neisseria meningitidis non-capsular vaccine, the recently licensed N. meningitidis serogroup B (MnB) vaccine, Trumenba(®). While other approaches have been followed in the identification of a MnB vaccine (Pizza et al. Science 287:1816-1820, 2000), the methods described here reflect the distinctive approach and experiences in discovering and developing Trumenba(®). In contrast to the development and licensure of polysaccharide-conjugate vaccines against meningococcal serotypes A, C, W, and Y, the development of a vaccine to produce broadly protective antibodies against meningococcal serogroup B has proved difficult, due to the antigenic mimicry of the serogroup B polysaccharide capsule, which is composed of polysialic acid structures similar to those expressed on human neuronal cells. Early development efforts for these vaccines failed because the MnB polysaccharide structures resemble autoantigens and thus were poorly immunogenic. The development of an MnB vaccine has therefore focused on non-polysaccharide approaches. It was critical to identify MnB cell surface-exposed antigens capable of inducing a protective response against diverse, circulating strains of invasive MnB to ensure global coverage. Once candidate antigens were identified, it was important to characterize antigenic variation and expression levels, and subsequently to assure that antigens were expressed broadly among diverse clinical isolates. Prior to the initiation of clinical trials in humans, candidate vaccine antigens were tested in functional immunogenicity assays and yielded responses that were correlated with protection from meningococcal disease. These functional immunogenicity assays (serum bactericidal assays using human complement, hSBAs) measure the titer of complement-dependent bactericidal antibodies in serum from immunized test animals using diverse clinical MnB isolates as

  19. The impact of pre-existing antibody on subsequent immune responses to meningococcal A-containing vaccines.

    PubMed

    Idoko, Olubukola T; Okolo, Seline N; Plikaytis, Brian; Akinsola, Adebayo; Viviani, Simonetta; Borrow, Ray; Carlone, George; Findlow, Helen; Elie, Cheryl; Kulkarni, Prasad S; Preziosi, Marie-Pierre; Ota, Martin; Kampmann, Beate

    2014-07-16

    Major epidemics of serogroup A meningococcal meningitis continue to affect the African meningitis belt. The development of an affordable conjugate vaccine against the disease became a priority for World Health Organization (WHO) in the late 1990s. Licensing of meningococcal vaccines has been based on serological correlates of protection alone, but such correlates might differ in different geographical regions. If high pre-vaccination antibody concentrations/titers impacts on the response to vaccination and possibly vaccine efficacy, is not clearly understood. We set out to define the pre-vaccination Meningococcal group A (Men A) antibody concentrations/titers in The Gambia and study their impact on the immunogenicity of Men A containing vaccines. Data from subjects originally enrolled in studies to test the safety and immunogenicity of the MenA vaccine recently developed for Africa meningococcal A polysaccharide conjugated to tetanus toxoid, MenAfriVac(®) (PsA-TT) were analyzed. Participants had been randomized to receive either the study vaccine PsA-TT or the reference quadrivalent plain polysaccharide vaccine containing meningococcal groups A, C, W, and Y, Mencevax(®) ACWY, GlaxoSmithKline (PsACWY) in a 2:1 ratio. Venous blood samples were collected before and 28 days after vaccination. Antibodies were assayed by enzyme-linked immunosorbent assay (ELISA) for geometric mean concentrations and serum bactericidal antibody (SBA) for functional antibody. The inter age group differences were compared using ANOVA and the pre and post-vaccination differences by t test. Over 80% of the ≥19 year olds had pre-vaccination antibody concentrations above putatively protective concentrations as compared to only 10% of 1-2 year olds. Ninety-five percent of those who received the study vaccine had ≥4-fold antibody responses if they had low pre-vaccination concentrations compared to 76% of those with high pre-vaccination concentrations. All subjects with low pre-vaccination

  20. Structural insights into antibody recognition of mycobacterial polysaccharides.

    PubMed

    Murase, Tomohiko; Zheng, Ruixiang Blake; Joe, Maju; Bai, Yu; Marcus, Sandra L; Lowary, Todd L; Ng, Kenneth K S

    2009-09-18

    Mycobacteria are major human pathogens responsible for such serious and widespread diseases as tuberculosis and leprosy. Among the evolutionary adaptations essential for pathogenicity in mycobacteria is a complex carbohydrate-rich cell-wall structure that contains as a major immunomodulatory molecule the polysaccharide lipoarabinomannan (LAM). We report here crystal structures of three fragments from the non-reducing termini of LAM in complex with a murine antibody Fab fragment (CS-35Fab). These structures reveal for the first time the three-dimensional structures of key components of LAM and the molecular basis of LAM recognition at between 1.8- and 2.0-A resolution. The antigen-binding site of CS-35Fab forms three binding pockets that show a high degree of complementarity to the reducing end, the branch point and one of the non-reducing ends of the Y-shaped hexasaccharide moiety found at most of the non-reducing termini of LAM. Structures of CS-35Fab bound to two additional tetrasaccharides confirm the general mode of binding seen in the hexasaccharide and indicate how different parts of LAM are recognized. Altogether, these structures provide a rational basis for understanding the overall architecture of LAM and identify the key elements of an epitope that may be exploited for the development of novel and more effective anti-mycobacterial vaccines. Moreover, this study represents the first high-resolution X-ray crystallographic investigation of oligofuranoside-protein recognition.

  1. Rapid kinetics of serum IgA after vaccination with Prevnar(®)13 followed by Pneumovax(®)23.

    PubMed

    Crowther, Rebecca R; Collins, Christine M; Conley, Cheryl; Lopez, Osvaldo J

    2017-02-01

    Streptococcus pneumoniae is a causative agent of community-acquired pneumonias. The recommendations of the 2012 Advisory Committee on Immunization Practices include vaccination with Prevnar(®)13 (protein-polysaccharide conjugate vaccine; PCV), followed by Pneumovax(®)23 (polysaccharide-based vaccine; PSV) in adults 65+ or the immunocompromised. In this experiment, a group of 4 healthy volunteers were vaccinated with PCV followed by PSV 60 days later. ELISAs were optimized to study kinetics of IgA, IgM, total IgG and its four subclasses against 14 polysaccharides of the pneumococcal capsule. Although this is a small sample, results from volunteers consistently showed that rapid induction of monomeric IgA followed by rapid decline is typical for both vaccines. IgA was not detected after PSV vaccination in those serotypes present in PCV, suggesting the population of B cells secreting IgA is not renewed within 60 days of activation by PCV. In contrast to mice, human neutrophils expressed a functional receptor for the constant region of monomeric IgA. Thus, the role of IgA early in the human immune response should be further investigated.

  2. Vaccines and vaccinations. The strategic issues.

    PubMed

    Ford, R B

    2001-05-01

    The rapid proliferation of companion animal vaccines, advances in diagnostic and vaccine technology, and concerns over vaccine safety are clearly among the most important issues practicing veterinarians face as we enter the 21st century. Although many would argue that these are already issues, the future promises to be especially challenging as the vaccines we currently use and the protocols we recommend undergo unprecedented review.

  3. Polysaccharide-based strategies for heart tissue engineering.

    PubMed

    Silva, Amanda K A; Juenet, Maya; Meddahi-Pellé, Anne; Letourneur, Didier

    2015-02-13

    Polysaccharides are abundant biomolecules in nature presenting important roles in a wide variety of living systems processes. Considering the structural and biological functions of polysaccharides, their properties have raised interest for tissue engineering. Herein, we described the latest advances in cardiac tissue engineering mediated by polysaccharides. We reviewed the data already obtained in vitro and in vivo in this field with several types of polysaccharides. Cardiac injection, intramyocardial in situ polymerization strategies, and scaffold-based approaches involving polysaccharides for heart tissue engineering are thus discussed.

  4. Phosphorylation of the synthetic hexasaccharide repeating unit is essential for the induction of antibodies to Clostridium difficile PSII cell wall polysaccharide.

    PubMed

    Adamo, Roberto; Romano, Maria R; Berti, Francesco; Leuzzi, Rosanna; Tontini, Marta; Danieli, Elisa; Cappelletti, Emilia; Cakici, Osman S; Swennen, Erwin; Pinto, Vittoria; Brogioni, Barbara; Proietti, Daniela; Galeotti, Cesira L; Lay, Luigi; Monteiro, Mario A; Scarselli, Maria; Costantino, Paolo

    2012-08-17

    Clostridium difficile is emerging worldwide as a major cause of nosocomial infections. The negatively charged PSII polysaccharide has been found in different strains of C. difficile and, thereby, represents an important target molecule for a possible carbohydrate-based vaccine. In order to identify a synthetic fragment that after conjugation to a protein carrier could be able to induce anti-PSII antibodies, we exploited a combination of chemical synthesis with immunochemistry, confocal immunofluorescence microscopy, and solid state NMR. We demonstrate that the phosphate group is crucial in synthetic glycans to mimic the native PSII polysaccharide; both native PSII and a phosphorylated synthetic hexasaccharide repeating unit conjugated to CRM(197) elicit comparable immunogenic responses in mice. This finding can aid design and selection of carbohydrate antigens to be explored as vaccine candidates.

  5. The Design of a Clostridium difficile Carbohydrate-Based Vaccine.

    PubMed

    Monteiro, Mario A

    2016-01-01

    Clostridium difficile vaccines composed of surface polysaccharides (PSs) have the potential to simultaneously control infection and colonization levels in humans. Hot water-phenol treatment of C. difficile biomass can extricate water-soluble PS-I and PS-II; and water- and phenol-soluble PS-III. C. difficile vaccines based on PS-II have attracted the most attention due its facile purification and ubiquitous expression by C. difficile ribotypes. Anti PS-II antibodies recognize both C. difficile vegetative cell and sporulating preparations and confer protection against C. difficile infection in a mouse model. The design of such an efficacious C. difficile PS-II conjugate vaccine is described here.

  6. Impact of Vi vaccination on spatial patterns of typhoid fever in the slums of Kolkata, India.

    PubMed

    Ali, Mohammad; Sur, Dipika; Kim, Deok Ryun; Kanungo, Suman; Bhattacharya, Sujit K; Manna, Byomkesh; Ochiai, R Leon; Clemens, John

    2011-11-08

    A mass typhoid Vi vaccination campaign was carried out among approximately 60,000 slum residents of Kolkata, India. This study evaluated the impact of the campaign on spatial patterns of typhoid fever. Eighty contiguous residential groups of households in the study area were randomized to receive either a single dose of the Vi polysaccharide vaccine or a single dose of the inactivated hepatitis A vaccine as the control agent. Persons aged two years and older were eligible to receive the vaccine. Vaccine protection against typhoid fever was monitored for two years after vaccination at both outpatient and inpatient facilities serving the study population. Geographic analytic and mapping tools were used in the analysis. Spatial randomness of the disease was observed during the pre-vaccination period, which turned into a significant pattern after vaccination. The high-risk areas for typhoid were observed in the area dominated by the control clusters, and the low-risk areas were in the area dominated by the Vi clusters. Furthermore, the control clusters surrounded by the Vi clusters were low risk for typhoid fever. The results demonstrated the ability of mass vaccination to change the spatial patterns of disease through the creation of spatial barriers to transmission of the disease. Understanding and mapping the disease risk could be useful for designing a community-based vaccination strategy to control disease.

  7. Vaccines based on structure-based design provide protection against infectious diseases.

    PubMed

    Thomas, Sunil; Luxon, Bruce A

    2013-11-01

    Vaccines elicit immune responses, provide protection against microorganisms and are considered as one of the most successful medical interventions against infectious diseases. Vaccines can be produced using attenuated virus or bacteria, recombinant proteins, bacterial polysaccharides, carbohydrates or plasmid DNA. Conventional vaccines rely on the induction of immune responses against antigenic proteins to be effective. The genetic diversity of microorganisms, coupled with the high degree of sequence variability in antigenic proteins, presents a challenge to developing broadly effective conventional vaccines. The observation that whole protein antigens are not necessarily essential for inducing immunity has led to the emergence of a new branch of vaccine design termed 'structural vaccinology'. Structure-based vaccines are designed on the rationale that protective epitopes should be sufficient to induce immune responses and provide protection against pathogens. Recent studies demonstrated that designing structure-based vaccine candidates with multiple epitopes induce a higher immune response. As yet there are no commercial vaccines available based on structure-based design and most of the structure-based vaccine candidates are in the preclinical stages of development. This review focuses on recent advances in structure-based vaccine candidates and their application in providing protection against infectious diseases.

  8. Global practices of meningococcal vaccine use and impact on invasive disease

    PubMed Central

    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

  9. Avian influenza vaccines and vaccination for poultry

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Vaccines against avian influenza (AI) have had more limited use in poultry than vaccines against other poultry diseases such as Newcastle disease (ND) and infectious bronchitis, and have been used more commonly in the developing world. Over the past 40 years, AI vaccines have been primarily based o...

  10. Extraction and characterization of sugar beet polysaccharides

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Sugar Beet Pulp (SBP), contains 65 to 80% (dry weight) of potentially valuable polysaccharides. We separated SBP into three fractions. The first fraction, extracted under acid conditions, was labeled pectin, the second was comprised of two sub fractions solubilized under alkaline conditions and wa...

  11. Fucoidans — sulfated polysaccharides of brown algae

    NASA Astrophysics Data System (ADS)

    Usov, Anatolii I.; Bilan, M. I.

    2009-08-01

    The methods of isolation of fucoidans and determination of their chemical structures are reviewed. The fucoidans represent sulfated polysaccharides of brown algae, the composition of which varies from simple fucan sulfates to complex heteropolysaccharides. The currently known structures of such biopolymers are presented. A variety of the biological activities of fucoidans is briefly summarised.

  12. Aldehyde-containing urea-absorbing polysaccharides

    NASA Technical Reports Server (NTRS)

    Mueller, W. A.; Hsu, G. C.; Marsh, H. E., Jr. (Inventor)

    1977-01-01

    A novel aldehyde containing polymer (ACP) is prepared by reaction of a polysaccharide with periodate to introduce aldehyde groups onto the C2 - C3 carbon atoms. By introduction of ether and ester groups onto the pendant primary hydroxyl solubility characteristics are modified. The ACP is utilized to absorb nitrogen bases such as urea in vitro or in vivo.

  13. Bacillus subtilis biofilm induction by plant polysaccharides

    PubMed Central

    Beauregard, Pascale B.; Chai, Yunrong; Vlamakis, Hera; Losick, Richard; Kolter, Roberto

    2013-01-01

    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. PMID:23569226

  14. Anticorrosive Microbial Polysaccharides: Structure-Function Relationships

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Water-soluble microbial polysaccharides are often implicated in biofilm formation and are believed to mediate cell-cell aggregation and adhesion to surfaces. Generally, biofilm formation is considered harmful or undesirable, as it leads to increased drag, plugging of pores, dimished heat transfer, ...

  15. Plant-Polysaccharide-Degrading Enzymes from Basidiomycetes

    PubMed Central

    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

  16. Sulfated polysaccharides and immune response: promoter or inhibitor?

    PubMed

    Chen, D; Wu, X Z; Wen, Z Y

    2008-06-01

    Sulfated polysaccharides, which frequently connect to core protein, are expressed not only on cell surface but also throughout the extracellular matrix. Besides providing structural integrity of cells, sulfated polysaccharides interact with a variety of sulfated polysaccharides-binding proteins, such as growth factors, cytokines, chemokines and proteases. Sulfated polysaccharides play two-edged roles, inhibitor and promoter, in immune response. Some sulfated polysaccharides act as the immunosuppressor by blocking inflammatory signal transduction induced by proinflammatory cytokines, suppressing the activation of complement and inhibiting the process that leukocytes adhere to and pass through endothelium. On the contrary, the interaction between immune cells and sulfated polysaccharides produced by bacteria, endothelial cells and immune cells initiate the occurrence of immune response. It promotes the processes of recognizing and arresting antigen, migrating transendothelium, moving into and out of immune organ and enhancing the proliferation of lymphocyte. The structure of sulfated polysaccharides, such as molecular weight and sulfated sites heterogeneity, especially the degree of disaccharide sulfation, position of the sulfate moiety and organization of sulfated domains, may play critical role in their controversial effects. As a consequence, the interaction between sulfated polysaccharides and sulfated polysaccharide-binding proteins may be changed by modifying the structure of sulfated polysaccharides chains. The administration of drug targeting sulfated polysaccharide-protein interaction may be useful in treating inflammatory related diseases.

