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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. Conjugate and 23-valent pneumococcal polysaccharide booster vaccination in asplenic patients with thalassemia major: A randomized clinical trial study

    PubMed Central

    Rezai, Mohammad Sadegh; Ghaffari, Javad; Mahdavi, Mohammadreza; Bahari, Amir; Ala, Shahram

    2017-01-01

    Background: Pneumococcal vaccine provides protection against invasive pneumococcal disease in population at risk. This study was conducted to compare the antibody response to 13-valent pneumococcal conjugate vaccine and 23-valent pneumococcal polysaccharide vaccine in patients with thalassemia major. Methods: A randomized cross-over clinical trial was performed on 50 asplenic patients with thalassemia major who referred to thalassemia center at Bouali Sina Hospital, Sari, Iran from 2013 to 2014. Patients were divided into two equal groups. The first group received 13-valent pneumococcal conjugate vaccine (PCV) injected into the deltoid muscle at first and received 23-valent polysaccharide vaccine (PPV) by the same way two months later. The second group received PPV vaccine at first and PCV13 two months later. Levels of serum antibody were checked and measured by enzyme-linked immunosorbent assay (ELISA) before vaccination, and then 8 weeks after the first injection and 2 months after the second injection in all patients. Each time 0.5-ml dose of the vaccine was injected. Results: Of the 50 patients, three cases were excluded due to lack of cooperation and avoidance of vaccination. From 47 patient participants, 28 (59.6%) were males and 19 (40.4%) were females with age ranged between 20 to 44 years (average age of 29.6±1.4 years). Pneumococcal IgG levels in a group that used PCV before PPV (Group A) increased from 114.5±87.7 to 1049±720 U/ml (p=0.0001) and in another group that used PPV before PCV (Group B) increased from 115±182.2 to 1497.3±920.3 U/ml (P=0.0001). Conclusion: It can be concluded that PCV vaccine before PPV can be more effective in asplenic thalassemia major patients as a booster dose. PMID:28503278

  5. 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

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

    PubMed

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

    2015-01-01

    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. 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. 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. 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.

  7. Evaluation of antibody levels over 3 years after 23-valent pneumococcal polysaccharide vaccination in patients with pulmonary diseases receiving steroids and immunosuppressive agents.

    PubMed

    Akamatsu, Taisuke; Inui, Naoki; Kusagaya, Hideki; Nakamura, Yutaro; Suda, Takafumi; Chida, Kingo

    2015-02-01

    Pneumococcal capsular polysaccharide vaccine is a mainstay for prevention of Streptococcus pneumoniae infection in adults. There is the possibility that this vaccine is less effective in patients undergoing immunosuppressive therapy. In the present study, we aimed to evaluate the immune response following 23-valent pneumococcal polysaccharide vaccination in pulmonary disease patients receiving steroids and immunosuppressive agents (immunosuppressive group). Antibody levels were measured over 3 years in the immunosuppressive group (median age: 68.5 years) and in aged-match pulmonary disease patients not being treated with immunosuppressive therapy (control group) using enzyme-linked immunosorbent assays. The geometric mean antibody levels were significantly increased after vaccination in both groups (p < 0.05) and remained above baseline for 3 years. The fold increases 1 month after vaccination were 9.4 (95% confidence interval [CI]: 5.7-15.6) and 8.8 (95% CI: 5.8-13.2) in the immunosuppressive and control groups, respectively (p = 0.813). There was no significant difference in the proportion of subjects with a ≥ two-fold increase of antibody level between the immunosuppressive and control groups at any point. These results suggest that immunization with the 23-valent pneumococcal polysaccharide vaccine was effective, even in patients undergoing immunosuppressive therapy and should be recommended for such patients. Copyright © 2014 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

  8. Immunogenicity and safety of a 13-valent pneumococcal conjugate vaccine in adults 70 years of age and older previously vaccinated with 23-valent pneumococcal polysaccharide vaccine.

    PubMed

    Jackson, Lisa A; Gurtman, Alejandra; Rice, Kathryn; Pauksens, Karlis; Greenberg, Richard N; Jones, Thomas R; Scott, Daniel A; Emini, Emilio A; Gruber, William C; Schmoele-Thoma, Beate

    2013-08-02

    The currently recommended single dose of the 23-valent pneumococcal free polysaccharide vaccine (PPSV23) for adults 65 years of age and older does not provide extended protection into older age. This reflects a significant unmet medical need for alternative strategies to protect older adults against pneumococcal infection, which may be met by the 13-valent polysaccharide conjugate vaccine (PCV13). We performed a randomized, modified double-blind trial in 936 adults aged 70 years and older who had previously received PPSV23 at least 5 years before study entry and were now vaccinated with PCV13 or PPSV23. At 1 year after enrollment, all subjects received a follow-on dose of PCV13. Anti-pneumococcal opsonophagocytic activity (OPA) titers were measured before and at 1 month after each vaccination. Following the enrollment vaccination, OPA titers were significantly greater in the PCV13 group compared to the PPSV23 group for 10 of the 12 serotypes common to both vaccines and to serotype 6A which is unique to PCV13. Responses were noninferior for the other 2 common serotypes. Responses to PCV13 given at 1 year were generally lower in the group that received PPSV23 at enrollment. In adults aged 70 years and older previously vaccinated with PPSV23, PCV13 was significantly more immunogenic than PPSV23 for most of the common serotypes and for serotype 6A. The OPA responses after a follow-on dose of PCV13 one year later indicate that a prior dose of PPSV23, but not PCV13, diminishes the response to the subsequent administration of PCV13. Copyright © 2013 The Authors. Published by Elsevier Ltd.. All rights reserved.

  9. Immunogenicity and safety of a 13-valent pneumococcal conjugate vaccine compared to a 23-valent pneumococcal polysaccharide vaccine in pneumococcal vaccine-naive adults.

    PubMed

    Jackson, Lisa A; Gurtman, Alejandra; van Cleeff, Martin; Jansen, Kathrin U; Jayawardene, Deepthi; Devlin, Carmel; Scott, Daniel A; Emini, Emilio A; Gruber, William C; Schmoele-Thoma, Beate

    2013-08-02

    Streptococcus pneumoniae is a major cause of morbidity and mortality among adults 50 years of age and older in the United States. Pneumococcal conjugate vaccines are efficacious against pneumococcal disease in children and may also offer advantages in adults. We performed a randomized, modified double-blind trial that compared a single dose of 13-valent pneumococcal conjugate vaccine (PCV13) with 23-valent pneumococcal polysaccharide vaccine (PPSV23) in 831 pneumococcal vaccine naive adults 60-64 years of age. An additional group of 403 adults 50-59 years of age received open-label PCV13. Anti-pneumococcal opsonophagocytic activity (OPA) titers were measured at baseline, and at 1 month and 1 year after vaccination. In the randomized trial, the month 1 post-vaccination OPA geometric mean titers in the PCV13 group were statistically significantly higher than in the PPSV23 group for 8 of the 12 serotypes common to both vaccines and for serotype 6A, a serotype unique to PCV13, and were comparable for the other 4 common serotypes. The immune response to PCV13 was generally greater in adults 50-59 years of age compared to adults 60-64 years of age. OPA titers declined from 1 month to 1 year after PCV13 administration but remained higher than pre-vaccination baseline titers. PCV13 induces a greater functional immune response than PPSV23 for the majority of serotypes covered by PCV13, suggesting that PCV13 could offer immunological advantages over PPSV23 for prevention of vaccine-type pneumococcal infection. Copyright © 2013 The Authors. Published by Elsevier Ltd.. All rights reserved.

  10. Use of 13-valent pneumococcal conjugate vaccine and 23-valent pneumococcal polysaccharide vaccine among adults aged ≥65 years: recommendations of the Advisory Committee on Immunization Practices (ACIP).

    PubMed

    Tomczyk, Sara; Bennett, Nancy M; Stoecker, Charles; Gierke, Ryan; Moore, Matthew R; Whitney, Cynthia G; Hadler, Stephen; Pilishvili, Tamara

    2014-09-19

    On August 13, 2014, the Advisory Committee on Immunization Practices (ACIP) recommended routine use of 13-valent pneumococcal conjugate vaccine (PCV13 [Prevnar 13, Wyeth Pharmaceuticals, Inc., a subsidiary of Pfizer Inc.]) among adults aged ≥65 years. PCV13 should be administered in series with the 23-valent pneumococcal polysaccharide vaccine (PPSV23 [Pneumovax23, Merck & Co., Inc.]), the vaccine currently recommended for adults aged ≥65 years. PCV13 was approved by the Food and Drug Administration (FDA) in late 2011 for use among adults aged ≥50 years. In June 2014, the results of a randomized placebo-controlled trial evaluating efficacy of PCV13 for preventing community-acquired pneumonia among approximately 85,000 adults aged ≥65 years with no prior pneumococcal vaccination history (CAPiTA trial) became available and were presented to ACIP. The evidence supporting PCV13 vaccination of adults was evaluated using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) framework and determined to be type 2 (moderate level of evidence); the recommendation was categorized as a Category A recommendation. This report outlines the new recommendations for PCV13 use, provides guidance for use of PCV13 and PPSV23 among adults aged ≥65 years, and summarizes the evidence considered by ACIP to make this recommendation.

  11. Sequential administration of 13-valent pneumococcal conjugate vaccine and 23-valent pneumococcal polysaccharide vaccine in pneumococcal vaccine-naïve adults 60-64 years of age.

    PubMed

    Greenberg, Richard N; Gurtman, Alejandra; Frenck, Robert W; Strout, Cynthia; Jansen, Kathrin U; Trammel, James; Scott, Daniel A; Emini, Emilio A; Gruber, William C; Schmoele-Thoma, Beate

    2014-04-25

    Unlike free pneumococcal polysaccharide vaccines (PPSVs), pneumococcal conjugate vaccines (PCVs) induce a T-cell-dependent immune response. The study assessed potential influence of initial 13-valent PCV (PCV13) or 23-valent PPSV (PPSV23) on subsequent vaccine administrations. We conducted a randomized, modified double-blind study in 720 pneumococcal vaccine-naïve adults 60-64 years of age. Subjects received either PCV13 at year 0 and PCV13 at year 1; PCV13 at year 0 and PPSV23 at year 1; or PPSV23 at year 0 and PCV13 at year 1. Antipneumococcal opsonophagocytic activity (OPA) titers were measured before and 1 month after each vaccination. OPA titers following PPSV23 given 1 year after PCV13 (PCV13/PPSV23) (a) were noninferior for the 12 common serotypes and significantly higher for 6 of 12 common serotypes than those following only an initial PPSV23; and (b) were significantly higher for 11 of 12 common serotypes compared with PPSV23 followed by PCV13 (PPSV23/PCV13). In addition, PPSV23 followed 1 year later by PCV13 (PPSV23/PCV13) elicited significantly lower OPA titers than after only an initial dose of PCV13 for all 13 serotypes. Responses after a second vaccination with either PCV13 (PCV13/PCV13) or PPSV23 (PCV13/PPSV23) were noninferior for 9 of 13 and 8 of 12 common serotypes compared with the initial PCV13 dose. In pneumococcal vaccine-naïve adults 60-64 years of age, an initial PCV13 augmented the antipneumococcal response to subsequent administration of PPSV23 for many of the serotypes in common to both vaccines. In contrast, an initial PPSV23 resulted in a diminished response to subsequent administration of PCV13 for all serotypes. With a relatively short 1-year interval between doses, responses after a second vaccination with PCV13 (PCV13/PCV13) or PPSV23 (PCV13/PPSV23) were noninferior for a majority of serotypes compared with the initial PCV13 dose, probably reflecting the need for a longer interval between vaccine administrations. Clinical

  12. Cost-effectiveness and Health Benefits of Pediatric 23-valent Pneumococcal Polysaccharide Vaccine, 7-valent Pneumococcal Conjugate Vaccine and Forecasting 13-valent Pneumococcal Conjugate Vaccine in China.

    PubMed

    Mo, Xiuting; Gai Tobe, Ruoyan; Liu, Xiaoyan; Mori, Rintaro

    2016-11-01

    Each year in China, approximately 700,000 children under 5 years old are diagnosed with pneumonia, and 30,000 die of the disease. Although 7-valent pneumococcal conjugate vaccine (PCV-7) and 23-valent pneumococcal polysaccharide vaccine (PPV-23) are available in China, the costs are borne by the consumer, resulting in low coverage for PCV-7. We aimed to conduct a simulation study to assess the cost-effectiveness and health benefits of PCV-7, 13-valent pneumococcal conjugate vaccine (PCV-13) and PPV-23 to prevent childhood pneumonia and other vaccine-preventive diseases in China. An economic evaluation was performed using a Markov simulation model. Parameters including demographic, epidemiological data, costs and efficacy of vaccines were obtained from previous studies. A hypothetical cohort of 100,000 newborns (focusing on pneumococcal diseases ≤7 years old) was followed up until death or 100 years of age. The model incorporated the impact of vaccination on reduction of incidence of pneumococcal diseases and mortality of children ≤7 years. Outcomes are presented in terms of disease cases averted, quality-adjusted life years (QALYs) and incremental cost-effectiveness ratio. Under baseline assumptions, PPV-23 is currently the only cost-effective option, whereas PCV-13 showed the greatest impact on pneumococcal disease burden, reducing invasive pneumococcal diseases by 31.3%, pneumonia by 15.3% and gaining 73.8 QALYs (10,000 individuals at discount rate of 3%). Incremental cost-effectiveness ratios of PCV-13 and PCV-7 are US$29,460/QALY and US$104,094/QALY, respectively, showing no cost-effectiveness based on the World Health Organization recommended willingness-to-pay threshold. On the other hand, the incremental cost-effectiveness ratios of PCVs were most sensitive to vaccination costs; if it reduces 4.7% and 32.2% for PCV-7 and PCV-13, respectively, the vaccination will be cost-effective. To scale up current vaccination strategies and achieve potential health

  13. 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.

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

    PubMed

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

    2017-08-24

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

  15. The 23-valent pneumococcal polysaccharide vaccine is effective in elderly adults over 75 years old--Taiwan's PPV vaccination program.

    PubMed

    Tsai, Ying-Huang; Hsieh, Meng-Jer; Chang, Chee-Jen; Wen, Yu-Wen; Hu, Han-Chung; Chao, Yen-Nan; Huang, Yhu-Chering; Yang, Cheng-Ta; Huang, Chung-Chi

    2015-06-09

    Pneumococcal infection is a serious cause of mortality and morbidity in the elderly. A nationwide pneumococcal polysaccharide vaccine (PPV) program for elderly adults aged 75 years and older was conducted in Taiwan in 2008. The efficacy of the PPV in this very elderly population was evaluated. The data were analyzed using the Taiwan National Health Insurance Research Database (NHIRD), the cause-of-death registration database and the invasive pneumococcal disease (IPD) notification database of Taiwan's Ministry of Health and Welfare. The efficacy of PPV administration in this very elderly population was evaluated using multivariate logistic regression after propensity score matching (PSM). The rates of IPD, death from IPD, pneumonia hospitalization, death from pneumonia, and all-cause mortality were compared for those who did and did not receive the PPV. Among the 1078,955 eligible people, 318,257 (29.5%) received the PPV, and 760,698 (70.5%) were not vaccinated. Using PSM to adjust for confounding factors, including age, gender, influenza vaccination status, associated chronic diseases and health care utilization, those who received the PPV had significantly lower odds ratios (ORs) for IPD (OR=0.24, 95% CI=0.123-0.461, p<0.001), death from IPD (OR=0.09, 95% CI=0.011-0.704, p<0.022, p<0.001), pneumonia hospitalization (OR=0.40, 95% CI=0.395-0.415, p<0.001), death from pneumonia (OR=0.07, 95% CI=0.059-0.082, p<0.001), and all-cause mortality (OR=0.07, 95% CI=0.069-0.072, p<0.001) compared with those who were not vaccinated. PPV vaccination in the previous year was associated with a 60% reduction in pneumonia hospitalization, a 76% reduction in IPD, and a greater than 90% reduction in death from pneumonia, IPD and all causes among people over 75 years old in Taiwan. Data from subsequent years in Taiwan and similar populations elsewhere are needed to evaluate the contribution of underlying variations in the mortality rate and the confounding effects of prior disease

  16. 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

  17. Cost-Effectiveness and Health Benefits of Pediatric 23-Valent Pneumococcal Polysaccharide Vaccine, 7-Valent and Forecasting 13-Valent Pneumococcal Conjugate Vaccines in China.

    PubMed

    Mo, Xiuting; Tobe, Ruoyan Gai; Liu, Xiaoyan; Mori, Rintaro

    2016-06-24

    Each year in China, approximately 700,000 children under 5 years old are diagnosed with pneumonia, and 30,000 die from the disease. Although 7-valent pneumococcal conjugate vaccine (PCV-7) and 23-valent pneumococcal polysaccharide vaccine (PPV-23) are available in China, the costs are borne by the consumer, resulting in low coverage for PCV-7. We aimed to conduct a simulation study to assess the cost-effectiveness and health benefits of PCV-7, 13-valent pneumococcal conjugate vaccine (PCV-13) and PPV-23 to prevent childhood pneumonia and other vaccine-preventive diseases in China. An economic evaluation was performed using a Markov simulation model. Parameters including demographic, epidemiological data, costs and efficacy of vaccines were obtained from previous studies. A hypothetical cohort of 100,000 newborns (focusing on pneumococcal diseases ≤7 years old) was followed up until death or 100 years of age. The model incorporated the impact of vaccination on reduction of incidence of pneumococcal diseases and mortality of children ≤7 years. Outcomes are presented in terms of disease cases averted, quality-adjusted life years (QALYs) and incremental cost-effectiveness ratio (ICER). Under baseline assumptions, PPV-23 is currently the only cost-effective option, while PCV-13 showed the greatest impact on pneumococcal disease burden, reducing invasive pneumococcal diseases by 31.3%, pneumonia by 15.3% and gaining 73.8 QALYs (10,000 individuals at discount rate of 3%). ICERs of PCV-13 and PCV-7 are US$29,460/QALY and US$104,094/QALY, respectively, showing no cost-effectiveness based on the World Health Organization recommended willingness-to-pay threshold. On the other hand, the ICERs of PCVs were most sensitive to vaccination costs: if it reduces 4.7% and 32.2% for PCV-7 and PCV-13 respectively, the vaccination will be cost-effective. To scale up current vaccination strategies and achieve potential health benefits, the replacement of PCV-7 with PCV-13 should be

  18. Effectiveness of 23-valent pneumococcal polysaccharide vaccine against invasive disease and hospital-treated pneumonia among people aged ≥65 years: a retrospective case-control study.

    PubMed

    Leventer-Roberts, Maya; Feldman, Becca S; Brufman, Ilan; Cohen-Stavi, Chandra J; Hoshen, Moshe; Balicer, Ran D

    2015-05-15

    Streptococcus pneumoniae contributes considerably to the burden of pneumonia and invasive pneumococcal disease (IPD), with the effectiveness of the 23-valent pneumococcal polysaccharide vaccine (PPSV23) for preventing all-cause pneumonia still undetermined. The aim of this study was to control for common biases and confounders associated with previous observational studies and to assess PPSV23 vaccine effectiveness in preventing IPD and the most resource-intensive type of community-acquired pneumonia, hospital-treated pneumonia (HTP). This was a retrospective case-control study nested in a population-based cohort, with age-, sex-, and risk-matched controls as the base case. Demographic information, laboratory data, and diagnoses were extracted from the chronic disease registry and from inpatient and outpatient records in the Clalit Health Services database. Vaccine effectiveness for PPSV23 was assessed using multivariable conditional logistic regression. Subgroup, sensitivity, and secondary analyses were conducted to validate findings. A total of 470 070 individuals aged ≥65 years were members of Clalit Health Services during the study period (1 January 2007 through 31 December 2010). The case cohort consisted of 212 participants with IPD and 23 441 with HTP. The adjusted association between vaccination and IPD was protective (odds ratio [OR], 0.58; 95% confidence interval [CI], .41-.81), whereas there was no demonstrated protective effect between vaccination and HTP (OR, 1.01; 95% CI, .97-1.04). The sensitivity analysis and all but 1 subgroup analysis provided consistent results to the base case. The PPSV23 vaccine is effective against the most severe invasive forms of pneumococcal disease, but the lack of effectiveness of PPSV23 in protecting against all-cause HTP should be considered for future vaccine policies. © The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions

  19. Immunogenicity and safety of a 13-valent pneumococcal conjugate vaccine in adults 18-49 years of age, naive to 23-valent pneumococcal polysaccharide vaccine.

    PubMed

    Bryant, K A; Frenck, R; Gurtman, A; Rubino, J; Treanor, J; Thompson, A; Jones, T R; Sundaraiyer, V; Baxter, L M; Gruber, W C; Emini, E A; Scott, D A; Schmoele-Thoma, B

    2015-10-26

    Based on the success of vaccination with pneumococcal conjugate vaccines (PCVs) in children, recent studies have focused on PCVs in adults. Data from a randomized, double-blind study comparing the immunogenicity, tolerability, and safety of the 13-valent PCV (PCV13) and the 23-valent pneumococcal polysaccharide vaccine (PPSV23) in PPSV23-naive adults 60-64 years of age have been published. The same study also included a cohort of adults aged 18-49 years that received open-label PCV13. The purpose of this cohort was to examine the immunogenicity, safety, and tolerability of PCV13 in adult subjects 18-49 years of age compared with adults 60-64 years of age for whom PCV13 is approved. Adults naive to PPSV23 were grouped by age into 2 cohorts: 18-49 years (n=899; further stratified by age into 3 subgroups 18-29, 30-39, and 40-49 years) and 60-64 years (n=417). All subjects received 1 dose of PCV13. In both age groups, immunogenicity was assessed by antipneumococcal opsonophagocytic activity (OPA) geometric mean titers (GMTs) and IgG geometric mean concentrations (GMCs) 1 month after vaccination. Safety and tolerability were evaluated. In adults aged 18-49 years, OPA GMTs and IgG GMCs were noninferior for all 13 serotypes and statistically significantly higher for all except 1 serotype (OPA GMT) and 5 serotypes (IgG GMCs) compared with adults 60-64 years. Immune responses were highest in the youngest age subgroup (18-29 years). Local reactions and systemic events were more common in adults 18-49 years compared with 60-64 years and were self-limited. Immune responses to PCV13 are robust in adults ≥18 years of age, with highest responses observed in the youngest subgroup. Based on its safety and immunologic profile, PCV13 may serve an important therapeutic role in younger adults, particularly those with underlying medical conditions who have an increased risk of serious pneumococcal infections. Copyright © 2015 Elsevier Ltd. All rights reserved.

  20. Effect of 23-Valent Pneumococcal Polysaccharide Vaccine Inoculated During Anti-Cancer Treatment Period in Elderly Lung Cancer Patients on Community-Acquired Pneumonia Hospitalization

    PubMed Central

    Chiou, Wen-Yen; Hung, Shih-Kai; Lai, Chun-Liang; Lin, Hon-Yi; Su, Yu-Chieh; Chen, Yi-Chun; Shen, Bing-Jie; Chen, Liang-Cheng; Tsai, Shiang-Jiun; Lee, Moon-Sing; Li, Chung-Yi

    2015-01-01

    Abstract To evaluate effectiveness of 23-valent pneumococcal polysaccharide vaccine (PPSV23) inoculated during defined “vaccination period,” first 6 months post cancer diagnosis (ie, an anti-cancer treatment period), in elderly lung cancer patients on community-acquired pneumonia (CAP) hospitalization incidence. This was a nationwide population-based cohort study of 157 newly diagnosed elderly lung cancer patients receiving PPSV23 during “vaccination period”, and 628 age and sex one-to-one matched controls enrolled in the National Health Insurance Research Database (NHIRD) of Taiwan between 2007 and 2010. All patients were ≥75 years old and still survival post “vaccination period.” Incidence density (ID) of all-cause inpatient CAP and cumulative survival risk were analyzed by multivariate Poisson regression and Kaplan–Meier method, respectively. After a 4-year follow-up, IDs of all-cause inpatient CAP for vaccination and control cohorts were 297 and 444 per 1000 PYs, respectively. Less vaccinated patients had CAP incidence density >1 time per PY (12.7% vs 21.2%) than non-vaccinated patients. After adjusting for potential confounding variables, like influenza vaccination, comorbidities, cancer treatment modalities, and socioeconomic status, adjusted inpatient CAP incidence rate in PPSV23 vaccination cohort was 0.74 times lower than control cohort (incidence rate ratio [IRR] = 0.740, P = 0.0339). Two-year cumulative CAP hospitalization rates and overall survival rates were 37.1% vs. 55.4%, and 46.6% vs. 26.2%, respectively, for lung cancer patients with and without PPSV23 (both P < 0.001). Subgroup analysis showed that for elderly lung cancer patients not ever receiving influenza vaccine, PPSV23 still had trend to reduce all-cause inpatient CAP. For elderly lung cancer patients aged ≥75 years, PPSV23 inoculated during anti-cancer treatment period could reduce CAP hospitalizations and improve survival. PMID:26131806

  1. 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

  2. Influence of initial vaccination with 13-valent pneumococcal conjugate vaccine or 23-valent pneumococcal polysaccharide vaccine on anti-pneumococcal responses following subsequent pneumococcal vaccination in adults 50 years and older.

    PubMed

    Jackson, Lisa A; Gurtman, Alejandra; van Cleeff, Martin; Frenck, Robert W; Treanor, John; Jansen, Kathrin U; Scott, Daniel A; Emini, Emilio A; Gruber, William C; Schmoele-Thoma, Beate

    2013-08-02

    Unlike free polysaccharide vaccines, pneumococcal polysaccharide conjugate vaccines (PCVs) induce a T cell-dependent immune response and have the potential to provide an extended duration of protection with repeated vaccinations. This was an extension of a previous study in pneumococcal vaccine-naïve adults aged 50-64 years in which adults 60-64 years of age were given 13-valent PCV (PCV13) or 23-valent pneumococcal polysaccharide vaccine (PPSV23) and adults aged 50-59 were given PCV13. In this follow up study conducted about 4 years later, the 60-64 year olds initially given PCV13 received PCV13 or PPSV23, and those initially given PPSV23 received another PPSV23. All adults aged 50-59 years were re-vaccinated with PCV13. Anti-pneumococcal opsonophagocytic activity (OPA) titers were measured before and 1 month after vaccination. A second PCV13 given about 4 years after a first vaccination induced OPA titers that were significantly higher than those following the initial vaccination for 7 of 13 serotypes in the older group, and 6 of 13 serotypes in the younger group, and responses to the remaining serotypes were largely non-inferior. In contrast, OPA titers following revaccination with PPSV23 were statistically significantly lower for 9 of the 13 serotypes, and non-inferior for the remaining serotypes, when compared to the responses to the first PPSV23. OPA titers in the older adults who received PPSV23 after initial PCV13 were significantly higher than those following a first PPSV23 for 10 of the 13 serotypes. In adults 50 to 64 years of age, initial vaccination with PCV13 establishes an immune state that results in recall anti-pneumococcal responses upon subsequent vaccination with either conjugated or free polysaccharide vaccine. In contrast, initial vaccination with PPSV23 results in an immune state in which subsequent PPSV23 administration yields generally lower responses compared with the initial responses. Copyright © 2013 The Authors. Published by Elsevier

  3. PneuMum: Impact from a randomised controlled trial of maternal 23-valent pneumococcal polysaccharide vaccination on middle ear disease amongst Indigenous infants, Northern Territory, Australia.

    PubMed

    Binks, Michael J; Moberley, Sarah A; Balloch, Anne; Leach, Amanda J; Nelson, Sandra; Hare, Kim M; Wilson, Cate; Morris, Peter S; Nelson, Jane; Chatfield, Mark D; Tang, Mimi L K; Torzillo, Paul; Carapetis, Jonathan R; Mulholland, E Kim; Andrews, Ross M

    2015-11-27

    We assessed maternal 23-valent pneumococcal polysaccharide (23vPPV) vaccine efficacy (VE) against middle ear disease and pneumococcal carriage amongst Australian Indigenous infants. In an open label, allocation concealed, outcome-assessor blinded, community stratified, randomised controlled trial, healthy pregnant Indigenous women aged 17-39 years in the Northern Territory of Australia received the 23vPPV (1:1:1) at: 30-36 weeks gestation, birth, or were unvaccinated (ClinicalTrials.gov NCT00714064). Co-primary outcomes were the point prevalences of infant middle ear disease and 23vPPV-type carriage at age 7 months. The consent rate was 50% (313/632). Among 227 eligible participants randomised, retention rates were 86% (66/77) controls; 89% (67/75) pregnancy vaccinees; 88% (66/75) birth vaccinees. At infant age 7 months, ear disease prevalence was: 71% (47/66) controls, 63% (42/67) pregnancy vaccinees, 76% (50/66) birth vaccinees; and 23vPPV-type carriage was: 26% (17/66) controls, 18% (12/67) pregnancy vaccinees, 18% (12/66) birth vaccinees. For pregnancy vaccinees, VE was 12% (95% CI -12% to 31%) against infant ear disease and 30% (95% CI -34% to 64%) against 23vPPV-type carriage. In a post-hoc analysis, VE against infant ear disease concurrent with carriage of 23vPPV or related types was 51% (95% CI -2% to 76%). There were no serious adverse effects following receipt of the 23vPPV in pregnancy or at birth. In a high risk population, our study was unable to demonstrate efficacy of 23vPPV in pregnancy against the co-primary outcomes of either all-cause infant ear disease or 23vPPV-type nasopharyngeal carriage at age 7 months. Efficacy against ear disease concurrent with carriage of vaccine-related serotypes (a more specific outcome) suggests 23vPPV in pregnancy may complement childhood pneumococcal vaccination programs. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

  4. Pneumococcal Vaccination Among Medicare Beneficiaries Occurring After the Advisory Committee on Immunization Practices Recommendation for Routine Use Of 13-Valent Pneumococcal Conjugate Vaccine and 23-Valent Pneumococcal Polysaccharide Vaccine for Adults Aged ≥65 Years.

    PubMed

    Black, Carla L; Williams, Walter W; Warnock, Rob; Pilishvili, Tamara; Kim, David; Kelman, Jeffrey A

    2017-07-14

    On September 19, 2014, CDC published the Advisory Committee on Immunization Practices (ACIP) recommendation for the routine use of 13-valent pneumococcal conjugate vaccine (PCV13) among adults aged ≥65 years, to be used in series with 23-valent pneumococcal polysaccharide vaccine (PPSV23) (1). This replaced the previous recommendation that adults aged ≥65 years should be vaccinated with a single dose of PPSV23. As a proxy for estimating PCV13 and PPSV23 vaccination coverage among adults aged ≥65 years before and after implementation of these revised recommendations, CDC analyzed claims for vaccination submitted for reimbursement to the Centers for Medicare & Medicaid Services (CMS). Claims from any time during a beneficiary's enrollment in Medicare Parts A (hospital insurance) and B (medical insurance) since reaching age 65 years were assessed among beneficiaries continuously enrolled in Medicare Parts A and B during annual periods from September 19, 2009, through September 18, 2016. By September 18, 2016, 43.2% of Medicare beneficiaries aged ≥65 years had claims for at least 1 dose of PPSV23 (regardless of PCV13 status), 31.5% had claims for at least 1 dose of PCV13 (regardless of PPSV23 status), and 18.3% had claims for at least 1 dose each of PCV13 and PPSV23. Claims for either type of pneumococcal vaccine were highest among beneficiaries who were older, white, or with chronic and immunocompromising medical conditions than among healthy adults. Implementation of the National Vaccine Advisory Committee's standards for adult immunization practice to assess vaccination status at every patient encounter, recommend needed vaccines, and administer vaccination or refer to a vaccinating provider might help increase pneumococcal vaccination coverage and reduce the risk for pneumonia and invasive pneumococcal disease among older adults (2).

  5. 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

  6. 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

  7. 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: a randomized open-label trial.

    PubMed

    Juergens, Christine; de Villiers, Pierre J T; 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 (AlPO 4); 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 AlPO 4 and PCV13 without AlPO 4 were similar for the majority, and noninferior for all PCV13 serotypes. PCV13 with AlPO 4 was generally more reactogenic, with reactions mainly mild or moderate. Thus, PCV13 with AlPO 4 (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 AlPO 4 is well tolerated and immunogenic in adults, is generally more immunogenic than PPSV23, and subsequent vaccination with PPSV23 is possible if required.