  17. Structure-function relationships of immunostimulatory polysaccharides: A review.

    PubMed

    Ferreira, Sónia S; Passos, Cláudia P; Madureira, Pedro; Vilanova, Manuel; Coimbra, Manuel A

    2015-11-05

    Immunostimulatory polysaccharides are compounds capable of interacting with the immune system and enhance specific mechanisms of the host response. Glucans, mannans, pectic polysaccharides, arabinogalactans, fucoidans, galactans, hyaluronans, fructans, and xylans are polysaccharides with reported immunostimulatory activity. The structural features that have been related with such activity are the monosaccharide and glycosidic-linkage composition, conformation, molecular weight, functional groups, and branching characteristics. However, the establishment of structure-function relationships is possible only if purified and characterized polysaccharides are used and selective structural modifications performed. Aiming at contributing to the definition of the structure-function relationships necessary to design immunostimulatory polysaccharides with potential for preventive or therapeutical purposes or to be recognized as health-improving ingredients in functional foods, this review introduces basic immunological concepts required to understand the mechanisms that rule the potential claimed immunostimulatory activity of polysaccharides and critically presents a literature survey on the structural features of the polysaccharides and reported immunostimulatory activity.

  18. Polysaccharide-producing bacteria isolated from paper machine slime deposits.

    PubMed

    Rättö, M; Suihko, M-L; Siika-aho, M

    2005-03-01

    Development of novel enzymatic methods for slime deposit control in paper mills requires knowledge of polysaccharide-producing organisms and the polysaccharide structures present in deposits. In this work, 27 polysaccharide-producing bacteria were isolated from slime samples collected from different parts of a paper machine. Most of the isolates produced polysaccharides in liquid culture and nine of them were selected for production of polysaccharides for characterisation. The selected isolates belonged to seven different genera: Bacillus, Brevundimonas, Cytophaga, Enterobacter, Klebsiella, Paenibacillus and Starkeya. Using ribotyping, partial 16S rDNA sequencing, physiological tests and fatty acid analysis, four of the nine isolates: Bacillus cereus, Brevundimonas vesicularis, K. pneumoniae and P. stellifer were identified to the species level. Production of polysaccharides by the selected isolates varied between 0.07 and 1.20 g L(-1), the highest amount being produced by B. vesicularis. The polysaccharides were heteropolysaccharides with varying proportions of galactose, glucose mannose, rhamnose fucose and uronic acids.

  19. Synthesis of di- and tri-saccharide fragments of Salmonella typhi Vi capsular polysaccharide and their zwitterionic analogues.

    PubMed

    Fusari, Matteo; Fallarini, Silvia; Lombardi, Grazia; Lay, Luigi

    2015-12-01

    Zwitterionic polysaccharides (ZPS) behave like traditional T cell-dependent antigens, suggesting the design of new classes of vaccines alternative to currently used glycoconjugates and based on the artificial introduction of a zwitterionic charge motif onto the carbohydrate structure of pathogen antigens. Here we report the new synthesis and antigenic evaluation of di-/tri-saccharide fragments of Salmonella typhi Vi polysaccharide, as well as of their corresponding zwitterionic analogues. Our strategy is based on versatile intermediates enabling chain elongation either by iterative single monomer attachment or by faster and more flexible approach using disaccharide donors. The effect of structural modifications of the synthetic compounds on antigenic properties was evaluated by competitive ELISA. All the oligosaccharides were recognized by specific anti-Vi polyclonal antibodies in a concentration-dependent manner, and the introduction of a zwitterionic motif into the synthetic molecules did not prevent the binding.

  20. History of vaccination

    PubMed Central

    Plotkin, Stanley

    2014-01-01

    Vaccines have a history that started late in the 18th century. From the late 19th century, vaccines could be developed in the laboratory. However, in the 20th century, it became possible to develop vaccines based on immunologic markers. In the 21st century, molecular biology permits vaccine development that was not possible before. PMID:25136134

  1. History of vaccination.

    PubMed

    Plotkin, Stanley

    2014-08-26

    Vaccines have a history that started late in the 18th century. From the late 19th century, vaccines could be developed in the laboratory. However, in the 20th century, it became possible to develop vaccines based on immunologic markers. In the 21st century, molecular biology permits vaccine development that was not possible before.

  2. Pneumococcal Vaccination Guidance for Post-Acute and Long-Term Care Settings: Recommendations From AMDA's Infection Advisory Committee.

    PubMed

    Nace, David A; Archbald-Pannone, Laurie R; Ashraf, Muhammad S; Drinka, Paul J; Frentzel, Elizabeth; Gaur, Swati; Mahajan, Dheeraj; Mehr, David R; Mercer, William C; Sloane, Philip D; Jump, Robin L P

    2017-02-01

    Efforts at preventing pneumococcal disease are a national health priority, particularly in older adults and especially in post-acute and long-term care settings The Advisory Committee on Immunization Practices recommends that all adults ≥65 years of age, as well as adults 18-64 years of age with specific risk factors, receive both the recently introduced polysaccharide-protein conjugate vaccine against 13 pneumococcal serotypes as well as the polysaccharide vaccine against 23 pneumococcal serotypes. Nursing facility licensure regulations require facilities to assess the pneumococcal vaccination status of each resident, provide education regarding pneumococcal vaccination, and administer the appropriate pneumococcal vaccine when indicated. Sorting out the indications and timing for 13 pneumococcal serotypes and 23 pneumococcal serotypes administration is complex and presents a significant challenge to healthcare providers. Here, we discuss the importance of pneumococcal vaccination for older adults, detail AMDA-The Society for Post-Acute and Long-Term Care Medicine (The Society)'s recommendations for pneumococcal vaccination practice and procedures, and offer guidance to postacute and long-term care providers supporting the development and effective implementation of pneumococcal vaccine policies.

  3. A peptide mimotope of type 8 pneumococcal capsular polysaccharide induces a protective immune response in mice.

    PubMed

    Buchwald, Ulrike K; Lees, Andrew; Steinitz, Michael; Pirofski, Liise-Anne

    2005-01-01

    Increasing antibiotic resistance and a rising patient population at risk for infection due to impaired immunity underscore the importance of vaccination against pneumococci. However, available capsular polysaccharide vaccines are often poorly immunogenic in patients at risk for pneumococcal disease. The goal of this study was to explore the potential of peptide mimotopes to function as alternative vaccine antigens to elicit a type-specific antibody response to pneumococci. We used a human monoclonal immunoglobulin A (IgA) antibody (NAD) to type 8 Streptococcus pneumoniae capsular polysaccharide (type 8 PS) to screen a phage display library, and the phage PUB1 displaying the peptide FHLPYNHNWFAL was selected after three rounds of biopanning. Inhibition studies with phage-displayed peptide or the peptide PUB1 and type 8 PS showed that PUB1 is a mimetic of type 8 PS. PUB1 conjugated to tetanus toxoid (PUB1-TT) induced a type 8 PS-specific antibody response in BALB/c mice, further defining it as a mimotope of type 8 PS. The administration of immune sera obtained from PUB1-TT-immunized mice earlier (days 14 and 21) and later (days 87 and 100) after primary and reimmunization resulted in a highly significant prolongation of the survival of naive mice after pneumococcal challenge compared to controls. The survival of PUB1-TT-immunized mice was also prolonged after pneumococcal challenge nearly 4 months after primary immunization. The efficacy of PUB1-TT-induced immune sera provides proof of principle that a mimotope-induced antibody response can protect against pneumococci and suggests that peptide mimotopes selected by type-specific human antibodies could hold promise as immunogens for pneumococci.

  4. Meningococcal serogroup B vaccines: Estimating breadth of coverage

    PubMed Central

    Donald, Robert G. K.; Hawkins, Julio Cesar; Hao, Li; Liberator, Paul; Jones, Thomas R.; Harris, Shannon L.; Perez, John L.; Eiden, Joseph J.; Jansen, Kathrin U.; Anderson, Annaliesa S.

    2017-01-01

    ABSTRACT Neisseria meningitidis serogroup B (MenB) is an important cause of invasive meningococcal disease. The development of safe and effective vaccines with activity across the diversity of MenB strains has been challenging. While capsular polysaccharide conjugate vaccines have been highly successful in the prevention of disease due to meningococcal serogroups A, C, W, and Y, this approach has not been possible for MenB owing to the poor immunogenicity of the MenB capsular polysaccharide. Vaccines based on outer membrane vesicles have been successful in the prevention of invasive MenB disease caused by the single epidemic strain from which they were derived, but they do not confer broad protection against diverse MenB strains. Thus, alternative approaches to vaccine development have been pursued to identify vaccine antigens that can provide broad protection against the epidemiologic and antigenic diversity of invasive MenB strains. Human factor H binding protein (fHBP) was found to be such an antigen, as it is expressed on nearly all invasive disease strains of MenB and can induce bactericidal responses against diverse MenB strains. A bivalent vaccine (Trumenba®, MenB-FHbp, bivalent rLP2086) composed of equal amounts of 2 fHBP variants from each of the 2 immunologically diverse subfamilies of fHBP (subfamilies A and B) was the first MenB vaccine licensed in the United States under an accelerated approval pathway for prevention of invasive MenB disease. Due to the relatively low incidence of meningococcal disease, demonstration of vaccine efficacy for the purposes of licensure of bivalent rLP2086 was based on vaccine-elicited bactericidal activity as a surrogate marker of efficacy, as measured in vitro by the serum bactericidal assay using human complement. Because bacterial surface proteins such as fHBP are antigenically variable, an important component for evaluation and licensure of bivalent rLP2086 included stringent criteria for assessment of breadth of

  5. Prevention of Community-Acquired Pneumonia with Available Pneumococcal Vaccines

    PubMed Central

    Principi, Nicola; Esposito, Susanna

    2016-01-01

    Community-acquired pneumonia (CAP) places a considerable burden on society. A substantial number of pediatric and adult CAP cases are due to Streptococcus pneumoniae, but fortunately there are effective vaccines available that have a significant impact on CAP-related medical, social, and economic problems. The main aim of this paper is to evaluate the published evidence concerning the impact of pneumococcal vaccines on the prevention of CAP in children and adults. Available data indicate that pneumococcal conjugate vaccines (PCVs) are effective in children, reducing all-cause CAP cases and bacteremic and nonbacteremic CAP cases. Moreover, at least for PCV7 and PCV13, vaccination of children is effective in reducing the incidence of CAP among adults. Recently use of PCV13 in adults alone or in combination with the pneumococcal polysaccharide vaccine has been suggested and further studies can better define its effectiveness in this group of subjects. The only relevant problem for PCV13 is the risk of a second replacement phenomenon, which might significantly reduce its real efficacy in clinical practice. Protein-based pneumococcal vaccines might be a possible solution to this problem. PMID:28029140

  6. Thermostable cross-protective subunit vaccine against Brucella species.

    PubMed

    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.

  7. The Type a and Type b Polysaccharide Capsules Predominate in an International Collection of Invasive Kingella kingae Isolates.

    PubMed

    Porsch, Eric A; Starr, Kimberly F; Yagupsky, Pablo; St Geme, Joseph W

    2017-01-01

    Kingella kingae is an encapsulated Gram-negative bacterium and an important etiology of osteoarticular infections in young children. A recent study examining a diverse collection of carrier and invasive K. kingae isolates from Israel revealed four distinct polysaccharide capsule types. In this study, to obtain a global view of K. kingae capsule type diversity, we examined an international collection of isolates using a multiplex PCR approach. The collection contained all four previously identified capsule types and no new capsule types. Over 95% of invasive isolates in the collection were type a or type b, similar to the findings in Israel. These results suggest that the type a and type b polysaccharide capsules may have enhanced pathogenic properties or may mark clonal groups of strains with specific virulence genes. In addition, they raise the possibility that a vaccine containing the type a and type b capsules might be an effective approach to preventing K. kingae disease. IMPORTANCEKingella kingae has emerged as a significant cause of septic arthritis, osteomyelitis, and bacteremia in young children. A recent study examining a diverse collection of K. kingae isolates from Israel revealed four different polysaccharide capsule types in this species, designated types a to d. To determine the global distribution of K. kingae capsule types, we assembled and capsule typed an international collection of K. kingae isolates. The findings reported here show that the type a and type b capsules represent >95% of the invasive isolates, similar to the Israeli isolate collection, suggesting that a polysaccharide-based vaccine targeting these two capsules could be an attractive approach to prevent K. kingae disease.

  8. The Type a and Type b Polysaccharide Capsules Predominate in an International Collection of Invasive Kingella kingae Isolates

    PubMed Central

    Porsch, Eric A.; Starr, Kimberly F.; Yagupsky, Pablo

    2017-01-01

    ABSTRACT Kingella kingae is an encapsulated Gram-negative bacterium and an important etiology of osteoarticular infections in young children. A recent study examining a diverse collection of carrier and invasive K. kingae isolates from Israel revealed four distinct polysaccharide capsule types. In this study, to obtain a global view of K. kingae capsule type diversity, we examined an international collection of isolates using a multiplex PCR approach. The collection contained all four previously identified capsule types and no new capsule types. Over 95% of invasive isolates in the collection were type a or type b, similar to the findings in Israel. These results suggest that the type a and type b polysaccharide capsules may have enhanced pathogenic properties or may mark clonal groups of strains with specific virulence genes. In addition, they raise the possibility that a vaccine containing the type a and type b capsules might be an effective approach to preventing K. kingae disease. IMPORTANCE Kingella kingae has emerged as a significant cause of septic arthritis, osteomyelitis, and bacteremia in young children. A recent study examining a diverse collection of K. kingae isolates from Israel revealed four different polysaccharide capsule types in this species, designated types a to d. To determine the global distribution of K. kingae capsule types, we assembled and capsule typed an international collection of K. kingae isolates. The findings reported here show that the type a and type b capsules represent >95% of the invasive isolates, similar to the Israeli isolate collection, suggesting that a polysaccharide-based vaccine targeting these two capsules could be an attractive approach to prevent K. kingae disease. PMID:28317027

  9. Vaccines today, vaccines tomorrow: a perspective

    PubMed Central

    2013-01-01

    Vaccines are considered as one of the major contributions of the 20th century and one of the most cost effective public health interventions. The International Vaccine Institute has as a mission to discover, develop and deliver new and improved vaccines against infectious diseases that affects developing nations. If Louis Pasteur is known across the globe, vaccinologists like Maurice Hilleman, Jonas Salk and Charles Mérieux are known among experts only despite their contribution to global health. Thanks to a vaccine, smallpox has been eradicated, polio has nearly disappeared, Haemophilus influenzae B, measles and more recently meningitis A are controlled in many countries. While a malaria vaccine is undergoing phase 3, International Vaccine Institute, in collaboration with an Indian manufacturer has brought an oral inactivated cholera vaccine to pre-qualification. The field of vaccinology has undergone major changes thanks to philanthropists such as Bill and Melinda Gates, initiatives like the Decade of Vaccines and public private partnerships. Current researches on vaccines have more challenging targets like the dengue viruses, malaria, human immunodeficiency virus, the respiratory syncytial virus and nosocomial diseases. Exciting research is taking place on new adjuvants, nanoparticles, virus like particles and new route of administration. An overcrowded infant immunization program, anti-vaccine groups, immunizing a growing number of elderlies and delivering vaccines to difficult places are among challenges faced by vaccinologists and global health experts. PMID:23596584

  10. Vaccine Policy Issues

    DTIC Science & Technology

    2005-05-19

    evidence “favors rejection” of the idea that either the measles- mumps-rubella vaccine or thimerosal-containing vaccines cause autism (IOM...Immunization Safety Review: Vaccines and Autism , Washington, D.C., National Academies Press, 2004). 46ACIP’s rotavirus vaccine fact sheet is at [http...that the vaccines or preservatives or packaging might cause autism and other neurodevelopmental disorders. One focus has been on thimerosal, a mercury

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

    PubMed Central

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

    2015-01-01

    Background. 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. Methods. 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. Results. 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. Conclusions. In June 2001

  12. Carriage rate and effects of vaccination after outbreaks of serogroup C meningococcal disease, Brazil, 2010.

    PubMed

    Sáfadi, Marco Aurelio Palazzi; Carvalhanas, Telma Regina Marques Pinto; Paula de Lemos, Ana; Gorla, Maria Cecilia Outeiro; Salgado, Maristela; Fukasawa, Lucila O; Gonçalves, Maria Gisele; Higa, Fabio; Brandileone, Maria Cristina Cunto; Sacchi, Claudio Tavares; Ribeiro, Ana Freitas; Sato, Helena Keico; Bricks, Lucia Ferro; Cassio de Moraes, José

    2014-05-01

    During 2010, outbreaks of serogroup C meningococcal (MenC) disease occurred in 2 oil refineries in São Paulo State, Brazil, leading to mass vaccination of employees at 1 refinery with a meningococcal polysaccharide A/C vaccine. A cross-sectional study was conducted to assess the prevalence of meningococci carriage among workers at both refineries and to investigate the effect of vaccination on and the risk factors for pharyngeal carriage of meningococci. Among the vaccinated and nonvaccinated workers, rates of overall meningococci carriage (21.4% and 21.6%, respectively) and of MenC carriage (6.3% and 4.9%, respectively) were similar. However, a MenC strain belonging to the sequence type103 complex predominated and was responsible for the increased incidence of meningococcal disease in Brazil. A low education level was associated with higher risk of meningococci carriage. Polysaccharide vaccination did not affect carriage or interrupt transmission of the epidemic strain. These findings will help inform future vaccination strategies.