  8. 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

  9. Vaccine profile of PPV23: Beijing Minhai Biotech 23-valent pneumococcal vaccine.

    PubMed

    Liang, Qi; Li, Gui-Fan; Zhu, Feng-Cai

    2016-10-04

    Diseases caused by Streptococcus pneumoniae are a major public health problem worldwide, which can be effectively prevented by the 23-valent pneumococcal polysaccharide vaccines (PPV23). Areas covered: The Beijing Minhai PPV23 showed good safety and immunogenicity profiles in clinical trials. The immunogenicity of Beijing Minhai PPV23 was non-inferior to other licensed PPVs. Although PPV23 has been proved to be highly efficient and cost-effective, and was recommended for vaccination in high-risk populations in industrialized countries, the coverage of PPV23 vaccination was relatively low in developing countries. Expert commentary: The low vaccination proportions of PPV23 in China have not been improved in recent decades. Most of the populations with indications for receiving PPV23 were not aware of the possible benefits of PPV23. Moreover, PPV23 had some limitations, which called for the development of a new generation of vaccines against pneumococcal infection.

  10. 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.

  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 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

  12. Effectiveness of 23-valent polysaccharide pneumococcal vaccine on pneumonia in HIV-infected adults in the United States, 1998--2003.

    PubMed

    Teshale, Eyasu H; Hanson, Debra; Flannery, Brendan; Phares, Christina; Wolfe, Mitchell; Schuchat, Anne; Sullivan, Patrick

    2008-10-29

    Pneumococcal polysaccharide vaccine (PPV-23) has been recommended for HIV-infected adults. We investigated factors that could influence PPV-23 effectiveness against all-cause pneumonia in a longitudinal cohort of 23,255 HIV-infected adults receiving care during 1998--2003. Patients who received PPV-23 had a lower rate of pneumonia (IRR = 0.8; 95% CI: 0.8-0.9) than patients who had never been vaccinated, independent of recent CD4 count, HIV viral load, antiretroviral therapy, and history of pneumonia. However, PPV-23 provided no benefit when patients were vaccinated at HIV viral load > 100,000 copies/ml, irrespective of CD4 count at vaccination. Receipt of PPV-23 was associated with lower incidence of all-cause pneumonia.

  13. 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

  14. 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.

  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. Economic Evaluation of Immunisation Programme of 23-Valent Pneumococcal Polysaccharide Vaccine and the Inclusion of 13-Valent Pneumococcal Conjugate Vaccine in the List for Single-Dose Subsidy to the Elderly in Japan

    PubMed Central

    Hoshi, Shu-ling; Kondo, Masahide; Okubo, Ichiro

    2015-01-01

    Background Currently in Japan, both 23-valent pneumococcal polysaccharide vaccine (PPSV–23) and 13-valent pneumococcal conjugate vaccine (PCV–13) are available for the elderly for the prevention of S. pneumoniae-related diseases. PPSV–23 was approved in 1988, while the extended use of PCV–13 was approved for adults aged 65 and older in June 2014. Despite these two vaccines being available, the recently launched national immunisation programme for the elderly only subsidised PPSV–23. The framework of the current immunisation programme lasts for five years. The elderly population eligible for the subsidised PPSV–23 shot for the 1st year are those aged 65, 70, 75, 80, 85, 90, 95 and ≥100. While from the 2nd year to the 5th year, those who will age 65, 70, 75, 80, 85, 90, 95 and 100 will receive the same subsidised shot. Methods We performed economic evaluations to (1) evaluate the efficiency of alternative strategies of PPSV–23 single-dose immunisation programme, and (2) investigate the efficiency of PCV–13 inclusion in the list for single-dose pneumococcal vaccine immunisation programme. Three alternative strategies were created in this study, namely: (1) current PPSV–23 strategy, (2) 65 to 80 (as “65–80 PPSV–23 strategy”), and (3) 65 and older (as “≥65 PPSV–23 strategy”). We constructed a Markov model depicting the S. pneumoniae-related disease course pathways. The transition probabilities, utility weights to estimate quality adjusted life year (QALY) and disease treatment costs were either calculated or cited from literature. Cost of per shot of vaccine was ¥8,116 (US$74; US$1 = ¥110) for PPSV–23 and ¥10,776 (US$98) for PCV–13. The model runs for 15 years with one year cycle after immunisation. Discounting was at 3%. Results Compared to current PPSV–23 strategy, 65–80 PPSV–23 strategy cost less but gained less, while the incremental cost-effectiveness ratios (ICERs) of ≥65 PPSV–23 strategy was ¥5,025,000 (US$45

  17. 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

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

    PubMed

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

    2014-12-01

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

  19. 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.

  20. Vaccination response to tetanus toxoid and 23-valent pneumococcal vaccines following administration of a single dose of abatacept: a randomized, open-label, parallel group study in healthy subjects

    PubMed Central

    Tay, Lee; Leon, Francisco; Vratsanos, George; Raymond, Ralph; Corbo, Michael

    2007-01-01

    The effect of abatacept, a selective T-cell co-stimulation modulator, on vaccination has not been previously investigated. In this open-label, single-dose, randomized, parallel-group, controlled study, the effect of a single 750 mg infusion of abatacept on the antibody response to the intramuscular tetanus toxoid vaccine (primarily a memory response to a T-cell-dependent peptide antigen) and the intramuscular 23-valent pneumococcal vaccine (a less T-cell-dependent response to a polysaccharide antigen) was measured in 80 normal healthy volunteers. Subjects were uniformly randomized to receive one of four treatments: Group A (control group), subjects received vaccines on day 1 only; Group B, subjects received vaccines 2 weeks before abatacept; Group C, subjects received vaccines 2 weeks after abatacept; and Group D, subjects received vaccines 8 weeks after abatacept. Anti-tetanus and anti-pneumococcal (Danish serotypes 2, 6B, 8, 9V, 14, 19F and 23F) antibody titers were measured 14 and 28 days after vaccination. While there were no statistically significant differences between the dosing groups, geometric mean titers following tetanus or pneumococcal vaccination were generally lower in subjects who were vaccinated 2 weeks after receiving abatacept, compared with control subjects. A positive response (defined as a twofold increase in antibody titer from baseline) to tetanus vaccination at 28 days was seen, however, in ≥ 60% of subjects across all treatment groups versus 75% of control subjects. Similarly, over 70% of abatacept-treated subjects versus all control subjects (100%) responded to at least three pneumococcal serotypes, and approximately 25–30% of abatacept-treated subjects versus 45% of control subjects responded to at least six serotypes. PMID:17425783

  1. 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.

  2. 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. Copyright © 2014 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

  3. Nasopharyngeal pneumococcal carriage after combined pneumococcal conjugate and polysaccharide vaccination in children with a history of recurrent acute otitis media.

    PubMed

    Veenhoven, Reinier H; Bogaert, Debby; Schilder, Anne G M; Rijkers, Ger T; Uiterwaal, Cuno S P M; Kiezebrink, Herma H; van Kempen, Muriel J P; Dhooge, Inge J; Bruin, Jacob; Ijzerman, Ed P F; de Groot, Ronald; Kuis, Wietse; Hermans, Peter W M; Sanders, Elisabeth A M

    2004-10-01

    We recently showed that vaccination with a 7-valent pneumococcal conjugate vaccine (PCV7) followed by a 23-valent pneumococcal polysaccharide vaccine (PPSV23) failed to prevent new episodes of acute otitis media (AOM) in previously unvaccinated toddlers and children with a history of recurrent AOM. We describe in detail the impact of pneumococcal vaccinations on nasopharyngeal carriage of S. pneumoniae in this study population. The impact of vaccination with PCV7 followed by PPSV23 on pneumococcal nasopharyngeal carriage was studied in a prospective, randomized trial involving 383 children (age range, 1-7 years) with previous AOM. Nasopharyngeal swab specimens were collected at the time of first vaccination and at 6-7-month intervals during the 26-month follow-up period. Overall, pneumococcal carriage rates did not diminish, remaining at approximately 50% in both PCV7/PPSV23 and control vaccinees. A significant shift from conjugate vaccine- to nonconjugate vaccine-type pneumococci was observed in children aged 1-2 years, who received the conjugate vaccine twice before the polysaccharide vaccine was administered. Conjugate vaccine serotype carriage was not influenced in older children, who received the conjugate vaccine once before receiving the polysaccharide booster. The administration of conjugate vaccines at least twice also after 2 years of age may be mandatory for reducing the carriage of conjugate vaccine serotypes in children with recurrent AOM. Polysaccharide booster vaccination did not affect nasopharyngeal colonization with serotypes not included in the conjugate vaccine.

  4. Pneumococcal polysaccharide conjugate vaccine (13-valent, adsorbed): in older adults.

    PubMed

    Sanford, Mark

    2012-06-18

    Pneumococcal polysaccharide conjugate vaccine (13-valent, adsorbed) [PCV13] is approved for protection against pneumococcal disease in children aged 6 weeks to 5 years and adults aged ≥50 years. In randomized trials in adults aged 60-64 years (not previously vaccinated with 23-valent pneumococcal polysaccharide vaccine [PPV23]) and ≥70 years (previously vaccinated with PPV23), PCV13 was noninferior to PPV23 in opsonophagocytic assay (OPA) geometric mean titres (GMTs) for all 12 serotypes common to the two vaccines. More PCV13 than PPV23 recipients had ≥4-fold increases in serotype 6A OPA GMTs (serotype 6A is not included in PPV23). PCV13 recipients also had higher OPA GMTs and met superiority criteria for most serotypes. Adults aged 50-59 years had antibody responses to PCV13 that were noninferior to those in adults aged 60-64 years for all included serotypes. PCV13 administered concomitantly with trivalent inactivated influenza vaccine in adults aged 50-59 or ≥65 years produced antibody responses that were noninferior to those following sequential administration, except for influenza strain A/H3N2 and pneumococcal serotype 19F in those aged ≥65 years. Antibody responses were numerically higher with sequential administration, although the clinical significance of this is unknown. Adverse events within 14 days of vaccination were mostly of mild-to-moderate severity, with serious events occurring in 0.2-1.4% of PCV13 and 0.4-1.7% of PPV23 recipients.

  5. 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

  6. 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.

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

    PubMed

    Neto, Joao Tonolio; de Araujo, Gabriela Tannus Branco; Gagliardi, Anna; Pinho, Amanda; Durand, Laure; Fonseca, Marcelo

    2011-10-01

    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.

  8. 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

  9. Antibody response to pneumococcal capsular polysaccharide vaccine in Down syndrome patients.

    PubMed

    Costa-Carvalho, B T; Martinez, R M A; Dias, A T N; Kubo, C A; Barros-Nunes, P; Leiva, L; Solé, D; Carneiro-Sampaio, M M S; Naspitz, C K; Sorensen, R U

    2006-12-01

    The majority of children with Down syndrome (DS) tend to have frequent bacterial infections including recurrent respiratory infections. Our objective was to evaluate the production of antibodies to pneumococcal polysaccharide antigens after active immunization in DS subjects. IgG antibodies to pneumococcal serotypes (1, 3, 6B, 9V, and 14) were measured before and 6 weeks after immunization with a 23-valent pneumococcal vaccine (Pneumo23, Pasteur-Merrieux) in 6- to 13-year-old DS children (N = 17) and in aged-matched normal controls (N = 30). An adequate response was defined as a 4-fold increase over baseline or a post-immunization level of specific pneumococcal serotype antibody > or = 1.3 microg/mL. After immunization, all DS children had an increase in post-immunization levels against all serotypes analyzed. A 4-fold or more increase was observed in all DS children concerning serotypes 1 and 14, in 90% of subjects for serotypes 3 and 9V, and in 65% for serotype 6B. Regarding this increase, 8 of the 17 DS children had an adequate response to all serotypes analyzed, 8/17 patients to 4 serotypes and 1/17 to 3 serotypes. However, when we compared post-immunization levels between DS children and controls, we observed lower levels in the former group (P < 0.05) for all serotypes except serotype 3. We conclude that pneumococcal polysaccharide immunization could be beneficial for these DS children.

  10. Immunogenicity of pneumococcal polysaccharide vaccine in adult systemic lupus erythematosus patients undergoing immunosuppressive treatment.

    PubMed

    Rezende, R P V; Ribeiro, F M; Albuquerque, E M N; Gayer, C R; Andrade, L E C; Klumb, E M

    2016-10-01

    To evaluate the immunogenicity of the 23-valent pneumococcal polysaccharide vaccine (PPSV23) in adult systemic lupus erythematosus patients undergoing (IS group) and not undergoing (non-IS group) immunosuppressive treatment. In this prospective open-label study from February 2013 to April 2014, 54 patients had blood samples collected immediately before PPSV23 immunization and 4-6 weeks thereafter for the ELISA measurement of IgG antibody levels against seven pneumococcal serotypes. Positive vaccine response for each serotype was defined as a four-fold or greater antibody response over baseline levels or as a post-vaccine anti-pneumococcal IgG level ≥1.3 µg/ml when baseline values were <1.3 µg/ml. Patients should have responded appropriately to ≥70% of the tested serotypes. We also calculated the mean ratio of post- to pre-vaccination anti-pneumococcal IgG levels. Twenty-eight patients were classified into the IS group and 26 into non-IS group. The median dose of prednisone at baseline was ≤5 mg/day in both groups. Serotype-specific vaccine response rates were not significantly different between the groups. Less than 40% of patients responded adequately by both vaccine response criteria, being numerically lower among IS patients. The mean ratio of increase in anti-pneumococcal levels was 6.4 versus 4.7 (p = 0.001) in non-IS and IS groups, respectively. The vaccine was poorly immunogenic, especially among adult systemic lupus erythematosus patients under immunosuppressive therapy. © The Author(s) 2016.

  11. Long-term Comparative Immunogenicity of Protein Conjugate and Free Polysaccharide Pneumococcal Vaccines in Chronic Obstructive Pulmonary Disease

    PubMed Central

    Dransfield, Mark T.; Harnden, Sarah; Burton, Robert L.; Albert, Richard K.; Bailey, William C.; Casaburi, Richard; Connett, John; Cooper, J. Allen D.; Criner, Gerard J.; Curtis, Jeffrey L.; Han, MeiLan K.; Make, Barry; Marchetti, Nathaniel; Martinez, Fernando J.; McEvoy, Charlene; Nahm, Moon H.; Niewoehner, Dennis E.; Porszasz, Janos; Reilly, John; Scanlon, Paul D.; Scharf, Steven M.; Sciurba, Frank C.; Washko, George R.; Woodruff, Prescott G.; Lazarus, Stephen C.

    2012-01-01

    Background. Although the 23-valent pneumococcal polysaccharide vaccine (PPSV23) protects against invasive disease in young healthy persons, randomized controlled trials in chronic obstructive pulmonary disease (COPD) have demonstrated no benefit in the intention-to-treat population. We previously reported that the 7-valent diphtheria-conjugated pneumococcal polysaccharide vaccine (PCV7) is safe and induced greater serotype-specific immunoglobulin G (IgG) and functional antibody than did PPSV23 1 month after vaccination. We hypothesized that these advantages would persist at 1 and 2 years. Methods. One hundred eighty-one patients with moderate to severe COPD were randomized to receive PPSV23 (n = 90) or PCV7 (1.0 mL; n = 91). We measured IgG by enzyme-linked immunosorbent assay and assessed functional antibody activity by a standardized opsonophagocytosis assay, reported as a killing index (OPK). We determined differences in IgG and OPK between vaccine groups at 1 and 2 years. Results. Relative to PPSV23, PCV7 induced greater OPK at both 1 and 2 years for 6 of 7 serotypes (not 19F). This response was statistically greater for 5 of 7 serotypes at 1 year and 4 of 7 at 2 years. Comparable differences in IgG were observed but were less often statistically significant. Despite meeting Centers for Disease Control and Prevention criteria for PPSV23 administration, almost 50% of individuals had never been vaccinated. No differences in the frequency of acute exacerbations, pneumonia, or hospitalization were observed. Conclusions. PCV7 induces a greater functional antibody response than PPSV23 in patients with COPD that persists for 2 years after vaccination. This superior functional response supports testing of conjugate vaccination in studies examining clinical end points. Clinical Trials Registration: NCT00457977. PMID:22652582

  12. 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.

  13. Association of time since pneumococcal polysaccharide vaccine receipt and CD4 count with antibody response to the 13-valent pneumococcal conjugate vaccine in HIV-infected adults.

    PubMed

    Rossheim, Alexandria E-B; Young, Anna Marie P; Siik, Julia; Cunningham, Tina D; Troy, Stephanie B

    2016-08-02

    Pneumococcal infection is a leading cause of illness and death in HIV-infected adults. Current United States guidelines for HIV-infected adults recommend a single dose of the 13-valent pneumococcal conjugate vaccine (PCV-13) at any CD4 count and at least 1 y after receipt of the 23-valent pneumococcal polysaccharide vaccine (PPV). PPV is known to lead to hyporesponsiveness to subsequent pneumococcal vaccines for at least 1 y Whether PCV-13 would be more immunogenic if administered later after PPV receipt or at higher CD4 counts has not been tested. We prospectively collected serum from 96 HIV-infected adults before and after PCV-13 receipt, and measured antibody concentrations against 4 pneumococcal serotypes (3, 6A, 7F, and 19A) via indirect ELISA according to the WHO protocol. Post-booster antibody concentrations and fold-rise in antibody concentrations were compared according to time from PPV receipt and baseline CD4 count using univariate and multivariate analyses. PPV receipt >3 versus 1-3 y prior did not significantly change post-vaccination antibody concentrations, but was associated with slightly higher fold-rise in antibody concentration for the 3 tested serotypes included in PPV, though this only reached significance for serotype 7F. CD4 count was significantly associated with post-vaccination antibody concentrations for 3 of 4 serotypes, but not for fold-rise in antibody concentration for any serotype. Waiting longer than 1 y after PPV receipt to administer PCV-13 may slightly improve the antibody response to serotypes included in both vaccines. While higher CD4 count at PCV-13 administration results in higher post-vaccination antibody concentrations, this is likely because higher CD4 count is also associated with higher pre-vaccination antibody concentrations.

  14. Association of time since pneumococcal polysaccharide vaccine receipt and CD4 count with antibody response to the 13-valent pneumococcal conjugate vaccine in HIV-infected adults

    PubMed Central

    Rossheim, Alexandria E.-B.; Young, Anna Marie P.; Siik, Julia; Cunningham, Tina D.; Troy, Stephanie B.

    2016-01-01

    ABSTRACT Introduction: Pneumococcal infection is a leading cause of illness and death in HIV-infected adults. Current United States guidelines for HIV-infected adults recommend a single dose of the 13-valent pneumococcal conjugate vaccine (PCV-13) at any CD4 count and at least 1 y after receipt of the 23-valent pneumococcal polysaccharide vaccine (PPV). PPV is known to lead to hyporesponsiveness to subsequent pneumococcal vaccines for at least 1 y Whether PCV-13 would be more immunogenic if administered later after PPV receipt or at higher CD4 counts has not been tested. Methods: We prospectively collected serum from 96 HIV-infected adults before and after PCV-13 receipt, and measured antibody concentrations against 4 pneumococcal serotypes (3, 6A, 7F, and 19A) via indirect ELISA according to the WHO protocol. Post-booster antibody concentrations and fold-rise in antibody concentrations were compared according to time from PPV receipt and baseline CD4 count using univariate and multivariate analyses. Results: PPV receipt >3 versus 1–3 y prior did not significantly change post-vaccination antibody concentrations, but was associated with slightly higher fold-rise in antibody concentration for the 3 tested serotypes included in PPV, though this only reached significance for serotype 7F. CD4 count was significantly associated with post-vaccination antibody concentrations for 3 of 4 serotypes, but not for fold-rise in antibody concentration for any serotype. Conclusion: Waiting longer than 1 y after PPV receipt to administer PCV-13 may slightly improve the antibody response to serotypes included in both vaccines. While higher CD4 count at PCV-13 administration results in higher post-vaccination antibody concentrations, this is likely because higher CD4 count is also associated with higher pre-vaccination antibody concentrations. PMID:27172241

  15. Repeat pneumococcal polysaccharide vaccine in Indigenous Australian adults is associated with decreased immune responsiveness.

    PubMed

    Moberley, Sarah; Licciardi, Paul V; Balloch, Anne; Andrews, Ross; Leach, Amanda J; Kirkwood, Marie; Binks, Paula; Mulholland, Kim; Carapetis, Jonathan; Tang, Mimi L K; Skull, Sue

    2017-05-19

    Indigenous adults residing in the Northern Territory of Australia experience elevated rates of invasive pneumococcal disease despite the routine use of 23-valent pneumococcal polysaccharide vaccine (23vPPV). We hypothesised that the limited protection from 23vPPV may be due to hyporesponsiveness as a result of vaccine failure from repeated vaccination. To explore this possibility, we evaluated the immune response to a first and second dose of 23vPPV in Indigenous adults and a first dose of 23vPPV in non-Indigenous adults. Serotype-specific IgG was measured by ELISA for all 23 vaccine serotypes at baseline and at one month post-vaccination. Individuals were considered to have an adequate immune response if paired sera demonstrated either: a four-fold rise in antibody concentration; a two-fold rise if the post vaccination antibody was >1.3μg/ml but <4.0μg/ml; or a post-vaccination antibody concentration >4.0μg/ml for at least half of the serotypes tested (12/23). Our per-protocol analysis included the comparison of outcomes for three groups: Indigenous adults receiving a second 23vPPV dose (N=20) and Indigenous (N=60) and non-Indigenous adults (N=25) receiving their first 23vPPV dose. All non-Indigenous adults receiving a first dose of 23vPPV mounted an adequate immune response (25/25). There was no significant difference in the proportion of individuals with an adequate response using our definition (primary endpoint), with 88% of Indigenous adults mounted an adequate response following first dose 23vPPV (53/60) compared to 70% having an adequate response following a second dose of 23vPPV (14/20; p=0.05). The risk difference between Indigenous participants receiving first dose compared to non-Indigenous participants receiving first dose was significant when comparing a response threshold of at least 70% (-27%, 95% CI: -43% to -11%; p=0.01) and 90% (-38%, 95% CI: -60% to -16%; p=0.006) of serotypes with a positive response. Indigenous participants demonstrated a

  16. 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.

  17. Pneumococcal polysaccharide vaccination among adults aged 65 years and older, U.S., 1989-2008.

    PubMed

    Lu, Peng-jun; Nuorti, J Pekka

    2010-10-01

    The 23-valent pneumococcal polysaccharide vaccine (PPSV23) has been recommended for all people aged ≥65 years in the U.S. since 1983; consistent surveillance for vaccine coverage has been conducted since 1989. To assess PPSV23 vaccination coverage among adults aged ≥65 years in the U.S. The data were analyzed from the 1989, 1991, 1993-1995, and 1997-2008 National Health Interview Surveys in 2009. Multivariable logistic regression and predictive marginal analyses were conducted to identify factors independently associated with receiving PPSV23 in 2008. Missed opportunities for vaccination were also assessed. Among people aged ≥65 years, PPSV23 coverage increased from 14.1% in 1989 to 60.1% in 2008. On average, vaccination coverage increased by 3.5% annually during 1989-2000 compared with 1.0% during 2001-2008. In 2008, coverage was significantly higher for people aged 75-84 years (68.8%), and ≥85 years (69.0%) compared with those aged 65-74 years (52.5%). Coverage was significantly higher for non-Hispanic whites (64.3%) compared with non-Hispanic blacks (44.6%) and those with Hispanic ethnicity (36.4%). Among people aged ≥65 years who reported never receiving PPSV23, 90.6% reported at least one missed opportunity. Characteristics independently associated with increased likelihood of ever receiving PPSV23 were higher age, female, non-Hispanic white race/ethnicity, not employed, higher education level, more physician visits in the past year, hospitalized within past year, having Medicare and other supplemental health insurance, and having a chronic medical condition. National PPSV23 coverage among people aged ≥65 years increased substantially until 2000, but the rate of increase was smaller after 2000 and coverage in 2008 remained well below the national Healthy People 2010 target of 90%. Increased efforts to avoid missed opportunities for pneumococcal vaccination are needed, especially among minority populations. Published by Elsevier Inc.

  18. Cost-effectiveness of polysaccharide pneumococcal vaccination in people aged 65 and above in Poland

    PubMed Central

    Grzesiowski, Pawel; Aguiar-Ibáñez, Raquel; Kobryń, Aleksandra; Durand, Laure; Puig, Pierre-Emmanuel

    2012-01-01

    Introduction: Invasive pneumococcal disease is associated with substantial morbidity, mortality and cost implications, which could be reduced by vaccination. Aim: To assess the cost-effectiveness of a 23-valent pneumococcal vaccine in the elderly (65 and older) in Poland. Methods: A Markov model with a 1-year cycle length was developed, allowing up to 10 cohorts to enter the model over the lifetime horizon (35 years). In the base case, costs and benefits were assessed using the public health care payer (NFZ) perspective. The analysis included routine vaccination of all elderly and high-risk (HR) elderly versus no vaccination. The analysis assumed that the government would reimburse 50% of the vaccine price. Costs and benefits were discounted 5%, with costs expressed in 2009 Polish Zloty (PLN). Extensive sensitivity analyses were carried out. Results: PPV23 vaccination targeting all elderly and HR elderly in Poland would avoid 8,935 pneumococcal infections, 2,542 hospitalisations, 671 deaths and 5,886 infections, 1,673 hospitalisations and 441 deaths respectively. The incremental cost per QALY gained would be PLN 3,382 in all elderly and PLN2,148 in HR elderly. Conclusion: Vaccinating adults 65 and older regardless of risk status with a 23-valent pneumococcal vaccine, is cost-effective, resulting in clinical and economic benefits including a non-negligible reduction of ambulatory doctor visits, hospitalizations and, deaths in Poland. PMID:23095867

  19. Campylobacter Polysaccharide Capsules: Virulence and Vaccines

    PubMed Central

    Guerry, Patricia; Poly, Frédéric; Riddle, Mark; Maue, Alexander C.; Chen, Yu-Han; Monteiro, Mario A.

    2012-01-01

    Campylobacter jejuni remains a major cause of bacterial diarrhea worldwide and is associated with numerous sequelae, including Guillain Barré Syndrome, inflammatory bowel disease, reactive arthritis, and irritable bowel syndrome. C. jejuni is unusual for an intestinal pathogen in its ability to coat its surface with a polysaccharide capsule (CPS). These capsular polysaccharides vary in sugar composition and linkage, especially those involving heptoses of unusual configuration and O-methyl phosphoramidate linkages. This structural diversity is consistent with CPS being the major serodeterminant of the Penner scheme, of which there are 47 C. jejuni serotypes. Both CPS expression and expression of modifications are subject to phase variation by slip strand mismatch repair. Although capsules are virulence factors for other pathogens, the role of CPS in C. jejuni disease has not been well defined beyond descriptive studies demonstrating a role in serum resistance and for diarrhea in a ferret model of disease. However, perhaps the most compelling evidence for a role in pathogenesis are data that CPS conjugate vaccines protect against diarrheal disease in non-human primates. A CPS conjugate vaccine approach against this pathogen is intriguing, but several questions need to be addressed, including the valency of CPS types required for an effective vaccine. There have been numerous studies of prevalence of CPS serotypes in the developed world, but few studies from developing countries where the disease incidence is higher. The complexity and cost of Penner serotyping has limited its usefulness, and a recently developed multiplex PCR method for determination of capsule type offers the potential of a more rapid and affordable method. Comparative studies have shown a strong correlation of the two methods and studies are beginning to ascertain CPS-type distribution worldwide, as well as examination of correlation of severity of illness with specific CPS types. PMID:22919599

  20. Immunogenicity and safety of pneumococcal conjugate polysaccharide and free polysaccharide vaccines alone or combined in HIV-infected adults in Brazil.

    PubMed

    Ho, Yeh-Li; Brandão, Angela Pires; de Cunto Brandileone, Maria Cristina; Lopes, Marta Heloisa

    2013-08-20

    Streptococcus pneumoniae is a leading cause of hospitalization in HIV-infected adults therefore pneumococcal vaccine is recommended. The ideal antipneumococcal vaccine and effective vaccination regimen remain controversial and needs further evaluation. To assess the efficacy of pneumococcal vaccines alone and combined, a randomized, blinded clinical trial was conducted in Brazil with 331 HIV-patients aged 18-60, with CD4-T cell count ≥ 200 cells/mm(3). Two interventions 60 days apart were done in three schedules: 23-valent pneumococcal polysaccharide vaccine (PPV23)/placebo; 7-valent pneumococcal conjugate vaccine (PCV7)/placebo; and PCV7 plus PPV23. Safety and reactogenicity were evaluated, and immunogenicity was assessed by an IgG enzyme-linked immunosorbent assay to S. pneumoniae serotypes 6B, 9V and 14, performed at baseline, 60 and 180 days after first intervention. Comparison of immunogenicity was based on geometric mean concentration (GMC), percentages of individuals with serotype-specific IgG ≥ 0.35μg/mL and ≥ 1.0 μg/mL and proportion of individuals with ≥ 4-fold increase in specific antibody concentrations for each serotype. Demographic and HIV conditions were similar, and both vaccines were well tolerated across vaccine groups. Significant increase in IgG-antibodies was observed to all serotypes evaluated. A greater proportion of PCV7 recipients reached and sustained IgG antibody concentrations at least four times as high as those at baseline, for serotypes 6B and 9V. A PPV23 dose after PCV7 did not enhance immunogenicity. In this first trial conducted with HIV-infected immunologically stable adults in South America, both PPV23 and PCV7 were safe and immunogenic. Evidence suggesting PCV7 was more immunogenic than PPV23, as it elicited higher and persistent ≥ 4-fold increase of antibodies for 6B and 9V serotypes in a greater proportion of HIV-patients is noteworthy. Despite current recommendation of schedules combining PCV7 and PPV23, there is

  1. [Efficacy of the meningococcal vaccine from Group C capsular polysaccharide].

    PubMed

    González Enríquez, J; García Comas, L; Alcaide Jiménez, J F; Sáenz Calvo, A; Conde Olasagasti, J

    1997-01-01

    This report is a systematic review of the effect intensity and duration of the immune response to meningococcal serogroup C vaccine. The vaccine safety, efficacy and effectiveness are also analyzed. MEDLINE literature search in the period 1970-1996. Meningoccocal polysaccharide vaccine clinical trials and human prospective studies were specifically searched. Quality of the retrieved studies were analyzed. Information available was integrated. Group C meningoccal polysaccharide vaccine is a safe product. Its efficacy is over 85% among adults and children over 5 years old. 70% (CI 95%: 5-91%) under 5 years old, and 55% among children 2-3 years old. The vaccine is not effective under 2 years. The duration of protective antibody levels decrease with age. The proportion of vaccinated children effectively protected one year after vaccination is low. Vaccination does not affect the immune response to ulterior revaccination. Group C meningococcal polysaccharide vaccine is indicated in adults and children over 2 years old to protect them from meningococcal disease due to group C when exposed to high risk of infection. The outbreaks control is the main indication for the use of this vaccine. Routine immunization in not outbreak situation is not recommended due to the small vaccine protection in children under 2 years old, the limited efficacy in children under 5, and the short duration of the immunity in children.

  2. The effectiveness of pneumococcal polysaccharide vaccine 23 (PPV23) in the general population of 50 years of age and older: A systematic review and meta-analysis.

    PubMed

    Kraicer-Melamed, Hannah; O'Donnell, Shauna; Quach, Caroline

    2016-03-18

    Two pneumococcal vaccines currently exist and have been recommended for the prevention of pneumococcal infection in adults 65 years of age and older: the 23-valent polysaccharide (PPV23) and the conjugate 13-valent (PCV13) vaccine. To evaluate and summarize the results from all studies reporting on the vaccine effectiveness of PPV23 in preventing invasive pneumococcal disease (IPD) and community-acquired pneumonia (CAP) in individuals over the age of 50. Systematic database searches were completed in PubMed, Medline, Embase, CINAHL, Web of Science, and Cochrane. Google Scholar and hand searches of seminal articles and past systematic reviews were employed. Studies were included if they independently evaluated the effect of PPV23 on IPD and/or CAP in adults (50+). Data extraction and quality assessment were both completed independently by two researchers. Quality was assessed using the National Advisory Committee on Immunization methodology for quality assessment. All conflicts were resolved by consensus. The vaccine effectiveness for PPV23 in preventing IPD was 50% (95% CI: 21%-69%) for cohort studies and 54% (95% CI: 32%-69%) for case-control studies. The VE estimates for CAP were 4% (95% CI: -26%-26%) for trials, 17% (95% CI: -26%-45%) for cohort studies, and 7% (95% CI: -10%-21%) for case-control studies. The vaccine effectiveness of PPV23 in preventing IPD and all-cause CAP was consistent with past systematic reviews and similar to the estimates that were reported in the CAPiTA trial evaluating the vaccine effectiveness of PCV13. Consistent benefits were also reported across ecological studies and reports of surveillance data for the general population 50 years and older. The results suggests that the current practice of vaccinating the adults 65 years of age and older with PPV23 would have similar benefits to PCV13 in preventing potential cases of all-serotype IPD and all-cause CAP. Copyright © 2016 Elsevier Ltd. All rights reserved.

  3. Impact of pneumococcal polysaccharide vaccine on incidence and mortality after pneumonia in adults aged ≥ 60 years - a population-based retrospective cohort study.