  13. Polysaccharide structure of tetrasporic red seaweed Tichocarpus crinitus.

    PubMed

    Byankina Barabanova, A O; Sokolova, E V; Anastyuk, S D; Isakov, V V; Glazunov, V P; Volod'ko, A V; Yakovleva, I M; Solov'eva, T F; Yermak, I M

    2013-10-15

    Sulfated polysaccharide isolated from tetrasporic plants of Tichocarpus crinitus was investigated. The polysaccharide was isolated by two methods: with water extraction at 80 °C (HT) and with a mild alkaline extraction (AE). The extracted polysaccharides were presented by non-gelling ones only, while galactose and 3,6-AG were the main monosaccharides, at the same time amount of 3,6-AG in AE polysaccharides was the similar to that of HT. According to methods of spectroscopy and mass spectrometry, the polysaccharide from tetrasporic T. crinitus contains main blocks of 1,3-linked β-D-galactopyranosyl-2,4-disulfates and 1,4-linked 3,6-anhydro-α-D-galactopyranosyl while 6-sulfated 4-linked galactopyranosyl resudies are randomly distributed along the polysaccharide chain. The alkaline treatment of HT polysaccharide results in obtaining polysaccharide with regular structure that composed of alternating 1,3-linked β-D-galactopyranosyl-2,4-disulfates and 1,4-linked 3,6-anhydro-α-D-galactopyranosyl residues. Native polysaccharide (HT) possessed both high anticoagulant and antiplatelet activity measured by fibrin clotting and platelet aggregation induced by collagen. This activity could be connected with peculiar chemical structure of HT polysaccharide which has high sulfation degree and contains also 3,6-anhydrogalactose in the polymer chain.

  14. α-Amylase-assisted extraction of polysaccharides from Panax ginseng.

    PubMed

    Sun, Lin; Wu, Di; Ning, Xin; Yang, Guang; Lin, Ziheng; Tian, Meihong; Zhou, Yifa

    2015-04-01

    In this paper, α-amylase-assisted extraction was used to isolate the polysaccharide that remained in hot water-extracted ginseng. The yield of the polysaccharide was 9.0%, almost equal to that of the hot water-extracted polysaccharide. Using anion exchange and gel permeation chromatography, the polysaccharide was fractionated into a neutral polysaccharide fraction and six pectic fractions. The neutral fraction accounted for 76% of the polysaccharide and contained both amylopectin and amylose. The pectic polysaccharide fractions were identified to be arabinogalactan, type-I rhamnogalacturonan and homogalacturonan-type pectin by high-performance liquid chromatography, Fourier transform-infrared and nuclear magnetic resonance analysis. Structural and lymphocyte proliferation activity results showed that these polysaccharides were different from those extracted by hot water, indicating that ginseng contains complex polysaccharides with diverse structures, which results in its diverse pharmacological activities. The α-amylase-assisted extraction is a novel method for preparing ginseng polysaccharides and could be applied toward the further study and exploration of ginseng. These findings provide technical and theoretical support for ginseng pharmacology.

  15. Simultaneous detection of Haemophilus influenzae type b polysaccharide-specific antibodies and Neisseria meningitidis serogroup A, C, Y, and W-135 polysaccharide-specific antibodies in a fluorescent-bead-based multiplex immunoassay.

    PubMed

    de Voer, Richarda M; Schepp, Rutger M; Versteegh, Florens G A; van der Klis, Fiona R M; Berbers, Guy A M

    2009-03-01

    We expanded the meningococcal serogroup A, C, Y, and W-135 multiplex immunoassay (MIA) to simultaneously detect immunoglobulin type G antibodies directed toward Haemophilus influenzae type b polysaccharide (HibPS). The monoplex HibPS assay was compared to a HibPS-specific competitive enzyme-linked immunosorbent assay and showed a good correlation (R=0.96). Furthermore, no cross-reactivity between HibPS and the four meningococcal serogroups was detected. This pentaplex meningococcal Hib MIA is a useful tool to investigate serological responses toward different childhood PS vaccines.

  16. Obesity vaccines.

    PubMed

    Monteiro, Mariana P

    2014-01-01

    Obesity is one of the largest and fastest growing public health problems in the world. Last century social changes have set an obesogenic milieu that calls for micro and macro environment interventions for disease prevention, while treatment is mandatory for individuals already obese. The cornerstone of overweight and obesity treatment is diet and physical exercise. However, many patients find lifestyle modifications difficult to comply and prone to failure in the long-term; therefore many patients consider anti-obesity drugs an important adjuvant if not a better alternative to behavioral approach or obesity surgery. Since the pharmacological options for obesity treatment remain quite limited, this is an exciting research area, with new treatment targets and strategies on the horizon. This review discusses the development of innovative therapeutic agents, focusing in energy homeostasis regulation and the use of molecular vaccines, targeting hormones such as somatostatin, GIP and ghrelin, to reduce body weight.

  17. [Pneumococcal vaccine recommendations in chronic respiratory diseases].

    PubMed

    Casas Maldonado, F; Alfageme Michavila, I; Barchilón Cohen, V S; Peis Redondo, J I; Vargas Ortega, D A

    2014-09-01

    Community-acquired pneumonia is an acute respiratory infectious disease which has an incidence of 3-8 cases/1,000 inhabitants, and increases with age and comorbidities. The pneumococcus is the organism most frequently involved in community-acquired pneumonia in the adult (30-35%). Around 40% of patients with community-acquired pneumonia require hospital admission, and around 10% need to be admitted to an intensive care unit. The most serious forms of pneumococcal infection include invasive pneumococcal disease (IPD), which covers cases of bacteremia (associated or not to pneumonia), meningitis, pleuritis, arthritis, primary peritonitis and pericarditis. Currently, the biggest problem with the pneumococcus is the emergence of resistance to antimicrobial agents, and its high morbimortality, despite the use of appropriate antibiotics and proper medical treatment. Certain underlying medical conditions increase the risk of IPD and its complications, especially, from the respiratory diseases point of view, smoking and chronic respiratory diseases. Pneumococcal disease, according to the WHO, is the first preventable cause of death worldwide in children and adults. Among the strategies to prevent IPD is vaccination. WHO considers that its universal introduction and implementation against pneumococcus is essential and a priority in all countries. There are currently 2 pneumococcal vaccines for adults: the 23 serotypes polysaccharide and conjugate 13 serotypes. The scientific societies represented here have worked to develop some recommendations, based on the current scientific evidence, regarding the pneumococcal vaccination in the immunocompetent adult with chronic respiratory disease and smokers at risk of suffering from IPD.

  18. What do we know about the cost-effectiveness of pneumococcal conjugate vaccination in older adults?

    PubMed

    Newall, A T

    2016-10-02

    The cost-effectiveness of 13-type pneumococcal conjugate vaccine (PCV13) use in older adults, and the relative merits when compared to the 23-type polysaccharide pneumococcal vaccine (PPV23), has been a topic of much debate. Although a number of economics evaluations have been conducted many of these were completed before the availability of critical data on PCV13 efficacy in older adults. Recent studies using this data have found conflicting results. This may in part reflect differences in the level of herd protection from infant pneumococcal vaccination programs in different countries. The costs and benefits of pneumococcal vaccination in adults are likely to rest on several critical parameters: the magnitude pneumococcal disease in older adults and the serotypes responsible for it, the efficacy of each vaccine against invasive and non-invasive pneumonia, the duration of vaccine protection, and differences in vaccine price. The ongoing changes in pneumococcal disease patterns highlight the need for economic evaluations to use recent serotype-specific disease estimates from the setting under consideration. In countries that do recommend PCV13 use in adults, post-implementation economic evaluation (using data from after a program is implemented) may be useful to help inform potential future changes to vaccine recommendations as well as the maximum price that should be paid for the vaccines in future negotiations.

  19. DNA Vaccination in Chickens.

    PubMed

    Gupta, Shishir Kumar; Dey, Sohini; Chellappa, Madhan Mohan

    2016-01-01

    Robust and sustainable development of poultry industry requires prevention of deadly infectious diseases. Vigorous vaccination of the birds is a routine practice; however, the live and inactivated vaccines that are used have inherent disadvantages. New-generation vaccines such as DNA vaccines offer several advantages over conventional vaccines. DNA vaccines, which encode an antigen of interest or multiple antigens in the target host, are stable, easy to produce and administer, do not require cold chain maintenance, and are not affected by the maternal antibodies. In addition, DNA vaccines can also be administered in ovo, and thus, mass vaccination and early induction of immune response can effectively be achieved. In this chapter, we focus on the development of DNA vaccines against important infectious viral as well as parasitic diseases of poultry.

  20. Effects of selenizing angelica polysaccharide and selenizing garlic polysaccharide on immune function of murine peritoneal macrophage.

    PubMed

    Gao, Zhenzhen; Liu, Kuanhui; Tian, Weijun; Wang, Hongchao; Liu, Zhenguang; Li, Youying; Li, Entao; Liu, Cui; Li, Xiuping; Hou, Ranran; Yue, Chanjuan; Wang, Deyun; Hu, Yuanliang

    2015-07-01

    The effects of two selenizing polysaccharides (sCAP2 and sGPS6) on immune function of murine peritoneal macrophages taking two non-selenizing polysaccharides (CAP and GPS) and modifier Na2SeO3 as control. In vitro test, the changes of selenizing polysaccharides, non-selenizing polysaccharides and Na2SeO3 on murine macrophages function were evaluated by phagocytosis and nitric oxide (NO) secretion tests. In vivo test, the mice were injected respectively with 0.2, 0.4 and 0.6 mg of sCAP2, sGPS6, CAP and GPS, or Na2SeO3 80 μg or normal saline 0.4 mL. The peritoneal macrophages were collected and cultured to determine the contents of TNF-α, IL-6 and IL-10 in supernatants by enzyme-linked immunosorbent assay. The results showed that sCAP2 and sGPS6 could significantly promote the phagocytosis and secretion of NO and three cytokines of macrophages in comparison with CAP and GPS. sCAP2 possessed the strongest activity. This indicates that selenylation modification can further improve the immune-enhancing activity of polysaccharide, and sCAP2 could be as a new immunopotentiator.

  1. Neurologic complications of vaccinations.

    PubMed

    Miravalle, Augusto A; Schreiner, Teri

    2014-01-01

    This chapter reviews the most common neurologic disorders associated with common vaccines, evaluates the data linking the disorder with the vaccine, and discusses the potential mechanism of disease. A literature search was conducted in PubMed using a combination of the following terms: vaccines, vaccination, immunization, and neurologic complications. Data were also gathered from publications of the American Academy of Pediatrics Committee on Infectious Diseases, the World Health Organization, the US Centers for Disease Control and Prevention, and the Vaccine Adverse Event Reporting System. Neurologic complications of vaccination are rare. Many associations have been asserted without objective data to support a causal relationship. Rarely, patients with a neurologic complication will have a poor outcome. However, most patients recover fully from the neurologic complication. Vaccinations have altered the landscape of infectious disease. However, perception of risk associated with vaccinations has limited the success of disease eradication measures. Neurologic complications can be severe, and can provoke fear in potential vaccines. Evaluating whether there is causal link between neurologic disorders and vaccinations, not just temporal association, is critical to addressing public misperception of risk of vaccination. Among the vaccines available today, the cost-benefit analysis of vaccinations and complications strongly argues in favor of vaccination.

  2. 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.

    PubMed

    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.

  3. Immunogenic properties of Klebsiella pneumoniae type 2 capsular polysaccharide.

    PubMed Central

    Robert, A; Jouin, H; Fournier, J M

    1986-01-01

    The immunoprotective activity of Klebsiella pneumoniae K2 cell surface preparations and purified capsular polysaccharide was tested in mice. The 50% protective dose (PD50), expressed as capsular polysaccharide content, was 2 ng for cell surface preparations and 50 ng for purified capsular polysaccharide. Both preparations lost their immunoprotective activity after alkali treatment. Immune sera were raised in rabbits immunized with cell surface preparations. The precipitating and hemagglutinating capacity of these antisera was tested against either purified capsular polysaccharide or alkali-treated capsular polysaccharide. No difference was observed between the reactivity of the antisera against each antigen. The protective activity of these sera was tested on mice in passive transfer experiments, before and after absorption with either purified capsular polysaccharide or alkali-treated capsular polysaccharide. The sera lost their protective activity after absorption with purified capsular polysaccharide and after absorption with alkali-treated capsular polysaccharide. These experiments show that the difference in immunoprotective activity of cell surface preparations, purified capsular polysaccharide, and alkali-treated capsular polysaccharide is not due to a difference in their antigenic determinants. Cell surface preparations and purified capsular polysaccharide were fractionated by gel filtration on Sepharose 4B and by ultracentrifugation on cesium chloride density gradients. Three forms of capsular polysaccharide have been characterized. (i) A form of capsular polysaccharide with a very high protective activity (PD50 = 2 ng) that copurified with protein and lipopolysaccharide and was characterized by a low coefficient of distribution (Kd = 0.20) and a low density (1.5 to 1.6 g/cm3). (ii) A form of capsular polysaccharide with an intermediate protective activity (PD50 = 50 ng), contamined by less than 3% protein and 1% lipopolysaccharide, with a Kd of 0.35, and

  4. POLYPEPTIDE AND POLYSACCHARIDE PROCESSING IN HYPERTHERMOPHILIC MICROORGANISMS

    SciTech Connect

    KELLY, ROBERT M.

    2008-12-22

    This project focused on the microbial physiology and biochemistry of heterotrophic hyperthermophiles with respect to mechanisms by which these organisms process polypeptides and polysaccharides under normal and stressed conditions. Emphasis is on two model organisms, for which completed genome sequences are available: Pyrococcus furiosus (growth Topt of 98°C), an archaeon, and Thermotoga maritima (growth Topt of 80°C), a bacterium. Both organisms are obligately anaerobic heterotrophs that reduce sulfur facultatively. Whole genome cDNA spotted microarrays were used to follow transcriptional response to a variety of environmental conditions in order to identify genes encoding proteins involved in the acquisition, synthesis, processing and utilization of polypeptides and polysaccharides. This project provided new insights into the physiological aspects of hyperthermophiles as these relate to microbial biochemistry and biological function in high temperature habitats. The capacity of these microorganisms to produce biohydrogen from renewable feedstocks makes them important for future efforts to develop biofuels.

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

    PubMed

    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.

  6. Recombinant Clostridium difficile toxin fragments as carrier protein for PSII surface polysaccharide preserve their neutralizing activity.

    PubMed

    Romano, Maria R; Leuzzi, Rosanna; Cappelletti, Emilia; Tontini, Marta; Nilo, Alberto; Proietti, Daniela; Berti, Francesco; Costantino, Paolo; Adamo, Roberto; Scarselli, Maria

    2014-04-22

    Clostridium difficile is a Gram-positive bacterium and is the most commonly diagnosed cause of hospital-associated and antimicrobial-associated diarrhea. Despite the emergence of epidemic C. difficile strains having led to an increase in the incidence of the disease, a vaccine against this pathogen is not currently available. C. difficile strains produce two main toxins (TcdA and TcdB) and express three highly complex cell-surface polysaccharides (PSI, PSII and PSIII). PSII is the more abundantly expressed by most C. difficile ribotypes offering the opportunity of the development of a carbohydrate-based vaccine. In this paper, we evaluate the efficacy, in naive mice model, of PSII glycoconjugates where recombinant toxins A and B fragments (TcdA_B2 and TcdB_GT respectively) have been used as carriers. Both glycoconjugates elicited IgG titers anti-PSII although only the TcdB_GT conjugate induced a response comparable to that obtained with CRM197. Moreover, TcdA_B2 and TcdB_GT conjugated to PSII retained the ability to elicit IgG with neutralizing activity against the respective toxins. These results are a crucial proof of concept for the development of glycoconjugate vaccines against C. difficile infection (CDI) that combine different C. difficile antigens to potentially prevent bacterial colonization of the gut and neutralize toxin activity.

  7. Ganoderma lucidum polysaccharides encapsulated in liposome as an adjuvant to promote Th1-bias immune response.

    PubMed

    Liu, Zhenguang; Xing, Jie; Zheng, Sisi; Bo, Ruonan; Luo, Li; Huang, Yee; Niu, Yale; Li, Zhihua; Wang, Deyun; Hu, Yuanliang; Liu, Jiaguo; Wu, Yi

    2016-05-20

    Liposome-based vaccine delivery systems are known to enhance immune responses. Ganoderma lucidum polysaccharides (GLP) have been widely studied as immunomodulator and it could be as inducers of strong immune responses. In the research, GLP and ovalbumin (OVA) were encapsulated into liposome as vaccine and inoculated to mice. The magnitude and kinetics of the humoral and cellular immune responses were investigated. The results showed that GLP-OVA-loaded liposomes (GLPL/OVA) could induce more powerful antigen-specific immune responses than each single-component formulation. Mice immunized with GLPL/OVA displayed higher antigen-specific IgG antibodies, better splenocytes proliferation, higher cytokine secretion by splenocytes and significant activation of CD3+CD4+ and CD3+CD8+ T cells. Thus the GLPL/OVA formulation produced a heightened humoral and cellular immune response, with an overall Th1 bias. Enhanced immune responses elicited by the GLPL/OVA formulation might be attributed to effective activation and mature of DC in draining lymph nodes. Overall, these findings indicate that GLPL have the potential to enhance immune responses as vaccine delivery systems.

  8. Vaccinations for Adults with Diabetes

    MedlinePlus

    Vaccinations for Adults with Diabetes The table below shows which vaccinations you should have to protect your health if ... sure you and your healthcare provider keep your vaccinations up to date. Vaccine Do you need it? ...

  9. Diabetes and Hepatitis B Vaccination

    MedlinePlus

    ... monitoring in close succession. CDC now recommends the hepatitis B vaccine for adults with diabetes. What is the recommendation ... As with other vaccines, the effectiveness of the hepatitis B vaccine decreases with age. Decisions to vaccinate should include ...

  10. Nasal spray flu vaccine (image)

    MedlinePlus

    The flu vaccine can also be administered as a nasal spray instead of the usual injection method. It can be ... the recombinant influenza vaccine (RIV). The nasal spray flu vaccine (live attenuated influenza vaccine or LAIV) should not ...

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

    PubMed

    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

  12. 42 CFR 410.57 - Pneumococcal vaccine and flu vaccine.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 42 Public Health 2 2012-10-01 2012-10-01 false Pneumococcal vaccine and flu vaccine. 410.57... § 410.57 Pneumococcal vaccine and flu vaccine. (a) Medicare Part B pays for pneumococcal vaccine and its administration when reasonable and necessary for the prevention of disease, if the vaccine is ordered by a...

  13. 42 CFR 410.57 - Pneumococcal vaccine and flu vaccine.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 42 Public Health 2 2013-10-01 2013-10-01 false Pneumococcal vaccine and flu vaccine. 410.57... § 410.57 Pneumococcal vaccine and flu vaccine. (a) Medicare Part B pays for pneumococcal vaccine and its administration when reasonable and necessary for the prevention of disease, if the vaccine is ordered by a...

  14. 42 CFR 410.57 - Pneumococcal vaccine and flu vaccine.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 42 Public Health 2 2014-10-01 2014-10-01 false Pneumococcal vaccine and flu vaccine. 410.57... § 410.57 Pneumococcal vaccine and flu vaccine. (a) Medicare Part B pays for pneumococcal vaccine and its administration when reasonable and necessary for the prevention of disease, if the vaccine is ordered by a...

  15. 42 CFR 410.57 - Pneumococcal vaccine and flu vaccine.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 42 Public Health 2 2011-10-01 2011-10-01 false Pneumococcal vaccine and flu vaccine. 410.57... § 410.57 Pneumococcal vaccine and flu vaccine. (a) Medicare Part B pays for pneumococcal vaccine and its administration when reasonable and necessary for the prevention of disease, if the vaccine is ordered by a...

  16. 42 CFR 410.57 - Pneumococcal vaccine and flu vaccine.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 42 Public Health 2 2010-10-01 2010-10-01 false Pneumococcal vaccine and flu vaccine. 410.57... § 410.57 Pneumococcal vaccine and flu vaccine. (a) Medicare Part B pays for pneumococcal vaccine and its administration when reasonable and necessary for the prevention of disease, if the vaccine is ordered by a...

  17. Vaccines against poverty

    PubMed Central

    MacLennan, Calman A.; Saul, Allan

    2014-01-01

    With the 2010s declared the Decade of Vaccines, and Millennium Development Goals 4 and 5 focused on reducing diseases that are potentially vaccine preventable, now is an exciting time for vaccines against poverty, that is, vaccines against diseases that disproportionately affect low- and middle-income countries (LMICs). The Global Burden of Disease Study 2010 has helped better understand which vaccines are most needed. In 2012, US$1.3 billion was spent on research and development for new vaccines for neglected infectious diseases. However, the majority of this went to three diseases: HIV/AIDS, malaria, and tuberculosis, and not neglected diseases. Much of it went to basic research rather than development, with an ongoing decline in funding for product development partnerships. Further investment in vaccines against diarrheal diseases, hepatitis C, and group A Streptococcus could lead to a major health impact in LMICs, along with vaccines to prevent sepsis, particularly among mothers and neonates. The Advanced Market Commitment strategy of the Global Alliance for Vaccines and Immunisation (GAVI) Alliance is helping to implement vaccines against rotavirus and pneumococcus in LMICs, and the roll out of the MenAfriVac meningococcal A vaccine in the African Meningitis Belt represents a paradigm shift in vaccines against poverty: the development of a vaccine primarily targeted at LMICs. Global health vaccine institutes and increasing capacity of vaccine manufacturers in emerging economies are helping drive forward new vaccines for LMICs. Above all, partnership is needed between those developing and manufacturing LMIC vaccines and the scientists, health care professionals, and policy makers in LMICs where such vaccines will be implemented. PMID:25136089

  18. Vaccines against poverty.

    PubMed

    MacLennan, Calman A; Saul, Allan

    2014-08-26

    With the 2010s declared the Decade of Vaccines, and Millennium Development Goals 4 and 5 focused on reducing diseases that are potentially vaccine preventable, now is an exciting time for vaccines against poverty, that is, vaccines against diseases that disproportionately affect low- and middle-income countries (LMICs). The Global Burden of Disease Study 2010 has helped better understand which vaccines are most needed. In 2012, US$1.3 billion was spent on research and development for new vaccines for neglected infectious diseases. However, the majority of this went to three diseases: HIV/AIDS, malaria, and tuberculosis, and not neglected diseases. Much of it went to basic research rather than development, with an ongoing decline in funding for product development partnerships. Further investment in vaccines against diarrheal diseases, hepatitis C, and group A Streptococcus could lead to a major health impact in LMICs, along with vaccines to prevent sepsis, particularly among mothers and neonates. The Advanced Market Commitment strategy of the Global Alliance for Vaccines and Immunisation (GAVI) Alliance is helping to implement vaccines against rotavirus and pneumococcus in LMICs, and the roll out of the MenAfriVac meningococcal A vaccine in the African Meningitis Belt represents a paradigm shift in vaccines against poverty: the development of a vaccine primarily targeted at LMICs. Global health vaccine institutes and increasing capacity of vaccine manufacturers in emerging economies are helping drive forward new vaccines for LMICs. Above all, partnership is needed between those developing and manufacturing LMIC vaccines and the scientists, health care professionals, and policy makers in LMICs where such vaccines will be implemented.

  19. Deletion of the GI-2 integrase and the wbkA flanking transposase improves the stability of Brucella melitensis Rev 1 vaccine.

    PubMed

    Mancilla, Marcos; Grilló, María-Jesús; de Miguel, María-Jesús; López-Goñi, Ignacio; San-Román, Beatriz; Zabalza-Baranguá, Ana; Moriyón, Ignacio

    2013-10-31

    Brucella melitensis Rev 1 is the best vaccine available for the prophylaxis of small ruminant brucellosis and, indirectly, for reducing human brucellosis. However, Rev 1 shows anomalously high rates of spontaneous dissociation from smooth (S) to rough (R) bacteria, the latter being inefficacious as vaccines. This S-R instability results from the loss of the O-polysaccharide. To overcome this problem, we investigated whether some recently described mechanisms promoting mutations in O-polysaccharide genes were involved in Rev 1 S-R dissociation. We found that a proportion of Rev 1 R mutants result from genome rearrangements affecting the wbo O-polysaccharide loci of genomic island GI-2 and the wbkA O-polysaccharide glycosyltransferase gene of the wbk region. Accordingly, we mutated the GI-2 int gene and the wbk IS transposase involved in those arrangements, and found that these Rev 1 mutants maintained the S phenotype and showed lower dissociation levels. Combining these two mutations resulted in a strain (Rev 2) displaying a 95% decrease in dissociation with respect to parental Rev 1 under conditions promoting dissociation. Rev 2 did not differ from Rev 1 in the characteristics used in Rev 1 typing (growth rate, colonial size, reactivity with O-polysaccharide antibodies, phage, dye and antibiotic susceptibility). Moreover, Rev 2 and Rev 1 showed similar attenuation and afforded similar protection in the mouse model of brucellosis vaccines. We conclude that mutations targeting genes and DNA sequences involved in spontaneous O-polysaccharide loss enhance the stability of a critical vaccine phenotype and complement the empirical stabilization precautions taken during S Brucella vaccine production.

  20. Microbial extracellular polysaccharides and plagioclase dissolution

    SciTech Connect

    Welch, S.A.; Barker, W.W.; Banfield, J.F.

    1999-05-01

    Bytownite feldspar was dissolved in batch reactors in solutions of starch (glucose polymer), gum xanthan (glucose, mannose, glucuronic acid), pectin (poly-galacturonic acid), and four alginates (mannuronic and guluronic acid) with a range of molecular weights (low, medium, high and uncharacterized) to evaluate the effect of extracellular microbial polymers on mineral dissolution rates. Solutions were analyzed for dissolved Si and Al as an indicator of feldspar dissolution. At neutral pH, feldspar dissolution was inhibited by five of the acid polysaccharides, gum xanthan, pectin, alginate low, alginate medium, alginate high, compared to an organic-free control. An uncharacterized alginate substantially enhanced both Si and Al release from the feldspar. Starch, a neutral polysaccharide, had no apparent effect. Under mildly acidic conditions, initial pH {approx} 4, all of the polymers enhanced feldspar dissolution compared to the inorganic controls. Si release from feldspar in starch solution exceeded the control by a factor of three. Pectin and gum xanthan increased feldspar dissolution by a factor of 10, and the alginates enhanced feldspar dissolution by a factor of 50 to 100. Si and Al concentrations increased with time, even though solutions were supersaturated with respect to several possible secondary phases. Under acidic conditions, initial pH {approx} 3, below the pK{sub a} of the carboxylic acid groups, dissolution rates increased, but the relative increase due to the polysaccharides is lower, approximately a factor of two to ten. Microbial extracellular polymers play a complex role in mineral weathering. Polymers appear to inhibit dissolution under some conditions, possibly by irreversibly binding to the mineral surfaces. The extracellular polysaccharides can also enhance dissolution by providing protons and complexing with ions in solution.

  1. Polysaccharide Nanosystems for Future Progress in Cardiovascular Pathologies

    PubMed Central

    Silva, Amanda Karine Andriola; Letourneur, Didier; Chauvierre, Cédric

    2014-01-01

    Natural polysaccharides have received a lot of attention in the biomedical field. Indeed, sources of polysaccharides, extracted or produced from plants, bacteria, fungi or algae, are diverse and renewable. Moreover, recent progresses in polysaccharide chemistry and nanotechnologies allow elaborating new dedicated nanosystems. Polysaccharide-based nanosystems may be designed for interacting in several biological processes. In particular, the atherothrombotic pathology is highly concerned by polysaccharide-mediated recognition. Atherothrombotic diseases, regardless of the anatomical localization, remain the main causes of morbidity and mortality in the industrialized world. This review intends to provide an overview on polysaccharide-based nanosystems as drug delivery systems and targeted contrast agents for molecular imaging with an emphasis on the treatment and imaging of cardiovascular pathologies. PMID:24723980

  2. Vaccines and Immunization Practice.

    PubMed

    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.

  3. Rheological studies of polysaccharides for skin scaffolds.

    PubMed

    Almeida, Nalinda; Mueller, Anja; Hirschi, Stanley; Rakesh, Leela

    2014-05-01

    Polysaccharide hydrogels are good candidates for skin scaffolds because of their inherent biocompatibility and water transport properties. In the current study, hydrogels were made from a mixture of four polysaccharides: xanthan gum, konjac gum, iota-carrageenan, and kappa-carrageenan. Gel formation, strength, and structure of these polysaccharides were studied using rheological and thermal techniques. All gel samples studied were strong gels at all times because of the gradual water loss. However, after 12 h of storage, elastic (G') and loss (G'') moduli of hydrogel mixture containing all the ingredients is of one to two orders of magnitude greater than that of mixtures not containing either xanthan gum or iota-carrageenan, which confirmed the varied levels of gel strength. This is mainly due to the rate of water loss in each of these mixtures, resulting in gels of varying structures and dynamic moduli over a period of time. Iota-carrageenan and xanthan gum differ in their effect on gel strength and stability in combination with konjac gum and kappa-carrageenan.

  4. Marine Origin Polysaccharides in Drug Delivery Systems

    PubMed Central

    Cardoso, Matias J.; Costa, Rui R.; Mano, João F.