    PubMed

    Kolditz, Martin; Schmitt, Jochen; Pletz, Mathias W; Tesch, Falko

    2017-08-19

    The 23-valent pneumococcal polysaccharide vaccine (PPV) is recommended for prevention of pneumococcal diseases in adults at risk. Few data exist on time- age- and sex-dependent vaccine effectiveness on outcomes in pneumonia. We performed a population based cohort study including adults ≥ 60 years of age (n=738.927) based on statutory health insurance data 2005-2011. Primary outcomes were all-cause pneumonia incidence and 30-day all-cause mortality. Pneumonia was identified via ICD-10 codes, ambulatory cases validated by antibiotic prescription within 7 days. The effect of PPV within 5 years was analysed after propensity score based matching (three controls per case with PPV vaccination) including comorbidities, care status, age, sex, and influenza vaccination. Evaluations were stratified by age group, sex and time of PPV. Two-year incidence of all-cause pneumonia in 213.431 vaccinated individuals was 7501/213.431 (3.51%) versus 23.243/640.293 (3.63%) in matched controls (difference -0.11, 95%CI -0.22-0.002, p=0.046). After sex-dependent analysis, PPV effectiveness on pneumonia incidence was observed only in females (difference -0.15, 95% CI -0.28 - -0.02, p=0.02). 30-day mortality in vaccinated individuals with pneumonia was 1302/7501 (17.36%) versus 4267/22.503 (18.96%) in matched controls (difference -1.60%, 95%CI -2.83-0.38, p=0.011). After analysis according to age group, significant mortality reduction was present only in adults of 60 to 79 years (difference -2.31, 95% CI -3.79 - -0.83, p=0.002). Year of PPV vaccination showed no effect on outcomes. The findings support consideration of sex- and age-dependence of PPV effectiveness within further studies. Copyright © 2017. Published by Elsevier Ltd.

  4. 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.

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

    PubMed

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

    2016-06-01

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

  6. 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.

  7. 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

  8. Pneumococcal polysaccharide conjugate vaccine (13-valent, adsorbed) [prevenar 13®].

    PubMed

    Duggan, Sean T

    2010-10-22

    The pneumococcal polysaccharide conjugate vaccine Prevenar 13® (PCV13) comprises 13 capsular Streptococcus pneumoniae polysaccharide serotypes that are individually conjugated to nontoxic diphtheria protein (cross-reactive material [CRM(197)]). In randomized, comparator-controlled, phase III trials in healthy infants aged 2-6 months, PCV13 elicited a strong immune response against all 13 pneumococcal serotypes in terms of the proportion of vaccinees achieving reference antibody levels with a two- or three-dose primary vaccination series. Immune responses for the seven serotypes common to PCV13 and the 7-valent pneumococcal conjugate vaccine Prevenar® (PCV7) were generally similar. Antibodies to all vaccine serotypes were functional. A booster dose of PCV13 administered between 11 and 15 months of age generally boosted the immune response against all 13 serotypes, regardless of whether infants had previously received PCV13 or PCV7 during the primary vaccination phase. Robust immune responses against all serotypes were achieved when PCV13 was administered as catch-up vaccination schedules in older infants and young children aged 7-72 months. Importantly, PCV13 did not interfere with the immune responses to coadministered routine paediatric vaccines. Based on data for PCV7, it is expected that PCV13 will also display protective efficacy against invasive pneumococcal disease, otitis media and pneumonia. PCV13 was generally well tolerated, with an adverse event profile similar to that of PCV7 after any vaccine dose.

  9. 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

    cine 3 c m a a f w [ a [ e h a S i o c o o t P r i p c a i p t p c a h d o w t i s i U b m e s a a t 1 t a [ p p s r p o n r i t K.L. Russell et al...attempts were made to also capture a convalescent serum sample 2 weeks after the acute presentation. These attempts were not always 1 cine 3 s v i s 2 u...129 vs 41 452, for vac- cine vs placebo) or when stratified by training site (data not shown). The highest number of

  10. 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

  11. 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.

  12. The effectiveness of the polysaccharide pneumococcal vaccine for the prevention of hospitalizations due to Streptococcus pneumoniae community-acquired pneumonia in the elderly differs between the sexes: results from the Community-Acquired Pneumonia Organization (CAPO) international cohort study.

    PubMed

    Wiemken, Timothy L; Carrico, Ruth M; Klein, Sabra L; Jonsson, Colleen B; Peyrani, Paula; Kelley, Robert R; Aliberti, Stefano; Blasi, Francesco; Fernandez-Gonzalez, Ricardo; Lopardo, Gustavo; Ramirez, Julio A

    2014-04-17

    The effectiveness of the 23-valent pneumococcal polysaccharide vaccine (PPV23) to prevent hospitalizations due to Streptococcus pneumoniae community-acquired pneumonia (SpCAP) is controversial. Recent literature suggests that vaccine effectiveness may be influenced by sex. In this study, we define the effectiveness of prior PPV23 vaccination for the prevention of hospitalizations due to SpCAP, and evaluate the impact of sex on this effectiveness. This was a nested case-control study from the CAPO international cohort study database. SpCAP was defined as CAP plus S. pneumoniae identified in blood, bronchoalveolar lavage, sputum, or urinary antigen. Vaccination with PPV23 prior to hospitalization was defined as documented in the medical record. A propensity score-weighted logistic regression model was used to calculate odds ratios. The adjusted vaccine effectiveness (aVE) was calculated as 1-adjusted odds ratio. From a total of 2688 elderly adult hospitalized patients with CAP, SpCAP was identified in 279 (10%). The overall aVE was 37% (95% CI: 10.1-55.4%, P=0.01). For males, the aVE was 34% (95% CI:-1.0% to 57.3%, P=0.06). For females the aVE was 68% (95% CI: 40.3-83.0%, P=0.001). PPV23 protects elderly patients from hospitalization due to SpCAP, but female sex drives the effectiveness. Future analysis of vaccine trials should consider the importance of sex as a stratification factor. Copyright © 2014 Elsevier Ltd. All rights reserved.

  13. 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

  14. Defective anti-polysaccharide IgG vaccine responses in IgA deficient mice.

    PubMed

    Furuya, Yoichi; Kirimanjeswara, Girish S; Roberts, Sean; Racine, Rachael; Wilson-Welder, Jennifer; Sanfilippo, Alan M; Salmon, Sharon L; Metzger, Dennis W

    2017-09-05

    We report that IgA(-/-) mice exhibit specific defects in IgG antibody responses to various polysaccharide vaccines (Francisella tularensis LPS and Pneumovax), but not protein vaccines such as Fluzone. This defect further included responses to polysaccharide-protein conjugate vaccines (Prevnar and Haemophilus influenzae type b-tetanus toxoid vaccine). In agreement with these findings, IgA(-/-) mice were protected from pathogen challenge with protein- but not polysaccharide-based vaccines. Interestingly, after immunization with live bacteria, IgA(+/+) and IgA(-/-) mice were both resistant to lethal challenge and their IgG anti-polysaccharide antibody responses were comparable. Immunization with live bacteria, but not purified polysaccharide, induced production of serum B cell-activating factor (BAFF), a cytokine important for IgG class switching; supplementing IgA(-/-) cell cultures with BAFF enhanced in vitro polyclonal IgG production. Taken together, these findings show that IgA deficiency impairs IgG class switching following vaccination with polysaccharide antigens and that live bacterial immunization can overcome this defect. Since IgA deficient patients also often show defects in antibody responses following immunization with polysaccharide vaccines, our findings could have relevance to the clinical management of this population. Copyright © 2017 Elsevier Ltd. All rights reserved.

  15. 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.

  16. Base hydrolysis of phosphodiester bonds in pneumococcal polysaccharides.

    PubMed

    Pujar, Narahari S; Huang, Ngan Fong; Daniels, Christopher L; Dieter, Lance; Gayton, Marshall G; Lee, Ann L

    2004-09-01

    A comprehensive study of the base hydrolysis of all phosphodiester bond-containing capsular polysaccharides of the 23-valent pneumococcal vaccine is described here. Capsular polysaccharides from serotypes 6B, 10A, 17F, 19A, 19F, and 20 contain a phosphodiester bond that connects the repeating units in these polysaccharides (also referred to as backbone phosphodiester bonds), and polysaccharides from serotypes 11A, 15B, 18C, and 23F contain a phosphodiester bond that links a side chain to their repeating units. Molecular weight measurements of the polysaccharides, using high performance size exclusion chromatography with tandem multiangle laser light scattering and refractive index detection, was used to evaluate the kinetics of hydrolysis. The measurement of molecular weight provides a high degree of sensitivity in the case of small extents of reaction, thus allowing reliable measurements of the kinetics over short times. Pseudo-first-order rate constants for these polysaccharides were estimated using a simple model that accounts for the polydispersity of the starting sample. It was found that the relative order of backbone phosphodiester bond instability due to base hydrolysis was 19A > 10A > 19F > 6B > 17F, 20. Degradation of side-chain phosphodiester bonds was not observed, although the high degree of sensitivity in measurements is lost in this case, due to the low contribution of the side chains to the total polysaccharide molecular weight. In comparison with literature data on pneumococcal polysaccharide 6A, 19A was found to be the more labile, and hence appears to be the most labile pneumococcal polysaccharide studied to date. The rate of hydrolysis increased at higher pH and in the presence of divalent cation, but the extent was lower than expected based on similar data on RNA. Finally, the differences in the phosphodiester bond stabilities were analyzed by considering stereochemical factors in these polysaccharides. These results also provide a framework

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

    PubMed Central

    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 VaxcineTM, 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 VaxcineTM 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. PMID:25483465

  18. 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.

  19. Vaccination of COPD patients with a pneumococcus type 6B tetanus toxoid conjugate vaccine.

    PubMed

    Jonsson, S; Vidarsson, G; Valdimarsson, H; Schiffman, G; Schneerson, R; Jonsdottir, I

    2002-10-01

    This paper examines how pneumococcal type 6B polysaccharide conjugated to tetanus toxoid (Pn6B-TT) compares to a 23 valent pneumococcal vaccine (pneumococcal polysaccharide (PPS)-23) with respect to immunogenicity and serum opsonic activity in patients with chronic obstructive pulmonary disease (COPD). Patients with COPD aged 55-75 yrs were vaccinated with Pn6B-TT (n=10) or with PPS-23 (n=9). Healthy young adults (HA) were vaccinated with Pn6B-TT as controls. Total antibodies to serotype 6B polysaccharide were measured by radioimmunoassay and immunoglobulin (Ig)G antibodies by enzyme-linked immunosorbent assay. Opsonic activity was measured by a phagocytosis assay using human neutrophils as effector cells. The patient groups were comparable by age, smoking history, lung function and use of steroids. COPD patients vaccinated with Pn6B-TT or PPS-23 showed an increase in IgG antibodies and a nonsignificant increase in opsonic activity. This was similar to the increase in IgG and opsonic activity seen in HA. There was a significant correlation between antibody levels and opsonic activity in COPD patients vaccinated both with Pn6B-TT and PPS-23. Pneumococcal antibodies have been shown to confer protection from infection. The results of the present study indicate that protective immunity can be expected in elderly chronic obstructive pulmonary disease patients vaccinated with conjugate vaccines.

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

    PubMed Central

    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

    2016-01-01

    ABSTRACT 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. PMID:27064311

  1. 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.

  2. Early-life and contemporaneous nutritional and environmental predictors of antibody response to vaccination in young Gambian adults.

    PubMed

    Moore, Sophie E; Richards, Anna A; Goldblatt, David; Ashton, Lindsey; Szu, Shousun Chen; Prentice, Andrew M

    2012-07-06

    Recent research links nutritional exposures early in life with alterations in functional immunity that persist beyond childhood. Here we investigate predictors of antibody response to polysaccharide vaccines in a cohort of Gambian adults with detailed records from birth and early infancy available. 320 adults were given a single dose of a Vi polysaccharide vaccine for Salmonella typhi and a 23-valent capsular polysaccharide pneumococcal vaccine. Anti-Vi antibody levels and antibodies against 4 pneumococcal serotypes (1, 5, 14 and 23F) were measured in serum samples collected at baseline and then 14 days following vaccination and compared to data available from birth and early infancy. Post-vaccination antibody titres to serotype 14 of the pneumococcal vaccine were negatively associated with rate of growth from birth to three months of age, infant weight at 12 months of age and season of birth, but no other associations were observed with early-life exposures. The strongest predictor of antibody levels was pre-vaccination antibody titres, with adult height and serum neopterin levels at time of vaccination also implicated. The current study does not support the hypothesis that nutritional exposures early in life consistently compromise antibody response to polysaccharide vaccines administered in young adulthood. Copyright © 2012 Elsevier Ltd. All rights reserved.

  3. Early-life and contemporaneous nutritional and environmental predictors of antibody response to vaccination in young Gambian adults

    PubMed Central

    Moore, Sophie E.; Richards, Anna A.; Goldblatt, David; Ashton, Lindsey; Szu, Shousun Chen; Prentice, Andrew M.

    2012-01-01

    Recent research links nutritional exposures early in life with alterations in functional immunity that persist beyond childhood. Here we investigate predictors of antibody response to polysaccharide vaccines in a cohort of Gambian adults with detailed records from birth and early infancy available. 320 adults were given a single dose of a Vi polysaccharide vaccine for Salmonella typhi and a 23-valent capsular polysaccharide pneumococcal vaccine. Anti-Vi antibody levels and antibodies against 4 pneumococcal serotypes (1, 5, 14 and 23F) were measured in serum samples collected at baseline and then 14 days following vaccination and compared to data available from birth and early infancy. Post-vaccination antibody titres to serotype 14 of the pneumococcal vaccine were negatively associated with rate of growth from birth to three months of age, infant weight at 12 months of age and season of birth, but no other associations were observed with early-life exposures. The strongest predictor of antibody levels was pre-vaccination antibody titres, with adult height and serum neopterin levels at time of vaccination also implicated. The current study does not support the hypothesis that nutritional exposures early in life consistently compromise antibody response to polysaccharide vaccines administered in young adulthood. PMID:22609011

  4. 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.

  5. [Evaluating efficiency of combined vaccination against influenza and pneumococcal infection in workers of "Gazprom transgaz Yekaterinburg" company].

    PubMed

    Lugovskaia, N A; Bushueva, L E; Tulupova, L G; Kholopov, I O

    2014-01-01

    Influenza-like diseases are among the causes of disability. Risk of these diseases is increased with other occupational hazards. The study covered efficiency of combined vaccination against influenza (annually, over 2 years, with inactivated split-vaccine Vaxigrip) and pneumococcal infection (single, with 23-valent pneumococcal polysaccharide vaccine Pneumo 23) in 318 workers of Neviansk branch of "Gazprom transgaz Yekaterinburg" company. Among them, 49 workers (welders and joiners) were exposed to occupational hazards. Findings are that general frequency of such diseases decreased by 17% over the first year after the vaccination and by 27% over the second year, and in welders and joiners group--by 33% and 44% respectively. The authors proved economic efficiency of combined vaccination with Vaxigrip and Pneumo 23.

  6. 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.

  7. 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

  8. 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

  9. 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.

  10. Evaluating the costs and benefits of pneumococcal vaccination in adults.

    PubMed

    Porchia, Barbara Rita; Bonanni, Paolo; Bechini, Angela; Bonaccorsi, Gugliemo; Boccalini, Sara

    2017-02-01

    Pneumococcal infection is a public health concern that disproportionately affects the young, the elderly, and the immunocompromised. There is an open debate on the implementation of polysaccharide and/or conjugate vaccines for pneumococcal diseases in adults and the elderly in many countries. The aim of this paper is to systematically review the economic profile of pneumococcal vaccines in adults in terms of costs and benefits. Areas covered: The search for economic studies on pneumococcal vaccination was carried out in Pubmed, Embase, Scopus, and the HTA and NHS EED databases and through a manual search in journals dealing with economic evaluations. We included original articles and reviews with economic evaluation of polysaccharide 23-valent (PPV23) and/or conjugate pneumococcal vaccine 13-valent (PCV13) use in adults, the elderly, and at-risk groups to provide a systematic review of economical evaluation. Expert commentary: Pneumococcal vaccination is strongly recommended for all adults, especially subjects at risk and the elderly. Pneumococcal vaccination with PCV13 or PPV23 in adults is good value for money and should be a priority for the decision-makers. The main issue is how vaccination could be offered.

  11. [Vaccinations from the pulmonologist's point of view].

    PubMed

    Forstner, C; Pletz, M W

    2015-07-01

    The best strategy for prevention of acute respiratory tract infections is primary prophylaxis against diseases preventable by vaccination. From the pulmonologist's point of view, vaccinations against pneumococci, influenza A and B viruses and Bordetella pertussis are of particular clinical relevance. This review article discusses the disease burden of these pathogens and the recommendations for immunization in adults. For immunization against pneumococci a less immunogenic but broad-spectrum 23-valent polysaccharide vaccine (PPV23) and a highly immunogenic 13-valent conjugate vaccine (PCV13) with a more narrow-spectrum are approved. A sequential vaccination with PCV13 followed by PPV23 is a new option in adults. In the US this vaccination strategy is recommended as routine vaccination for all adults over 65. In Germany sequential pneumococcal vaccination is proposed only in special indications such as patients with asplenia. Trivalent and quadrivalent split-virus vaccines are the standard vaccines against seasonal influenza in adults. The Standing Committee on Vaccinations (STIKO) recommends a yearly vaccination as standard over 60 and in indications for special risk groups (e.g. infants with underlying diseases, immunocompromised patients, chronically ill patients and pregnant women). For the primary prophylaxis of pertussis only an acellular vaccine is available. Neither vaccination nor a previous infection provide lifelong immunity; therefore, the STIKO recommends an additional booster vaccine for all adults. Vaccination against pneumococci, influenza A and B viruses as well as Bordetella pertussis are recommended as standard and in special indications for adults by the STIKO at the Robert Koch Institute. For selection of the various vaccines individual factors such as age, immune status, comorbidities and pregnancy have to be considered.

  12. Determination of free polysaccharide in Vi glycoconjugate vaccine against typhoid fever.

    PubMed

    Giannelli, C; Cappelletti, E; Di Benedetto, R; Pippi, F; Arcuri, M; Di Cioccio, V; Martin, L B; Saul, A; Micoli, F

    2017-05-30

    Glycoconjugate vaccines based on the Vi capsular polysaccharide directed against Salmonella enterica serovar Typhi are licensed or in development against typhoid fever, an important cause of morbidity and mortality in developing countries. Quantification of free polysaccharide in conjugate vaccines is an important quality control for release, to monitor vaccine stability and to ensure appropriate immune response. However, we found that existing separation methods based on size are not appropriate as free Vi non-specifically binds to unconjugated and conjugated protein. We developed a method based on free Vi separation by Capto Adhere resin and quantification by HPAEC-PAD. The method has been tested for conjugates of Vi derived from Citrobacter freundii with different carrier proteins such as CRM197, Tetanus Toxoid and Diphtheria Toxoid. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

  13. 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

  14. Differential regulation of polysaccharide-specific antibody responses to isolated polysaccharides, conjugate vaccines, and intact Gram-positive versus Gram-negative extracellular bacteria.

    PubMed

    Snapper, Clifford M

    2016-06-24

    Bacterial capsular polysaccharides are major virulence factors and are key targets in a number of licensed anti-bacterial vaccines. Their major characteristics are their large molecular weight and expression of repeating antigenic epitopes that mediate multivalent B cell receptor cross-linking. In addition, since the majority of these antigens cannot associate with MHC-II they fail to recruit CD4+ T cell help and are referred to as T cell-independent antigens. In this review I will discuss a series of studies from my laboratory that have underscored the importance of understanding polysaccharide-specific antibody responses within the context in which the PS is expressed (i.e. in isolation, as a component of conjugate vaccines, and expressed naturally by intact bacteria). We have shown that multivalent B cell receptor crosslinking, as mediated by polysaccharides, uniquely determines the qualitative response of the B cell to subsequent stimuli, but by itself is insufficient to induce antibody secretion or class switching. For these latter events to occur, second signals must act in concert with primary signals derived from the B cell receptor. The co-expression of polysaccharide and protein within intact bacteria promotes recruitment of CD4+ T cell help for the associated PS-specific IgG response, in contrast to isolated polysaccharides. Further, the particulate nature of extracellular bacteria confers properties to the polysaccharide-specific IgG response that makes it distinct immunologically from soluble conjugate vaccines. Finally, the underlying biochemical and/or structural differences that distinguish Gram-positive and Gram-negative bacteria appear to play critical roles in differentially regulating the associated polysaccharide-specific IgG responses to these groups of pathogens. These studies have a number of implications for the understanding and future design of polysaccharide-based vaccines. Published by Elsevier Ltd.

  15. 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

  16. [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.

  17. Pneumococcal polysaccharide vaccine - what you need to know

    MedlinePlus

    ... As with any medicine, there is a very remote chance of a vaccine causing a serious injury ... state health department . Contact the Centers for Disease Control and Prevention (CDC): Call 1-800-232-4636 ( ...

  18. Pneumococcal Polysaccharide Vaccine: What You Need to Know

    MedlinePlus

    ... As with any medicine, there is a very remote chance of a vaccine causing a serious injury ... state health department. • Contact the Centers for Disease Control and Prevention (CDC): - Call 1-800-232-4636 ( ...

  19. 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.

  20. Effectiveness of Vi capsular polysaccharide typhoid vaccine among children: a cluster randomized trial in Karachi, Pakistan.

    PubMed

    Khan, M Imran; Soofi, Sajid Bashir; Ochiai, R Leon; Habib, Mohammad Atif; Sahito, Shah Muhammad; Nizami, S Qamaruddin; Acosta, Camilo J; Clemens, John D; Bhutta, Zulfiqar A

    2012-08-03

    Typhoid fever is endemic in Karachi, with an incidence among children ranging from 170 to 450 per 100,000 child-years. Vaccination strategies are important for prevention, and the Vi capsular polysaccharide (ViCPS) vaccine has been shown to be effective in reducing the burden of typhoid fever. A cluster randomized trial was conducted in three low socioeconomic urban squatter settlements in Karachi, Pakistan between 2002 and 2007. Subsamples were followed up for assessment of immune response and adverse events after vaccination. The study participants were similar in a wide variety of socio-demographic and economic characteristics at baseline. A total of 27,231 individuals of the total target population of 51,965 in 120 clusters either received a ViCPS vaccine (13,238 [52% coverage]) or the control Hepatitis A vaccine (13,993 [53%]). Typhoid fever was diagnosed in 30 ViCPS vaccine recipients and 49 Hepatitis A vaccine recipients with an adjusted total protective effectiveness of 31% (95%CI: -28%, 63%). The adjusted total vaccine protective effectiveness was -38% (95%CI: -192%, 35%) for children aged 2-5 years and 57% (95%CI: 6%, 81%) for children 5-16 years old. The ViCPS vaccine did not confer statistically significant protection to children in the study areas, and there was a decline in antibody response 2 years post-vaccination. However, the ViCPS vaccine showed significant total protection in children 5-16 years of age, which is consistent with other studies of ViCPS vaccine conducted in India, Nepal, China and South Africa. These findings suggest that ViCPS vaccination of school-aged children will protect the children of urban, typhoid endemic areas against typhoid fever. Copyright © 2012 Elsevier Ltd. All rights reserved.

  1. 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

  2. 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

  3. 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

  4. 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

  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. 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.

  7. 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

  8. 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

  9. 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.

  10. 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

  11. 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

  12. 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

  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. [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.

  15. 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

  16. 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

  17. 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.

  18. 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

  19. 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

  20. 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.

  1. Effects of Taishan Pinus massoniana pollen polysaccharide on the subunit vaccine of Proteus mirabilis in birds.

    PubMed

    Cui, Guolin; Zhong, Shixun; Yang, Shifa; Zuo, Xuemei; Liang, Manfei; Sun, Jing; Liu, Jingjing; Zhu, Ruiliang

    2013-05-01

    Three adjuvants, namely, Taishan Pinus massoniana pollen polysaccharide (TPPPS), white mineral oil (WO) and propolis (PP), were added to the outer membrane protein (OMP) of Proteus mirabilis (P. mirabilis) and their effects were compared. Three hundred 1-day-old chicks were randomly divided into five groups (I-V), with 60 chicks per group, and injected subcutaneously with WO-OMP vaccine (I), PP-OMP vaccine (II), TPPPS-OMP vaccine (III), OMP-only vaccine (IV) and physiological saline (V) at 3, 7 and 12 days old. On days 3, 7, 14, 21, 28, 35, 42 and 49 after the first vaccination, the antibody titers, interleukin-2 levels (IL-2) and T-lymphocyte proliferation rates in the peripheral blood as well as the secreting-type IgA levels (SIgA) in the duodenum were measured. On day 7 after the third vaccination, the chicks were challenged with P. mirabilis strain Q1 and the protective effects of each group were observed. The highest protective rate was observed in group III. Moreover, the antibody titers as well as IL-2, SIgA and T-lymphocyte proliferation rates in this group significantly increased and were significantly higher than those in the other groups at most time points. The results indicate that TPPPS could significantly enhance the effects of the subunit vaccine of P. mirabilis; induced stronger humoral, cellular and mucosal immunity as compared with WO and PP; and should be developed as a vaccine adjuvant. Crown Copyright © 2013. Published by Elsevier B.V. All rights reserved.

  2. 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

  3. 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. Copyright © 2011 Elsevier Ltd. All rights reserved.

  4. 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.

  5. 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.

  6. Pneumococcal Type 22F Polysaccharide Absorption Improves the Specificity of a Pneumococcal-Polysaccharide Enzyme-Linked Immunosorbent Assay

    PubMed Central

    Concepcion, Nelydia F.; Frasch, Carl E.

    2001-01-01

    The specificity of the immune response to the 23-valent pneumococcal-polysaccharide (PS) vaccine in healthy adults and to a pneumococcal conjugate vaccine in infants was examined by measuring immunoglobulin G (IgG) antibody titers by enzyme-linked immunosorbent assay (ELISA) and the opsonophagocytosis assay. ELISA measures total antipneumococcal IgG titers including the titers of functional and nonfunctional antibodies, while the opsonophagocytosis assay measures only functional-antibody titers. Twenty-four pairs of pre- and post-pneumococcal vaccination sera from adults were evaluated (ELISA) for levels of IgG antibodies against serotypes 4, 6B, 9V, 14, 18C, 19F, and 23F. Twelve of the pairs were also examined (opsonophagocytosis assay) for their functional activities. The correlation coefficients between assay results for most types ranged from 0.75 to 0.90, but the correlation coefficient was only about 0.6 for serotypes 4 and 19F. The specificities of these antibodies were further examined by the use of competitive ELISA inhibition. A number of heterologous polysaccharides (types 11A, 12F, 15B, 22F, and 33A) were used as inhibitors. Most of the sera tested showed cross-reacting antibodies, in addition to those removed by pneumococcal C PS absorption. Our data suggest the presence of a common epitope that is found on most pneumococcal PS but that is not absorbed by purified C PS. Use of a heterologous pneumococcal PS (22F) to adsorb the antibodies to the common epitope increased the correlation between the IgG ELISA results and the opsonophagocytosis assay results. The correlation coefficient improve from 0.66 to 0.92 for type 4 and from 0.63 to 0.80 for type 19F. These common-epitope antibodies were largely absent in infants at 7 months of age, suggesting the carbohydrate nature of the epitope. PMID:11238206

  7. 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

  8. 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. Copyright © 2015 Elsevier Ltd. All rights reserved.

  9. Comparison of the immunogenicity and safety of two different brands of Salmonella typhi Vi capsular polysaccharide vaccine.

    PubMed

    Sabitha, P; Prabha Adhikari, M R; Chowdary, Abhijit; Prabhu, Malathi; Soofi, Mohammad; Shetty, Meenakshi; Kamath, Asha; Lokaranjan, S S; Bangera, S S

    2004-04-01

    The recent emergence of multi-drug-resistant Salmonella strains highlights the need for better preventive measures, including vaccination. Safe and immunologic vaccines have been developed based on purified Vi polysaccharide. To compare the immune response elicited by two different brands of Salmonella Vi capsular polysaccharide vaccine (ViCPS). Double blind, randomized (3:1), controlled, parallel, phase III study was conducted at two centres in India to compare the safety and immunogenicity of Typbar, the investigational vaccine with an already marketed vaccine "X", in healthy subjects aged between 12 -25 years. A sample size of 184 subjects was calculated. Subjects were randomly distributed in two groups, immunized with single dose of Typbar or Vaccine "X". Serum samples were taken before 7 days and 4 weeks after immunization for the determination of antibodies to Vi polysaccharide, by ELISA method. Safety was assessed by physical examination, laboratory parameters before and after vaccination and by monitoring adverse events. The geometric mean antibody titre (GMT) 4 weeks after vaccination was compared from respective pre-vaccination values by Wilcoxon signed rank test. Geometric mean of antibody levels before and after immunization and the ratio between them (Mann-Whitney test), the Seroconversion rates (Z test of proportions) and the adverse events (Fisher's exact test and Chi square test), were compared between two groups. P value < 0.05 was considered statistically significant. P values and 95% confidence intervals were estimated in two-tailed fashion. 153 subjects (Typbar =116 and Vaccine "X" =37) were studied. 71.6% (95% CI=63.4%-79.8%) and 75.7% (95% CI=64.9% - 89.5%) were the seroconversion rates with Typbar and vaccine "X" respectively. The GMT values for Vi antibodies induced after Typbar and vaccine "X" were 10.23 Typbar and 13.46 mg/mL respectively and these values showed high significance when compared to their respective pre-immunization GMT

  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. Induction of functional secretory IgA responses in breast milk, by pneumococcal capsular polysaccharides.

    PubMed

    Finn, Adam; Zhang, Qibo; Seymour, Lynn; Fasching, Claudine; Pettitt, Emily; Janoff, Edward N

    2002-11-15

    Capsule-specific secretory IgA (s-IgA) in breast milk may enhance protection against pneumococcal disease in infants. After immunization of 3 lactating mothers with 23-valent polysaccharide vaccine, specific s-IgA, but not IgG, increased by >2-fold in milk of at least 1 subject for 6 of 7 serotypes. The s-IgA was predominantly IgA1, in secretory form, and highly specific with avidity distinct from serum IgA and IgG. Milk whey from 2 immunized women supported dose- and complement-dependent killing of Streptococcus pneumoniae serotypes 19F and 14 by human neutrophils, as did purified s-IgA to serotype 19F. These data reveal that capsule-specific human s-IgA in breast milk can initiate killing of S. pneumoniae, providing proof of concept that vaccine-induced human mucosal s-IgA can support functional bactericidal activity. Determining the biologic role for s-IgA in killing and inhibiting adherence of S. pneumoniae in vivo will contribute to the development of mucosal vaccines against S. pneumoniae.

  13. Use of the 13-valent pneumococcal conjugate vaccine in children and adolescents aged 6 - 17 years.

    PubMed

    Mitchell, Ruth; Trück, Johannes; Pollard, Andrew J

    2013-10-01

    The introduction of pneumococcal conjugate vaccines into infant immunization schedules has successfully reduced the incidence of pneumococcal disease caused by vaccine serotypes. Disease incidence is low in healthy 6 - 17-year-old children and young people; however, there are a number of clinical conditions that put individuals in this age group at increased risk. Expansion of the license of a 13-valent pneumococcal conjugate vaccine , PCV-13, to include the 6 - 17 age group has recently been approved by European and American regulatory bodies. Studies assessing the safety, immunogenicity, and efficacy of pneumococcal conjugate vaccines in both healthy and high-risk 6 - 17-year-old children and adolescents are covered and the potential impact of PCV-13 in these populations is discussed. The use of the 23-valent pneumococcal polysaccharide vaccine, PPV-23, in high-risk children and adolescents is also considered. Expanding the use of PCV-13 to include high-risk children and adolescents aged 6 - 17 has the potential to prevent additional cases of disease; however, vaccination of this population may no longer be necessary when herd immunity to PCV-13 serotypes becomes fully established. Despite the broader serotype coverage of PPV-23, the benefits of this vaccine in high-risk populations are uncertain.

  14. 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

  15. 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. Copyright © 2014 Elsevier Ltd. All rights reserved.

  16. Capsule polysaccharide conjugate vaccine against diarrheal disease caused by Campylobacter jejuni.

    PubMed

    Monteiro, Mario A; Baqar, Shahida; Hall, Eric R; Chen, Yu-Han; Porter, Chad K; Bentzel, David E; Applebee, Lisa; Guerry, Patricia

    2009-03-01

    The capsule polysaccharide (CPS) of Campylobacter jejuni is one of the few identified virulence determinants of this important human pathogen. Since CPS conjugate vaccines have been so effective against other mucosal pathogens, we evaluated this approach using CPSs from two strains of C. jejuni, 81-176 (HS23 and HS36 serotype complex) and CG8486 (HS4 serotype complex). The CPSs of 81-176 and CG8486 were independently linked to the carrier protein CRM(197) by reductive amination between an aldehyde(s), strategically created at the nonreducing end of each CPS, and accessible amines of CRM(197). In both cases, the CPS:CRM(197) ratio used was 2:1 by weight. Mass spectrometry and gel electrophoresis showed that on average, each glycoconjugate preparation contained, at least in part, two to five CPSs attached to one CRM(197). When administered subcutaneously to mice, these vaccines elicited robust immune responses and significantly reduced the disease following intranasal challenge with the homologous strains of C. jejuni. The CPS(81-176)-CRM(197) vaccine also provided 100% protection against diarrhea in the New World monkey Aotus nancymaae following orogastric challenge with C. jejuni 81-176.

  17. Pneumococcal polysaccharide vaccine responses are impaired in a subgroup of children with cystic fibrosis.

    PubMed

    Browning, Michael J; Lim, Michael T C; Kenia, Priti; Whittle, Michelle; Doffinger, Rainer; Barcenas-Morales, Gabriela; Kumararatne, Dinakantha; Viskaduraki, Maria; O'Callaghan, Christopher; Gaillard, Erol A

    2014-12-01

    Pneumococcal immunization is recommended in children with cystic fibrosis (CF). To date, however, there are no published studies on the efficacy of pneumococcal vaccination in this group of patients. We carried out a retrospective study of serotype-specific pneumococcal antibody responses to immunization with Prevenar 7 and Pneumovax II in a cohort of children with CF. Nine children had been immunized with Prevenar 7, and all had serotype-specific pneumococcal antibody levels in the protective range (>0.35mg/L) to all 7 immunizing serotypes. In contrast, only 7 of 33 patients (21%) immunized with Pneumovax II made protective antibody responses to all 7 serotypes, and 3 failed to make protective antibodies to any of the serotypes. Controlling for age as a confounder in the analysis, children with impaired antibody responses to pneumococcal polysaccharide (Pneumovax II) immunization had lower Shwachman-Kulczycki scores than children with normal polysaccharide antibody responses. All isolates of Pseudomonas aeruginosa occurred in patients with impaired anti-pneumococcal antibody responses, and a broader range of respiratory pathogens was isolated from these children. Impaired antibody responses to immunization with Pneumovax II are common in children with CF and this may be associated with increased disease severity. Copyright © 2014 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.

  18. 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

  19. 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.

  20. 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. Copyright © 2013 Elsevier Ltd. All rights reserved.

  1. The tetravalent meningococcal serogroups A, C, W-135, and Y tetanus toxoid conjugate vaccine is immunogenic with a clinically acceptable safety profile in subjects previously vaccinated with a tetravalent polysaccharide vaccine.

    PubMed

    Dbaibo, Ghassan; Van der Wielen, Marie; Reda, Mariam; Medlej, Fouad; Tabet, Carelle; Boutriau, Dominique; Sumbul, Anne; Anis, Sameh; Miller, Jacqueline M

    2012-08-01

    The immunogenicity and safety of the tetravalent meningococcal serogroups A, C, W-135, and Y tetanus toxoid conjugate vaccine (MenACWY-TT) were evaluated in subjects previously vaccinated with a tetravalent meningococcal polysaccharide vaccine and in subjects without previous meningococcal vaccination. In this phase II, open, controlled study (NCT00661557), healthy subjects aged 4.5-34 years received one dose of MenACWY-TT at month 0. Subjects in the MPS group (n=192) had received polysaccharide vaccine in a study conducted 30-42 months earlier; age-matched subjects in the noMPS control group (n=79) had received no meningococcal vaccination within the past 10 years. Serum bactericidal activity using rabbit complement (rSBA) was measured at month 0 and month 1. At month 1, ≥97.0% of subjects had rSBA titers ≥1:128. Post-vaccination rSBA geometric mean titers (GMTs) were ≥3.9-fold higher than pre-vaccination in both treatment groups. Exploratory analyses showed no statistically significant differences between groups in percentages of subjects with rSBA titers ≥1:8 and ≥1:128, but significantly lower rSBA GMTs and vaccine response rates for each serogroup in the MPS versus the noMPS group. MenACWY-TT had an acceptable safety profile in both groups. These results suggest that MenACWY-TT could be used in vaccination programs irrespective of the pre-vaccination status with polysaccharide vaccine. Copyright © 2012 International Society for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

  2. 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

  3. 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

  4. Advances in pneumococcal vaccines: what are the advantages for the elderly?

    PubMed

    Vila-Córcoles, Angel

    2007-01-01

    Streptococcus pneumoniae causes considerable morbidity and mortality in the elderly. There are three established approaches to pneumococcal vaccination: polysaccharide vaccines, protein-polysaccharide conjugate vaccines and protein-based vaccines. This article reviews advances in anti-pneumococcal vaccines, with reference to advantages and shortcomings for the elderly in particular. The 23-valent polysaccharide pneumococcal vaccine (PPV) is currently recommended for high-risk patients and the general elderly population. Although the effectiveness of PPV against pneumonia is unclear, recent studies point to significant protective effects in preventing pneumococcal pneumonia and reducing the severity of disease in vaccinated elderly patients. PPV offers high serotype coverage and, although it is poorly immunogenic in some individuals, provides approximately 60% protection against invasive disease in the general elderly population. PPV vaccination appears cost effective for elderly patients although the vaccine might only be effective in preventing invasive disease. Additional benefits could mean a greater level of vaccine cost effectiveness. However, it is important to understand that PPV provides incomplete protection, especially in those with underlying high-risk conditions, and development of more effective pneumococcal vaccination strategies for elderly patients is still needed. In recent years, the most important advance in the prevention of pneumococcal infections in the elderly has been the introduction of a 7-valent conjugate pneumococcal vaccine (CPV) as a routine vaccination for infants. In addition to dramatically reducing invasive infection in children, CPV has been observed to have a considerable indirect protective effect in parents and grandparents. While the possibility of using CPV in elderly patients has been suggested, currently there are only limited immunogenicity data and no efficacy data in adults. The low serotype coverage is an important

  5. 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.

  6. 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

  7. Evaluation in mice of a conjugate vaccine for cholera made from Vibrio cholerae O1 (Ogawa) O-specific polysaccharide.

    PubMed

    Alam, Mohammad Murshid; Bufano, Megan Kelly; Xu, Peng; Kalsy, Anuj; Yu, Y; Freeman, Y Wu; Sultana, Tania; Rashu, Md Rasheduzzaman; Desai, Ishaan; Eckhoff, Grace; Leung, Daniel T; Charles, Richelle C; LaRocque, Regina C; Harris, Jason B; Clements, John D; Calderwood, Stephen B; Qadri, Firdausi; Vann, W F; Kováč, Pavol; Ryan, Edward T

    2014-02-01

    Protective immunity against cholera is serogroup specific. Serogroup specificity in Vibrio cholerae is determined by the O-specific polysaccharide (OSP) of lipopolysaccharide (LPS). Generally, polysaccharides are poorly immunogenic, especially in young children. Here we report the evaluation in mice of a conjugate vaccine for cholera (OSP:TThc) made from V. cholerae O1 Ogawa O-Specific Polysaccharide-core (OSP) and recombinant tetanus toxoid heavy chain fragment (TThc). We immunized mice intramuscularly on days 0, 21, and 42 with OSP:TThc or OSP only, with or without dmLT, a non-toxigenic immunoadjuvant derived from heat labile toxin of Escherichia coli. We detected significant serum IgG antibody responses targeting OSP following a single immunization in mice receiving OSP:TThc with or without adjuvant. Anti-LPS IgG responses were detected following a second immunization in these cohorts. No anti-OSP or anti-LPS IgG responses were detected at any time in animals receiving un-conjugated OSP with or without immunoadjuvant, and in animals receiving immunoadjuvant alone. Responses were highest following immunization with adjuvant. Serum anti-OSP IgM responses were detected in mice receiving OSP:TThc with or without immunoadjuvant, and in mice receiving unconjugated OSP. Serum anti-LPS IgM and vibriocidal responses were detected in all vaccine cohorts except in mice receiving immunoadjuvant alone. No significant IgA anti-OSP or anti-LPS responses developed in any group. Administration of OSP:TThc and adjuvant also induced memory B cell responses targeting OSP and resulted in 95% protective efficacy in a mouse lethality cholera challenge model. We describe a protectively immunogenic cholera conjugate in mice. Development of a cholera conjugate vaccine could assist in inducing long-term protective immunity, especially in young children who respond poorly to polysaccharide antigens.

  8. 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.

  9. 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

  10. 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.

  11. Evolution of vaccination rates after the implementation of a free systematic pneumococcal vaccination in Catalonian older adults: 4-years follow-up.

    PubMed

    Vila-Córcoles, Angel; Ochoa-Gondar, Olga; Ester, Francisco; Sarrá, Nuria; Ansa, Xabier; Saún, Neus

    2006-09-18

    The systematic vaccination with 23-valent polysaccharide pneumococcal vaccine (PPV) was introduced as a strategic objective of health for all the people over 65 in Catalonia in 1999. We analysed the evolution of the pneumococcal vaccination rates from 2000 to 2003. We conducted a retrospective population-based study including all the individuals 65 years or older assigned to 8 Primary Care Centres (PCCs) in Tarragona (Catalonia, Spain), who figured in the administrative population databases on 31 December 2003 (n = 10,410 persons). We assessed whether every person had received PPV during the last four years (2000 to 2003) or whether they had received it before January 2000. Data sources were the computerised clinical records of the 8 participating PCCs, which included adult vaccination registries and diagnoses coded of International Classification of Diseases 9th The overall vaccination uptake increased to 38.6% at the end of 2000. Global accumulated coverages increased more slowly the following years: 44.4% in 2001, 50.9% in 2002, and 53.1% at the end of 2003. Vaccine uptake varied significantly according to age (46.7% in people 65-74 years-old, 60.9% in people 75 years or more; p < 0.001) and number of diseases or risk factors (DRFs) for pneumonia (47.1% vaccinated in people without DRFs, 56.8% in patients with one DRF, and 62.2% in patients with two or more DRFs; p < 0.001). The highest coverages were observed among those patients with: diabetes (65.9%), active neoplasia (64.8%), history of stroke (63.7%), and chronic lung disease (63.5%). The lowest uptake was observed among smokers (48.7%). The pneumococcal vaccination coverage increased quickly after the introduction of the recommendation for free vaccination in all the elderly people (with and without risk factors), but two years after the improvement the coverage became stable and increased slowly.

  12. Burkholderia pseudomallei Capsular Polysaccharide Recognition by a Monoclonal Antibody Reveals Key Details toward a Biodefense Vaccine and Diagnostics against Melioidosis.

    PubMed

    Marchetti, Roberta; Dillon, Michael J; Burtnick, Mary N; Hubbard, Mark A; Kenfack, Marielle Tamigney; Blériot, Yves; Gauthier, Charles; Brett, Paul J; AuCoin, David P; Lanzetta, Rosa; Silipo, Alba; Molinaro, Antonio

    2015-10-16

    Burkholderia pseudomallei is the bacterium responsible for melioidosis, an infectious disease with high mortality rates. Since melioidosis is a significant public health concern in endemic regions and the organism is currently classified as a potential biothreat agent, the development of effective vaccines and rapid diagnostics is a priority. The capsular polysaccharide (CPS) expressed by B. pseudomallei is a highly conserved virulence factor and a protective antigen. Because of this, CPS is considered an attractive antigen for use in the development of both vaccines and diagnostics. In the present study, we describe the interactions of CPS with the murine monoclonal antibody (mAb) 4C4 using a multidisciplinary approach including organic synthesis, molecular biology techniques, surface plasmon resonance, and nuclear magnetic spectroscopy. Using these methods, we determined the mode of binding between mAb 4C4 and native CPS or ad hoc synthesized capsular polysaccharide fragments. Interestingly, we demonstrated that the O-acetyl moiety of CPS is essential for the interaction of the CPS epitope with mAb 4C4. Collectively, our results provide important insights into the structural features of B. pseudomallei CPS that enable antibody recognition that may help the rational design of CPS-based vaccine candidates. In addition, our findings confirm that the mAb 4C4 is suitable for use in an antibody-based detection assay for diagnosis of B. pseudomallei infections.

  13. Increased genetic diversity of Neisseria meningitidis isolates after the introduction of meningococcal serogroup C polysaccharide conjugate vaccines.

    PubMed

    Diggle, Mathew A; Clarke, Stuart C

    2005-09-01

    During the 1990s, the incidence of meningococcal disease was high in the United Kingdom. This was due primarily to an increase in serogroup C disease, particularly that within the ET-37/ST-11 genetic lineage. Serogroup C meningococcal polysaccharide conjugate vaccines were introduced in the United Kingdom in 1999, but the sequence types of meningococci causing disease since that time have not yet been reported. We have used serogrouping and multilocus sequence typing to characterize meningococci from patients with invasive disease over a 4-year period and show that there is a significant increase in genetic diversity but no genetic evidence of capsule switching.

  14. 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.

  15. 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. Copyright © 2011 Elsevier Ltd. All rights reserved.

  16. Induction of immunologic memory following primary vaccination with the 10-valent pneumococcal nontypeable Haemophilus influenzae protein D conjugate vaccine in infants.

    PubMed

    Knuf, Markus; Pankow-Culot, Heidemarie; Grunert, Detlef; Rapp, Michael; Panzer, Falko; Köllges, Ralph; Fanic, Aurélie; Habib, Ahsan; Borys, Dorota; Dieussaert, Ilse; Schuerman, Lode

    2012-01-01

    Induction of immunologic memory was assessed following primary vaccination with 10-valent pneumococcal nontypeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV). Infants were randomized (1:1) to receive 3 doses of PHiD-CV or 7vCRM (7-valent CRM197-conjugated pneumococcal conjugate vaccine [PCV]) at 2, 3, and 4 months of age followed by 23-valent pneumococcal polysaccharide vaccine (23vPS) booster dose at 11 to 14 months of age. Pneumococcal geometric mean antibody concentrations (GMCs) and opsonophagocytic activity (OPA) geometric mean titers were measured. Postprimary immune responses were consistent with those in previous PHiD-CV and 7vCRM studies. Following 23vPS boosting, vaccine serotype-specific antibody GMCs increased 6.5- to 33.3-fold and 4.8- to 32.2-fold versus prebooster in the PHiD-CV and 7vCRM groups, respectively. Postbooster OPA titers increased 2.8- to 38.8-fold and 2.6- to 58.9-fold, respectively. Postbooster antibody GMCs exceeded postprimary levels but, for some serotypes, postbooster OPA geometric mean titers were lower than postprimary in both groups. An additional dose of the same PCV received for priming was administered to 52 children aged 46 to 50 months, resulting in higher responses versus postprimary vaccination for all serotypes, but not always higher than post-23vPS booster. Induction of immunologic memory following PHiD-CV priming was confirmed. Additional PCV boosting in 4-year-olds did not provide strong evidence of hyporesponsiveness induced by previous 23vPS boosting. However, our results did not rule out depletion of the memory B cell pool following 23vPS vaccination, resulting in subsequent attenuated immune responses, and therefore support the use of PCV rather than 23vPS for booster vaccination in the second year of life.

  17. Safety and immunogenicity of a booster dose of meningococcal (groups A, C, W, and Y) polysaccharide diphtheria toxoid conjugate vaccine.

    PubMed

    Robertson, Corwin A; Greenberg, David P; Hedrick, James; Pichichero, Michael; Decker, Michael D; Saunders, Martha

    2016-10-17

    Quadrivalent meningococcal conjugate vaccines (MenACWY) were developed to offer long-term protection against invasive disease caused by serogroups A, C, W, and Y. Reduced MenACWY effectiveness within 5 years after primary vaccination (likely due to declining bactericidal antibody titers) has been described, particularly with respect to C and Y disease in the United States. We evaluated the safety and immunogenicity of a single booster dose of quadrivalent meningococcal polysaccharide diphtheria toxoid conjugate vaccine (MenACWY-D) in adolescents and adults who received a previous dose 4-6 years earlier. This phase 2, open-label, multicenter study of 834 persons was conducted in the United States. Participants received a single 0.5-mL booster dose of MenACWY-D. Serogroup-specific bactericidal antibody geometric mean titers (GMTs) were measured with a serum bactericidal antibody assay using human complement (hSBA). Proportions of participants achieving antibody titers of ⩾1:8 for each vaccine serogroup on Days 6 and 28 were determined. Rates of adverse events (AEs), including serious adverse events (SAEs), were also assessed. Before booster vaccination, 38.7-68.5% of participants had an hSBA titer ⩾1:8, depending on vaccine serogroup. By Day 6 post-vaccination, 98.2-99.1% of participants had hSBA titers ⩾1:8. By Day 28, >99% of participants achieved this threshold and the primary hypothesis (lower limit of the one-sided 95% confidence limit ⩾85% for each serogroup) was met. The GMT ratios (post-vaccination divided by pre-vaccination) at Day 28 ranged from 47.2 (serogroup A) to 209.1 (serogroup Y). Rates of AEs, including SAEs, were similar to those observed among adolescents and adults who received a primary dose of MenACWY-D in previous studies. There were no study discontinuations due to an AE and no deaths. Booster vaccination with MenACWY-D was safe and induced robust bactericidal antibody responses, consistent with immune memory, among adolescents and

  18. Can the success of pneumococcal conjugate vaccines for the prevention of pneumococcal diseases in children be extrapolated to adults?

    PubMed

    Weil-Olivier, Catherine; Gaillat, Jacques

    2014-04-11

    Before conjugate pneumococcal vaccines (PCVs) were introduced it was estimated that Streptococcus pneumoniae caused 500,000 cases of pneumonia, 50,000 cases of bacteremia and 3000 cases of meningitis annually in the United States in both children and adults. After 10 years of routine use of the 7-valent pneumococcal conjugate vaccine (PCV7) the incidence of vaccine-type pneumococcal diseases (PDs) had significantly decreased in vaccinated children (direct effect) and unvaccinated subjects of all ages (indirect effect). Second generation, higher-valent PCVs, especially 13-valent (PCV13), routinely implemented since 2010, have reduced the incidence of PDs caused by the six additional non-PCV7 serotypes, in both vaccinated and unvaccinated subjects. The licence for this vaccine has recently been extended to include adults aged 18 to 49 in Europe. Although PCV13 has an indirect effect on IPD in adults, this will probably not achieve the same level of disease control in adults and the elderly (especially those at high risk) as that obtained in vaccinated children. As highlighted in this paper, differences exist between children and adults for PD manifestations (incidence, morbidity and mortality) and serotypes isolated in nasopharyngeal carriage and diseases, so benefits from adult vaccination must be considered in this light. PCV13 induces an immune response in adults that is non-inferior for all serotypes common with the 23-valent plain polysaccharide vaccine that is currently recommended for adults and even superior for many serotypes. Although there is no evidence that this immune response translates to clinical efficacy in adults as seen in children, the results from a randomised trial in The Netherlands, expected in 2014, should provide the missing evidence. This evidence and efficient surveillance systems should provide the necessary data, essential for policy makers in their decisions on adult pneumococcal vaccination policies. Copyright © 2014 Elsevier Ltd

  19. Increasing exposure to antibody-stimulating proteins and polysaccharides in vaccines is not associated with risk of autism.

    PubMed

    DeStefano, Frank; Price, Cristofer S; Weintraub, Eric S

    2013-08-01

    To evaluate the association between autism and the level of immunologic stimulation received from vaccines administered during the first 2 years of life. We analyzed data from a case-control study conducted in 3 managed care organizations (MCOs) of 256 children with autism spectrum disorder (ASD) and 752 control children matched on birth year, sex, and MCO. In addition to the broader category of ASD, we also evaluated autistic disorder and ASD with regression. ASD diagnoses were validated through standardized in-person evaluations. Exposure to total antibody-stimulating proteins and polysaccharides from vaccines was determined by summing the antigen content of each vaccine received, as obtained from immunization registries and medical records. Potential confounding factors were ascertained from parent interviews and medical charts. Conditional logistic regression was used to assess associations between ASD outcomes and exposure to antigens in selected time periods. The aOR (95% CI) of ASD associated with each 25-unit increase in total antigen exposure was 0.999 (0.994-1.003) for cumulative exposure to age 3 months, 0.999 (0.997-1.001) for cumulative exposure to age 7 months, and 0.999 (0.998-1.001) for cumulative exposure to age 2 years. Similarly, no increased risk was found for autistic disorder or ASD with regression. In this study of MCO members, increasing exposure to antibody-stimulating proteins and polysaccharides in vaccines during the first 2 years of life was not related to the risk of developing an ASD. Copyright © 2013 Mosby, Inc. All rights reserved.

  20. 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.

  1. A novel monoclonal antibody to Neisseria meningitidis serogroup X capsular polysaccharide and its potential use in quantitation of meningococcal vaccines.

    PubMed

    Reyes, Fátima; Otero, Oscar; Camacho, Frank; Amin, Nevis; Ramírez, Fidel; Valdés, Yolanda; Acevedo, Reynaldo; García, Luis; Cardoso, Daniel; Cuello, Maribel

    2014-11-01

    A novel murine hybridoma monoclonal antibody (MAb) was produced against the capsular polysaccharide (CP) of Neisseria meningitidis serogroup X (MenX) in order to develop a sandwich enzyme linked immunosorbent assay (ELISA) for the quantitation of the meningococcal polysaccharide. The MAb only reacted with the CP from MenX and did not react with CPs from N. meningitidis serogroups A, C, Y and W (MenA, MenC, MenY, MenW). The affinity constant (Ka) of the MAb measured by non-competitive ELISA was 7.25 × 10(7) M(-1). The application of this MAb in a sandwich ELISA was demonstrated by its ability to properly quantitate three lots of an experimental meningococcal CP-based vaccine. The MAb obtained in this work could be a valuable reagent for the detection and quantitation of future meningococcal vaccines containing MenX CP. Copyright © 2014 The International Alliance for Biological Standardization. Published by Elsevier Ltd. All rights reserved.

  2. 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.

  3. Factors associated with pneumococcal vaccination among an urban elderly population in China

    PubMed Central

    Liu, Shijun; Xu, Erping; Liu, Yan; Xu, Yuyang; Wang, Jun; Du, Jian; Zhang, Xiaoping; Che, Xinren; Gu, Wenwen

    2014-01-01

    Objectives: To investigate the coverage of the 23-valent pneumococcal polysaccharide vaccine (23-PPV) in the Chinese urban elderly population and to understand the attitudes, knowledge and beliefs of this population toward the 23-PPV vaccination. Methods: A cross-sectional approach was employed to survey the willingness of this population to receive the 23-PPV vaccination. Two thousand 9 hundred 2 six subjects over the age of 60 y were enrolled via a multi-stage random sampling method from the urban community population in Hangzhou, China. The relationships between the variables and the willingness to receive the 23-PPV vaccination were computed as odds ratios (ORs) by multivariate analysis. Results Of the participants, 21.77% were willing to undergo 23-PPV vaccination, and 61.65% of the subjects agreed that pneumonia is a serious disease among elderly people. The rate of reasonable perceptions about vaccination, including the perception about vaccine efficacy and safety, among the subjects was below 50%. Only 1.23% of subjects had been vaccinated with 23-PPV, and a similarly low rate was observed for the seasonal influenza vaccine (4.17%). The factors that were independently related to the willingness to receive the 23-PPV vaccine included consensus with the hazards of pneumonia (OR = 1.67, 95% CI: 1.28 – 2.17), the safety of vaccination (OR = 2.00, 95% CI: 1.54 – 2.59), advice about the 23-PPV vaccination from family members (OR = 2.37, 95% CI: 1.39 – 4.40), influenza vaccination history (OR = 2.57, 95% CI: 1.66 – 3.98) and pneumococcal vaccination history (OR = 7.48, 95% CI: 2.4–22.92). Conclusion: The administration of the 23-PPV vaccine among the urban elderly population is not optimistic in China. Emphasis on persuasion from families and the improvement of knowledge about vaccination might encourage elderly people to get the 23-PPV vaccination. Suggestions from physicians did not affect the participants’ willingness to get the 23-PPV vaccination

  4. 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.

  5. 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.

  6. 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

  7. Safety and Immunogenicity of a 13-Valent Pneumococcal Conjugate Vaccine in Adults 50 to 65 Years of Age in India: An Open-Label Trial.

    PubMed

    Solanki, Bhagirath B; Juergens, Christine; Chopada, Manojkumar B; Supe, Pravin; Sundaraiyer, Vani; Le Dren-Narayanin, Natacha; Cutler, Mark W; Gruber, William C; Scott, Daniel A; Schmoele-Thoma, Beate

    2017-09-07

    Streptococcus pneumoniae infection is a major global public health concern in older adults, especially as life expectancy continues to increase in most countries, including India. Recently, a 13-valent pneumococcal conjugate vaccine (PCV13) with the ability to enhance immunity (immunologic memory) on natural exposure or revaccination has been shown to protect against community-acquired pneumonia and invasive pneumococcal disease in adults 65 years of age and older. An unconjugated 23-valent pneumococcal polysaccharide vaccine has been available for decades; however, data on protection against pneumonia are inconsistent. For the first time, a multicenter study has been conducted in India to assess the safety and immunogenicity of a single dose of PCV13 in adults aged 50 to 65 years. In this study, PCV13 elicited robust immune responses against all 13 pneumococcal serotypes as reflected by the magnitude of geometric mean fold rises (range, 6.6-102.7) in functional antibody levels from before to 1 month after vaccination. No serious adverse events occurred. These clinical trial findings support the safety and immunogenicity of PCV13 when administered to adults in India and indicate that a single dose of PCV13 has the potential to protect against vaccine-type pneumococcal disease in adults aged 50 to 65 years.

  8. Immunogenicity and safety of 13-valent pneumococcal conjugate vaccine when administered to healthy Japanese adults aged ≥50 years. An open-label trial.

    PubMed

    Shiramoto, Masanari; Irie, Shin; Juergens, Christine; Yamaji, Masako; Tamai, Satoshi; Aizawa, Masakazu; Belanger, Todd; Gruber, William C; Scott, Daniel A; Schmoele-Thoma, Beate

    2014-01-01

    This open-label study was designed to assess immunogenicity and safety of 13-valent pneumococcal conjugate vaccine (PCV13) when administered to Japanese adults aged ≥50 years not previously vaccinated with 23-valent pneumococcal polysaccharide vaccine and to compare this Japanese study population with similar study populations in the United States (US; 50-64 years age group) and European Union (EU; ≥65 years age group). Functional antibody immune responses were measured by opsonophagocytic activity assays. Immune responses in both Japanese age groups showed significant pre/postvaccination fold rises for each serotype. In the Japanese 50-64 years age group, immune responses for the majority of serotypes were significantly lower than in the ≥65 years Japanese age group and generally lower than in the 50-64 years age group in the US study. Immune responses in the Japanese ≥65 years age group were significantly higher for the majority of serotypes compared with the ≥65 years age group in the EU study. The safety profiles across age groups and studies were generally similar. In conclusion, PCV13 elicited robust immune responses in the Japanese study population. The unanticipated higher immune responses observed in the older age group in the Japanese study are of interest and of potential benefit given the higher incidence of pneumococcal disease in older adults. PCV13 was well tolerated and safe.

  9. Alterations in serotype-specific B cell responses to the 13-valent pneumococcal conjugate vaccine in aging HIV-infected adults.

    PubMed

    Ohtola, Jennifer A; Khaskhely, Noor M; Saul-Mcbeth, Jessica L; Iyer, Anita S; Leggat, David J; Khuder, Sadik A; Westerink, M A Julie

    2016-01-20

    Advanced age and human immunodeficiency virus (HIV) infection are associated with increased pneumococcal disease risk. The impact of these factors on cellular responses to vaccination is unknown. HIV-infected (HIV+) individuals 50-65 years old with CD4(+) Tcells/μl (CD4) >200 on antiretroviral therapy (ART) ≥1 year received either the 13-valent pneumococcal conjugate vaccine followed by the 23-valent pneumococcal polysaccharide vaccine (PCV/PPV) or PPV only. HIV-uninfected (HIV-) controls received PCV/PPV. Phenotype distribution and surface expression of complement receptor CD21 and tumor necrosis factor superfamily receptors (TNFRs) were compared on serotype-specific B cells postvaccination. Postvaccination serotype-specific B cell percentages were significantly lower in HIV+ PCV/PPV compared to PPV groups, but similar between HIV+ or HIV- PCV/PPV groups. Transmembrane activator and calcium-modulating cyclophilin ligand interactor (TACI)(+) serotype-specific B cell percentages were significantly decreased in HIV+ PCV/PPV compared to PPV groups. CD21(+) serotype-specific B cells were significantly higher in HIV- compared to HIV+ PCV/PPV groups. An initial dose of PCV reduced the frequency, but not phenotype distribution, of serotype-specific B cells and also lowered TACI expression in aging HIV+ subjects postvaccination with PPV. These findings suggest that PCV does not enhance cellular responses to revaccination with PPV. Published by Elsevier Ltd.

  10. 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.

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

    DTIC Science & Technology

    1985-02-15

    vinbiastifle further argues against a critical role for a protein seenl In cystic fibrosis patients (24). dictates a need for further contaminant, study of the...strains, and assessment of the role of lipopolysaccharide (LPS) as an immunogenic or biologically active component of the vaccine. The vaccine under...hpoPoiicaCri’de (LPS). 4N. The uMve- the role of 2-keto-3-deoxyoctonoate in the Iipopolaoccharide ot Salmonella sponalvenvesa of C3H/HeJ mouse spleen

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

    PubMed

    Vila-Corcoles, Angel; Ochoa-Gondar, Olga; Rodriguez-Blanco, Teresa; Gutierrez-Perez, Antonia; Vila-Rovira, Angel; Gomez, Frederic; Raga, Xavier; de Diego, Cinta; Satue, Eva; Salsench, Elisabet

    2012-03-22

    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. 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). 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). 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.

  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 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

  18. 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.

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

    PubMed

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

    2014-09-01

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

  20. 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.

  1. 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.

  2. 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

  3. Effective inhibition of melanoma tumorigenesis and growth via a new complex vaccine based on NY-ESO-1-alum-polysaccharide-HH2

    PubMed Central

    2014-01-01

    Background A safe and effective adjuvant plays an important role in the development of a vaccine. However, adjuvants licensed for administration in humans remain limited. Here, for the first time, we developed a novel combination adjuvant alum-polysaccharide-HH2 (APH) with potent immunomodulating activities, consisting of alum, polysaccharide of Escherichia coli and the synthetic cationic innate defense regulator peptide HH2. Methods The adjuvant effects of APH were examined using NY-ESO-1 protein-based vaccines in prophylactic and therapeutic models. We further determined the immunogenicity and anti-tumor effect of NY-ESO-1-APH (NAPH) vaccine using adoptive cellular/serum therapy in C57/B6 and nude mice. Cell-mediated and antibody-mediated immune responses were evaluated. Results The APH complex significantly promoted antigen uptake, maturation and cross-presentation of dendritic cells and enhanced the secretion of TNF-α, MCP-1 and IFN-γ by human peripheral blood mononuclear cells compared with individual components. Vaccination of NAPH resulted in significant tumor regression or delayed tumor progression in prophylactic and therapeutic models. In addition, passive serum/cellular therapy potently inhibited tumor growth of NY-ESO-1-B16. Mice treated with NAPH vaccine produced higher antibody titers and greater antibody-dependent/independent cellular cytotoxicity. Therefore, NAPH vaccination effectively stimulated innate immunity, and boosted both arms of the adaptive humoral and cellular immune responses to suppress tumorigenesis and growth of melanoma. Conclusions Our study revealed the potential application of APH complex as a novel immunomodulatory agent for vaccines against tumor refractory and growth. PMID:25070035

  4. Acquisition of Meningococcal Serogroup W-135 Carriage in Turkish Hajj Pilgrims Who Had Received the Quadrivalent Meningococcal Polysaccharide Vaccine

    PubMed Central

    Celik, M.; Demir, E. T.; Gurbuz, V.; Aycan, A. E.; Unal, S.

    2013-01-01

    Invasive meningococcal disease is a recognized public health problem worldwide, with a dynamic and changeable epidemiology. In Turkey, the second most common pathogenic meningococcal serogroup (after serogroup B) is W-135, including an epidemic in 2005, which has been strongly associated with Hajj pilgrims and their close contacts. In two studies conducted in 2010, we assessed meningococcal carriage in intending Turkish pilgrims to the Hajj when they attended to receive a plain polysaccharide vaccine against serogroups A, C, W-135, and Y and, upon their return, to determine the acquisition of meningococcal carriage by the pilgrims themselves and subsequently their household contacts. Nasopharyngeal swabs were obtained from pilgrims before the Hajj and upon their return. Swabs were then obtained from 39 household contacts of pilgrims who were shown to have acquired carriage during the Hajj. Of the 472 pilgrims before the Hajj, 63 (13%) were positive for meningococcal carriage, of which 52 cases (83%) were serogroup W-135. In the 296 pilgrims tested after the Hajj, 81 (27%) were positive for meningococcal carriage, including 74 (91%) with W-135. In 11 family members of pilgrims who acquired W-135 carriage at the Hajj, 10 (91%) had acquired carriage of serogroup W-135. This study illustrates the acquisition of meningococcal carriage, predominantly of serogroup W-135 by pilgrims attending the Hajj, and the transmission of this carriage to their family members on their return, explaining the source of W-135 meningococcal disease in Turkey. PMID:23136117

  5. Acquisition of meningococcal serogroup W-135 carriage in Turkish Hajj pilgrims who had received the quadrivalent meningococcal polysaccharide vaccine.