    2016-01-01

    Oceans are a vast source of natural substances. In them, we find various compounds with wide biotechnological and biomedical applicabilities. The exploitation of the sea as a renewable source of biocompounds can have a positive impact on the development of new systems and devices for biomedical applications. Marine polysaccharides are among the most abundant materials in the seas, which contributes to a decrease of the extraction costs, besides their solubility behavior in aqueous solvents and extraction media, and their interaction with other biocompounds. Polysaccharides such as alginate, carrageenan and fucoidan can be extracted from algae, whereas chitosan and hyaluronan can be obtained from animal sources. Most marine polysaccharides have important biological properties such as biocompatibility, biodegradability, and anti-inflammatory activity, as well as adhesive and antimicrobial actions. Moreover, they can be modified in order to allow processing them into various shapes and sizes and may exhibit response dependence to external stimuli, such as pH and temperature. Due to these properties, these biomaterials have been studied as raw material for the construction of carrier devices for drugs, including particles, capsules and hydrogels. The devices are designed to achieve a controlled release of therapeutic agents in an attempt to fight against serious diseases, and to be used in advanced therapies, such as gene delivery or regenerative medicine. PMID:26861358

  5. Iron oxyhydroxide mineralization on microbial extracellular polysaccharides

    SciTech Connect

    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.

  6. Marine Origin Polysaccharides in Drug Delivery Systems.

    PubMed

    Cardoso, Matias J; Costa, Rui R; Mano, João F

    2016-02-05

    Oceans are a vast source of natural substances. In them, we find various compounds with wide biotechnological and biomedical applicabilities. The exploitation of the sea as a renewable source of biocompounds can have a positive impact on the development of new systems and devices for biomedical applications. Marine polysaccharides are among the most abundant materials in the seas, which contributes to a decrease of the extraction costs, besides their solubility behavior in aqueous solvents and extraction media, and their interaction with other biocompounds. Polysaccharides such as alginate, carrageenan and fucoidan can be extracted from algae, whereas chitosan and hyaluronan can be obtained from animal sources. Most marine polysaccharides have important biological properties such as biocompatibility, biodegradability, and anti-inflammatory activity, as well as adhesive and antimicrobial actions. Moreover, they can be modified in order to allow processing them into various shapes and sizes and may exhibit response dependence to external stimuli, such as pH and temperature. Due to these properties, these biomaterials have been studied as raw material for the construction of carrier devices for drugs, including particles, capsules and hydrogels. The devices are designed to achieve a controlled release of therapeutic agents in an attempt to fight against serious diseases, and to be used in advanced therapies, such as gene delivery or regenerative medicine.

  7. Nanofiltration of polysaccharides from Agaricus subrufescens.

    PubMed

    Camelini, C M; Rezzadori, K; Benedetti, S; Proner, M C; Fogaça, L; Azambuja, A A; Giachini, A J; Rossi, M J; Petrus, J C C

    2013-12-01

    A simplified submerged airlift cultivation was established for the production of biomass from Agaricus subrufescens. In this work, soluble polysaccharides extracted from fungal mycelium, fruiting bodies, and the residual culture media were concentrated by nanofiltration. Total and high molar mass polysaccharides and soluble solids were determined in the concentrate for the three extracts. Additionally, the permeate flow, the influences of temperature and pressure, and the resistance to the permeate flow during filtration were also evaluated. Ayield of 5.5 g/L of biomass with 35%glucose conversion was obtained when 0.5 g/L of initial inoculum was employed. Average specific speed of growth was 0.4/day, with biomass productivity of about 0.76 g/(L day). Nanofiltration has yielded polysaccharide increases of 85, 82, and 92% in the extracts from fruiting bodies, mycelium, and liquid media, respectively. A reduction in the permeate flow was observed during filtration, and it was compensated by higher pressures and temperatures. The higher resistance to the permeate flux was caused by polarization due to concentration (polarized gel layer), reaching values of 88% for the culture media. Maximal resistance caused by the membrane reached values of 40% for the extract from the fruiting bodies. On the other hand, resistance caused by fouling was responsible for less than 3.5%. In conclusion, nanofiltration is efficient to concentrate these functional compounds extracted from A. subrufescens and can, therefore, be applied in different biotechnological areas.

  8. Evaluation of Phosphorylated Psyllium Seed Polysaccharide as a Release Retardant

    PubMed Central

    Rao, Monica R. P.; Warrier, Deepa U.; Rao, Shivani H.

    2015-01-01

    The aim of the present study was to modify psyllium seed polysaccharide and evaluate the modified polysaccharide as release retardant in tablets employing ciprofloxacin hydrochloride as model drug. Studies on polysaccharide from psyllium husk has been reported but no work has been reported on characterization and modification of the polysaccharide present in the psyllium (Plantago ovata) seed and the use of the modified polysaccharide as a release retardant in tablets. In this study, the seed gum was modified using sodium trimetaphosphate as crosslinking agent. Sustained release matrix tablets of ciprofloxacin hydrochloride were prepared by wet granulation using various drug-polymer ratios. The polymers investigated were psyllium polysaccharide, phosphorylated psyllium polysaccharide and widely used release retardant hydroxypropyl methylcellulose K100M. The tablets were evaluated for hardness, friability, drug content, swelling profile and in vitro dissolution studies. The matrix tablets containing 1:3 proportion of drug-phosphorylated psyllium polysaccharide was found to have higher hardness as compared to tablets containing 1:1 and 1:2 proportions. The results of swelling behavior in water showed that the tablets containing 1:3 drug:phosphorylated psyllium polysaccharide ratio had swelling comparable to that of tablets containing 1:3 drug:hydroxypropyl methylcellulose ratio. The in vitro dissolution studies shows that the dissolution rate was retarded from 98.41 to 37.6% in 6 h with increase in concentration of phosphorylated psyllium polysaccharide from 100 to 300 mg. Formulations containing psyllium polysaccharide showed complete drug release in 8 h whereas those formulated with phosphorylated psyllium polysaccharide exhibited extended drug release over the 12 h period. Drug release kinetic studies revealed that drug release followed Korsmeyer-Peppas model. PMID:26798177

  9. Universal fungal vaccines

    PubMed Central

    Hamad, Mawieh

    2012-01-01

    The complex nature of fungal pathogens, the intricate host-pathogen relationship and the health status of subjects in need of antifungal vaccination continue to hamper efforts to develop fungal vaccines for clinical use. That said, the rise of the universal vaccine concept is hoped to revive fungal vaccine research by expanding the pool of vaccine candidates worthy of clinical evaluation. It can do so through antigenic commonality-based screening for vaccine candidates from a wide range of pathogens and by reassessing the sizable collection of already available experimental and approved vaccines. Development of experimental vaccines protective against multiple fungal pathogens is evidence of the utility of this concept in fungal vaccine research. However, universal fungal vaccines are not without difficulties; for instance, development of vaccines with differential effectiveness is an issue that should be addressed. Additionally, rationalizing the development of universal fungal vaccines on health or economic basis could be contentious. Herein, universal fungal vaccines are discussed in terms of their potential usefulness and possible drawbacks. PMID:22922769

  10. Assignment of Weight-Based Antibody Units for Seven Additional Serotypes to a Human Pneumococcal Standard Reference Serum, 007sp.

    PubMed

    Goldblatt, D; Tan, C Y; Burbidge, P; McElhiney, S; McLaughlin, L; Tucker, R; Rauh, M; Sidhu, M; Giardina, P C

    2015-11-01

    The pneumococcal enzyme-linked immunosorbent assay (ELISA) reference standard serum, lot 89SF, has been in use since 1990 and was replaced in 2013 with a new reference standard, 007sp, that is projected to be available for the next 25 years. 007sp was generated under an FDA-approved clinical protocol; 278 adult volunteers were immunized with the 23-valent unconjugated polysaccharide vaccine Pneumovax II, and a unit of blood was obtained twice from each immunized subject within 120 days following immunization. Pooled serum was prepared from the plasma of 262 subjects, filled at 6 ml per vial, and lyophilized. Five independent laboratories participated in bridging the serotype-specific IgG assignments for 89SF to the new reference standard, 007sp, to establish equivalent reference values for 13 pneumococcal capsular serotypes (1,3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, and 23F) by using the WHO reference ELISA. In a second study involving three laboratories, a similar protocol was used to assign weight-based IgG concentrations in micrograms per ml to 007sp of seven serotypes (8, 10A, 11A, 12F, 15B, 22F, and 33F) also present in the 23-valent pneumococcal unconjugated polysaccharide vaccine. In addition, the IgG assignments for a 12-member WHO quality control (QC) serum panel were also extended to cover these seven serotypes. Agreement was excellent, with a concordance correlation coefficient (r(c)) of >0.996 when each laboratory was compared to the assigned values for the 12 WHO QC serum samples. There are four remaining pneumococcal serotypes (2, 9N, 17F, and 20) found in Pneumovax II for which IgG assignments exist for 89SF and remain to be bridged.

  11. Development of approaches to a third-generation carbohydrate-conjugate vaccine against Streptococcus pneumoniae: the search for optimal oligosaccharide ligands

    NASA Astrophysics Data System (ADS)

    Gening, M. L.; Kurbatova, E. A.; Tsvetkov, Yu E.; Nifantiev, N. E.

    2015-11-01

    The review addresses the application of synthetic oligosaccharides related to fragments of capsular polysaccharides from different serotypes of the bacterium Streptococcus pneumoniae for the design of third-generation pneumococcal conjugate vaccines. Special focus is given to characteristic features of the chemical structures of oligosaccharides required for the induction of the protective immune response when using synthetic glycoconjugate vaccines based on oligosaccharide ligands and carrier proteins. The bibliography includes 101 references.

  12. [Improvement on microwave technology of extracting polysaccharide from yacon leaves].

    PubMed

    Li, Jing-wei; Liu, Jian; Yang, Yong; Zheng, Ming-min; Rong, Ting-zhao

    2007-11-01

    According to the extraction ratio of polysaccharide in yacon leaves, the comparison between microwave extraction and traditional hot water extraction was conducted, and the two-factor and three-level experiment on the microwave extraction of polysaccharide from yacon leaves was investigated. The result showed that the extraction ratio of polysaccharide by using microwave extraction was better than that by using traditional hot water extraction. Moreover, according to the result of variance analysis and multiple comparison, the optimum conditions for extraction of polysaccharide by using microwave technology from yacon leaves were as follows: 280W microwave power for 2 times and 15 minutes at every time.

  13. Antibacterial and antiviral study of dialdehyde polysaccharides

    NASA Astrophysics Data System (ADS)

    Song, Le

    Concerns for microbial contamination and infection to the general population, especially the spread of drug-resistant microorganisms, have greatly increased. Polymeric biocides have been found to be a feasible strategy to inactivate drug-resistant bacteria. However, current polymeric biocide systems involve multi-step chemical reactions and they are not cost-effective. Desirable antimicrobial systems need to be designed to be environmentally friendly, broad-spectrum effective against microorganisms, flexible for various delivery methods and economically affordable. We demonstrated that dialdehyde polysaccharides (including dialdehyde starch and dialdehdye cellulose) were broad-spectrum polymeric biocides against gram-positive/negative bacteria, bacteriophages and human virus. These polymers can be easily converted from starch and cellulose through one-step periodate oxidation. Destructions of microorganism by dialdehyde polysaccharides have been achieved in aqueous suspension or by solid surface contact. The dialdehdye functions of dialdehdye polysaccharides were found to be the dominant action against microorganism. The reactivity of the dialdehyde functionality was found to be pH-dependent as well as related to the dispersion of dialdehyde polysaccharides. Degradation of dialdehyde starch during cooking was confirmed. Degradation of dialdehyde starch was more liable in alkaline condition. Carboxylic acid and conjugated aldehyde functionalities were the two main degradation products, confirmed from the spectroscopic studies. The pH effect on the polysaccharide structure and the corresponding antimicrobial activity was very complicated. No decisive conclusions could be obtained from this study. Liner inactivation kinetics was found for dialdehyde starch aqueous suspension against bacteria. This linear inactivation kinetics was derived from the pseudo-first chemical reaction between the dialdehyde starch and the bacteria. The established inactivation kinetics was

  14. Vaccine Safety Datalink

    Cancer.gov

    The Vaccine Safety Datalink is part of the National Immunization Program within the Centers for Disease Control and Prevention and was started in recognition of gaps in the scientific knowledge of rare vaccine side effects.

  15. Pneumococcal Vaccines (PCV, PPSV)

    MedlinePlus

    ... to 2-Year-Old Your Child's Immunizations: Pneumococcal Vaccines (PCV, PPSV) KidsHealth > For Parents > Your Child's Immunizations: ... or HIV infection); or cochlear implants. Why the Vaccines Are Recommended Children younger than 2 years old, ...

  16. Vaccines and Pregnancy

    MedlinePlus

    ... best live chat Live Help Fact Sheets Share Vaccines and Pregnancy Thursday, 01 September 2016 In every ... risk. This sheet talks about whether exposure to vaccines may increase the risk for birth defects over ...

  17. National Vaccine Program Office

    MedlinePlus

    ... Track Your Community Vaccine Safety Scientific Agenda Newsletter Sign Up Subscribe to newsletter updates for the latest information ... National Vaccine Program Office. Email Connect With NVPO Sign Up for NVPO Updates To sign up for updates ...

  18. China's emerging vaccine industry.

    PubMed

    Hendriks, Jan; Liang, Yan; Zeng, Bing

    2010-07-01

    The Chinese vaccine industry is developing rapidly due to an emerging and large market for current and new vaccines, a large potential for local vaccine manufacturing both in the public and private domain, and a governmental orientation towards national vaccine self-sufficiency. There are currently over 40 companies and institutions manufacturing a large variety of traditional (EPI) and some new vaccines. The innovative development capacity of state vaccine institutions is stimulated by significant government investments. Various Chinese influenza manufacturers were in 2009 among the first worldwide to obtain national license for their pandemic H1N1 flu vaccines. It is of interest to note that private but also governmental entities are committed to raise manufacturing quality standards to reach WHO prequalification. It is expected that WHO prequalification for at least one product from a Chinese manufacturer will have been obtained by 2011. This will open the door to the global market for Chinese vaccines.

  19. Live Virus Smallpox Vaccine

    MedlinePlus

    ... Submit What's this? Submit Button The Live Virus Smallpox Vaccine Language: English Español (Spanish) Recommend on Facebook ... the vaccinia virus. Who should NOT get the smallpox vaccine? People most likely to have side effects ...

  20. Screening Tests and Vaccines

    MedlinePlus

    ... Contact Us Text size | Print | Screening Tests and Vaccines This information in Spanish ( en español ) Getting important screening tests and vaccines can save your life. Check this section of ...

  1. The HPV Vaccination Crisis

    Cancer.gov

    Following the release of a consensus statement from the NCI-Designated Cancer Centers urging HPV vaccination in the United States, Dr. Noel Brewer discusses the country’s low vaccination rates and how clinicians can help to improve them.

  2. Clinical vaccine development

    PubMed Central

    2015-01-01

    Vaccination is regarded as one of the biggest triumphs in the history of medicine. We are living in the most successful period of vaccine development. The accumulation of multidisciplinary knowledge and the investment of massive funding have enabled the development of vaccines against many infectious diseases as well as other diseases including malignant tumors. The paradigm of clinical vaccine evaluation and licensure has also been modernized based on scientific improvements and historical experience. However, there remain a number of hurdles to overcome. Continuous efforts are focused on increasing the efficacy and reducing the risks related to vaccine use. Cutting-edge knowledge about immunology and microbiology is being rapidly translated to vaccine development. Thus, physicians and others involved in the clinical development of vaccines should have sufficient understanding of the recent developmental trends in vaccination and the diseases of interest. PMID:25648742

  3. Vaccines in Multiple Sclerosis.

    PubMed

    Williamson, Eric M L; Chahin, Salim; Berger, Joseph R

    2016-04-01

    Vaccinations help prevent communicable disease. To be valuable, a vaccine's ability to prevent disease must exceed the risk of adverse effects from administration. Many vaccines present no risk of infection as they are comprised of killed or non-infectious components while other vaccines consist of live attenuated microorganisms which carry a potential risk of infection-particularly, in patients with compromised immunity. There are several unique considerations with respect to vaccination in the multiple sclerosis (MS) population. First, there has been concern that vaccination may trigger or aggravate the disease. Second, disease-modifying therapies (DMTs) employed in the treatment of MS may increase the risk of infectious complications from vaccines or alter their efficacy. Lastly, in some cases, vaccination strategies may be part of the treatment paradigm in attempts to avoid complications of therapy.