    PubMed

    Ceyhan, M; Celik, M; Demir, E T; Gurbuz, V; Aycan, A E; Unal, S

    2013-01-01

    Invasive meningococcal disease is a recognized public health problem worldwide, with a dynamic and changeable epidemiology. In Turkey, the second most common pathogenic meningococcal serogroup (after serogroup B) is W-135, including an epidemic in 2005, which has been strongly associated with Hajj pilgrims and their close contacts. In two studies conducted in 2010, we assessed meningococcal carriage in intending Turkish pilgrims to the Hajj when they attended to receive a plain polysaccharide vaccine against serogroups A, C, W-135, and Y and, upon their return, to determine the acquisition of meningococcal carriage by the pilgrims themselves and subsequently their household contacts. Nasopharyngeal swabs were obtained from pilgrims before the Hajj and upon their return. Swabs were then obtained from 39 household contacts of pilgrims who were shown to have acquired carriage during the Hajj. Of the 472 pilgrims before the Hajj, 63 (13%) were positive for meningococcal carriage, of which 52 cases (83%) were serogroup W-135. In the 296 pilgrims tested after the Hajj, 81 (27%) were positive for meningococcal carriage, including 74 (91%) with W-135. In 11 family members of pilgrims who acquired W-135 carriage at the Hajj, 10 (91%) had acquired carriage of serogroup W-135. This study illustrates the acquisition of meningococcal carriage, predominantly of serogroup W-135 by pilgrims attending the Hajj, and the transmission of this carriage to their family members on their return, explaining the source of W-135 meningococcal disease in Turkey.

  6. Effect of a polysaccharide from Poria cocos on humoral response in mice immunized by H1N1 influenza and HBsAg vaccines.

    PubMed

    Wu, Yajun; Li, Shuai; Li, Haixia; Zhao, Chunzhi; Ma, Hao; Zhao, Xiunan; Wu, Junhua; Liu, Kunlu; Shan, Junjie; Wang, Yuxia

    2016-10-01

    Poria cocos has a long history of medicinal use in China. Polysaccharides and their derivatives in the medicine exhibit many beneficial biological activities including anticancer, anti-inflammatory, antioxidant and antiviral activities. In this study, a new polysaccharide (PCP-II) was isolated from sclerotium of Poria cocos. Its physico-chemical characters were identified and its adjuvant activity was investigated in mice co-immunized with H1N1 influenza vaccine and hepatitis B surface antigen (HBsAg). The results revealed that PCP-II has a molecular weight of 29.0kDa. It was composed of fucose, mannose, glucose and galactose in molar ration of 1.00:1.63:0.16:6.29 respectively. Pharmacological data demonstrated that PCP-II increased antigen-specific antibody levels in mice immunized with influenza vaccine. PCP-II also elicited anti-HBsAg antibodies at significantly higher titers and generated robust and durable immunity compared to mice immunized with HBsAg-alum following two administrations. PCP-II improved proliferation of splenocytes, stimulated IL-12p70 and TNF-α productions in dendritic cells and macrophages respectively. These results suggested that PCP-II-adjuvanted vaccines enhanced humoral and cellular immunity. PCP-II could be developed as an efficacious adjuvant in human and animal vaccines. Copyright © 2016 Elsevier B.V. All rights reserved.

  7. 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

  8. 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.

  9. 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.

  10. 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.

  11. Intranasal Immunization with Pneumococcal Polysaccharide Conjugate Vaccines with Nontoxic Mutants of Escherichia coli Heat-Labile Enterotoxins as Adjuvants Protects Mice against Invasive Pneumococcal Infections

    PubMed Central

    Jakobsen, Håvard; Schulz, Dominique; Pizza, Mariagrazia; Rappuoli, Rino; Jónsdóttir, Ingileif

    1999-01-01

    Host defenses against Streptococcus pneumoniae depend largely on phagocytosis following opsonization by polysaccharide-specific immunoglobulin G (IgG) antibodies and complement. Since colonization of the respiratory mucosa is the first step in pneumococcal pathogenesis, mucosal immune responses may play a significant role. In addition to inducing systemic immune responses, mucosal vaccination with an effective adjuvant has the advantage of inducing mucosal IgA antibodies. The heat-labile enterotoxin (LT) of Escherichia coli is a well-studied mucosal adjuvant, and adjuvant activity of nontoxic LT mutants has been demonstrated for several protein antigens. We investigated the immunogenicity of pneumococcal polysaccharide conjugate vaccines (PNC) of serotypes 1 and 3 in mice after intranasal (i.n.) immunization by using as an adjuvant the nontoxic LT mutant LT-K63 or LT-R72, which has minimal residual toxicity. Pneumococcal serotype-specific antibodies were measured in serum (IgM, IgG, and IgA) and saliva (IgA), and vaccine-induced protection was evaluated by i.n. challenge with virulent pneumococci of the homologous serotype. When administered with LT mutants, i.n. immunization with both conjugates induced systemic and mucosal immune responses, and serum IgG antibody levels were significantly higher than after subcutaneous immunization. All mice immunized i.n. with PNC-1 and LT mutants were protected against bacteremia and cleared the pneumococci from the lung 24 h after i.n. challenge; pneumococcal density correlated significantly with serum IgG antibody levels. Similarly, the survival of mice immunized i.n. with PNC-3 and LT mutants was significantly prolonged. These results demonstrate that i.n. vaccination with PNC and potent adjuvants can protect mice against invasive and lethal pneumococcal infections, indicating that mucosal vaccination with PNC may be an alternative vaccination strategy for humans. PMID:10531245

  12. The Majority of Adult Pneumococcal Invasive Infections in Portugal Are Still Potentially Vaccine Preventable in Spite of Significant Declines of Serotypes 1 and 5

    PubMed Central

    Horácio, Andreia N.; Diamantino-Miranda, Jorge; Aguiar, Sandra I.; Ramirez, Mário; Melo-Cristino, José

    2013-01-01

    In Portugal, pneumococcal conjugate vaccines have been administered to children outside of the national immunization plan since 2001. We determined the serotype and antimicrobial susceptibility of 1265 isolates responsible for adult invasive pneumococcal infections (IPD) between 2009 and 2011 and compared the results with previously published data from 1999 to 2008. Serotypes 3 (12.6%), 7F (10.0%), 19A (9.1%), 14 (8.4%), 1 (6.9%) and 8 (6.2%) were the most frequent and together accounted for 53.2% of adult IPD. Serotypes 1 and 5 declined significantly while serotype 34, not included in any vaccine, increased. Taken together, the serotypes included in the 13-valent conjugate vaccine (PCV13) peaked among adult IPD isolates in 2008 (70.2%) and declined since then reaching 53.5% in 2011. The decline in the serotypes included in the 23-valent polysaccharide vaccine since 2007 was also significant but much more modest with 79.2% of the isolates causing IPD in 2011 expressing these serotypes. Since the changes in serotypes causing IPD in adults coincided with the 10-valent and PCV13 introduction in children, it is unlikely that vaccination triggered these changes although it may have accelerated them. The proportion of IPD caused by serotypes included in the 7-valent conjugate vaccine remained stable (19.0%). Both penicillin non-susceptibility and erythromycin resistance increased in the study period, with serotypes 14 and 19A accounting for the majority of resistant isolates. PMID:24066064

  13. Mortality reductions for older adults differ by race/ethnicity and gender since the introduction of adult and pediatric pneumococcal vaccines.

    PubMed

    Soneji, Samir; Metlay, Joshua

    2011-01-01

    We determined the effectiveness of a 23-valent-polysaccharide pneumococcal vaccine (PPV-23) and pneumococcal conjugate vaccine (PCV-7) in reducing adult pneumococcal mortality by comparing historically predicted declines in pneumococcal disease mortality with observed patterns since the introduction of PPV-23 and PCV-7, including analyses of age, gender, and racial/ethnic subgroups. We analyzed all deaths registered on U.S. death certificates reporting any site of pneumococcal infection (e.g., meningitis, sepsis, pneumonia, bacteremia, and peritonitis) from 1968 to 2006. We used time-series dynamic linear regression on annual pneumococcal mortality rates to determine the percentage reduction in post-1983 mortality rates for a given increase in PPV-23 vaccination rates and post-2000 mortality rates for a given increase in PCV-7 vaccination rates. Pneumococcal mortality decreased well before the introduction of PPV-23 in 1983 and again before the introduction of PCV-7 in 2000. The level of PPV-23 vaccination was associated with a direct and significant reduction in adult mortality, especially white female adults > or = 65 years of age. In contrast, the level of PCV-7 vaccination in the population was not associated with an indirect and significant reduction in pneumococcal mortality beyond the historical pace of decline. PPV-23 introduction was associated with a reduction in pneumococcal mortality among older adults > or = 65 years of age beyond levels predicted by secular trends, whereas PCV-7 introduction was not. Mortality reduction was not uniformly experienced across the population, revealing the need for additional strategies to reduce pneumococcal mortality in older adults.

  14. Cost Effectiveness of the 13-Valent Pneumococcal Conjugate Vaccination Program in Chronic Obstructive Pulmonary Disease Patients Aged 50+ Years in Spain.

    PubMed

    Rodríguez González-Moro, Jose Miguel; Menéndez, Rosario; Campins, Magda; Lwoff, Nadia; Oyagüez, Itziar; Echave, María; Rejas, Javier; Antoñanzas, Fernando

    2016-01-01

    Patients with chronic obstructive pulmonary disease (COPD) are at elevated risk of pneumococcal infection. A 13-valent pneumococcal conjugate vaccine (PCV13) was approved for protection against invasive disease and pneumonia caused by Streptococcus pneumoniae in adults. This study estimated the incremental cost-effectiveness ratio (ICER) of vaccinating COPD patients ≥50 years old with PCV13 compared with current vaccination policy (CVP) with 23-valent pneumococcal polysaccharide vaccine. A Markov model accounting for the risks and costs for all-cause non-bacteremic pneumonia (NBP) and invasive pneumococcal disease (IPD) was developed. All parameters, such as disease incidence and costs (€; 2015 values), were based on published data. The perspective of the analysis was that of the Spanish National Healthcare System, and the horizon of evaluation was lifetime in the base case. Vaccine effectiveness considered waning effect over time. Outcomes and costs were both discounted by 3% annually. Over a lifetime horizon and for a 629,747 COPD total population, PCV13 would prevent 2224 cases of inpatient NBP, 3134 cases of outpatient NBP, and 210 IPD extra cases in comparison with CVP. Additionally, 398 related deaths would be averted. The ICER was €1518 per quality-adjusted life-year (QALY) gained for PCV13 versus CVP. PCV13 was found to be cost effective versus CVP from a 5-year modelling horizon (1302 inpatient NBP and 1835 outpatient NBP cases together with 182 deaths would be prevented [ICER €25,573/QALY]). Univariate and probabilistic sensitivity analyses confirmed the robustness of the model. At the commonly accepted willingness-to-pay threshold of €30,000/QALY gained, PCV13 vaccination in COPD patients aged ≥50 years was a cost-effective strategy compared with CVP from 5 years to lifetime horizon in Spain.

  15. Colonisation of Irish patients with chronic obstructive pulmonary disease by Streptococcus pneumoniae and analysis of the pneumococcal vaccine coverage: a non-interventional, observational, prospective cohort study

    PubMed Central

    McCarthy, Hannah; Jackson, Mandy; Corcoran, Mary; McElligott, Martha; MacHale, Elaine; Sulaiman, Imran; Cushen, Breda; Costello, Richard W; Humpreys, Hilary

    2017-01-01

    Objectives To characterise the pattern of colonisation and serotypes of Streptococcus pneumoniae among patients with chronic obstructive pulmonary disease (COPD) who currently receive the 23-valent pneumococcal polysaccharide vaccine (PPV-23) according to vaccination status, use of antibiotics and steroids. To investigate the prevalence of PPV-23 and 13-valent pneumococcal conjugate vaccine (PCV-13) serotypes within the study cohort. Design A non-interventional, observational, prospective cohort study with a 12 -month follow-up period inclusive of quarterly study visits. Setting Beaumont Hospital and The Royal College of Surgeons in Ireland Clinical Research Centre, Dublin, Ireland. Participants Patients with an established diagnosis of COPD attending a tertiary medical centre. Primary outcome measure Colonisation rate of S. pneumoniae in patients with COPD and characterisation of serotypes of S. pneumoniae with correlation to currently available pneumococcal vaccines. Sputum and oropharyngeal swab samples were collected for the isolation of S. pneumoniae. Secondary outcome measure Seasonality of colonisation of S. pneumoniae and its relationship with the incidence of exacerbations of COPD. Results S. pneumoniae was detected in 16 of 417 samples, a colonisation incident rate of 3.8% and in 11 of 133 (8%) patients at least once during the study. The majority of S. pneumoniae isolates were identified in spring and were non-vaccine serotypes for either the PPV-23 or PCV-13 (63%). The colonisation incident rate of S. pneumoniae fluctuated over the four seasons with a peak of 6.6% in spring and the lowest rate of 2.2% occurring during winter. Antibiotic use was highest during periods of low colonisation. Conclusions There is seasonal variation in S. pneumoniae colonisation among patients with COPD which may reflect antibiotic use in autumn and winter. The predominance of non-vaccine types suggests that PCV-13 may have limited impact among patients with COPD in Ireland

  16. 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

  17. 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

  18. 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.

  19. 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

  20. 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

    Leung, Daniel T; 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; Kovác, Pavol; Qadri, Firdausi; Ryan, Edward T

    2013-06-01

    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.

  1. 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

  2. Standing orders for influenza and pneumococcal polysaccharide vaccination: Correlates identified in a national survey of U.S. Primary care physicians

    PubMed Central

    2012-01-01

    Background Standing orders programs (SOPs) allow non-physician medical staff to assess eligibility and administer vaccines without a specific physician's order. SOPs increase vaccination rates but are underutilized. Method In 2009, correlates of SOPs use for influenza vaccine and pneumococcal polysaccharide vaccination (PPV) were assessed in a nationally representative, stratified random sample of U.S. physicians (n = 880) in family and internal medicine who provided office immunization. The response rate was 67%. Physicians reporting no SOPs, only influenza SOPs, and joint influenza and PPV SOPs were compared using multinomial and logistic regression models to examine individual and practice-level correlates. Results 23% reported using SOPs consistently for both influenza vaccine and PPV, and 20% for influenza vaccination only, with the remainder not using SOPs. Practice-level factors that distinguished practices with joint influenza-PPV SOPs included perceived practice openness to change, strong practice teamwork, access to an electronic medical record, presence of an immunization champion in the practice, and access to nurse/physician assistant staff as opposed to medical assistants alone. Discussion Physicians in practices with SOPs for both vaccines reported greater awareness of ACIP recommendations and/or Medicare regulations and were more likely to agree that SOPs are an effective way to boost vaccination coverage. However, implementation of both influenza and PPV SOPs was also associated with a variety of practice-level factors, including teamwork, the presence of an immunization champion, and greater availability of clinical assistants with advanced training. Conclusions Practice-level factors are critical for the adoption of more complex SOPs, such as joint SOPs for influenza and PPV. PMID:22433118

  3. 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

  4. 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.

  5. Evolution of vaccination rates after the implementation of a free systematic pneumococcal vaccination in Catalonian older adults: 4-years follow-up

    PubMed Central

    Vila-Córcoles, Angel; Ochoa-Gondar, Olga; Ester, Francisco; Sarrá, Nuria; Ansa, Xabier; Saún, Neus

    2006-01-01

    Background The systematic vaccination with 23-valent polysaccharide pneumococcal vaccine (PPV) was introduced as a strategic objective of health for all the people over 65 in Catalonia in 1999. We analysed the evolution of the pneumococcal vaccination rates from 2000 to 2003. Methods We conducted a retrospective population-based study including all the individuals 65 years or older assigned to 8 Primary Care Centres (PCCs) in Tarragona (Catalonia, Spain), who figured in the administrative population databases on 31 December 2003 (n = 10,410 persons). We assessed whether every person had received PPV during the last four years (2000 to 2003) or whether they had received it before January 2000. Data sources were the computerised clinical records of the 8 participating PCCs, which included adult vaccination registries and diagnoses coded of International Classification of Diseases 9th Review Results The overall vaccination uptake increased to 38.6% at the end of 2000. Global accumulated coverages increased more slowly the following years: 44.4% in 2001, 50.9% in 2002, and 53.1% at the end of 2003. Vaccine uptake varied significantly according to age (46.7% in people 65–74 years-old, 60.9% in people 75 years or more; p < 0.001) and number of diseases or risk factors (DRFs) for pneumonia (47.1% vaccinated in people without DRFs, 56.8% in patients with one DRF, and 62.2% in patients with two or more DRFs; p < 0.001). The highest coverages were observed among those patients with: diabetes (65.9%), active neoplasia (64.8%), history of stroke (63.7%), and chronic lung disease (63.5%). The lowest uptake was observed among smokers (48.7%). Discussion The pneumococcal vaccination coverage increased quickly after the introduction of the recommendation for free vaccination in all the elderly people (with and without risk factors), but two years after the improvement the coverage became stable and increased slowly. PMID:16981982

  6. 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.

  7. Pneumococcal Polysaccharide Vaccination Elicits IgG Anti-A/B Blood Group Antibodies in Healthy Individuals and Patients with Type I Diabetes Mellitus.

    PubMed

    Wolfram, Wendelin; Sauerwein, Kai M T; Binder, Christoph J; Eibl-Musil, Nicole; Wolf, Hermann M; Fischer, Michael B

    2016-01-01

    Blood group antibodies are natural antibodies that develop early in life in response to cross-reactive environmental antigens in the absence of antigen encounter. Even later in life structural similarities in saccharide composition between environmental antigens such as bacterial polysaccharides and blood group A/B antigens could lead to changes in serum levels, IgM/IgG isotype, and affinity maturation of blood group anti-A/B antibodies. We addressed the question whether immunization with pneumococcal polysaccharide (PnP) vaccine Pneumo 23 Vaccine "Pasteur Merieux" (Pn23) could have such an effect in patients with type I diabetes mellitus (DM I), an autoimmune disease where an aberrant immune response to microbial antigens likely plays a role. Anti-PnP IgM and IgG responses were determined by ELISA, and the DiaMed-ID Micro Typing System was used to screen anti-A/B antibody titer before and after Pn23 immunization in 28 healthy individuals and 16 patients with DM I. In addition, surface plasmon resonance (SPR) technology using the Biacore(®) device and a synthetic blood group A/B trisaccharide as the antigen was applied to investigate IgM and IgG anti-A/B antibodies and to measure antibody binding dynamics. All healthy individuals and DM I patients responded with anti-PnP IgM and IgG antibody production 4-6 weeks after Pn23 immunization, while no increase in blood group anti-A/B antibody titer was observed when measured by the DiaMed-ID Micro Typing System. Interestingly, isotype-specific testing by SPR technology revealed an increase in blood group anti-A/B IgG, but not IgM, following Pn23 immunization in both patients and controls. No change in binding characteristics of blood group anti-A/B antibodies could be detected following Pn23 vaccination, supporting the assumption of an increase in IgG antibody titer with no or very little affinity maturation. The study provides evidence for epitope sharing between pneumococcal polysaccharides and blood group ABO

  8. Enzyme-Linked Immunosorbent Assay for Measuring Antibodies to Pneumococcal Polysaccharides for the PNEUMOVAX 23 Vaccine: Assay Operating Characteristics and Correlation to the WHO International Assay

    PubMed Central

    Marchese, Rocio D.; Jain, Neil T.; Antonello, Joseph; Mallette, Laura; Butterfield-Gerson, Kristin L.; Raab, Jennifer; Burke, Pamela; Schulman, Cheryl; Adgate, Hilary; Sikkema, Daniel J.; Chirmule, Narendra

    2006-01-01

    The Merck pneumococcal (Pn) enzyme-linked immunosorbent assays (ELISAs) for measuring antibodies to 12 serotypes (serotypes 1, 3, 4, 6B, 7F, 8, 9V, 12F, 14, 18C, 19F, and 23F) were validated in 1999. Merck Laboratories developed the Pn assays using 10 μg/ml C polysaccharide, 100 μg/ml Pn polysaccharide (PnPs) 25, and 100 μg/ml PnPs 72 for preadsorption of samples, standards, and controls in order to improve the specificity to the Pn serotypes in the vaccine. The Pn assays utilize postimmunization sera obtained from subjects immunized with PNEUMOVAX 23 as standards for measuring immunoglobulin G concentrations in sera obtained from vaccine clinical trials with adults and infants. This material was calibrated to the Pn reference standard serum, 89SF, subjected to the Merck Pn ELISA adsorbants. Comparisons were made between the Merck Pn assay and the international Pn assay, showing moderate agreement between the two assay formats. This work describes the test procedures and operating characteristics of the Merck Pn assays and the results of experiments performed to compare the Merck Pn ELISAs to the international Pn ELISAs. PMID:16893991

  9. Specific and cross-reactive immune response to oral Salmonella Typhi Ty21a and parenteral Vi capsular polysaccharide typhoid vaccines administered concomitantly.

    PubMed

    Pakkanen, Sari H; Kantele, Jussi M; Savolainen, Laura E; Rombo, Lars; Kantele, Anu

    2015-01-09

    Since protective efficacy of the current typhoid vaccines-oral whole-cell Salmonella Typhi Ty21a and parenteral Vi-capsular polysaccharide preparation-is not optimal, and no vaccines are available against paratyphoid or non-typhoidal Salmonella (NTS) serotypes, new approaches deserve to be explored. The immunological mechanisms elicited by the two typhoid vaccines are mainly targeted against different structures. We studied whether these vaccines would enhance S. Typhi-specific immune response and cross-reactivity against other Salmonellae, if administered concomitantly. Volunteers were immunized simultaneously with Ty21a and Vi vaccines (Ty21a+Vi group) or with either of the two singly (Ty21a and Vi groups). All volunteers were investigated for circulating specific and cross-reactive plasmablasts, identified by ELISPOT as IgA, IgG or IgM antibody-secreting cells (ASC) reactive with S. Typhi, S. Paratyphi A/B/C, or selected NTS serotypes (S. Enteritidis, S. Typhimurium). In the Ty21a+Vi group, no specific or cross-reactive plasmablasts were detected before vaccination. After vaccination, the number of S. Typhi-specific plasmablasts (878 ASC/10(6) PBMC, 95%CI 554-1201) proved higher than in the Ty21a (339 ASC/10(6) PBMC; p<0.001) and Vi (149 ASC/10(6) PBMC; p<0.001) groups. Likewise, cross-reactive responses in the Ty21a+Vi group were higher than in the Ty21a and Vi groups (Ty21a+Vi vs Ty21a: ASC against S. Paratyphi A/B, S. Enteritidis and S. Typhimurium p<0.05, against S. Paratyphi C p<0.01; Ty21a+Vi vs Vi: against S. Paratyphi C not significant, others p<0.0001). A gut-directed homing profile was seen among O antigen-specific and a systemic one among Vi antigen-specific plasmablasts. Concomitant administration of Ty21a and Vi vaccines is well tolerated and induces an additive immune response to the two vaccines. Thus it enhances the magnitude of both typhoid-specific plasmablast responses and those cross-reacting with paratyphoid and most important NTS serotypes

  10. 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

  11. 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

  12. Evaluation of De-O-Acetylated Meningococcal C Polysaccharide-Tetanus Toxoid Conjugate Vaccine in Infancy: Reactogenicity, Immunogenicity, Immunologic Priming, and Bactericidal Activity against O-Acetylated and De-O-Acetylated Serogroup C Strains

    PubMed Central

    Richmond, Peter; Borrow, Ray; Findlow, Jamie; Martin, Sarah; Thornton, Carol; Cartwright, Keith; Miller, Elizabeth

    2001-01-01

    The polysaccharide capsule of serogroup C Neisseria meningitidis (MenC) has been integral to vaccine development. Licensed MenC vaccines contain the O-acetylated (OAc+) form of polysaccharide. Some MenC strains have de-O-acetylated (OAc−) polysaccharide, which may affect antibody specificity and functional activity when used in a vaccine. We evaluated an OAc-MenC conjugate-tetanus toxoid conjugate (MCC-TT) vaccine given concomitantly with whole-cell diphtheria-tetanus-pertussis, Haemophilus influenzae type b, and oral polio immunization in 83 infants at 2, 3, and 4 months of age. Serum bactericidal activities (SBA) against OAc+ and OAc− MenC strains and OAc+ and OAc− polysaccharide-specific immunoglobulin G (IgG) levels were evaluated. MCC-TT vaccine was well tolerated. All infants produced SBA titers of ≥8 after a single dose at 2 months of age. The SBA geometric mean titer for OAc+ strain C11 increased from 2.7 (95% confidence interval [CI] 2.2 to 3.2) to 320 (95% CI, 237 to 432), 773 (95% CI, 609 to 982), and 1,063 (95% CI, 856 to 1319) after one, two, and three doses of MCC-TT, respectively. OAc− IgG levels were twice as high as OAc+ IgG levels after the primary series of MCC-TT vaccine, and the SBA was significantly higher against the OAc− MenC strain. Antibody responses to booster vaccination with either OAc+ MenC polysaccharide vaccine (MACP) or a fourth dose of MCC-TT at 14 months of age provided evidence of immunologic memory. The acetylation status of the booster vaccine influenced the specificity of the response, with significantly higher OAc− IgG levels and SBA after MCC-TT vaccine compared to MACP vaccine but similar OAc+ antibody levels. MCC-TT vaccine is highly immunogenic and primes for immunologic memory against OAc+ and OAc− MenC strains in infancy. PMID:11254596

  13. 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

  14. Agreement between patients' self-report and medical records for vaccination: the PGRx database.

    PubMed

    Grimaldi-Bensouda, Lamiae; Aubrun, Elodie; Leighton, Pamela; Benichou, Jacques; Rossignol, Michel; Abenhaim, Lucien

    2013-03-01

    Patients' self-reported vaccine exposure (PS) may be subject to memory errors and other biases. Physicians' prescription records and other medical records (MR) do not capture noncompliance with vaccination. This study compared PS with MR for influenza, 23-valent pneumococcal, and human papillomavirus (HPV) vaccines. The Pharmacoepidemiologic General Research Extension (PGRx) database uses a network of over 300 general practitioners across France, who systematically recruit an age- and sex-stratified sample of patients (≥ 14 years old), without reference to their diagnoses or prescriptions. Patients received a structured telephone interview, combined with an interview guide listing vaccines commonly given. Patients' self-reported vaccination in the 3 years before their recruitment was compared with medical records kept by the physician or the patient. Concordance between PS and MR was assessed for 7613 patients for whom both sources of information were available. Agreement within 3 years before the recruitment date was substantial for influenza vaccines (prevalence and bias-adjusted kappa [PABAK] = 0.74, sensitivity PS relative to MR 81.5%) and high for 23-valent pneumococcal vaccines (PABAK = 0.98, sensitivity PS 49.6) and HPV vaccines (PABAK = 0.92, sensitivity PS 91.6). In adjusted analyses, agreement varied with sociodemographic and health-related factors, particularly for influenza and 23-valent pneumococcal vaccines. The PGRx method for drug exposure assessment is a new tool in pharmacoepidemiology that shows substantial to high agreement between PS and MR for exposure to various vaccines. Our finding of high agreement between PS and MR for HPV vaccination status in young women is a significant addition to the literature. Copyright © 2013 John Wiley & Sons, Ltd.

  15. Persistence of serum bactericidal antibody one year after a booster dose of either a glycoconjugate or a plain polysaccharide vaccine against serogroup C Neisseria meningitidis given to adolescents previously immunized with a glycoconjugate vaccine.

    PubMed

    de Whalley, Philip C S; Snape, Matthew D; Kelly, Dominic F; Banner, Carly; Lewis, Susan; Diggle, Linda; John, Tessa M; Yu, Ly-Mee; Omar, Omar; Borkowski, Astrid; Pollard, Andrew J

    2011-11-01

    Bactericidal antibody induced by immunization of infants with serogroup C Neisseria meningitidis (MenC) vaccines wanes rapidly during childhood. Adolescents are at particular risk from meningococcal disease, therefore they might benefit from a booster dose of vaccine. The duration of serologic response to such a booster in adolescents is unknown. In a previous study, English schoolchildren, aged 9 to 12 years, who had received a monovalent MenC glycoconjugate vaccine in 1999-2000, were given either a plain polysaccharide vaccine (MenC-PS group, n = 150) or a glycoconjugate vaccine (MenC-CRM group, n = 95) at 13 to 15 years of age. In this follow-up study, serum bactericidal antibody titers and specific immunoglobulin G concentrations were assessed 1 year later. Results were compared with unboosted controls of similar age (control group, n = 298). Compliance with study protocol was achieved for 146 of the MenC-PS group, 92 of the MenC-CRM group, and 293 of the control group. Compared with the control group, both the MenC-PS and MenC-CRM groups had a significantly higher (P < 0.0001) geometric mean serum bactericidal antibody titers 1 year after the booster dose (geometric mean titers for MenC-PS group 3388 [95% confidence interval {CI}: 2460-4665]; MenC-CRM group 4417 [95% CI: 2951-6609]; control group 316 [95% CI: 252-396]). Specific immunoglobulin G concentration also rose and remained elevated 1 year after the booster. A booster dose of MenC vaccine given to adolescents produced a marked rise in bactericidal antibody, which remained elevated 1 year later. Introduction of an adolescent booster of MenC vaccine might provide enhanced long-term population control of the disease.

  16. 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.

  17. 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 ...

  18. 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.

  19. 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

  20. Recognition of flavin mononucleotide, Haemophilus influenzae type b and its capsular polysaccharide vaccines by antibodies specific to D-ribitol-5-phosphate.

    PubMed

    Ravi, G; Venkatesh, Yeldur P

    2014-11-01

    D-Ribitol-5-phosphate (Rbt-5-P) is an important metabolite in the pentose phosphate pathway and an integral part of bacterial cell wall polysaccharides, specifically as polyribosyl ribitol phosphate (PRP) in Haemophilus influenzae type b (Hib). The major objective of this study was to investigate whether an antibody specific to Rbt-5-P can recognize the PRP of Hib. D-Ribose-5-phosphate was reacted with proteins in the presence of sodium cyanoborohydride to obtain Rbt-5-P epitopes; 120 h reaction resulted in conjugation of ~30 and ~17 moles of Rbt-5-P/mole of BSA and OVA, respectively, based on decrease in amino groups, MALDI-TOF analyses, an increase in apparent molecular weight (SDS-PAGE) and glycoprotein staining. Immunization of rabbits with Rbt-5-P-BSA conjugate generated antibodies to Rbt-5-P as demonstrated by dot immunoblot and non-competitive ELISA. Homogeneous Rbt-5-P-specific antibody was purified from Rbt-5-P-BSA antiserum subjected to caprylic acid precipitation followed by hapten-affinity chromatography; its affinity constant is 7.1 × 10(8) M(-1). Rbt-5-P antibody showed 100 % specificity to Rbt-5-P, ~230 %, 10 % and 3.4 % cross-reactivity to FMN, riboflavin and FAD, respectively; the antibody showed ~4 % cross-reactivity to D-ribitol and <3 % to other sugars/sugar alcohols. Rbt-5-P-specific antibody recognized Hib conjugate vaccines containing PRP which was inhibited specifically by Rbt-5-P, and also detected Hib cell-surface capsular polysaccharides by immunofluorescence. In conclusion, Rbt-5-P-protein conjugate used as an immunogen elicited antibodies binding to an epitope also present in PRP and Hib bacteria. Rbt-5-P-specific antibody has potential applications in the detection and quantification of free/bound Rbt-5-P and FMN as well as immunological recognition of Hib bacteria and its capsular polysaccharide.

  1. Meningococcal Polysaccharide Vaccine Failure in a Patient with C7 Deficiency and a Decreased Anticapsular Antibody Response

    DTIC Science & Technology

    2012-05-01

    Antibodies directed against the polysaccharide capsule increase serum bactericidal activity in complement sufficient individuals and are good...membrane proreins24 and lipooligosaccharides2 5 enhance bactericidal activity against the infecting strain and provide varying degrees of cross...protection ro strains from other sero groups in complement sufficient individuals, bur they are less effective at mediating opsonophagocyrosis.23 As a

  2. 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

  3. 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

  4. Pneumococcal vaccination coverages among low-, intermediate-, and high-risk adults in Catalonia.

    PubMed

    Vila-Corcoles, Angel; Ochoa-Gondar, Olga; Hospital, Imma; de Diego, Cinta; Satué, Eva; Bladé, Jordi; Ansa, Xabier; Guzmán, Jorge A; Salsench, Elisabet; Ramos, Francisca

    2016-11-01

    There is scarce data about pneumococcal vaccination coverages among adults in recent years. We investigated current pneumococcal vaccination coverages in Catalonia, Spain, with a cross-sectional population-based study including 2,033,465 individuals aged 50 y or older assigned to the Catalonian Health Institute at 01/01/2015 (date of survey). A previously validated institutional research clinical Database was used to classify study subjects by their vaccination status for both 23-valent pneumococcal polysaccharide vaccine (PPSV23) and 13-valent pneumococcal conjugate vaccine (PCV13), to identify comorbidities and underlying conditions, and establish the risk stratum of each individual: High risk stratum: functional or anatomic asplenia, cochlear implants, CSF leaks, or immunocompromising conditions; medium risk stratum: immunocompetent persons with history of chronic cardiac or respiratory disease, liver disease, diabetes mellitus, alcoholism and/or smoking; low risk stratum: persons without high or medium risk conditions. Of the total 2,033,465 study population, an amount of 789,098 (38.8%) had received PPVS23, whereas 5031 (0.2%) had received PCV13. PPSV23 coverages increased largely with increasing age: 4.8% in 50-59 y vs 35.5% in 60-69 y vs 71.9% in 70-79 y vs 79.5% in 80 y or older; p < 0.001). PCV13 coverages also increased with age, although they were very low in all age groups. PPSV23 coverages were 59.2% in high risk stratum, 48.3% in medium risk stratum and 28.1% in low risk stratum (p < 0.001). For the PCV13, uptakes were 1.2%, 0.3% and 0.1% in high, medium and low stratum, respectively (p < 0.001). In conclusion, pneumococcal vaccination coverages in Catalonian adults are not optimal, being especially small for the PCV13 (even in high-risk subjects).

  5. Preparation of Burkholderia pseudomallei Polysaccharide-CRM197 Conjugate, a Potential Vaccine Candidate for Glanders and Melioidosis

    DTIC Science & Technology

    2005-10-01

    Acetolysis- 2 % HAc, 1000 C, 2h: – Cleaves the linkage at KDO in LPS to release lipid A, core oligosaccharides, and O-antigens (repeating sugar units...display a currently valid OMB control number. 1. REPORT DATE 01 OCT 2005 2 . REPORT TYPE N/A 3. DATES COVERED - 4. TITLE AND SUBTITLE...Western blot: – Polysaccharide-protein conjugate, Antibody produced against the whole cells, capsule, LPS Rationale for Choosing a Protein Carrier To

  6. A novel hepatitis B vaccine containing Advax™, a polysaccharide adjuvant derived from delta inulin, induces robust humoral and cellular immunity with minimal reactogenicity in preclinical testing

    PubMed Central

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

    2013-01-01

    Although current HBV vaccines have an outstanding record of safety and efficacy, reduced immunogenicity is a problem in those of older age, or having renal impairment or diabetes mellitus. In this study, we tested the ability of Advax™ adjuvant, a novel polysaccharide adjuvant based on delta inulin, to enhance the immunogenicity of hepatitis B surface antigen (HBs) in mice and guinea pigs by comparison to the traditional alum adjuvant. Advax™ provided antigen-sparing and significantly enhanced both anti-HBs antibody titers and anti-HBs CD4 and CD8 T-cells, with increases in Th1, Th2 and Th17 cytokine responses. Unlike alum, the adjuvant effect of Advax™ was seen even when injected 24 hours before the HBs antigen. Advax™ adjuvant similarly enhanced humoral and cellular immune responses in guinea pigs to a third generation preS-HBs antigen. Inclusion Advax™ adjuvant when combined with HBs antigen could provide enhanced protection over current generation HBV vaccines for immunization of low responder populations. PMID:23306367

  7. A novel hepatitis B vaccine containing Advax™, a polysaccharide adjuvant derived from delta inulin, induces robust humoral and cellular immunity with minimal reactogenicity in preclinical testing.

    PubMed

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

    2013-04-08

    Although current HBV vaccines have an outstanding record of safety and efficacy, reduced immunogenicity is a problem in those of older age, or having renal impairment or diabetes mellitus. In this study, we tested the ability of Advax™ adjuvant, a novel polysaccharide adjuvant based on delta inulin, to enhance the immunogenicity of hepatitis B surface antigen (HBs) in mice and guinea pigs by comparison to the traditional alum adjuvant. Advax™ provided antigen-sparing, significantly enhanced both anti-HBs antibody titers, and anti-HBs CD4 and CD8 T-cells, with increases in Th1, Th2 and Th17 cytokine responses. Unlike alum, the adjuvant effect of Advax™ was seen even when injected 24h before the HBs antigen. Advax™ adjuvant similarly enhanced humoral and cellular immune responses in guinea pigs to a third generation preS-HBs antigen. Advax™ adjuvant when combined with HBs antigen could provide enhanced protection over current generation HBV vaccines for immunization of low responder populations. Copyright © 2013 Elsevier Ltd. All rights reserved.

  8. 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. Copyright © 2014 Elsevier Ltd. All rights reserved.

  9. Exploring the immunopotentiation of Chinese yam polysaccharide poly(lactic-co-glycolic acid) nanoparticles in an ovalbumin vaccine formulation in vivo.

    PubMed

    Luo, Li; Qin, Tao; Huang, Yifan; Zheng, Sisi; Bo, Ruonan; Liu, Zhenguang; Xing, Jie; Hu, Yuanliang; Liu, Jiaguo; Wang, Deyun

    2017-11-01

    Biocompatible and biodegradable poly(lactic-co-glycolic acid) (PLGA) has been approved by the US Food and Drug Administration and has frequently been used to develop potential vaccine delivery systems. The immunoregulation and immunopotentiation of Chinese yam polysaccharide (CYP) have been widely demonstrated. In the current study, cell uptake mechanisms in dendritic cells (DCs) were monitored in vitro using confocal laser scanning microscopy, transmission electron microscopy, and flow cytometry. To study a CYP-PLGA nanoparticle-adjuvanted delivery system, CYP and ovalbumin (OVA) were encapsulated in PLGA nanoparticles (CYPPs) to act as a vaccine, and the formulation was tested in immunized mice. The CYPPs more easily underwent uptake by DCs in vitro, and CYPP/OVA could stimulate more effective antigen-specific immune responses than any of the single-component formulations in vivo. Mice immunized using CYPP/OVA exhibited more secretion of OVA-specific IgG antibodies, better proliferation, and higher cytokine secretion by splenocytes and significant activation of CD3(+)CD4(+) and CD3(+)CD8(+) T cells. Overall, the CYPP/OVA formulation produced a stronger humoral and cellular immune response and a mixed Th1/Th2 immune response with a greater Th1 bias in comparison with the other formulations. In conclusion, the data demonstrate that the CYPP-adjuvanted delivery system has the potential to strengthen immune responses and lay the foundation for novel adjuvant design.

  10. Plasma and memory B-cell kinetics in infants following a primary schedule of CRM197-conjugated serogroup C meningococcal polysaccharide vaccine

    PubMed Central

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

    2009-01-01

    The induction of persistent protective levels of pathogen-specific antibody is an important goal of immunization against childhood infections. However, antibody persistence is poor after immunization in infancy versus later in life. Serogroup C meningococci (MenC) are an important cause of bacteraemia and meningitis in children. The use of protein–polysaccharide conjugate vaccines against MenC has been associated with a significant decline in the incidence of invasive disease. However, vaccine effectiveness is negligible by more than 1 year after a three-dose priming series in infancy and corresponds to a rapid decline in antibody following an initial immune response. The cellular mechanisms underlying the generation of persistent antibody in this age group are unclear. An essential prelude to larger studies of peripheral blood B cells is an understanding of B-cell kinetics following immunization. We measured MenC- and diphtheria-specific plasma and memory B-cell kinetics in infants receiving a CRM197 (cross-reactive material; mutant diphtheria toxoid)-conjugated MenC vaccine at 2, 3 and 4 months of age. Plasma cell responses were more delayed after the first dose when compared with the rapid appearance of plasma cells after the third dose. Memory B cells were detectable at all time-points following the third dose as opposed to the low frequency seen following a first dose. This study provides data on B-cell kinetics following a primary schedule of immunization in young infants upon which to base further studies of the underlying cellular mechanism of humoral immunity. PMID:19175802

  11. Differences in Homing Potentials of Streptococcus pneumoniae–Specific Plasmablasts in Pneumococcal Pneumonia and After Pneumococcal Polysaccharide and Pneumococcal Conjugate Vaccinations

    PubMed Central

    Palkola, Nina V.; Pakkanen, Sari H.; Kantele, Jussi M.; Pakarinen, Laura; Puohiniemi, Ritvaleena; Kantele, Anu

    2015-01-01

    Background. Mucosal immune mechanisms in the upper and lower respiratory tracts may serve a critical role in preventing pneumonia due to Streptococcus pneumoniae. Streptococcus pneumoniae–specific plasmablasts presumably originating in the lower respiratory tract have recently been found in the circulation in patients with pneumonia. The localization of an immune response can be evaluated by exploring homing receptors on such plasmablasts, yet no data have thus far described homing receptors in pneumonia. Methods. The expression of α4β7, L-selectin, and cutaneous lymphocyte antigen (CLA) on S. pneumoniae–specific plasmablasts was examined in patients with pneumonia (n = 16) and healthy volunteers given pneumococcal polysaccharide vaccine (PPV; n = 14) or pneumococcal conjugate vaccine (PCV; n = 11). Results. In patients with pneumonia, the proportion of S. pneumoniae–specific plasmablasts expressing L-selectin was high, the proportion expressing α4β7 was moderate, and the proportion expressing CLA was low. The homing receptor α4β7 was expressed more frequently in the pneumonia group than in the PPV (P = .000) and PCV (P = .029) groups, L-selectin was expressed more frequently in the PPV group than in the PCV group (P = .014); and CLA was expressed more frequently in the pneumonia group than in the PPV group (P = .001). Conclusions. The homing receptor profile in patients with pneumonia was unique yet it was closer to that in PCV recipients than in PPV recipients. These data suggest greater mucosal localization for immune response in natural infection, which is clinically interesting, especially considering the shortcomings of vaccines in protecting against noninvasive pneumonia. PMID:25838267

  12. Differences in Homing Potentials of Streptococcus pneumoniae-Specific Plasmablasts in Pneumococcal Pneumonia and After Pneumococcal Polysaccharide and Pneumococcal Conjugate Vaccinations.

    PubMed

    Palkola, Nina V; Pakkanen, Sari H; Kantele, Jussi M; Pakarinen, Laura; Puohiniemi, Ritvaleena; Kantele, Anu

    2015-10-15

    Mucosal immune mechanisms in the upper and lower respiratory tracts may serve a critical role in preventing pneumonia due to Streptococcus pneumoniae. Streptococcus pneumoniae-specific plasmablasts presumably originating in the lower respiratory tract have recently been found in the circulation in patients with pneumonia. The localization of an immune response can be evaluated by exploring homing receptors on such plasmablasts, yet no data have thus far described homing receptors in pneumonia. The expression of α4β7, L-selectin, and cutaneous lymphocyte antigen (CLA) on S. pneumoniae-specific plasmablasts was examined in patients with pneumonia (n = 16) and healthy volunteers given pneumococcal polysaccharide vaccine (PPV; n = 14) or pneumococcal conjugate vaccine (PCV; n = 11). In patients with pneumonia, the proportion of S. pneumoniae-specific plasmablasts expressing L-selectin was high, the proportion expressing α4β7 was moderate, and the proportion expressing CLA was low. The homing receptor α4β7 was expressed more frequently in the pneumonia group than in the PPV (P = .000) and PCV (P = .029) groups, L-selectin was expressed more frequently in the PPV group than in the PCV group (P = .014); and CLA was expressed more frequently in the pneumonia group than in the PPV group (P = .001). The homing receptor profile in patients with pneumonia was unique yet it was closer to that in PCV recipients than in PPV recipients. These data suggest greater mucosal localization for immune response in natural infection, which is clinically interesting, especially considering the shortcomings of vaccines in protecting against noninvasive pneumonia. © The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases Society of America.

  13. 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

  14. 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

  15. 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.).

  16. 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

  17. 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

  18. Immunochemical studies of Shigella flexneri 2a and 6, and Shigella dysenteriae type 1 O-specific polysaccharide-core fragments and their protein conjugates as vaccine candidates

    PubMed Central

    Kubler-Kielb, Joanna; Vinogradov, Evgeny; Mocca, Christopher; Pozsgay, Vince; Coxon, Bruce; Robbins, John B.; Schneerson, Rachel

    2010-01-01

    There is no licensed vaccine for the prevention of shigellosis. Our approach to the development of Shigella vaccine is based on inducing serum IgG antibodies to the O-specific polysaccharide (O-SP) domain of their lipopolysaccharides (LPS). We have shown that low molecular mass O-SP-core (O-SPC) fragments isolated from Shigella sonnei LPS conjugated to proteins induced significantly higher antibody levels in mice than the full length O-SP conjugates. This finding is now extended to the O-SPC of S. flexneri 2a and 6, and S. dysenteriae type 1. The structures of O-SPC, containing core plus 1–4 O-SP repeat units (RU), were analyzed by NMR and mass spectroscopy. The first RUs attached to the cores of S. flexneri 2a and 6 LPS were different from the following RUs in their O-acetylation and/or glucosylation. Conjugates of core plus more than 1 RUs were necessary to induce LPS antibodies in mice. The resulting antibody levels were comparable to those induced by the full length O-SP conjugates. In S. dysenteriae type 1, the first RU was identical to the following RUs, with the exception that the GlcNAc was bound to the core in the β-configuration, while in all other RUs the GlcNAc was present in the α-configuration. In spite of this difference, conjugates of S. dysenteriae type 1 core with 1, 2, or 3 RUs induced LPS antibodies in mice with levels statistically higher than those of the full size O-SP conjugates. O-SPC conjugates are easy to prepare, characterize, and standardize, and their clinical evaluation is planned. PMID:20542498

  19. Cost-effectiveness of new adult pneumococcal vaccination strategies in Italy

    PubMed Central

    Boccalini, Sara; Bechini, Angela; Levi, Miriam; Tiscione, Emila; Gasparini, Roberto; Bonanni, Paolo

    2013-01-01

    Community-acquired pneumonia (CAP) and invasive pneumococcal disease (IPD) are very relevant pathologies among elderly people (≥ 65 y old), with a consequent high disease burden. Immunization with the 23-valent pneumococcal polysaccharide vaccine (PPV23) has been differently implemented in the Italian regions in the past years, reaching overall low coverage rates even in those with medical indications. In 2010, the 13-valent pneumococcal conjugate vaccine (PCV13) became available and recommended in the universal Italian infant immunization program. Since October 2012, indications for use of PCV13 were extended to subjects ≥ 50 y to prevent invasive pneumococcal diseases. The Italian decision makers should now revise regional indications for the prevention of pneumococcal diseases in the elderly. Pharmaco-economic analyses represent a useful tool to value the feasibility of new immunization programs and their sustainability. Therefore, an ad hoc population model was developed in order to value the clinical and economic impact of an adult pneumococcal vaccination program in Italy. Particularly, different immunization scenarios were modeled: vaccination of 65 y-olds (1 cohort strategy), simultaneous vaccination of people aged 65 and 70 y (double cohort strategy) and, lastly, immunization of people aged 65, 70 and 75 y (triple cohort strategy), thus leading to the vaccination of 5, 10 and 15 cohorts during the 5 y of the program. In addition, the administration of a PPV23 dose one year after PCV13 was evaluated, in order to verify the economic impact of the supplemental serotype coverage in elderly people. The mathematical model valued the clinical impact of PCV13 vaccination on the number of bacteraemic pneumococcal pneumonia (BPP) and pneumococcal meningitis (PM) cases, and related hospitalizations and deaths. Although PCV13 is not yet formally indicated for the prevention of pneumococcal CAP by the European Medicine Agency (differently from FDA, whose

  20. Antibody persistence and immunologic memory after sequential pneumococcal conjugate and polysaccharide vaccination in HIV-infected children on highly active antiretroviral therapy.

    PubMed

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

    2013-10-01

    The capacity of pneumococcal vaccination to confer memory in HIV-infected children is critical for durable protection. 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 4-5 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. Prior to boosting, 4-5 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. Protective antibody concentrations, high avidity, and booster responses to PCV7 or PPV indicative of memory were present 4-5 years after PCV7-PCV7-PPV in HIV-infected children on HAART. Copyright © 2013 Elsevier Ltd. All rights reserved.

  1. 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

  2. Capsular polysaccharide vaccine for Group B Neisseria meningitidis, Escherichia coli K1, and Pasteurella haemolytica A2.

    PubMed

    Robbins, John B; Schneerson, Rachel; Xie, Guilin; Hanson, Lars Å; Åke-Hanson, Lars; Miller, Mark A

    2011-11-01

    We reviewed the literature that is the basis for our proposal that (2→8)-α-Neu5Ac conjugates will be safe and effective vaccines for Group B meningococci (GBMs), Escherichia coli K1, and Pasteurella haemolytica A2. Although (2→8)-α-Neu5Ac is a virulence factor and a protective antigen of these three pathogens, it is also a component of normal tissues (neural cell adhesion molecule). Natural, anti-(2→8)-α-Neu5Ac present in most adults, vaccine-induced antibodies, and even high levels of spontaneously appearing monoclonal anti-(2→8)-α-Neu5Ac did not cause autoimmunity. Although it is not possible to prove a null hypothesis, there are no epidemiologic, serologic, immunologic, or clinical data to indicate that (2→8)-α-Neu5Ac antibodies will induce pathology or an autoimmune disease. No increased pathology caused by these antibodies was found, even in neonates and infants of mothers recovered from GBM meningitis. The lack of pathology mediated by anti-(2→8)-α-Neu5Ac may be explained by different presentations of (2→8)-α-Neu5Ac on bacterial and mammalian cells and by the unusual physicochemical properties of anti-(2→8)-α-Neu5Ac. Based on clinical and experimental data collected over 30 y and because (2→8)-α-Neu5Ac is an essential virulence factor and a protective antigen for GBM, E. coli K1, and P. haemolytica A2, protein conjugates of it are easy to prepare using inexpensive and plentiful ingredients, and they would be compatible with routinely administered infant vaccines, clinical studies of these conjugates should proceed.

  3. Pneumococcal conjugate vaccine (Prevnar; PNCRM7): a review of its use in the prevention of Streptococcus pneumoniae infection.

    PubMed

    Darkes, Malcolm J M; Plosker, Greg L

    2002-01-01

    PNCRM7 (Prevnar) is a pneumococcal vaccine containing seven capsular polysaccharide antigens from the bacterium Streptococcus pneumoniae, each of which is conjugated to diphtheria protein [cross-reactive material (CRM(197))]. CRM(197) is an inert but immunogenic variant of diphtheria toxoid that is also used as a carrier molecule in one Haemophilus influenzae type b conjugate vaccine. Unlike the 23-valent unconjugated pneumococcal vaccines, PNCRM7 elicits a T cell-dependent response and thus protects young children against pneumococcal disease. The immunogenicity of PNCRM7 has been demonstrated in both healthy children aged <2 years and older children in high-risk groups. Two randomized, double-blind trials conducted in the US demonstrated that all PNCRM7 serotypes were immunogenic in healthy infants and young children when compared with a control vaccine. A booster dose of PNCRM7 elicited an anamnestic response to all seven serotypes. Data from a large, randomized, double-blind study conducted in California (US) have confirmed the protective efficacy of PNCRM7 against invasive pneumococcal disease (e.g. bacteremia, meningitis) caused by serotypes included in the vaccine. The vaccine efficacy in the per-protocol analysis was 97.4% and its efficacy against invasive disease caused by any pneumococcal serotype in the intent-to-treat (ITT) analysis was 89.1%. Indeed, a postlicense surveillance study (n = 211,565) showed that the introduction and routine use of PNCRM7 was associated with a marked reduction in invasive pneumococcal disease in children <5 years of age. In addition, the US trial and another randomized, double-blind trial conducted in Finland, showed that PNCRM7 vaccine efficacy against all otitis media episodes was between 6 and 7%. PNCRM7 vaccine was generally well tolerated and had a similar local and systemic adverse events profile to other pediatric vaccines. The most common local adverse event associated with PNCRM7 administration was inflammation at

  4. 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

  5. Vaccines

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    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 ...

  6. 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.

  7. 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

  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. Copyright © 2015 Elsevier España, S.L.U. y Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. All rights reserved.

  9. Survey of Obstetrics and Gynecology Residents Regarding Pneumococcal Vaccination in Pregnancy: Education, Knowledge, and Barriers to Vaccination

    PubMed Central

    Fay, Emily E.; Hoppe, Kara K.; Schulkin, Jay; Eckert, Linda O.

    2016-01-01

    Objective. The 23-valent pneumococcal vaccine is recommended for adults over 65 years of age and younger adults with certain medical conditions. The Centers for Disease Control and Prevention (CDC) state insufficient evidence to recommend routine pneumococcal vaccination during pregnancy, but the vaccine is indicated for pregnant women with certain medical conditions. We designed this project to gauge obstetrics and gynecology (OB/GYN) resident knowledge of maternal pneumococcal vaccination. Methods. We administered a 22-question survey to OB/GYN residents about maternal pneumococcal vaccination. We performed descriptive analysis for each question. Results. 238 OB/GYN residents responded. Overall, 69.3% of residents reported receiving vaccination education and 86.0% reported having ready access to vaccine guidelines and safety data. Most residents knew that asplenia (78.2%), pulmonary disease (77.3%), and HIV/AIDS (69.4%) are indications for vaccination but less knew that cardiovascular disease (45.0%), diabetes (35.8%), asthma (42.8%), nephrotic syndrome (19.7%), and renal failure (33.6%) are also indications for vaccination. Conclusion. OB/GYN residents are taught about vaccines and have ready access to vaccine guidelines and safety data. However, knowledge of indications for pneumococcal vaccination in pregnancy is lacking. Likely, the opportunity to vaccinate at-risk pregnant patients is being missed. PMID:26949324

  10. 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

  11. 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

  12. 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.

  13. [Vaccination].

    PubMed

    Graubner, U B; Liese, J; Belohradsky, B H

    2001-09-01

    Vaccination has been an important part of antiinfectious prophylaxis in pediatric oncology comprising immunizations with special indication like varicella vaccine and follow-up of routine immunizations after chemotherapy and bone marrow transplantation (BMT). Studies from the last decade demonstrate a loss of long term immunity to immunization preventable disease in most patients with chemotherapy and BMT who had received appropriate immunization before. So far routine vaccination programs following intensive chemotherapy have not been studied prospectively. Immunization programs following BMT have shown that immunizations with tetanus toxoid, diphtheria toxoid, inactivated poliovirus vaccine and influenza vaccine - given at least 12 months after transplantation - are safe and effective. Vaccination with live attenuated trivalent vaccine against measles, mumps and rubella in patients without chronic "graft versus host disease" (GVHD) and without ongoing immunosuppressive therapy, performed 24 months after transplantation, proved to be safe too. Recommendations have been published by 5 different official groups: (1.) "Ständige Impfkommission" (STIKO) and (2.) "Deutsche Gesellschaft für pädiatrische Infektiologie" (DGPI) recommend varicella vaccine für children with leukemia in remission for at least 12 months, for children with solid tumors and for patients getting an organ transplantation. Both societies do not comment on the schedule of booster vaccinations (with live attenuated vaccines) after the end of chemotherapy and after BMT. (3.) "Qualitätssicherungsgruppe" der "Gesellschaft für pädiatrische Onkologie und Hämatologie" (QS-GPOH) recommends immunization with nonliving vaccines when the patient is off therapy for at least 3 months and immunization with live attenuated vaccines when he is off therapy for at least 6 months. This group does not comment on varicella vaccine which has been controversial among pediatric oncologists. (4.) The " Infectious

  14. 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

  15. Vaccinations

    MedlinePlus

    ... be spread from animals to people. For example, rabies is a serious, often fatal, disease that can ... animals to people. By vaccinating your pets for rabies, you are protecting your family as well as ...

  16. Limited impact of neonatal or early infant schedules of 7-valent pneumococcal conjugate vaccination on nasopharyngeal carriage of Streptococcus pneumoniae in Papua New Guinean children: A randomized controlled trial.

    PubMed

    Aho, Celestine; Michael, Audrey; Yoannes, Mition; Greenhill, Andrew; Jacoby, Peter; Reeder, John; Pomat, William; Saleu, Gerard; Namuigi, Pioto; Phuanukoonnon, Suparat; Smith-Vaughan, Heidi; Leach, Amanda J; Richmond, Peter; Lehmann, Deborah

    2016-12-01

    Streptococcus pneumoniae is a leading cause of pneumonia, the most common cause of childhood death. Papua New Guinean children experience high rates of nasopharyngeal pneumococcal colonization within weeks of birth, predisposing them to pneumococcal disease. In a trial to determine the safety and immunogenicity of early infant vaccination with 7-valent pneumococcal conjugate vaccine (7vPCV), we investigated the impact of early schedules on pneumococcal carriage. Infants were randomized at birth to receive 7vPCV in a 0-1-2-month (n = 101) or a 1-2-3-month (n = 105) schedule or no 7vPCV (n = 106). All children received 23-valent pneumococcal polysaccharide vaccine at age 9 months. We cultured nasopharyngeal swabs (NPS) collected at ages 1, 2, 3, 4 weeks and 3, 9, 18 months, and middle ear discharge if present. Pneumococcal serotypes were identified by the Quellung reaction. A total of 1761 NPS were cultured. The prevalence of pneumococcal carriage was 22% at 1 week of age, rising to 80% by age 3 months and remained >70% thereafter, with high-density carriage in 42% of pneumococcus-positive samples. We identified 63 different serotypes; 43% of isolates from controls were 13vPCV serotypes. There were no significant differences in 7vPCV serotype carriage between 7vPCV recipients and controls at any age (22% vs. 31% at 9 months, p = 0.2). At age 9 months the prevalence of non-7vPCV carriage was 17% higher in 7vPCV recipients (48%) than in controls (25%, p = 0.02). More non-7vPCV serotypes were isolated from ear discharge in 16 7vPCV recipients than from 4 controls (48% vs. 25%, p = 0.13). The limited impact of neonatal or accelerated infant 7vPCV schedules on vaccine serotype carriage is probably due to the early onset of dense carriage of a broad range of pneumococcal serotypes. While serotype-independent pneumococcal vaccines are needed in high-risk populations, the underlying environmental factors and sources of infection must be investigated. http

  17. 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.

  18. 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.

  19. Safety and Immunogenicity of Neonatal Pneumococcal Conjugate Vaccination in Papua New Guinean Children: A Randomised Controlled Trial

    PubMed Central

    Phuanukoonnon, Suparat; Francis, Jacinta; Jacoby, Peter; Siba, Peter M.; Alpers, Michael P.; Reeder, John C.; Holt, Patrick G.; Richmond, Peter C.; Lehmann, Deborah

    2013-01-01

    Background Approximately 826,000 children, mostly young infants, die annually from invasive pneumococcal disease. A 6-10-14-week schedule of pneumococcal conjugate vaccine (PCV) is efficacious but neonatal PCV may provide earlier protection and better coverage. We conducted an open randomized controlled trial in Papua New Guinea to compare safety, immunogenicity and priming for memory of 7-valent PCV (PCV7) given in a 0-1-2-month (neonatal) schedule with that of the routine 1-2-3-month (infant) schedule. Methods We randomized 318 infants at birth to receive PCV7 in the neonatal or infant schedule or no PCV7. All infants received 23-valent pneumococcal polysaccharide vaccine (PPV) at age 9 months. Serotype-specific serum IgG for PCV7 (VT) serotypes and non-VT serotypes 2, 5 and 7F were measured at birth and 2, 3, 4, 9, 10 and 18 months of age. Primary outcomes were geometric mean concentrations (GMCs) and proportions with concentration ≥0.35 µg/ml of VT serotype-specific pneumococcal IgG at age 2 months and one month post-PPV. Results We enrolled 101, 105 and 106 infants, respectively, into neonatal, infant and control groups. Despite high background levels of maternally derived antibody, both PCV7 groups had higher GMCs than controls at age 2 months for serotypes 4 (p<0.001) and 9V (p<0.05) and at age 3 months for all VTs except 6B. GMCs for serotypes 4, 9V, 18C and 19F were significantly higher (p<0.001) at age 2 months in the neonatal (one month post-dose2 PCV7) than in the infant group (one month post-dose1 PCV7). PPV induced significantly higher VT antibody responses in PCV7-primed than unprimed infants, with neonatal and infant groups equivalent. High VT and non-VT antibody concentrations generally persisted to age 18 months. Conclusions PCV7 is well-tolerated and immunogenic in PNG neonates and young infants and induces immunologic memory to PPV booster at age 9 months with antibody levels maintained to age 18 months. Trial Registration Clinical

  20. Safety and immunogenicity of neonatal pneumococcal conjugate vaccination in Papua New Guinean children: a randomised controlled trial.

    PubMed

    Pomat, William S; van den Biggelaar, Anita H J; Phuanukoonnon, Suparat; Francis, Jacinta; Jacoby, Peter; Siba, Peter M; Alpers, Michael P; Reeder, John C; Holt, Patrick G; Richmond, Peter C; Lehmann, Deborah

    2013-01-01

    Approximately 826,000 children, mostly young infants, die annually from invasive pneumococcal disease. A 6-10-14-week schedule of pneumococcal conjugate vaccine (PCV) is efficacious but neonatal PCV may provide earlier protection and better coverage. We conducted an open randomized controlled trial in Papua New Guinea to compare safety, immunogenicity and priming for memory of 7-valent PCV (PCV7) given in a 0-1-2-month (neonatal) schedule with that of the routine 1-2-3-month (infant) schedule. We randomized 318 infants at birth to receive PCV7 in the neonatal or infant schedule or no PCV7. All infants received 23-valent pneumococcal polysaccharide vaccine (PPV) at age 9 months. Serotype-specific serum IgG for PCV7 (VT) serotypes and non-VT serotypes 2, 5 and 7F were measured at birth and 2, 3, 4, 9, 10 and 18 months of age. Primary outcomes were geometric mean concentrations (GMCs) and proportions with concentration ≥ 0.35 µg/ml of VT serotype-specific pneumococcal IgG at age 2 months and one month post-PPV. We enrolled 101, 105 and 106 infants, respectively, into neonatal, infant and control groups. Despite high background levels of maternally derived antibody, both PCV7 groups had higher GMCs than controls at age 2 months for serotypes 4 (p<0.001) and 9V (p<0.05) and at age 3 months for all VTs except 6B. GMCs for serotypes 4, 9V, 18C and 19F were significantly higher (p<0.001) at age 2 months in the neonatal (one month post-dose2 PCV7) than in the infant group (one month post-dose1 PCV7). PPV induced significantly higher VT antibody responses in PCV7-primed than unprimed infants, with neonatal and infant groups equivalent. High VT and non-VT antibody concentrations generally persisted to age 18 months. PCV7 is well-tolerated and immunogenic in PNG neonates and young infants and induces immunologic memory to PPV booster at age 9 months with antibody levels maintained to age 18 months. ClinicalTrials.gov NCT00219401.

  1. 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.

  2. 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

    Sayeed, Md Abu; Bufano, Meagan Kelly; Xu, Peng; 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

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

  3. 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

  4. [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.

  5. Missed opportunities in antipneumococcal vaccination. Can something more be done for prevention?

    PubMed

    Arencibia Jiménez, Mercedes; Navarro Gracia, Juan Francisco; Delgado de Los Reyes, José Antonio; Pérez Torregrosa, Gerardo; López Parra, David; López García, Pilar

    2014-03-01

    Vaccination is the most effective measure in the prevention of invasive pneumococcal disease (IPD). High-risk patients immunized during medical visits would benefit from the vaccine. To describe the IPD cases. To assess the most prevalent causative serotypes and to evaluate the missed opportunities for vaccination. This is a descriptive retrospective study of the incidence of IPD cases in Elche during 5 years. It was reviewed the vaccination status and the visits to specialized care prior to disease. It was also calculated the vaccine effectiveness with the 23-valent pneumococcal vaccine in our population. Between 2007 and 2011 were notified 181 of IPD, the most frequent medical conditions were pneumonia and sepsis, with a mortality rate of 12%. 80% of the causative serotypes are included in the vaccine. More than the half of the cases had at least one of the risk factor for indicating the vaccination. This percentage decreases by 6.2% in cases below 65 years of age with any risk factor. After 10 years of introducing the vaccine into the adult immunization schedule the coverage it is still low among the patients with risk factors. In our study, 75% of the cases were not vaccinated. Taking in count the vaccine effectiveness for preventing IPD, among the patients attended at the hospital by the specialist prior their IPD, it could have been prevented in the best assumption (85% vaccine effectiveness) 60 IPD cases. Copyright © 2013 SEPAR. Published by Elsevier Espana. All rights reserved.