  4. Vaccines against malaria.

    PubMed

    Ouattara, Amed; Laurens, Matthew B

    2015-03-15

    Despite global efforts to control malaria, the illness remains a significant public health threat. Currently, there is no licensed vaccine against malaria, but an efficacious vaccine would represent an important public health tool for successful malaria elimination. Malaria vaccine development continues to be hindered by a poor understanding of antimalarial immunity, a lack of an immune correlate of protection, and the genetic diversity of malaria parasites. Current vaccine development efforts largely target Plasmodium falciparum parasites in the pre-erythrocytic and erythrocytic stages, with some research on transmission-blocking vaccines against asexual stages and vaccines against pregnancy-associated malaria. The leading pre-erythrocytic vaccine candidate is RTS,S, and early results of ongoing Phase 3 testing show overall efficacy of 46% against clinical malaria. The next steps for malaria vaccine development will focus on the design of a product that is efficacious against the highly diverse strains of malaria and the identification of a correlate of protection against disease.

  5. Mathematical models of vaccination.

    PubMed

    Scherer, Almut; McLean, Angela

    2002-01-01

    Mathematical models of epidemics have a long history of contributing to the understanding of the impact of vaccination programmes. Simple, one-line models can predict target vaccination coverage that will eradicate an infectious agent, whilst other questions require complex simulations of stochastic processes in space and time. This review introduces some simple ordinary differential equation models of mass vaccination that can be used to address important questions about the predicted impact of vaccination programmes. We show how to calculate the threshold vaccination coverage rate that will eradicate an infection, explore the impact of vaccine-induced immunity that wanes through time, and study the competitive interactions between vaccine susceptible and vaccine resistant strains of infectious agent.

  6. Evaluation of adjuvant effects of fucoidan for improving vaccine efficacy.

    PubMed

    Kim, Su-Yeon; Joo, Hong-Gu

    2015-01-01

    Fucoidan is a sulfated polysaccharide derived from brown seaweed, including Fucus vesiculosus. This compound is known to have immunostimulatory effects on various types of immune cells including macrophages and dendritic cells. A recent study described the application of fucoidan as a vaccine adjuvant. Vaccination is regarded as the most efficient prophylactic method for preventing harmful or epidemic diseases. To increase vaccine efficacy, effective adjuvants are needed. In the present study, we determined whether fucoidan can function as an adjuvant using vaccine antigens. Flow cytometric analysis revealed that fucoidan increases the expression of the activation markers major histocompatibility complex class II, cluster of differentiation (CD)25, and CD69 in spleen cells. In combination with Bordetella bronchiseptica antigen, fucoidan increased the viability and tumor necrosis factor-α production of spleen cells. Furthermore, fucoidan increased the in vivo production of antigen-specific antibodies in mice inoculated with Mycoplasma hyopneumoniae antigen. Overall, this study has provided valuable information about the use of fucoidan as a vaccine adjuvant.

  7. Status of vaccine research and development for Campylobacter jejuni.

    PubMed

    Riddle, Mark S; Guerry, Patricia

    2016-06-03

    Campylobacter jejuni is one of the leading causes of bacterial diarrhea worldwide and is associated with a number of sequelae, including Guillain-Barre Syndrome, reactive arthritis, irritable bowel syndrome and growth stunting/malnutrition. Vaccine development against C. jejuni is complicated by its antigenic diversity, a lack of small animal models, and a poor understanding of the bacterium's pathogenesis. Vaccine approaches have been limited to recombinant proteins, none of which have advanced beyond Phase I testing. Genomic analyses have revealed the presence of a polysaccharide capsule on C. jejuni. Given the success of capsule-conjugate vaccines for other mucosal pathogens of global importance, efforts to evaluate this established approach for C. jejuni are also being pursued. A prototypical capsule-conjugate vaccine has demonstrated efficacy against diarrheal disease in non-human primates and is currently in Phase I testing. In addition to proof of concept studies, more data on the global prevalence of capsular types, and a better understanding of the acute and chronic consequences of C. jejuni are needed to inform investments for a globally relevant vaccine.

  8. Ongoing pharmacovigilance on vaccines.

    PubMed

    Santuccio, Carmela; Trotta, Francesco; Felicetti, Patrizia

    2015-02-01

    Vaccines have peculiar characteristics as well as their surveillance. Specific requirements, needs and challenges for the vaccine vigilance are discussed in the perspective to improve the whole system in order to guarantee a safer vaccine use and the keeping of the public confidence in vaccinations. Key elements for the routine safety monitoring, new regulations and some available tools are taken into account. Finally, the Italian experience is shortly described.

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

    PubMed

    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.

  10. Vaccine against herpes zoster.

    PubMed

    Pasternak, Jacyr

    2013-01-01

    The herpes zoster vaccine is made using high doses of live attenuated varicella/zoster virus. The vaccine is well tolerated and has few adverse effects: the most common one is pain at the injection site. Complications can occur mainly in persons who had prior zoster keratitis or uveitis. The vaccine can prevent this disease with low mortality but high morbidity.

  11. [Improving vaccination measures].

    PubMed

    Iannazzo, S

    2014-01-01

    Despite the benefits of routine vaccination of newborns are known and widely documented, in recent years we are observing a gradual increase in the number of parents who express doubts and concerns about the safety of vaccines and the real need to submit their children to vaccinations included in the national recommendations. This attitude is reinforced by the current epidemiological profile, in Western countries, of many vaccine preventable diseases, accompanied by a low risk perception among parents. Institutions and all the actors involved in vaccination programs have a duty to investigate the reasons for the loss of confidence in vaccination among the population in order to identify and implement appropriate and effective interventions. The improvement of vaccination should, theoretically, goes on a double track, placing side by side the provision of effective vaccines, safe and necessary, and interventions designed to increase demand for vaccination among the population, improve access to vaccination services, improve the system as a whole. But to actually improve the vaccinations' offer it is necessary also to provide interventions aimed at regaining the confidence of the population in relation to vaccination and the institutions that promote them. Particular attention should be given to the aspects of communication and risk communication.

  12. Yellow Fever Vaccine

    MedlinePlus

    What is yellow fever?Yellow fever is a serious disease caused by the yellow fever virus. It is found in certain parts of Africa ... How can I prevent yellow fever?Yellow fever vaccine can prevent yellow fever. ... only at designated vaccination centers. After getting the vaccine, you ...

  13. A Dengue Vaccine.

    PubMed

    Durbin, Anna P

    2016-06-30

    Denvaxia is the first licensed vaccine for the prevention of dengue. It is a live vaccine developed using recombinant DNA technology. The vaccine is given as three doses over the course of a year and has the potential to prevent hundreds of thousands of hospitalizations each year.

  14. Dengue vaccines for travelers.

    PubMed

    Wilder-Smith, Annelies; Deen, Jacqueline L

    2008-07-01

    Dengue is an arthropod-borne infection caused by a flavivirus and spread by the Aedes mosquitoes. Many of the countries where dengue is endemic are popular tourist destinations and the disease is an increasingly important problem encountered by international travelers. Personal protection against the day-feeding dengue vectors is problematic, indicating the urgent need for a dengue vaccine. This review discusses the challenges of vaccine development, current vaccine strategies and the prospects for the availability of a vaccine for travelers in the future. Cost-effectiveness studies will need to take into account many factors, including the attack rate of dengue in travelers, the proportion of travelers who will need hospitalization, the cost of altered travel itineraries, the cost of the vaccine, duration of travel, destination and season. To be licensed as a travelers' vaccine, vaccine trials must address safety, immunogenicity, duration of protection, schedules and boosters in adults (in particular in immunologically naive adults), trials that may differ from those conducted in endemic countries. Vaccine schedules with long intervals would be a major obstacle to the uptake of the vaccine by travelers. Enhanced reactogenicity or interference with immunization must be effectively excluded for travelers with prior or concurrent vaccination against other flaviviruses, such as yellow fever or Japanese encephalitis. Licensing dengue as a travelers' vaccine poses unique challenges beyond the development of a vaccine for the endemic population.

  15. Immunomodulatory dietary polysaccharides: a systematic review of the literature

    PubMed Central

    2010-01-01

    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 mushroom improved survival and

  16. Compared effectiveness of the 7-valent pneumococcal conjugate vaccine in children with the 13-valent vaccine in adults.

    PubMed

    Gaillat, J

    2013-06-01

    13-valent-pneumococcal conjugated vaccine was recently approved in the USA and Europe for adults 50 years of age or more. But this approval was followed by recommendations limiting its use to immunocompromised and asplenic patients. The extension of indications to adults was based on the well-demonstrated clinical effectiveness in infants less than 2 years of age, and on a better immune response either quantitatively or qualitatively with conjugated vaccines compared to the immunogenicity of plain polysaccharide vaccines. Nevertheless, the issue was to know whether results observed with the 7-valent pneumococcal conjugate vaccine in children are reproducible in adults with the 13-valent. The answer was given by comparing the epidemiological and physiopathological data, and the immunological response of the two populations. Very few clinical effectiveness studies in adults are available. We had for aim to assess these various issues in infants and adults. A lot of questions remain, such as the unknown impact of serotype replacement with the 13-valent pneumococcal conjugated vaccine on the clinical epidemiology and emergent Streptococcus pneumoniae pathogenicity, while waiting for the CAPITA study results expected in 2014.

  17. Improving newcastle disease vaccination with homologous vaccines

    Technology Transfer Automated Retrieval System (TEKTRAN)

    All Newcastle disease viruses (NDVs) belong to a single serotype; however, current vaccine strains display important amino acid differences at the F and HN protein compared with virulent outbreak strains (vNDV). Previous studies have shown decreased viral shedding after challenge when vaccines were...

  18. Antigenicity and immunogenicity of a synthetic oligosaccharide-protein conjugate vaccine against Haemophilus influenzae type b.

    PubMed

    Fernández-Santana, V; Cardoso, Félix; Rodriguez, Arlene; Carmenate, Tania; Peña, Luis; Valdés, Yuri; Hardy, Eugenio; Mawas, Fatme; Heynngnezz, Lazaro; Rodríguez, Maria C; Figueroa, Ignacio; Chang, Janoi; Toledo, Maria E; Musacchio, Alexis; Hernández, Ibis; Izquierdo, Mabel; Cosme, Karelia; Roy, Rene; Verez-Bencomo, V

    2004-12-01

    Polysaccharide-protein conjugates as vaccines have proven to be very effective in preventing Haemophilus influenzae type b infections in industrialized countries. However, cost-effective technologies need to be developed for increasing the availability of anti-H. influenzae type b vaccines in countries from the developing world. Consequently, vaccine production with partially synthetic antigens is a desirable goal for many reasons. They may be rigidly controlled for purity and effectiveness while at the same time being cheap enough that they may be made universally available. We describe here the antigenicity and immunogenicity of several H. influenzae type b synthetic oligosaccharide-protein conjugates in laboratory animals. The serum of H. influenzae type b-immunized animals recognized our synthetic H. influenzae type b antigens to the same extent as the native bacterial capsular polysaccharide. Compared to the anti-H. influenzae type b vaccine employed, these synthetic versions induced similar antibody response patterns in terms of titer, specificity, and functional capacity. The further development of synthetic vaccines will meet urgent needs in the less prosperous parts of the world and remains our major goal.

  19. Importance of vaccination habit and vaccine choice on influenza vaccination among healthy working adults.

    PubMed

    Lin, Chyongchiou J; Nowalk, Mary Patricia; Toback, Seth L; Rousculp, Matthew D; Raymund, Mahlon; Ambrose, Christopher S; Zimmerman, Richard K

    2010-11-10

    This randomized cluster trial was designed to improve workplace influenza vaccination rates using enhanced advertising, choice of vaccine type (intranasal or injectable) and an incentive. Workers aged 18-49 years were surveyed immediately following vaccination to determine factors associated with vaccination behavior and choice. The questionnaire assessed attitudes, beliefs and social support for influenza vaccine, demographics, and historical, current, and intentional vaccination behavior. Of the 2389 vaccinees, 83.3% received injectable vaccine and 16.7% received intranasal vaccine. Factors associated with previous influenza vaccination were older age, female sex, higher education and greater support for injectable vaccine (all P<.02). Current influenza vaccination with intranasal vaccine vs. injectable vaccine was associated with higher education, the study interventions, greater support for the intranasal vaccine and nasal sprays, less support of injectable vaccine, more negative attitudes about influenza vaccine, and a greater likelihood of reporting that the individual would not have been vaccinated had only injectable vaccine been offered (all P<.01). Intentional vaccine choice was most highly associated with previous vaccination behavior (P<.001). A key to long term improvements in workplace vaccination is to encourage first time influenza vaccination through interventions that include incentives, publicity and vaccine choice.

  20. Advisory committee on immunization practices recommended immunization schedule for adults aged 19 years or older--United States, 2015.

    PubMed

    Kim, David K; Bridges, Carolyn B; Harriman, Kathleen H

    2015-02-06

    In October 2014, the Advisory Committee on Immunization Practices (ACIP) approved the Recommended Immunization Schedule for Adults Aged 19 Years or Older, United States, 2015. This schedule provides a summary of ACIP recommendations for the use of vaccines routinely recommended for adults aged 19 years or older in two figures, footnotes for each vaccine, and a table that describes primary contraindications and precautions for commonly used vaccines for adults. Changes in the 2015 adult immunization schedule from the 2014 schedule included the August 2014 recommendation for routine administration of the 13-valent pneumococcal conjugate vaccine (PCV13) in series with the 23-valent pneumococcal polysaccharide vaccine (PPSV23) for all adults aged 65 years or older, the August 2014 revision on contraindications and precautions for the live attenuated influenza vaccine (LAIV), and the October 2014 approval by the Food and Drug Administration to expand the approved age for use of recombinant influenza vaccine (RIV). These revisions were also reviewed and approved by the American College of Physicians, American Academy of Family Physicians, American College of Obstetricians and Gynecologists, and American College of Nurse-Midwives.

  1. Solomonseal Polysaccharide and Sulfated Codonopsis pilosula Polysaccharide Synergistically Resist Newcastle Disease Virus

    PubMed Central

    Liu, Cui; Chen, Jin; Li, Entao; Fan, Qiang; Wang, Deyun; Zhang, Cunshuai; Li, Peng; Li, Xiuping; Chen, Xingying; Qiu, Shulei; Gao, Zhenzhen; Li, Hongquan; Hu, Yuanliang

    2015-01-01

    Five combinations of three ratios (PS9-sPS1, PS7-sPS3 and PS6-sPS4) were prepared with polysaccharide (PS) and sulfated polysaccharide (sPS). The antiviral activities of these compounds were subsequently compared in vitro using the MTT assay, observation of the virus structure and immunofluorescence. The results demonstrated that SP9-sCP1, CP7-sCA3, EP7-sAP3, CA9-sEP1 and EP7-sCA3 presented higher activities, and SP9-sCP1 displayed the highest virus inhibition rate and clearly killed the virus and inhibited viral antigen expression. In an in vivo test, 28-day-old chickens were challenged with Newcastle disease virus (NDV) and were administered the five drug combinations. On day 14 after the challenge, the morbidity, mortality and cure rate in each group were calculated. The results indicated that SP9-sCP1 presented the lowest morbidity and mortality and the highest cure rate. These results indicate that Solomonseal polysaccharide and sulfated Codonopsis pilosula polysaccharide synergistically resist NDV. Moreover, SP9-sCP1 had the highest efficacy and may be used as a new antiviral drug. PMID:25692886

  2. A cryptococcal capsular polysaccharide mimotope prolongs the survival of mice with Cryptococcus neoformans infection.

    PubMed

    Fleuridor, R; Lees, A; Pirofski, L

    2001-01-15

    Defined Abs to the Cryptococcus neoformans capsular polysaccharide glucuronoxylomannan (GXM) have been shown to be protective against experimental cryptococcosis. This suggests that if a vaccine could induce similar Abs it might protect against infection. However, the potential use of a GXM-based vaccine has been limited by evidence that GXM is a poor immunogen that can induce nonprotective and deleterious, as well as protective, Abs, and that the nature of GXM oligosaccharide epitopes that can elicit a protective response is unknown. In this study, we investigated whether a peptide surrogate for a GXM epitope could induce an Ab response to GXM in mice. The immunogenicity of peptide-protein conjugates produced by linking a peptide mimetic of GXM, P13, to either BSA, P13-BSA, or tetanus toxoid, P13-tetanus toxoid, was examined in BALB/c and CBA/n mice that received four s.c. injections of the conjugates at 14- to 30-day intervals. All mice immunized with conjugate produced IgM and IgG to P13 and GXM. Challenge of conjugate-immunized mice with C. neoformans revealed longer survival and lower serum GXM levels than control mice. These results indicate that 1) P13 is a GXM mimotope and 2) that it induced a protective response against C. neoformans in mice. P13 is the first reported mimotope of a C. neoformans Ag. Therefore, the P13 conjugates are vaccine candidates for C. neoformans and their efficacy in this study suggests that peptide mimotopes selected by protective Abs deserve further consideration as vaccine candidates for encapsulated pathogens.