  6. 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

  7. Immune Responses to O-Specific Polysaccharide and Lipopolysaccharide of Vibrio cholerae O1 Ogawa in Adult Bangladeshi Recipients of an Oral Killed Cholera Vaccine and Comparison to Responses in Patients with Cholera

    PubMed Central

    Uddin, Taher; Aktar, Amena; Xu, Peng; Johnson, Russell A.; Rahman, M. Arifur; Leung, Daniel T.; Afrin, Sadia; Akter, Aklima; Alam, Mohammad Murshid; Rahman, Atiqur; Chowdhury, Fahima; Khan, Ashraful I.; Bhuiyan, Taufiqur Rahman; Bufano, Meagan K.; Rashu, Rasheduzzaman; Yu, Yanan; Wu-Freeman, Ying; Harris, Jason B.; LaRocque, Regina C.; Charles, Richelle C.; Kováč, Pavol; Calderwood, Stephen B.; Ryan, Edward T.; Qadri, Firdausi

    2014-01-01

    Protective immunity to cholera is serogroup specific, and serogrouping is defined by the O-specific polysaccharide (OSP) of lipopolysaccharide (LPS). We characterized OSP-specific immune responses in adult recipients of an oral killed cholera vaccine (OCV WC-rBS) and compared these with responses in patients with cholera caused by Vibrio cholerae O1 Ogawa. Although vaccinees developed plasma immunoglobulin G (IgG), IgM, IgA antibody and antibody secreting cell (ASC, marker of mucosal response) to Ogawa OSP and LPS 7 days after vaccination, responses were significantly lower than that which occurred after cholera. Similarly, patients recovering from cholera had detectable IgA, IgM, and IgG memory B cell (MBC) responses against OSP and LPS on Day 30 and Day 90, whereas vaccinees only developed IgG responses to OSP 30 days after the second immunization. The markedly lower ASC and MBC responses to OSP and LPS observed among vaccinees might explain, in part, the lower protection of an OCV compared with natural infection. PMID:24686738

  8. Immune responses to O-specific polysaccharide and lipopolysaccharide of Vibrio cholerae O1 Ogawa in adult Bangladeshi recipients of an oral killed cholera vaccine and comparison to responses in patients with cholera.

    PubMed

    Uddin, Taher; Aktar, Amena; Xu, Peng; Johnson, Russell A; Rahman, M Arifur; Leung, Daniel T; Afrin, Sadia; Akter, Aklima; Alam, Mohammad Murshid; Rahman, Atiqur; Chowdhury, Fahima; Khan, Ashraful I; Bhuiyan, Taufiqur Rahman; Bufano, Meagan K; Rashu, Rasheduzzaman; Yu, Yanan; Wu-Freeman, Ying; Harris, Jason B; LaRocque, Regina C; Charles, Richelle C; Kováč, Pavol; Calderwood, Stephen B; Ryan, Edward T; Qadri, Firdausi

    2014-05-01

    Protective immunity to cholera is serogroup specific, and serogrouping is defined by the O-specific polysaccharide (OSP) of lipopolysaccharide (LPS). We characterized OSP-specific immune responses in adult recipients of an oral killed cholera vaccine (OCV WC-rBS) and compared these with responses in patients with cholera caused by Vibrio cholerae O1 Ogawa. Although vaccinees developed plasma immunoglobulin G (IgG), IgM, IgA antibody and antibody secreting cell (ASC, marker of mucosal response) to Ogawa OSP and LPS 7 days after vaccination, responses were significantly lower than that which occurred after cholera. Similarly, patients recovering from cholera had detectable IgA, IgM, and IgG memory B cell (MBC) responses against OSP and LPS on Day 30 and Day 90, whereas vaccinees only developed IgG responses to OSP 30 days after the second immunization. The markedly lower ASC and MBC responses to OSP and LPS observed among vaccinees might explain, in part, the lower protection of an OCV compared with natural infection.

  9. Safety and immunogenicity of a Vi polysaccharide-tetanus toxoid conjugate vaccine (Typbar-TCV) in healthy infants, children, and adults in typhoid endemic areas: a multicenter, 2-cohort, open-label, double-blind, randomized controlled phase 3 study.

    PubMed

    Mohan, Vadrevu Krishna; Varanasi, Vineeth; Singh, Anit; Pasetti, Marcela F; Levine, Myron M; Venkatesan, Ramasamy; Ella, Krishna M

    2015-08-01

    Enteric fever caused by Salmonella Typhi remains a major public health problem in developing countries. Typbar-TCV is a single-dose typhoid Vi polysaccharide-tetanus toxoid conjugate vaccine for persons ≥6 months of age. Six hundred fifty-four healthy subjects aged 2-45 years enrolled in a double-blind, randomized controlled trial (RCT) received a single dose of Typbar-TCV or comparator "Vi polysaccharide" (Typbar), and 327 healthy subjects aged 6-23 months received a single dose of Typbar-TCV in an open-label trial (OLT); both received single- or multidose presentations from different lots. After 2 years, subsets in each group received a booster dose. The primary objective included analysis of geometric mean titer (GMTs) and 4-fold rise of anti-Vi serum immunoglobulin G (IgG) enzyme-linked immunosorbent assay titers over baseline (seroconversion [SCN]) 42 days after immunization. Typbar-TCV recipients in the RCT attained higher anti-Vi IgG GMTs 42 days after immunization (SCN, 97%; GMT, 1293 [95% confidence interval {CI}, 1153-1449]) than recipients of Typbar (SCN, 93%; GMT, 411 [95% CI, 359-471]) (P < .001). Typbar-TCV was highly immunogenic in the OLT (SCN, 98%; GMT, 1937 [95% CI, 1785-2103]). Two years after vaccination, anti-Vi titers remained higher in Typbar-TCV subjects (GMT, 82 [95% CI, 73-92]); and exhibited higher avidity (geometric mean avidity index [GMAI], 60%) than in Typbar recipients (GMT, 46 [95% CI, 40-53]; GMAI 46%) in the RCT (P < .001). OLT Typbar-TCV recipients achieved GMT of 48 (95% CI, 42-55) and GMAI of 57%. Typbar-TCV induced multiple IgG subclasses and strong booster responses in all ages. No serious vaccine-attributable adverse events were observed. Single-dose Typbar-TCV is well tolerated and induces robust and long-lasting serum anti-Vi IgG across age groups. CTRI/2011/08/001957, CTRI/2014/01/004341. © The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved

  10. 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

  11. 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.

  12. Differential idiotype utilization for the in vivo type 14 capsular polysaccharide-specific immunoglobulin responses to intact Streptococcus pneumoniae versus a pneumococcal conjugate vaccine

    PubMed Central

    Colino, Jesus; Duke, Leah; Arjunaraja, Swadhinya; Chen, Quanyi; Liu, Leyu; Lucas, Alexander H.; Snapper, Clifford M.

    2012-01-01

    Murine IgG responses specific for the capsular polysaccharide (PPS14) of Streptococcus pneumoniae type 14 (Pn14) induced in response to intact Pn14 or a PPS14-protein conjugate are both dependent on CD4+ T cell help, but appear to utilize marginal zone versus follicular B cells, respectively. Here we identify an idiotype (44.1-Id) that dominates the PPS14-specific IgG, but not IgM, responses to intact Pn14, isolated PPS14 and Group B Streptococcus (strain COH1-11) expressing capsular polysaccharide structurally identical to PPS14. The 44.1-Id is however not expressed in the repertoire of natural PPS14-specific antibodies. In distinct contrast, PPS14-specific IgG responses to a soluble PPS14-protein conjugate exhibits minimal usage of the 44.1-Id, although significant 44.1-Id expression is elicited in response to conjugate attached to particles. The 44.1-Id elicited in response to intact Pn14 was expressed in similar proportions among all 4 IgG subclasses during both the primary and secondary responses. 44.1-Id usage was linked to the Igha, but not Ighb, allotype and was associated with induction of relatively high total PPS14-specific IgG responses. In contrast to PPS14-protein conjugate, avidity maturation of the 44.1-Id-dominant PPS14-specific IgG responses were limited, even during the highly boosted T cell-dependent PPS14-specific secondary responses to COH1-11. These results indicate that different antigenic forms of the same capsular polysaccharide can recruit distinct B cell clones expressing characteristic idiotypes under genetic control, and suggest that the 44.1-Id is derived from marginal zone B cells. PMID:22706079

  13. Immunology Update: New Vaccines.

    PubMed

    Starr, S Paul

    2016-11-01

    A new 9-valent human papillomavirus (HPV) vaccine is effective against more cancer-causing HPV types than previous vaccines. HPV vaccine series started with previous vaccines can be completed with the 9-valent vaccine. Two new influenza vaccines are available for adults 65 years and older: a high-dose vaccine and an enhanced adjuvant vaccine. These elicit stronger antibody responses than standard-dose vaccines. Current guidelines specify no preference for the new versus standard-dose vaccines. Two new group B meningococcal vaccines are intended for use during outbreaks and for patients with asplenia, complement deficiencies, frequent occupational meningococcus exposure, or for patients who desire protection from type B meningococcus. These are not substitutes for the quadrivalent vaccine already in use. For pneumococcus, new recommendations state that 13-valent pneumococcal conjugate vaccine (PCV13) should be administered to patients 65 years and older, followed at least 1 year later by the polyvalent pneumococcal polysaccharide vaccine (PPSV23). For patients ages 19 to 64 years with immunocompromise and not previously vaccinated against pneumococcus, administration of these two vaccines should be separated by at least 8 weeks. Rotavirus vaccine is standard for infants at age 2 months. Also, there is a new cholera vaccine approved for use in the United States. Written permission from the American Academy of Family Physicians is required for reproduction of this material in whole or in part in any form or medium.

  14. Capsular polysaccharide typing of domestic mastitis-causing Staphylococcus aureus strains and its potential exploration of bovine mastitis vaccine development. I. Capsular polysaccharide typing, isolation and purification of the strains.

    PubMed

    Han, H R; Pak, S I; Kang, S W; Jong, W S; Youn, C J

    2000-06-01

    One hundred seven isolates of Staphylococcus aureus from bovine mastitis were investigated for colony morphology in serum-soft agar (SSA), autoagglutination in salt, and capsular serotype. Capsular polysaccharide (CP) was purified and quantified from the extracts of clinical isolates. Overall, 89 isolates (83.2%) were diffuse in the SSA, without any difference in the proportion of diffuse colony between type 5 and type 8 strains. Some strains exhibited compact colonies in the SSA and expressed CP as determined by an enzyme-linked immunosorbent assay, indicating that compact morphology does not exclude encapsulation. The majority of the strains (11/12) showed autoagglutination in the salt aggregation test. The serotype 336 accounted for 46.7% of the isolates followed by serotype 5 (12.1%) and serotype 8 (12.1%). Particularly, twenty-six (24.3%) isolates reacted with two serotypes; 7 for type 8/336 and 19 for type 5/336. Five isolates (4.7%) were nontypeable with monoclonal antibodies specific for CP serotype 5, 8, or 336. The CP concentration in culture supernatants varied with the serotypes, and the total amount of CP produced by cells grown in a liquid medium was much less than that produced by cells grown on a solid medium. The Western blotting indicated that the CP bands of S. aureus serotype 5 and 8 were ranged in the molecular mass of 58-84 kilodalton (kDa), with additional bands in the region of approximately >/= 48 or

  15. 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.

  16. 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.

  17. 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.

  18. 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.

  19. Synthesis of synthetic mannan backbone polysaccharides found on the surface of Mycobacterium tuberculosis as a vaccine adjuvant and their immunological properties.

    PubMed

    Wattanasiri, Chakree; Paha, Jiraporn; Ponpuak, Marisa; Ruchirawat, Somsak; Boonyarattanakalin, Siwarutt

    2017-11-01

    Surface components of Mycobacterium tuberculosis (Mtb) play crucial roles in modulating host immune responses. Thorough understandings of immunological properties of the Mtb's surface components are essential for the development of tuberculosis treatment and prevention. Unfortunately, the accessibility to the molecules on the surface of Mtb is limited by the structural complexity due to their various macromolecular nature and the hazard of culturing Mtb. In this study, we reveal a practical synthesis of lipomannan (LM) backbone polysaccharides - the core glycans found on Mtb's surface. A rapid synthetic approach based on a controlled polymerization was developed for the chemical synthesis of mannopyranans, the core structure of LM. The size of the LM glycans can be controlled by using specific monomer concentrations in addition to stereo- and regioselectivity derived from the versatile tricyclic orthoester mannose monomer. The immunological properties of the synthesized mannopyranans were investigated and their adjuvant potential was revealed. The adjuvanticity mechanism of the synthetic mannopyranans appears to involve the NF-κB and inflammasome pathways. Copyright © 2017 Elsevier Ltd. All rights reserved.

  20. Enzymatic Modifications of Polysaccharides

    USDA-ARS?s Scientific Manuscript database

    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. ...

  1. 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. Copyright © 2015. Published by

  2. 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.

  3. 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.

  4. 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

  5. Pneumococcal vaccination may induce anti-oxidized low-density lipoprotein antibodies that have potentially protective effects against cardiovascular disease.

    PubMed

    Suthers, B; Hansbro, P; Thambar, S; McEvoy, M; Peel, R; Attia, J

    2012-06-08

    Many animal and human studies have found an inverse association between anti-oxidized low-density lipoprotein (oxLDL) antibodies (anti-oxLDL) and atherosclerotic burden. Furthermore, anti-oxLDL antibodies have been shown to cause regression of atherosclerotic plaque in mice. Animal studies indicate that the 23-valent pneumococcal vaccine may induce the production of these potentially protective anti-oxLDL antibodies, and human epidemiological studies support their potentially beneficial effect in reducing cardiovascular events. Here we describe the association between self-reported pneumococcal vaccination, vaccination verified by linkage to health records, and anti-pneumococcal antibody titers, and anti-ox-LDL titers in a group of 116 older people. We found a bimodal distribution of anti-oxLDL antibodies, and a significant association between pneumococcal IgG and anti-oxLDL antibody titers that remained after multivariate adjustment for potential confounders (p=0.04). There was no significant association between self-reported vaccination or vaccination verified by health record linkage and ox-LDL titers, which may be due to reporting error or variability in response to the vaccine. These results support a mechanistic link between pneumococcal vaccination and a potential protective effect on cardiovascular disease, and indicate that self-reported or verified vaccine status may not be sufficient to detect this association. Copyright © 2012 Elsevier Ltd. All rights reserved.

  6. Adjuvanticity of compound astragalus polysaccharide and sulfated epimedium polysaccharide per os.

    PubMed

    Chen, Xingying; Chen, Xiaolan; Qiu, Shulei; Hu, Yuanliang; Wang, Deyun; Liu, Xu; Zhao, Xiaojuan; Liu, Cui; Chen, Xinghui

    2013-11-01

    On the basis of previous researches, compound astragalus polysaccharide (APS) and sulfated epimedium polysaccharide (sEPS) oral liquid (AEO) was prepared. Three hundred and twenty 14-day-old chickens were randomly assigned into eight groups and vaccinated with ND vaccine except for blank control (BC) group, repeated vaccination at 28 days old. At the same time of each vaccination, the chickens in three experimental groups were taken orally with AEO, respectively, at three doses, in two component control groups with APS and sEPS, once a day for three successive days; in injection control group were injected with AEI once, and in vaccination control (VC) and BC groups were not administrated. On days 7, 14, 21, 28 and 35 after the first vaccination, peripheral lymphocyte proliferation, the serum antibody titer, IFN-γ and IL-2 concentrations and on day 35 immune organ index were measured. The results showed that AEO at high and medium doses could significantly promote lymphocyte proliferation and development of immune organ, enhance antibody titer and IFN-γ and IL-2 concentration, which was stronger than actions of AEI and two components. The results confirmed that AEO possessed reliable immunoenhancement and could be exploited into an oral immunopotentiator. Copyright © 2013 Elsevier B.V. All rights reserved.

  7. 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

  8. 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

  9. 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

  10. Polysaccharide biological response modifiers.

    PubMed

    Leung, M Y K; Liu, C; Koon, J C M; Fung, K P

    2006-06-15

    Biological response modifiers (BRMs) are substances which augment immune response. BRMs can be cytokines which are produced endogenously in our body by immune cells or derivatives of bacteria, fungi, brown algae, Aloe vera and photosynthetic plants. Such exogeneous derivatives (exogeneous BRMs) can be nucleic acid (CpG), lipid (lipotechoic acid), protein or polysaccharide in nature. The receptors for these exogeneous BRMs are pattern recognition receptors. The binding of exogeneous BRMs to pattern recognition receptors triggers immune response. Exogenous BRMs have been reported to have anti-viral, anti-bacterial, anti-fungal, anti-parasitic, and anti-tumor activities. Among different exogeneous BRMs, polysaccharide BRMs have the widest occurrence in nature. Some polysaccharide BRMs have been tested for their therapeutic properties in human clinical trials. An overview of current understandings of polysaccharide BRMs is summarized in this review.

  11. 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.

  12. [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.

  13. 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

  14. 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

  15. 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. Copyright © 2016 Sociedade Brasileira de Infectologia. Published by Elsevier Editora Ltda. All rights reserved.

  16. 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.

  17. Quantitative high throughput analytics to support polysaccharide production process development.

    PubMed

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

    2014-05-19

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

  18. 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

  19. Demonstration of immunologic memory using serogroup C meningococcal glycoconjugate vaccine.

    PubMed

    Snape, Matthew D; Maclennan, Jenny M; Lockhart, Stephen; English, Mike; Yu, Ly-Mee; Moxon, Richard E; Pollard, Andrew J

    2009-02-01

    Studies of glycoconjugate vaccines have traditionally used an immune challenge with a plain polysaccharide vaccine to demonstrate immunologic memory. Plain polysaccharide vaccines are poorly immunogenic in children and can induce subsequent immunologic hyporesponsiveness. We therefore assessed the use of glycoconjugate vaccines as an alternative method of demonstrating immunologic memory. Children immunized with hepatitis B vaccine or serogroup C meningococcal glycoconjugate vaccine (MenCC) at age 2, 3, 4 months received a plain polysaccharide meningococcal serogroup A/C vaccine (MenACP) or MenCC at age 12 months. A post hoc analysis of serum bactericidal activity responses to MenCC assessed whether this differed in MenCC primed and MenCC naive infants. MenCC primed children displayed higher geometric mean serum bactericidal titers than MenCC naive children following MenACP (1518 compared with 30; P = 0.003). A similar difference was seen after a dose of MenCC to toddlers (MenCC primed: 8663, MenCC naive: 710; P < 0.001). The latter comparison became a borderline significance after adjusting for higher pretoddler immunization serum bactericidal geometric mean titers in the MenCC primed group (P = 0.068). Administration of glycoconjugate vaccines provides an important alternative method of demonstrating immunologic memory, avoiding the use of plain polysaccharide vaccines that are potentially deleterious in children. This has implications for the design of all future clinical trials of glycoconjugate vaccines.

  20. 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

  1. 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.

  2. 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

  3. 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

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

    PubMed

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

    2006-07-12

    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. 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. 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.

  5. Proprietary arabinogalactan extract increases antibody response to the pneumonia vaccine: a randomized, double-blind, placebo-controlled, pilot study in healthy volunteers

    PubMed Central

    2010-01-01

    Background Arabinogalactan from Larch tree (Larix spp.) bark has previously demonstrated immunostimulatory activity. The purpose of this study was to test the hypothesis that ingestion of a proprietary arabinogalactan extract, ResistAid™, would selectively enhance the antibody response to the pneumococcal (pneumonia) vaccine in healthy adults. Methods This randomized, double-blind, placebo-controlled, parallel group pilot study included 45 healthy adults who had not previously been vaccinated against Streptococcus pneumoniae. The volunteers began taking the study product or placebo (daily dosage 4.5 g) at the screening visit (V1-Day 0) and continued over the entire 72 day study period. After 30 days the subjects received the 23-valent pneumococcal vaccine (V2). They were monitored the following day (V3-Day 31), as well as 21 days (V4-Day 51) and 42 days (V5-Day 72) after vaccination. Responses by the adaptive immune system (antigen specific) were measured via pneumococcal IgG antibodies (subtypes 4, 6B, 9V, 14, 18C, 19F, and 23F) and salivary IgA levels. Responses by the innate immune system (non-specific) were measured via white blood cell counts, inflammatory cytokines and the complement system. Results Vaccination significantly increased pneumococcal IgG levels as expected. The arabinogalactan group demonstrated a statistically significant greater IgG antibody response than the placebo group in two antibodies subtypes (18C and 23F) at both Day 51 (p = 0.006 and p = 0.002) and at Day 72 (p = 0.008 and p = 0.041). These same subtypes (18C and 23F) also demonstrated change scores from baseline which were significant, in favor of the arabinogalactan group, at Day 51 (p = 0.033 and 0.001) and at Day 72 (p = 0.012 and p = 0.003). Change scores from baseline and mean values were greater in the arabinogalactan group than placebo for most time points in antibody subtypes 4, 6B, 9V, and 19F, but these differences did not reach statistical significance. There was no

  6. 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.

  7. HPV vaccine

    MedlinePlus

    ... 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; ...

  8. [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.

  9. Vaccine candidates in STD.

    PubMed

    Fletcher, Mark A

    2002-12-01

    Sexually transmitted diseases (STDs) are caused by organisms that infect the mucosal surfaces of the genitourinary tract. In spite of its public health importance, current STD vaccine research lags behind work against pathogens that target another mucosal region, the respiratory tract. In the latter case, live-attenuated viral vaccines, killed whole-cell bacterial vaccines, subunit/protein bacterial vaccines, and bacterial polysaccharide vaccines have been enormously successful. To move STD vaccine research forward, complex issues must be resolved. Those include selection of an appropriate antigen (e.g. scientific feasibility and intellectual property rights), the manufacture of the vaccine (e.g. delivery systems, formulation processes, and production steps), and the appropriate public health approach (e.g. medical indications and marketing aspects). Particular scientific problems have delayed STD vaccine development, like incomplete attenuation (human herpes simplex virus type 2), accentuated immunopathology (Chlamydia trachomatis), poor immunogenicity (Treponema pallidum), and broad antigenic heterogeneity (Neisseria gonorrhoeae). Nevertheless, efforts continue with the use of protein antigens: for example, the haemolysin toxoid of Haemophilus ducreyi; the major outer membrane protein(s) of N. gonorrhoeae and C. trachomatis; the glycoprotein D of human herpes simplex virus type 2; and the proteins E6 and E7 of human papilloma virus. It may be predicted that eventual STD vaccines (administered either for prophylaxis or for therapy) will use approaches that include (1) live-attenuated viruses, (2) subunit proteins or inactivated whole organisms given with mucosal adjuvants or with cellular immune response adjuvants, and (3) DNA plasmids expressing the vaccine antigen.

  10. Review of meningococcal vaccines with updates on immunization in adults

    PubMed Central

    Zahlanie, Yorgo C; Hammadi, Moza M; Ghanem, Soha T; Dbaibo, Ghassan S

    2014-01-01

    Meningococcal disease is a serious and global life-threatening disease. Six serogroups (A, B, C, W-135, X, and Y) account for the majority of meningococcal disease worldwide. Meningococcal polysaccharide vaccines were introduced several decades ago and have led to the decline in the burden of disease. However, polysaccharide vaccines have several limitations, including poor immunogenicity in infants and toddlers, short-lived protection, lack of immunologic memory, negligible impact on nasopharyngeal carriage, and presence of hyporesponsiveness after repeated doses. The chemical conjugation of plain polysaccharide vaccines has the potential to overcome these drawbacks. Meningococcal conjugate vaccines include the quadrivalent vaccines (MenACWY-DT, MenACWY-CRM, and MenACWY-TT) as well as the monovalent A and C vaccines. These conjugate vaccines were shown to elicit strong immune response in adults. This review addresses the various aspects of meningococcal disease, the limitations posed by polysaccharide vaccines, the different conjugate vaccines with their immunogenicity and reactogenicity in adults, and the current recommendations in adults. PMID:24500529

  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. 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.

  13. Costs of adult vaccination in medical settings and pharmacies: an observational study.

    PubMed

    Singhal, Puneet K; Zhang, Dongmu

    2014-09-01

    Community pharmacies are a convenient setting for vaccinating adults against infectious diseases in the United States. Whether the costs paid for vaccination in pharmacies differ from those in medical settings is unclear. To examine whether the direct medical costs paid for adult vaccination differ by vaccination setting. This was an observational retrospective study using 2010 MarketScan Commercial Claims and Encounters and Medicare Supplemental and Coordination of Benefits databases. Adults receiving herpes zoster or shingles vaccine, pneumococcal vaccine 23-valent, or influenza vaccines were identified using Current Procedural Terminology codes and National Drug Code numbers from medical and pharmacy claims files, respectively, between January 1 and December 31, 2010, in 1 of the following 3 settings: physician offices; other medical settings (e.g., inpatient/outpatient hospitals, emergency rooms); and pharmacies. Patients were adults aged ≥60 years on the date of zoster vaccination and aged ≥19 years on the date of pneumococcal or influenza vaccinations. The final study samples meeting inclusion/exclusion criteria were 54,042 for zoster vaccine, 154,994 for pneumococcal vaccine, and 1,657,264 for influenza vaccine. The vaccination costs included the health plan and enrollee paid amounts for the product; vaccine administration; dispensing fee; and, where applicable, the visit. The mean (SD) vaccination costs paid per vaccine administration were estimated by vaccine and type of setting, overall, and by geographic region and type of health plan. The costs paid for the same vaccine across vaccination settings were compared using analysis of variance with post hoc tests (Tukey). Of those receiving zoster, pneumococcal, and influenza vaccines, 25%, 1%, and 7%, respectively, received the vaccines at a pharmacy. Compared with other U.S. regions, pharmacy-based vaccination for these 3 vaccines was generally more frequent in the West and the South. Overall, the mean

  14. Polysaccharides: Occurrence, Significance, and Properties

    NASA Astrophysics Data System (ADS)

    Bemiller, James N.

    Polysaccharides are properties present significance in all living organisms where they carry out one or more of their diverse functions. While there is no specific category or definition of a complex polysaccharide, most are structurally complex. Polysaccharides contain 1-5 different monosaccharide (sugar) units. The different sugar units may have different anomeric configurations and/or be joined by different glycosidic linkages. Polysaccharides may be linear or branched. Branches may be short saccharide units on a linear backbone or the molecule may have a branch-on-branch structure; in either case, the branches may be isolated or clustered. Polysaccharides may contain non-carbohydrate groups. Esters or cyclic acetal groups, when present, can be removed by appropriate treatments. All polysaccharides are polydisperse, i. e., are present in a range of molecular weights rather than having a single molecular weight. Most are polymolecular, i. e., differ in fine structure from molecule to molecule. So most polysaccharides can be said to be structurally complex. They may be attached to protein molecules or to other polysaccharide molecules. They are solvated by water. Most dissolve in aqueous systems, especially if they are alkaline. Polysaccharides can be depolymerized by acids and heat, specific enzymes, and high pH systems following oxidation. Their hydroxyl groups can be esterified (acylated), etherified (alkylated), and oxidized. Amino groups can be acylated (and deacylated). Carboxyl groups can be converted into esters, amides, and amines. Structural modification makes the molecules even more complex and polymolecular and, perhaps, polydisperse.

  15. [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.

  16. Active vaccination in patients with common variable immunodeficiency (CVID).

    PubMed

    Goldacker, S; Draeger, R; Warnatz, K; Huzly, D; Salzer, U; Thiel, J; Eibel, H; Schlesier, M; Peter, H H

    2007-09-01

    Active vaccination of CVID patients with standard vaccines has rarely been studied in depth although some patients have been shown to develop transient vaccine-specific immunity. We addressed the question whether these patients can be identified by functional classification of their B cell subsets in vitro. Twenty-one CVID patients receiving regular IgG substitution were immunized with anti-peptide and anti-polysaccharide vaccines. Humoral vaccination responses were compared to the numbers of circulating memory B cells, CD21(low) B cells and the capacity to produce antibodies in vitro. Our findings allow four conclusions: (1) positive vaccination responses are not contradictory to the diagnosis of CVID; they occurred against polypeptide vaccines in 23% and against polysaccharide antigens in 18% of all vaccinations. (2) Class-switched antibody responses occur preferentially in patients of CVID group II. (3) A normal percentage of IgM memory B cells is necessary but not sufficient for a vaccination response to polysaccharide antigens. (4) Active vaccination in addition to IgG replacement therapy should be performed in patients of CVID type II - especially in case of vaccines for which passive protection cannot be guaranteed.

  17. 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.

  18. [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.

  19. Meningococcal conjugate vaccines: optimizing global impact

    PubMed Central

    Terranella, Andrew; Cohn, Amanda; Clark, Thomas

    2011-01-01

    Meningococcal conjugate vaccines have several advantages over polysaccharide vaccines, including the ability to induce greater antibody persistence, avidity, immunologic memory, and herd immunity. Since 1999, meningococcal conjugate vaccine programs have been established across the globe. Many of these vaccination programs have resulted in significant decline in meningococcal disease in several countries. Recent introduction of serogroup A conjugate vaccine in Africa offers the potential to eliminate meningococcal disease as a public health problem in Africa. However, the duration of immune response and the development of widespread herd immunity in the population remain important questions for meningococcal vaccine programs. Because of the unique epidemiology of meningococcal disease around the world, the optimal vaccination strategy for long-term disease prevention will vary by country. PMID:22114508

  20. Iodine-Catalyzed Polysaccharide Esterification

    USDA-ARS?s Scientific Manuscript database

    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...

  1. 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.

  2. 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.

  3. 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.

  4. Pneumococcal vaccines for cystic fibrosis.

    PubMed

    Burgess, Laura; Southern, Kevin W

    2014-08-05

    Invasive pneumococcal disease is associated with significant mortality and many countries have introduced routine pneumococcal vaccination into their childhood immunisation programmes. Whilst pneumococcal disease in cystic fibrosis is uncommon, pneumococcal immunisation may offer some protection against pulmonary exacerbations caused by this pathogen. In the USA and UK pneumococcal vaccination is currently recommended for all children and adults with cystic fibrosis. To assess the efficacy of pneumococcal vaccines in reducing morbidity in people with cystic fibrosis. We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Cystic Fibrosis Trials Register, which comprises references identified from comprehensive electronic database searches and handsearches of relevant journals and abstract books of conference proceedings. In addition, the pharmaceutical manufacturers of the polysaccharide and conjugate pneumococcal vaccines were approached.Date of the most recent search: 15 May 2014. Randomised and quasi-randomised controlled trials comparing pneumococcal vaccination (with either a polysaccharide or conjugate pneumococcal vaccine) with non-vaccination or placebo in children or adults with cystic fibrosis were eligible for inclusion. No relevant trials were identified. There are no trials included in this review. As no trials were identified we cannot draw conclusions on the efficacy of routine pneumococcal immunisation in people with cystic fibrosis in reducing their morbidity or mortality. As many countries now include pneumococcal immunisation in their routine childhood vaccination schedule it is unlikely that future randomised controlled trials will be initiated. Rigorously conducted epidemiological studies may offer the opportunity to evaluate the efficacy of pneumococcal vaccination in reducing morbidity and mortality in people with cystic fibrosis.

  5. Pneumococcal vaccines for cystic fibrosis.

    PubMed

    Burgess, Laura; Southern, Kevin W

    2012-09-12

    Invasive pneumococcal disease is associated with significant mortality and many countries have introduced routine pneumococcal vaccination into their childhood immunisation programmes. Whilst pneumococcal disease in cystic fibrosis is uncommon, pneumococcal immunisation may offer some protection against pulmonary exacerbations caused by this pathogen. In the USA and UK pneumococcal vaccination is currently recommended for all children and adults with cystic fibrosis. To assess the efficacy of pneumococcal vaccines in reducing morbidity in people with cystic fibrosis. We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Cystic Fibrosis Trials Register, which comprises references identified from comprehensive electronic database searches and handsearches of relevant journals and abstract books of conference proceedings. In addition, the pharmaceutical manufacturers of the polysaccharide and conjugate pneumococcal vaccines were approached.Date of the most recent search: 10 July 2012. Randomised and quasi-randomised controlled trials comparing pneumococcal vaccination (with either a polysaccharide or conjugate pneumococcal vaccine) with non-vaccination or placebo in children or adults with cystic fibrosis were eligible for inclusion. No relevant trials were identified. There are no trials included in this review. As no trials were identified we cannot draw conclusions on the efficacy of routine pneumococcal immunisation in people with cystic fibrosis in reducing their morbidity or mortality. As many countries now include pneumococcal immunisation in their routine childhood vaccination schedule it is unlikely that future randomised controlled trials will be initiated. Rigorously conducted epidemiological studies may offer the opportunity to evaluate the efficacy of pneumococcal vaccination in reducing morbidity and mortality in people with cystic fibrosis.