  3. Study of various presentation forms for a peptide mimetic of Neisseria meningitidis serogroup B capsular polysaccharide.

    PubMed

    Garay, Hilda; Menéndez, Tamara; Cruz-Leal, Yoelys; Coizeau, Edelgis; Noda, Jesus; Morera, Vivian; Guillén, Gerardo; Albericio, Fernando; Reyes, Osvaldo

    2011-01-19

    The formulation of a broadly protective vaccine to prevent the serogroup B Neisseria meningitidis (MenB) disease is still an unmet medical need. We have previously reported the induction of bactericidal and protective antibodies against MenB after immunization of mice with a phage-displayed peptide named 4 L-5. This peptide mimics a capsular polysaccharide (CPS) epitope in MenB. With the aim of developing vaccine formulations that could be used in humans, we evaluate in this study various forms of presentation to the immune system of the 4 L-5 sequence, based on synthetic peptides. We synthesized the following: (i) a linear 4 L-5 peptide, (ii) a multiple antigen peptide containing four copies of the 4 L-5 sequence (named MAP), which was then dimerized, and the product named dimeric MAP, and (iii) a second multiple antigen peptide, in this case with two copies of the 4 L-5 sequence and a copy of a T-helper cell epitope of tetanus toxoid, which was then dimerized and the product named MAP-TT. The linear peptide, the MAP, and the dimeric MAP were conjugated to the carrier protein P64K by different conjugation methods. Plain antigens and antigens coupled to P64K were used to immunize BALB/c mice. Of those variants that gave immunogenic results, MAP-TT rendered the highest levels of specific antipeptide IgG antibodies and serum bactericidal activity. These results can find application in the development of meningococcal vaccine candidates and in peptide-based vaccines strategies.

  4. Brucellosis vaccines for livestock.

    PubMed

    Goodwin, Zakia I; Pascual, David W

    2016-11-15

    Brucellosis is a livestock disease responsible for fetal loss due to abortions. Worldwide, this disease has profound economic and social impact by reducing the ability of livestock producers to provide an adequate supply of disease-free meat and dairy products. In addition to its presence in domesticated animals, brucellosis is harbored in a number of wildlife species creating new disease reservoirs, which adds to the difficulty of eradicating this disease. Broad and consistent use of the available vaccines would contribute in reducing the incidence of brucellosis. Unfortunately, this practice is not common. In addition, the current brucellosis vaccines cannot provide sterilizing immunity, and in certain circumstances, vaccinated livestock are not protected against co-mingling Brucella-infected wildlife. Given that these vaccines are inadequate for conferring complete protection for some vaccinated livestock, alternatives are being sought, and these include genetic modifications of current vaccines or their reformulations. Alternatively, many groups have sought to develop new vaccines. Subunit vaccines, delivered as a combination of soluble vaccine plus adjuvant or the heterologous expression of Brucella epitopes by different vaccine vectors are currently being tested. New live attenuated Brucella vaccines are also being developed and tested in their natural hosts. Yet, what is rarely considered is the route of vaccination which could improve vaccine efficacy. Since Brucella infections are mostly transmitted mucosally, mucosal delivery of a vaccine has the potential of eliciting a more robust protective immune response for improved efficacy. Hence, this review will examine these questions and provide the status of new vaccines for livestock brucellosis.

  5. Diagnostic and vaccine chapter.

    PubMed

    Wolfram, J H; Kokanov, S K; Verkhovsky, O A

    2010-10-01

    The first report in this chapter describes the development of a killed composite vaccine. This killed vaccine is non-infectious to humans, other animals, and the environment. The vaccine has low reactivity, is non-abortive, and does not induce pathomorphological alterations to the organs of vaccinated animals. The second report of this chapter describes the diagnostic value of a competitive enzyme-linked immunosorbent assay for detecting Brucella-specific antibodies and its ability to discriminate vaccinated cattle from infected cattle. The results indicated that the competitive enzyme-linked immunosorbent assay is more sensitive than traditional tests for detecting antibodies to Brucella abortus in naturally and experimentally infected cattle.

  6. Patenting malarial vaccine.

    PubMed

    Wiwanitkit, Viroj

    2008-01-01

    Malaria is an important tropical infection affecting millions of world population each year. Malarial vaccine development is the hope for successful control of malaria. Knowledge on malaria vaccine has been considered patentable subject for decades. Due to the present advance biotechnology, the number of patent applications related to malarial vaccine is growing exponentially. Several malarial vaccine candidates have been recently identified and the genetic manipulation of these candidates is becoming more efficient with the advancement of new biotechnologies. This review summarizes some of the recent published patents on malarial vaccines covering antigens, candidate epitopes and recombinant processing.

  7. Vaccination for Disease

    NASA Astrophysics Data System (ADS)

    Oehen, Stephan; Hengartner, Hans; Zinkernagel, Rolf M.

    1991-01-01

    Recombinant virus vaccines that express a limited number of epitopes are currently being developed to prevent disease by changing the relative balance between viral spread and the immune response. Some circumstances, however, were found in infections with a noncytopathic virus in which vaccination caused disease; sensitive parameters included the genetic background of the host, the time or dose of infection, and the constituents of the vaccine. Thus, immunopathologic damage by T cells may be an unwanted consequence of vaccination with the new types of peptide or recombinant vaccines that are being investigated for the human immunodeficiency viruses and other pathogens.

  8. Macrophage immunomodulatory activity of polysaccharides isolated from Opuntia polyacantha

    PubMed Central

    Schepetkin, Igor A.; Xie, Gang; Kirpotina, Liliya N.; Klein, Robyn A.; Jutila, Mark A.; Quinn, Mark T.

    2008-01-01

    Opuntia polyacantha (prickly pear cactus) has been used extensively for its nutritional properties; however, less is known regarding medicinal properties of Opuntia tissues. In the present study, we extracted polysaccharides from O. polyacantha and used size-exclusion chromatography to fractionate the crude polysaccharides into four polysaccharide fractions (designated as Opuntia polysaccharides C-I to C-IV). The average Mr of fractions C-I through C-IV was estimated to be 733, 550, 310, and 168 kDa, respectively, and sugar composition analysis revealed that Opuntia polysaccharides consisted primarily of galactose, galacturonic acid, xylose, arabinose, and rhamnose. Analysis of the effects of Opuntia polysaccharides on human and murine macrophages demonstrated that all four fractions had potent immunomodulatory activity, inducing production of reactive oxygen species, nitric oxide, tumor necrosis factor α, and interleukin 6. Furthermore, modulation of macrophage function by Opuntia polysaccharides was mediated, at least in part, through activation of nuclear factor κB. Together, our results provide a molecular basis to explain a portion of the beneficial therapeutic properties of extracts from O. polyacantha and support the concept of using Opuntia polysaccharides as an immunotherapeutic adjuvant. PMID:18597716

  9. Bacterial Extracellular Polysaccharides in Biofilm Formation and Function

    PubMed Central

    Limoli, Dominique H.; Jones, Christopher J.; Wozniak, Daniel J.

    2015-01-01

    Microbes produce a biofilm matrix consisting of proteins, extracellular DNA, and polysaccharides that is integral in the formation of bacterial communities. Historical studies of polysaccharides revealed that their overproduction often alters the colony morphology and can be diagnostic in identifying certain species. The polysaccharide component of the matrix can provide many diverse benefits to the cells in the biofilm, including adhesion, protection, and structure. Aggregative polysaccharides act as molecular glue, allowing the bacterial cells to adhere to each other as well as surfaces. Adhesion facilitates the colonization of both biotic and abiotic surfaces by allowing the bacteria to resist physical stresses imposed by fluid movement that could separate the cells from a nutrient source. Polysaccharides can also provide protection from a wide range of stresses, such as desiccation, immune effectors, and predators such as phagocytic cells and amoebae. Finally, polysaccharides can provide structure to biofilms, allowing stratification of the bacterial community and establishing gradients of nutrients and waste products. This can be advantageous for the bacteria by establishing a heterogeneous population that is prepared to endure stresses created by the rapidly changing environments that many bacteria encounter. The diverse range of polysaccharide structures, properties, and roles highlight the importance of this matrix constituent to the successful adaptation of bacteria to nearly every niche. Here, we present an overview of the current knowledge regarding the diversity and benefits that polysaccharide production provides to bacterial communities within biofilms. PMID:26185074

  10. Macrophage immunomodulatory activity of polysaccharides isolated from Opuntia polyacantha.

    PubMed

    Schepetkin, Igor A; Xie, Gang; Kirpotina, Liliya N; Klein, Robyn A; Jutila, Mark A; Quinn, Mark T

    2008-10-01

    Opuntia polyacantha (prickly pear cactus) has been used extensively for its nutritional properties; however, less is known regarding medicinal properties of Opuntia tissues. In the present study, we extracted polysaccharides from O. polyacantha and used size-exclusion chromatography to fractionate the crude polysaccharides into four polysaccharide fractions (designated as Opuntia polysaccharides C-I to C-IV). The average M(r) of fractions C-I through C-IV was estimated to be 733, 550, 310, and 168 kDa, respectively, and sugar composition analysis revealed that Opuntia polysaccharides consisted primarily of galactose, galacturonic acid, xylose, arabinose, and rhamnose. Analysis of the effects of Opuntia polysaccharides on human and murine macrophages demonstrated that all four fractions had potent immunomodulatory activity, inducing production of reactive oxygen species, nitric oxide, tumor necrosis factor alpha, and interleukin 6. Furthermore, modulation of macrophage function by Opuntia polysaccharides was mediated, at least in part, through activation of nuclear factor kappaB. Together, our results provide a molecular basis to explain a portion of the beneficial therapeutic properties of extracts from O. polyacantha and support the concept of using Opuntia polysaccharides as an immunotherapeutic adjuvant.

  11. In vitro antioxidant activity of polysaccharide from Gardenia jasminoides ellis

    USGS Publications Warehouse

    Fan, Y.; Ge, Z.; Luo, A.

    2011-01-01

    A water-soluble polysaccharide, GP, was isolated from Gardenia jasminoides Ellis through hot water extraction followed by ethanol precipitation. The in vitro free radicals scavenging tests exhibited that GP has significant scavenging abilities especially for ABTS, DPPH, and hydroxyl radicals, which suggests that the polysaccharide GP is a novel antioxidant. ?? 2011 Academic Journals.

  12. Structural modification of polysaccharides: A biochemical-genetic approach

    NASA Technical Reports Server (NTRS)

    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.

  13. Nasal immunization of mice with AFCo1 or AFPL1 plus capsular polysaccharide Vi from Salmonella typhi induces cellular response and memory B and T cell responses.

    PubMed

    Romeu, Belkis; Lastre, Miriam; Reyes, Laura; González, Elizabeth; Borrero, Yusnaby; Lescaille, Diandra; Pérez, Rocmira; Nuñez, Darzy; Pérez, Oliver

    2014-12-05

    The response to infection against Salmonella involves both B and T cell mediated immunity. An effective immunization can activate an adequate immune response capable to control the primary infection and protect against a secondary infection. Mucosal vaccination, by inducing local pathogen-specific immune responses, has the potential to counter mucosally transmitted pathogens at the portal of entry, thereby increasing the efficacy of vaccines. The aim of this work was to explore the efficacy of AFCo1 or AFPL1, as mucosal adjuvants to stimulate cell immunity and memory responses against Vi polysaccharide antigen of Salmonella typhi (PsVi). Mice immunized with 3 intranasal doses exhibited high levels of PsVi-specific IgG (p<0.05), IgG2a and IgG2c subclasses. Also, an amplified recall response after a booster immunization with a plain polysaccharide vaccine was induced. Avidities index were higher in mice immunized with adjuvanted formulations at different chaotropic concentrations. Furthermore, IL-12 and IFN-γ levels in nasally vaccinated mice with both adjuvants were induced. Moreover, priming with 3 doses followed by booster immunization with VaxTyVi(®) resulted in high levels of anti-Vi specific IgG, IgG subclasses and antibody avidity. Long lived plasma cells in bone marrow, memory B cells and long-term memory T cells after booster dose were induced. The combined formulation of Vi polysaccharide with mucosal adjuvants provides an improved immunogenicity, in particular with regard to cellular responses and long lasting cells responses.

  14. Methods of saccharification of polysaccharides in plants

    DOEpatents

    Howard, John; Fake, Gina

    2014-04-29

    Saccharification of polysaccharides of plants is provided, where release of fermentable sugars from cellulose is obtained by adding plant tissue composition. Production of glucose is obtained without the need to add additional .beta.-glucosidase. Adding plant tissue composition to a process using a cellulose degrading composition to degrade cellulose results in an increase in the production of fermentable sugars compared to a process in which plant tissue composition is not added. Using plant tissue composition in a process using a cellulose degrading enzyme composition to degrade cellulose results in decrease in the amount of cellulose degrading enzyme composition or exogenously applied cellulase required to produce fermentable sugars.

  15. (Lipo)polysaccharide interactions of antimicrobial peptides.

    PubMed

    Schmidtchen, Artur; Malmsten, Martin

    2015-07-01

    Due to rapidly increasing resistance development against conventional antibiotics, as well as problems associated with diseases either triggered or deteriorated by infection, antimicrobial and anti-inflammatory peptides have attracted considerable interest during the last few years. While there is an emerging understanding of the direct antimicrobial function of such peptides through bacterial membrane destabilization, the mechanisms of their anti-inflammatory function are less clear. We here summarize some recent results obtained from our own research on anti-inflammatory peptides, with focus on peptide-(lipo)polysaccharide interactions.

  16. Gut microbiota, host health, and polysaccharides.

    PubMed

    Xu, Xiaofei; Xu, Pingping; Ma, Chungwah; Tang, Jian; Zhang, Xuewu

    2013-01-01

    The intestinal microbiota is a complicated ecosystem that influences many aspects of host physiology (i.e. diet, disease development, drug metabolism, and regulation of the immune system). It also exhibits spatial patterning and temporal dynamics. In this review, the effects of internal and external (environmental) factors on intestinal microbiota are discussed. We describe the roles of the gut microbiota in maintaining intestinal and immune system homeostasis and the relationship between gut microbiota and diseases. In particular, the contributions of polysaccharides, as the most abundant diet components in intestinal microbiota and host health are presented. Finally, perspectives for research avenues relating to gut microbiota are also discussed.

  17. E. coli Group 1 Capsular Polysaccharide Exportation Nanomachinary as a Plausible Antivirulence Target in the Perspective of Emerging Antimicrobial Resistance

    PubMed Central

    Sachdeva, Shivangi; Palur, Raghuvamsi V.; Sudhakar, Karpagam U.; Rathinavelan, Thenmalarchelvi

    2017-01-01

    Bacteria evolving resistance against the action of multiple drugs and its ability to disseminate the multidrug resistance trait(s) across various strains of the same bacteria or different bacterial species impose serious threat to public health. Evolution of such multidrug resistance is due to the fact that, most of the antibiotics target bacterial survival mechanisms which exert selective pressure on the bacteria and aids them to escape from the action of antibiotics. Nonetheless, targeting bacterial virulence strategies such as bacterial surface associated polysaccharides biosynthesis and their surface accumulation mechanisms may be an attractive strategy, as they impose less selective pressure on the bacteria. Capsular polysaccharide (CPS) or K-antigen that is located on the bacterial surface armors bacteria from host immune response. Thus, unencapsulating bacteria would be a good strategy for drug design, besides CPS itself being a good vaccine target, by interfering with CPS biosynthesis and surface assembly pathway. Gram-negative Escherichia coli uses Wzy-polymerase dependent (Groups 1 and 4) and ATP dependent (Groups 1 and 3) pathways for CPS production. Considering E. coli as a case in point, this review explains the structure and functional roles of proteins involved in Group 1 Wzy dependent CPS biosynthesis, surface expression and anchorage in relevance to drug and vaccine developments. PMID:28217109

  18. Immune adjuvant effect of V. cholerae O1 derived Proteoliposome coadministered by intranasal route with Vi polysaccharide from Salmonella Typhi.

    PubMed

    Acevedo, Reinaldo; Callicó, Adriana; Aranguren, Yisabel; Zayas, Caridad; Valdés, Yolanda; Pérez, Oliver; García, Luis; Ferro, Valerie A; Pérez, José Luis

    2013-01-01

    The proteoliposome derived from Vibrio cholerae O1 (PLc) is a nanoscaled structure obtained by a detergent extraction process. Intranasal (i.n) administration of PLc was immunogenic at mucosal and systemic level vs. V. cholerae; however the adjuvant potential of this structure for non-cholera antigens has not been proven yet. The aim of this work was to evaluate the effect of coadministering PLc with the Vi polysaccharide antigen (Poli Vi) of S. Typhi by the i.n route. The results showed that Poli Vi coadministered with PLc (PLc+Poli Vi) induce a higher IgA response in saliva (p<0.01) and faeces (p<0.01) than Poli Vi administered alone. Likewise, the IgG response in sera was higher in animals immunised with PLc+Poli Vi (p<0.01). Furthermore, IgG induced in sera of mice immunised with PLc+Poli Vi was similar (p>0.05) to that induced in a group of mice immunised by the parenteral route with the Cuban anti-typhoid vaccine vax-TyVi, although this vaccine did not induce a mucosal response. In conclusion, this work demonstrates that PLc can be used as a mucosal adjuvant to potentiate the immune response against a polysaccharide antigen like Poli Vi.

  19. Immune adjuvant effect of V. cholerae O1 derived Proteoliposome coadministered by intranasal route with Vi polysaccharide from Salmonella Typhi

    PubMed Central

    2013-01-01

    The proteoliposome derived from Vibrio cholerae O1 (PLc) is a nanoscaled structure obtained by a detergent extraction process. Intranasal (i.n) administration of PLc was immunogenic at mucosal and systemic level vs. V. cholerae; however the adjuvant potential of this structure for non-cholera antigens has not been proven yet. The aim of this work was to evaluate the effect of coadministering PLc with the Vi polysaccharide antigen (Poli Vi) of S. Typhi by the i.n route. The results showed that Poli Vi coadministered with PLc (PLc+Poli Vi) induce a higher IgA response in saliva (p<0.01) and faeces (p<0.01) than Poli Vi administered alone. Likewise, the IgG response in sera was higher in animals immunised with PLc+Poli Vi (p<0.01). Furthermore, IgG induced in sera of mice immunised with PLc+Poli Vi was similar (p>0.05) to that induced in a group of mice immunised by the parenteral route with the Cuban anti-typhoid vaccine vax-TyVi®, although this vaccine did not induce a mucosal response. In conclusion, this work demonstrates that PLc can be used as a mucosal adjuvant to potentiate the immune response against a polysaccharide antigen like Poli Vi. PMID:23458379

  20. Evaluation of the saccharide content and stability of the first WHO International Standard for Haemophilus influenzae b capsular polysaccharide.

    PubMed

    Mawas, Fatme; Bolgiano, Barbara; Rigsby, Peter; Crane, Dennis; Belgrave, Danielle; Corbel, Michael J

    2007-10-01

    Haemophilus influenzae b conjugate vaccines (Hib) are almost entirely evaluated by physico-chemical methods to ensure the consistency of manufacture of batches. As different assays are employed for the quantification of Hib capsular polysaccharide PRP (polyribosyl ribitol phosphate; 5-D-ribitol-(1-->1)-beta-D-ribose-3-phosphate) in final formulations and bulk components, there was deemed a need for an International Standard of Hib PRP polysaccharide to be made available. Ten laboratories from 8 different countries participated in a collaborative study to determine the PRP content and assess the suitability of a candidate International Standard PRP preparation (02/208). The results illustrate that a reduction in between-laboratory variability could be achieved by use of a common reference preparation and data analysis showed no significant differences in the values obtained by the different assays: ribose, phosphorus, and high performance anion exchange chromatography-pulsed amperometric detection (HPAEC-PAD), suggesting the suitability of the proposed reference for use across these assays for quantification of PRP content in Hib vaccines. On the basis of the results of this study, the First International Standard for PRP, NIBSC Code 02/208, has been established by the Expert Committee of Biological Standards of the World Health Organisation, with a content of 4.933+/-0.267mg/ampoule, as determined by the ribose assays carried out by 7 of the participating laboratories.

  1. Emerging Vaccine Informatics

    PubMed Central

    He, Yongqun; Rappuoli, Rino; De Groot, Anne S.; Chen, Robert T.

    2010-01-01

    Vaccine informatics is an emerging research area that focuses on development and applications of bioinformatics methods that can be used to facilitate every aspect of the preclinical, clinical, and postlicensure vaccine enterprises. Many immunoinformatics algorithms and resources have been developed to predict T- and B-cell immune epitopes for epitope vaccine development and protective immunity analysis. Vaccine protein candidates are predictable in silico from genome sequences using reverse vaccinology. Systematic transcriptomics and proteomics gene expression analyses facilitate rational vaccine design and identification of gene responses that are correlates of protection in vivo. Mathematical simulations have been used to model host-pathogen interactions and improve vaccine production and vaccination protocols. Computational methods have also been used for development of immunization registries or immunization information systems, assessment of vaccine safety and efficacy, and immunization modeling. Computational literature mining and databases effectively process, mine, and store large amounts of vaccine literature and data. Vaccine Ontology (VO) has been initiated to integrate various vaccine data and support automated reasoning. PMID:21772787

  2. Vaccinations for pregnant women.

    PubMed

    Swamy, Geeta K; Heine, R Phillips

    2015-01-01

    In the United States, eradication and reduction of vaccine-preventable diseases through immunization has directly increased life expectancy by reducing mortality. Although immunization is a public priority, vaccine coverage among adult Americans is inadequate. The Institute of Medicine, the Community Preventive Services Task Force, and other public health entities have called for the development of innovative programs to incorporate adult vaccination into routine clinical practice. Obstetrician-gynecologists are well suited to serve as vaccinators of women in general and more specifically pregnant women. Pregnant women are at risk for vaccine-preventable disease-related morbidity and mortality and adverse pregnancy outcomes, including congenital anomalies, spontaneous abortion, preterm birth, and low birth weight. In addition to providing direct maternal benefit, vaccination during pregnancy likely provides direct fetal and neonatal benefit through passive immunity (transplacental transfer of maternal vaccine-induced antibodies). This article reviews: 1) types of vaccines; 2) vaccines specifically recommended during pregnancy and postpartum; 3) vaccines recommended during pregnancy and postpartum based on risk factors and special circumstances; 4) vaccines currently under research and development for licensure for maternal-fetal immunization; and 5) barriers to maternal immunization and available patient and health care provider resources.

  3. Vaccination against Klebsiella aerogenes.

    PubMed Central

    Roe, E. A.; Jones, R. J.

    1984-01-01

    Klebsiella vaccine was prepared from strains of Klebsiella aerogenes with capsular types K1, K36, K44 and K Cross (a type which cross-reacts in vitro with sera from many klebsiella capsular types). The vaccine was extracted by dialysis and ultrafiltration from capsular material released during growth of the bacteria in a five-day batch culture. Mice given one dose of vaccine from K1a (1.0 microgram/mouse) survived lethal intraperitoneal challenge of 11/11 homologous klebsiella strains four days after vaccination; 14 days after vaccination protection against the same challenge strains had declined to 5/11 strains. Vaccines from K1a, b, c, K36, K44 and K Cross induced homologous protection and protected mice against different ranges of heterologous klebsiella capsular types. The protective response of the mice was greatly enhanced by administering three doses of the vaccines. Vaccines from K1, K36, K44 and K Cross protected mice against 14/20, 11/20, 10/20 and 9/20 homologous and heterologous klebsiella challenge strains respectively. None of the klebsiella vaccines was toxic for mice at the immunizing dose (1.0 microgram/mouse). Vaccine from K36 was the most lethal, killing mice at 10(3) immunizing doses. The least toxic vaccine was from K44, which killed mice at 10(4) immunizing doses. PMID:6389699

  4. [Vaccinations for international travelers].

    PubMed

    Berens-Riha, N; Alberer, M; Löscher, T

    2014-03-01

    Vaccinations are a prominent part of health preparations before international travel. They can avoid or significantly reduce the risk of numerous infectious diseases. Until recently, vaccination against yellow fever was the only obligatory vaccination. However, according to updated international health regulations, other vaccinations and prophylactic measures may be required at entry from certain countries. For all routine vaccinations as recommended in Germany, necessary revaccination and catch-up of missed vaccinations should be administered before travel. At most destinations the risk of infection is higher than in Germany. Hepatitis A vaccine is generally recommended for travelers to areas of increased risk, polio vaccine for all destinations where eradication is not yet confirmed (Asia and Africa). The indications for other travel vaccines must take into consideration travel destination and itinerary, type and duration of travel, individual risk of exposure as well as the epidemiology of the disease to be prevented. Several vaccines of potential interest for travel medicine, e.g., new vaccines against malaria and dengue fever, are under development.

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

    PubMed Central

    Fuery, Angela; Richmond, Peter C.; Currie, Andrew J.

    2015-01-01

    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. Conclusion: 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. PMID:26191794

  6. Endotoxins in commercial vaccines.

    PubMed Central

    Geier, M R; Stanbro, H; Merril, C R

    1978-01-01

    Twenty samples of commercial vaccines intended for administration to humans were assayed for the presence of bacterial endotoxins by using the Limulus amebocyte lysate test. Sixteen of the vaccines contained more than 0.1 ng of endotoxin per ml (which corresponds to 103 bacterial cell wall equivalents per ml in the undiluted vaccines). These results suggest that at some stage of preparation, the vaccines have contained varying amounts of gram-negative bacteria and may indicate the presence of other bacterial products as well. It might be useful to list the level of endotoxins, phage, and other contaminants on each vaccine lot to facilitate studies on any side effects of these contaminants. Selection of vaccine lots with the least endotoxin might reduce some of the adverse effects of vaccinations. PMID:727776

  7. Vaccines for allergy

    PubMed Central

    Linhart, Birgit; Valenta, Rudolf

    2012-01-01

    Vaccines aim to establish or strengthen immune responses but are also effective for the treatment of allergy. The latter is surprising because allergy represents a hyper-immune response based on immunoglobulin E production against harmless environmental antigens, i.e., allergens. Nevertheless, vaccination with allergens, termed allergen-specific immunotherapy is the only disease-modifying therapy of allergy with long-lasting effects. New forms of allergy diagnosis and allergy vaccines based on recombinant allergen-derivatives, peptides and allergen genes have emerged through molecular allergen characterization. The molecular allergy vaccines allow sophisticated targeting of the immune system and may eliminate side effects which so far have limited the use of traditional allergen extract-based vaccines. Successful clinical trials performed with the new vaccines indicate that broad allergy vaccination is on the horizon and may help to control the allergy pandemic. PMID:22521141

  8. Vaccine epidemiology: A review

    PubMed Central

    Lahariya, Chandrakant

    2016-01-01

    This review article outlines the key concepts in vaccine epidemiology, such as basic reproductive numbers, force of infection, vaccine efficacy and effectiveness, vaccine failure, herd immunity, herd effect, epidemiological shift, disease modeling, and describes the application of this knowledge both at program levels and in the practice by family physicians, epidemiologists, and pediatricians. A case has been made for increased knowledge and understanding of vaccine epidemiology among key stakeholders including policy makers, immunization program managers, public health experts, pediatricians, family physicians, and other experts/individuals involved in immunization service delivery. It has been argued that knowledge of vaccine epidemiology which is likely to benefit the society through contributions to the informed decision-making and improving vaccination coverage in the low and middle income countries (LMICs). The article ends with suggestions for the provision of systematic training and learning platforms in vaccine epidemiology to save millions of preventable deaths and improve health outcomes through life-course. PMID:27453836

  9. Sulfation of tea polysaccharides: synthesis, characterization and hypoglycemic activity.

    PubMed

    Wang, Yuanfeng; Peng, Yonghua; Wei, Xinlin; Yang, Zhiwei; Xiao, Jianbo; Jin, Zhengyu

    2010-03-01

    Neutral polysaccharides (NTPS) and acid polysaccharides (ATPS) from tea leaves were obtained on a D315 macroporous anion-exchange resin column chromatography. NTPS and ATPS were sulfated by the pyridine-sulfonic acid method to obtain NTPS-S and ATPS-S. It was found that NTPS was easier sulfated than ATPS. There are strong characteristic absorption peaks located in 1258 cm(-1), 1146 cm(-1), 832 cm(-1) and 617 cm(-1) in the FTIR spectra of sulfated polysaccharides. Sulfation of polysaccharides also affected the endothermic and exothermic peaks via the DSC scan analysis. The appearance of exothermic peaks in both NTPS-S and ATPS-S indicated that the redox reaction might happen. The comparative study of hypoglycemic effect on mice showed that the sulfation of polysaccharides significantly improved hypoglycemic activity.

  10. Characterisation of cell wall polysaccharides from rapeseed (Brassica napus) meal.

    PubMed

    Pustjens, Annemieke M; Schols, Henk A; Kabel, Mirjam A; Gruppen, Harry

    2013-11-06

    To enable structural characteristics of individual cell wall polysaccharides from rapeseed (Brassica napus) meal (RSM) to be studied, polysaccharide fractions were sequentially extracted. Fractions were analysed for their carbohydrate (linkage) composition and polysaccharide structures were also studied by enzymatic fingerprinting. The RSM fractions analysed contained pectic polysaccharides: homogalacturonan in which 60% of the galacturonic acid residues are methyl-esterified, arabinan branched at the O-2 position and arabinogalactan mainly type II. This differs from characteristics previously reported for Brassica campestris meal, another rapeseed cultivar. Also, in the alkali extracts hemicelluloses were analysed as xyloglucan both of the XXGG- and XXXG-type decorated with galactosyl, fucosyl and arabinosyl residues, and as xylan with O-methyl-uronic acid attached. The final residue after extraction still contained xyloglucan and remaining (pectic) polysaccharides next to cellulose, showing that the cell wall matrix of RSM is very strongly interconnected.

  11. Methods for degrading or converting plant cell wall polysaccharides

    DOEpatents

    Berka, Randy; Cherry, Joel

    2008-08-19

    The present invention relates to methods for converting plant cell wall polysaccharides into one or more products, comprising: treating the plant cell wall polysaccharides with an effective amount of a spent whole fermentation broth of a recombinant microorganism, wherein the recombinant microorganism expresses one or more heterologous genes encoding enzymes which degrade or convert the plant cell wall polysaccharides into the one or more products. The present invention also relates to methods for producing an organic substance, comprising: (a) saccharifying plant cell wall polysaccharides with an effective amount of a spent whole fermentation broth of a recombinant microorganism, wherein the recombinant microorganism expresses one or more heterologous genes encoding enzymes which degrade or convert the plant cell wall polysaccharides into saccharified material; (b) fermenting the saccharified material of step (a) with one or more fermenting microoganisms; and (c) recovering the organic substance from the fermentation.

  12. Principles of Vaccination.