  6. 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.

  7. Vaccines for preventing typhoid fever.

    PubMed

    Anwar, Elspeth; Goldberg, Elad; Fraser, Abigail; Acosta, Camilo J; Paul, Mical; Leibovici, Leonard

    2014-01-02

    Typhoid fever and paratyphoid fever continue to be important causes of illness and death, particularly among children and adolescents in south-central and southeast Asia. Two typhoid vaccines are commercially available, Ty21a (oral) and Vi polysaccharide (parenteral), but neither is used routinely. Other vaccines, such as a new, modified, conjugated Vi vaccine called Vi-rEPA, are in development. To evaluate the efficacy and adverse effects of vaccines used to prevent typhoid fever. In June 2013, we searched the Cochrane Infectious Diseases Group Specialized Register, CENTRAL, MEDLINE, EMBASE, LILACS, and mRCT. We also searched relevant conference proceedings up to 2013 and scanned the reference lists of all included trials. Randomized and quasi-randomized controlled trials (RCTs) comparing typhoid fever vaccines with other typhoid fever vaccines or with an inactive agent (placebo or vaccine for a different disease). Two review authors independently applied inclusion criteria and extracted data. We computed vaccine efficacy per year of follow-up and cumulative three-year efficacy, stratifying for vaccine type and dose. The outcome addressed was typhoid fever, defined as isolation of Salmonella typhi in blood. We calculated risk ratios (RRs) and efficacy (1-RR as a percentage) with 95% confidence intervals (CIs). In total, 18 RCTs were included in this review; 12 evaluated efficacy (Ty21a: five trials; Vi polysaccharide: six trials; Vi-rEPA: one trial), and 11 reported on adverse events. Ty21a vaccine (oral vaccine, three doses) A three-dose schedule of Ty21a vaccine prevents around one-third to one-half of typhoid cases in the first two years after vaccination (Year 1: 35%, 95% CI 8% to 54%; Year 2: 58%, 95% CI 40% to 71%; one trial, 20,543 participants; moderate quality evidence; data taken from a single trial conducted in Indonesia in the 1980s). No benefit was detected in the third year after vaccination. Four additional cluster-RCTs have been conducted, but the

  8. 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.

  9. 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.

  10. 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.

  11. 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.

  12. Haemophilus influenzae type b conjugate vaccines

    PubMed Central

    Kelly, Dominic F; Moxon, E Richard; Pollard, Andrew J

    2004-01-01

    Haemophilus influenzae type b (Hib) is one of the leading causes of invasive bacterial infection in young children worldwide. During childhood, acquisition of antibody directed against the polysaccharide capsule of the organism, presumably as a result of asymptomatic carriage, confers protection and disease is much less common after the age of 4 years. Like other polysaccharides, the polyribosyl ribitol phosphate (PRP) of the Hib capsule is a T-independent antigen and not immunogenic when administered as a vaccine in infancy. Because the highest rates of disease occur in the first 2 years of life, efficacious Hib vaccines have been designed by covalently linking the PRP capsule to a carrier protein that recruits T-cell help for the polysaccharide immune response and induces anti-PRP antibody production even in the first 6 months of life. Introduction of Hib protein–polysaccharide conjugate vaccines into many industrialized countries over the past 15 years has resulted in the virtual elimination of invasive Hib disease. However, despite the success of the vaccine programme several factors may interfere with the effectiveness of the vaccine in the routine programme, as observed in the UK recently. Such factors may include interference with other concomitant vaccines, waning immunity in the absence of booster doses of vaccine, and reduced natural boosting as a result of decreased transmission of the organism. However, the burden of disease remains highest in resource-poor countries and urgent efforts are needed to provide the benefits of this vaccine for children living in regions where it cannot be used for economic and logistical reasons. PMID:15379976

  13. 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 ...

  14. Polio Vaccine

    MedlinePlus

    ... staff Home Family Health Infants and Toddlers Polio Vaccine Polio Vaccine Share Print Polio Vaccine What is polio? Poliomyelitis (polio) is a serious ... each year. Fortunately, the use of the polio vaccine has made the disease very rare in most ...

  15. Purification of capsular polysaccharide from Neisseria meningitidis serogroup C by liquid chromatography.

    PubMed

    Pato, Tânia Pinheiro; Barbosa, Antonio de Pádua R; da Silva Junior, José Godinho

    2006-03-07

    Neisseria meningitidis serogroup C capsular polysaccharide (MenCPS) is an important antigen against meningococcal infection. This paper describes a new purification methodology employing liquid chromatography that resulted in a polysaccharide showing the characteristics recommended by the World Health Organization for vaccine purposes. In this method, steps of the traditional procedure that yield low recovery and use toxic materials were modified. The present process consists in the following steps: (1) continuous flow centrifugation of the culture for removal of the cells; (2) supernatant concentration by tangential filtration (100 kDa cutoff); (3) addition of 0.5% DOC, heating to 55 degrees C during 30 min and tangential filtration (100 kDa cutoff); (4) anion exchange chromatography (Source 15Q) and (5) size exclusion chromatography (Sepharose CL-4B). The polysaccharide C fraction obtained in that way was dialyzed and freeze-dried. The structural identity of the polysaccharide was demonstrated by (1)H-NMR spectrometry.

  16. 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

  17. 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.

  18. Pneumococcal Carriage and Vaccine Coverage in Retirement Community Residents.

    PubMed

    Becker-Dreps, Sylvia; Kistler, Christine E; Ward, Kimberly; Killeya-Jones, Ley A; Better, Olga Maria; Weber, David J; Zimmerman, Sheryl; Nicholson, Bradly P; Woods, Chris W; Sloane, Philip

    2015-10-01

    To evaluate pneumococcal immunization in older adults living in retirement communities and to measure nasopharyngeal carriage of Streptococcus pneumoniae to better assess the potential for herd protection from the 13-valent pneumococcal conjugate vaccine (PCV-13) in these settings. Cross-sectional observational study of adults aged 65 and older living in retirement communities to determine coverage with 23-valent pneumococcal vaccine (PPSV-23), coverage with PCV-13 in immuncompromised individuals according to 2012 Advisory Committee on Immunization Practices (ACIP) guidelines, and nasopharyngeal carriage of S. pneumoniae. Two retirement communities in North Carolina. Older adults recruited between December 2013 and April 2014 (N = 21, 64.8% female, mean age 81.4). A survey was used to assess chronic illnesses, immunization history, and potential risk factors for pneumococcal carriage; a chart review was used to confirm immunization history and abstract chronic conditions; and a nasopharyngeal swab was collected and cultured for S. pneumoniae. Eighty-seven percent of participants reported receiving PPSV-23 since age 65. Of the 16.2% of participants with an immunocompromising condition, only one had received PCV-13. Nasopharyngeal carriage with S. pneumoniae was detected in 1.9% (95% confidence interval = 0.0-3.8%) of participants. In this select sample, PPSV-23 coverage was high, but adherence to the ACIP recommendation for PCV-13 in immunocompromised groups was low. Nasopharyngeal carriage of S. pneumoniae was present, although infrequent, suggesting that immunization with PCV-13 could provide an individual benefit and a small degree of herd protection. © 2015, Copyright the Authors Journal compilation © 2015, The American Geriatrics Society.

  19. Novel nanoparticle vaccines for Listeriosis.

    PubMed

    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.

  20. 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

  1. [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.

  2. Vaccines (immunizations) - overview

    MedlinePlus

    Vaccinations; Immunizations; Immunize; Vaccine shots; Prevention - vaccine ... component) of the vaccine. VACCINE SCHEDULE The recommended vaccination (immunization) schedule is updated every 12 months by ...

  3. 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.

  4. 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

  5. Vaccines against invasive Salmonella disease

    PubMed Central

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

    2014-01-01

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

  6. Protective Effect of Ginseng Polysaccharides on Influenza Viral Infection

    PubMed Central

    Yoo, Dae-Goon; Kim, Min-Chul; Park, Min-Kyung; Park, Kyoung-Mi; Quan, Fu-Shi; Song, Jae-Min; Wee, Jae Joon; Wang, Bao-Zhong; Cho, Young-Keol; Compans, Richard W.; Kang, Sang-Moo

    2012-01-01

    Ginseng polysaccharide has been known to have multiple immunomodulatory effects. In this study, we investigated whether Panax ginseng polysaccharide (GP) would have a preventive effect on influenza infection. Administration of mice with GP prior to infection was found to confer a survival benefit against infection with H1N1 (A/PR/8/34) and H3N2 (A/Philippines/82) influenza viruses. Mice infected with the 2009 H1N1 virus suspended in GP solution showed moderately enhanced survival rates and lower levels of lung viral titers and the inflammatory cytokine (IL-6). Daily treatment of vaccinated mice with GP improved their survival against heterosubtypic lethal challenge. This study demonstrates the first evidence that GP can be used as a remedy against influenza viral infection. PMID:22442708

  7. 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

  8. 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.

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

    NASA Astrophysics Data System (ADS)

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

    2003-09-01

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

  10. Haemophilus influenzae type b vaccine formulation and risk of childhood leukaemia.

    PubMed

    Groves, F; Sinha, D; Auvinen, A

    2002-08-27

    Incidence of childhood leukaemia was studied among subjects of a vaccine trial in Finland comparing the polysaccharide-diptheria toxoid conjugate and oligosaccharide-CRM197 conjugate Haemophilus influenzae type b conjugate vaccine formulations. Eighty cases of childhood leukaemia were detected: 35 among children on the polysaccharide-diptheria toxoid conjugate arm, and 45 among children on the oligosaccharide-CRM197 conjugate arm, which was not statistically significant.

  11. [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.

  12. 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.

  13. 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.

  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. 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.

  16. 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

  17. 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

  18. Rotavirus Vaccine

    MedlinePlus

    ... have had a type of bowel blockage called "intussusception" should not get rotavirus vaccine. Babies who are ... of rotavirus vaccine.Severe problems following rotavirus vaccine:Intussusception is a type of bowel blockage that is ...

  19. [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.

  20. 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

  1. The Antioxidant Activities of Natural Polysaccharides.

    PubMed

    Huang, Gangliang; Mei, Xinya; Hu, Jinchuan

    2017-01-01

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

  2. 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.

  3. Comparative simulation of pneumococcal serogroup 19 polysaccharide repeating units with two carbohydrate force fields.

    PubMed

    Kuttel, Michelle; Gordon, Marc; Ravenscroft, Neil

    2014-05-22

    Streptococcus pneumoniae causes meningitis, pneumonia and severe invasive disease (IPD) in young children. Although widespread infant immunisation with the PCV7 seven-valent pneumococcal conjugate vaccine has led to a dramatic decrease in IPD, infections due to non-vaccine serotypes, particularly serotype 19A, have increased. As the 19F polysaccharide differs from 19A at a single linkage position, it was assumed that PCV7 (containing 19F) would cross-protect against 19A disease. However, vaccination with PCV7 results in only 26% effectiveness against IPD caused by 19A. We explored the conformations and dynamics of the polysaccharide repeating units from serotypes 19F and 19A, comparing free energy surfaces for glycosidic linkages with 100ns aqueous molecular dynamics simulations of the di- and trisaccharide components. All calculations were performed with both the CHARMM and the GLYCAM carbohydrate force fields to establish whether the choice of model affects the predicted molecular behaviour. Although we identified key differences between the force fields, overall they were in agreement in predicting a 19F repeating unit with a wider range of conformation families than the more restricted 19A trisaccharide. This suggests a probable conformational difference between the 19F and 19A polysaccharides, which may explain the low cross-protection of 19F vaccines against 19A disease. Copyright © 2014 Elsevier Ltd. All rights reserved.

  4. Two variants among Haemophilus influenzae serotype b strains with distinct bcs4, hcsA and hcsB genes display differences in expression of the polysaccharide capsule

    PubMed Central

    Schouls, Leo; van der Heide, Han; Witteveen, Sandra; Zomer, Bert; van der Ende, Arie; Burger, Marina; Schot, Corrie

    2008-01-01

    Background Despite nearly complete vaccine coverage, a small number of fully vaccinated children in the Netherlands have experienced invasive disease caused by Haemophilus influenzae serotype b (Hib). This increase started in 2002, nine years after the introduction of nationwide vaccination in the Netherlands. The capsular polysaccharide of Hib is used as a conjugate vaccine to protect against Hib disease. To evaluate the possible rise of escape variants, explaining the increased number of vaccine failures we analyzed the composition of the capsular genes and the expressed polysaccharide of Dutch Hib strains collected before and after the introduction of Hib vaccination. Results The DNA sequences of the complete capsular gene clusters of 9 Dutch Hib strains were assessed and two variants, designated type I and type II were found. The two variants displayed considerable sequence divergence in the hcsA and hcsB genes, involved in transport of capsular polysaccharide to the cell surface. Application of hcsA type specific PCRs on 670 Hib strains collected from Dutch patients with invasive Hib disease showed that 5% of the strains collected before 1996 were type II. No endogenous type II Hib strains were isolated after 1995 and all type II strains were isolated from 0–4 year old, non-vaccinated children only. Analysis of a worldwide collection of Hib strains from the pre-vaccination era revealed considerable geographic differences in the distribution of the type I and type II strains with up to 73% of type II strains in the USA. NMR analysis of type I and type II capsule polysaccharides did not reveal structural differences. However, type I strains were shown to produce twice as much surface bound capsular polysaccharide. Conclusion Type II strains were only isolated during the pre-vaccination era from young, non-vaccinated individuals and displayed a lower expression of capsular polysaccharide than type I strains. The higher polysaccharide expression may have

  5. 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.

  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. 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.

  8. Conjugate vaccines for preventing meningococcal C meningitis and septicaemia.

    PubMed

    Conterno, L O; Silva Filho, C R; Rüggeberg, J U; Heath, P T

    2006-07-19

    Meningococcal polysaccharide (MPLS) vaccines protect against Serogroup C disease, but do not produce an immune response in infants less than two years of age. This limitation can be overcome by linking C polysaccharide to carrier proteins ('conjugating'), to create meningococcal serogroup C conjugate (MCC) vaccines. In the absence of trial data, the immune response to vaccination has been considered to be a reasonable surrogate for vaccine protection. To assess the immunogenicity, safety and efficacy of MCC vaccines for preventing meningitis and septicaemia. We searched the Cochrane Central Register Controlled Trials (CENTRAL) (The Cochrane Library Issue 3, 2005); MEDLINE (1966 to September, Week 1 2005); and EMBASE (1990 to June 2005) and references of studies. Randomised controlled trials (RCTs) and controlled clinical trials (CCTs) in humans comparing MCC vaccines against a control vaccine or none. In the absence of any trials on vaccine efficacy, population-based observational studies about effectiveness were included. Two authors independently screened the results of the literature searches, selected eligible studies, extracted the data and evaluated the quality of them. The studies showed that MCC vaccine was highly immunogenic in infants after two and three doses, in toddlers after one and two doses and in older age groups after one dose. In general higher titres were generated after MCC than after MPLS vaccines. Immunological hypo-responsiveness seen after repeated doses of MPLS vaccine may be overcome with MCC. Observational studies have documented a significant decline in meningococcal C disease in countries where MCC vaccines have been widely used. The timing of the vaccinations schedules, the specific conjugate used, and the vaccines given concomitantly or combined, may be important. The MCC vaccine appears to be safe, immunogenic and able to induce immunological memory in all age groups. Observational studies strongly suggest that MCC is clinically

  9. WITHDRAWN: Conjugate vaccines for preventing meningococcal C meningitis and septicaemia.

    PubMed

    Conterno, Lucieni O; da Silva Filho, Carlos Rodrigues; Ruggeberg, Jens U; Heath, Paul T

    2011-07-06

    Meningococcal polysaccharide (MPLS) vaccines protect against Serogroup C disease, but do not produce an immune response in infants less than two years of age. This limitation can be overcome by linking C polysaccharide to carrier proteins ('conjugating'), to create meningococcal serogroup C conjugate (MCC) vaccines. In the absence of trial data, the immune response to vaccination has been considered to be a reasonable surrogate for vaccine protection. To assess the immunogenicity, safety and efficacy of MCC vaccines for preventing meningitis and septicaemia. We searched the Cochrane Central Register Controlled Trials (CENTRAL) (The Cochrane Library 2005, issue 3); MEDLINE (1966 to September, Week 1 2005); and EMBASE (1990 to June 2005) and references of studies. Randomised controlled trials (RCTs) and controlled clinical trials (CCTs) in humans comparing MCC vaccines against a control vaccine or none. In the absence of any trials on vaccine efficacy, population-based observational studies about effectiveness were included. Two authors independently screened the results of the literature searches, selected eligible studies, extracted the data and evaluated the quality of them. The studies showed that MCC vaccine was highly immunogenic in infants after two and three doses, in toddlers after one and two doses and in older age groups after one dose. In general higher titres were generated after MCC than after MPLS vaccines. Immunological hypo-responsiveness seen after repeated doses of MPLS vaccine may be overcome with MCC. Observational studies have documented a significant decline in meningococcal C disease in countries where MCC vaccines have been widely used. The timing of the vaccinations schedules, the specific conjugate used, and the vaccines given concomitantly or combined, may be important. The MCC vaccine appears to be safe, immunogenic and able to induce immunological memory in all age groups. Observational studies strongly suggest that MCC is clinically

  10. 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

  11. Polysaccharide-modified synthetic polymeric biomaterials.

    PubMed

    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. (c) 2010 Wiley Periodicals, Inc.

  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. 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.

  14. 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.

  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. 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.

  17. 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

  18. 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.

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

    PubMed

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

    2017-06-29

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

  1. 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

  2. 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.

  3. 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.

  4. 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

  5. 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.

  6. 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

  7. 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

  8. 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.

  9. 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.

  10. 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

  11. 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 ...

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

    PubMed

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

    2016-11-15

    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. Expression of a capsular polysaccharide is among the principal virulence factors of Streptococcus pneumoniae and is the basis for successful vaccines against infections caused by this important pathogen. Contrasting with previous

  13. 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

  14. 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

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

    PubMed

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

    2017-03-01

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

  16. 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

  17. 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.

  18. 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

  19. [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.

  20. 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.

  1. 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.

  2. 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

  3. Carbohydrate vaccines: developing sweet solutions to sticky situations?

    PubMed Central

    Astronomo, Rena D.; Burton, Dennis R.

    2013-01-01

    The realm of carbohydrate vaccines has expanded far beyond the capsular polysaccharides of bacterial pathogens to include a diverse collection of targets representing nearly every biological kingdom. Recent technological advances in glycobiology and glycochemistry are paving the way for a new era in carbohydrate vaccine design enabling greater efficiency in the identification, synthesis and evaluation of unique glycan epitopes found on a plethora of pathogens and malignant cells. This article reviews the progress being made in addressing challenges posed by targeting the surface carbohydrates of bacteria, protozoa, helminths, viruses, fungi and cancer for vaccine purposes. PMID:20357803

  4. Bioactive polysaccharides and gut microbiome (abstract)

    USDA-ARS?s Scientific Manuscript database

    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...

  5. Solution NMR spectroscopy of food polysaccharides

    USDA-ARS?s Scientific Manuscript database

    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...

  6. 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.

  7. 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.

  8. 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

  9. 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.

  10. 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.

  11. Safety of vaccinations in patients with cryopyrin-associated periodic syndromes: a prospective registry based study.

    PubMed

    Jaeger, Veronika K; Hoffman, Hal M; van der Poll, Tom; Tilson, Hugh; Seibert, Julia; Speziale, Antonio; Junge, Guido; Franke, Kristina; Vritzali, Eleni; Hawkins, Philip N; Kuemmerle-Deschner, Jasmin; Walker, Ulrich A

    2017-09-01

    Pneumococcal, tetanus and influenza vaccinations are recommended for patients with cryopyrin-associated periodic syndromes (CAPS) when treated with immunosuppressive medication. The aim of this publication is to report the safety of pneumococcal and other vaccinations in CAPS patients. All CAPS patients followed in the β-CONFIDENT (Clinical Outcomes and Safety Registry study of Ilaris patients) registry were analysed if they had received a vaccination. The β-CONFIDENT registry is a global, long-term, prospective, observational registry, capturing and monitoring patients treated with canakinumab. Sixty-eight CAPS patients had received a total of 159 vaccine injections, 107 injections against influenza, 19 pneumococcal vaccinations, 12 against tetanus/diphtheria antigens and 21 other vaccinations. Fourteen per cent of injections had elicited at least one vaccine reaction. All five vaccine-related serious adverse events were associated with pneumococcal vaccination. Vaccine reactions were observed in 70% of pneumococcal vaccinations, compared with 7% in influenza and 17% in tetanus/diphtheria vaccinations. The odds ratios to react to the pneumococcal vaccines compared with influenza and tetanus/diphtheria vaccines were 31.0 (95% CI: 8, 119) and 10.8 (95% CI: 2, 74). Vaccine reactions after pneumococcal vaccinations were more severe and lasted significantly longer (up to 3 weeks) compared with other vaccinations. In two patients, pneumococcal vaccination also elicited symptoms consistent with systemic inflammation due to CAPS reactivation. Pneumococcal vaccines, unlike other vaccines, frequently trigger severe local and systemic inflammation in CAPS patients. Clinicians must balance potential benefits of pneumococcal immunization against safety concerns. The 13-valent pneumococcal conjugate vaccine might be favourable over the polysaccharide vaccine in CAPS patients.

  12. Sociobehavioural research methods for the introduction of vaccines in the Diseases of the Most Impoverished Programme.

    PubMed

    Kaljee, Linda M; Pack, Rob; Pach, Al; Nyamete, Andrew; Stanton, Bonita F

    2004-09-01

    Participation in vaccination campaigns worldwide, particularly the Expanded Programme on Immunization, has increased significantly in recent years. However, there remain multiple and integrated behavioural, sociocultural and political-economic barriers to vaccination. The Diseases of the Most Impoverished (DOMI) Programme has undertaken shigellosis disease-burden studies and oral cholera and typhoid Vi polysaccharide vaccine trials in seven Asian countries. As part of these projects, sociobehavioural studies have been undertaken to determine the potential demand for vaccines for these diseases and the obstacles and enabling factors that may affect acceptance, delivery, and use of vaccines. A theoretical model of acceptance of vaccination and a triangulation of qualitative and quantitative methods have been used for fully elucidating the range of issues relating to vaccination for shigellosis, cholera, and typhoid fever. In this paper, the theoretical and methodological basis of the DOMI projects has been reviewed in a context of current sociobehavioural research on the acceptability and desirability of vaccination.

  13. Thin film of biocompatible polysaccharides

    NASA Astrophysics Data System (ADS)

    Richert, Ludovic; Lavalle, Philippe; Schaaf, Pierre; Voegel, Jean-Claude; Picart, Catherine

    2003-03-01

    The layer-by-layer deposition method proposed by Decher et al. (1991) is a very simple and versatile method used to build thin films. These films are of interest for bioengineering because of their unique properties and of the possible insertion of bioactive molecules. We present here the peculiar properties of a new kind of film formed with natural biopolymers, namely hyaluronan (HA)and chitosan (CHI). The films may be used as biomimetic substrates to control bacterial and cell adhesion. These polysaccharides are of particular interest because they are biodegradable, non toxic, and can be found in various tissues. Hyaluronan is also a natural ligand for a numerous type of cells through the CD44 receptor. Chitosan has already largely been used for its biological and anti-microbial properties. (CHI/HA) films were built in acidic pH at different ionic strength. The buildup was followed in situ by optical waveguide lightmode spectroscopy (OWLS), quartz crystal microbalance, streaming potential measurements and atomic force microscopy. The kinetics of adsorption and desorption of the polyelectrolytes depended on the ionic strength. Small islands were initially present on the surface which grew by mutual coalescence until becoming a flat film. The films were around 200 nm in thickness. These results suggest that different types of thin films constituted of polysaccharides can be built on any type of surface. These films are currently investigated toward their cell adhesion and bacterial adhesion properties.

  14. Microalgal vaccines.

    PubMed

    Siripornadulsil, Surasak; Dabrowski, Konrad; Sayre, Richard

    2007-01-01

    A variety of recombinant vaccines and vaccine delivery systems are currently under development as alternatives to vaccines produced in animals that are primarily administered by injections. These nonanimal alternatives do not transmit animal pathogens, are often rapid to develop, and can be produced on a large scale at low costs. Many of these new vaccine technologies are based on oral delivery systems and avoid the risks of disease transmission associated with the use of syringes for injectable vaccines. In addition, many of these novel systems have extended shelf life, often not requiring refrigeration and thus are applicable in developing countries or remote locations. Here we describe the development of microalgal-based immunization systems. Antigens expressed in the chloroplast or anchored to the surface of plasma membrane are shown to effectively immunize fish and rabbits. The effective oral delivery of antigens by microalgae provides a safe and inexpensive mechanism to immunize animals. The applications of microalgal vaccines are currently being investigated.

  15. 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.

  16. Opsonophagocytosis of Fluorescent Polystyrene Beads Coupled to Neisseria meningitidis Serogroup A, C, Y, or W135 Polysaccharide Correlates with Serum Bactericidal Activity

    PubMed Central

    Martinez, Joseph; Pilishvili, Tamara; Barnard, Suzanne; Caba, Joseph; Spear, Willie; Romero-Steiner, Sandra; Carlone, George M.

    2002-01-01

    We developed a polysaccharide-specific flow cytometric opsonophagocytic assay (OPA) for the simultaneous measurement of functional antibody to Neisseria meningitidis serogroups A, C, Y, and W135. OPA titers significantly correlated with serum bactericidal assay titers for all serogroups tested (mean r = 0.96; P < 0.001). OPA could be used in meningococcal vaccine evaluation. PMID:11874898

  17. 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 ...

  18. 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 ...

  19. Vi Capsular Polysaccharide Produced by Recombinant Salmonella enterica Serovar Paratyphi A Confers Immunoprotection against Infection by Salmonella enterica Serovar Typhi.

    PubMed

    Xiong, Kun; Zhu, Chunyue; Chen, Zhijin; Zheng, Chunping; Tan, Yong; Rao, Xiancai; Cong, Yanguang

    2017-01-01

    Enteric fever is predominantly caused by Salmonella enterica serovar Typhi and Salmonella enterica serovar Paratyphi A, and accounts for an annual global incidence of 26.9 millions. In recent years, the rate of S. Paratyphi A infection has progressively increased. Currently licensed vaccines for typhoid fever, live Ty21a vaccine, Vi subunit vaccine, and Vi-conjugate vaccine, confer inadequate cross immunoprotection against enteric fever caused by S. Paratyphi A. Therefore, development of bivalent vaccines against enteric fever is urgently required. The immunogenic Vi capsular polysaccharide is characteristically produced in S. Typhi, but it is absent in S. Paratyphi A. We propose that engineering synthesis of Vi in S. Paratyphi A live-attenuated vaccine may expand its protection range to cover S. Typhi. In this study, we cloned the viaB locus, which contains 10 genes responsible for Vi biosynthesis, and integrated into the chromosome of S. Paratyphi A CMCC 50093. Two virulence loci, htrA and phoPQ, were subsequently deleted to achieve a Vi-producing attenuated vaccine candidate. Our data showed that, despite more than 200 passages, the viaB locus was stably maintained in the chromosome of S. Paratyphi A and produced the Vi polysaccharide. Nasal immunization of the vaccine candidate stimulated high levels of Vi-specific and S. Paratyphi A-specific antibodies in mice sera as well as total sIgA in intestinal contents, and showed significant protection against wild-type challenge of S. Paratyphi A or S. Typhi. Our study show that the Vi-producing attenuated S. Paratyphi A is a promising bivalent vaccine candidate for the prevention of enteric fever.

  20. Vi Capsular Polysaccharide Produced by Recombinant Salmonella enterica Serovar Paratyphi A Confers Immunoprotection against Infection by Salmonella enterica Serovar Typhi

    PubMed Central

    Xiong, Kun; Zhu, Chunyue; Chen, Zhijin; Zheng, Chunping; Tan, Yong; Rao, Xiancai; Cong, Yanguang

    2017-01-01

    Enteric fever is predominantly caused by Salmonella enterica serovar Typhi and Salmonella enterica serovar Paratyphi A, and accounts for an annual global incidence of 26.9 millions. In recent years, the rate of S. Paratyphi A infection has progressively increased. Currently licensed vaccines for typhoid fever, live Ty21a vaccine, Vi subunit vaccine, and Vi-conjugate vaccine, confer inadequate cross immunoprotection against enteric fever caused by S. Paratyphi A. Therefore, development of bivalent vaccines against enteric fever is urgently required. The immunogenic Vi capsular polysaccharide is characteristically produced in S. Typhi, but it is absent in S. Paratyphi A. We propose that engineering synthesis of Vi in S. Paratyphi A live-attenuated vaccine may expand its protection range to cover S. Typhi. In this study, we cloned the viaB locus, which contains 10 genes responsible for Vi biosynthesis, and integrated into the chromosome of S. Paratyphi A CMCC 50093. Two virulence loci, htrA and phoPQ, were subsequently deleted to achieve a Vi-producing attenuated vaccine candidate. Our data showed that, despite more than 200 passages, the viaB locus was stably maintained in the chromosome of S. Paratyphi A and produced the Vi polysaccharide. Nasal immunization of the vaccine candidate stimulated high levels of Vi-specific and S. Paratyphi A-specific antibodies in mice sera as well as total sIgA in intestinal contents, and showed significant protection against wild-type challenge of S. Paratyphi A or S. Typhi. Our study show that the Vi-producing attenuated S. Paratyphi A is a promising bivalent vaccine candidate for the prevention of enteric fever. PMID:28484685

  1. [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.

  2. [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.

  3. Filovirus vaccines

    PubMed Central

    Bradfute, Steven B; Dye, John M

    2011-01-01

    Filoviruses can cause severe and often fatal hemorrhagic fever in humans and non-human primates (NHPs). Although there are currently no clinically proven treatments for filovirus disease, much progress has been made in recent years in the discovery of therapeutics and vaccines against these viruses. A variety of vaccine platforms have been shown to be effective against filovirus infection. This review summarizes the literature in this field, focusing on vaccines that have been shown to protect NHPs from infection. Furthermore, the uses of rodent models in vaccine development, as well as correlates of immunity, are discussed. PMID:21519188

  4. [Vaccination programmes].

    PubMed

    Varela, M Carmen

    2009-01-01

    Immunization is a highly cost-effective intervention that saves many lives. Its objective is to control and eliminate vaccine-preventable diseases (when the characteristics of the disease and the vaccine make it possible), resulting in improvements in the health of the population. In Spain, the first vaccination schedule was introduced in 1975 and currently coverages > 95% are achieved in children aged < 2 years of age. Before deciding to introduce a vaccination programme in a community or country, a series of aspects should be considered, including the disease burden in the population, the effectiveness and safety of the vaccine, the changes in the dynamics of the infection when the vaccine is introduced, the cost-effectiveness of the vaccine, the theoretical potential of elimination/eradication of the disease and the existence of other preventive or therapeutic measures. Once the programme has been introduced it should be subject to evaluation, considering aspects such as the coverage, effectiveness, safety and the impact on the population. This work defines different vaccination strategies for three diseases for which efficacious and safe vaccines are available: hepatitis A, influenza and varicella.

  5. Antibody response to meningococcal polysaccharides A and C in patients with complement defects.

    PubMed

    Biselli, R; Casapollo, I; D'Amelio, R; Salvato, S; Matricardi, P M; Brai, M

    1993-06-01

    Patients with defects of terminal complement components are particularly exposed to the risk of developing neisserial infections and seem to respond poorly to meningococcal capsular polysaccharide (PS) C via natural immunization. The sole meningococcal PSC is, on the other hand, an excellent immunogen in normal people. Considering the great importance of vaccine prophylaxis for the prevention of meningococcal infections in patients with complement defects, it is crucial to study the antibody response to the sole meningococcal PS in these patients. We therefore analysed the levels of anti-PSA and PSC antibodies in the members of four families including patients with homozygous and heterozygous defects of C7, C8 or factor H, before and after vaccination with the sole PSA + C. Surprisingly, we found the highest levels of antibodies before vaccination in homozygous subjects, followed by heterozygous and normal controls, whereas, after vaccination, homozygous subjects showed the lowest increase of specific antibodies, indicating their relative incapability to respond to sole meningococcal PS. In conclusion, this study demonstrates (1) the capacity to respond to meningococcal PS via natural immunization by patients with total complement defects, and (2) the low responsiveness to meningococcal PS via vaccine immunization by the same patients. We propose that vaccination should be given to patients lacking specific antibodies and their serological response should be assessed. In addition this study confirms previous observations on a likely lower immunogenic power of mening