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1

Meningococcal serogroups A, C, W-135, and Y tetanus toxoid conjugate vaccine: a new conjugate vaccine against invasive meningococcal disease  

PubMed Central

Invasive meningococcal disease is a serious infection that occurs worldwide. It is caused by Neisseria meningitidis, of which six serogroups (A, B, C, W-135, X, and Y) are responsible for most infections. The case fatality rate of meningococcal disease remains high and can lead to significant sequelae. Vaccination remains the best strategy to prevent meningococcal disease. Polysaccharide vaccines were initially introduced in the late 1960s but their limitations (poor immunogenicity in infants and toddlers and hyporesponsiveness after repeated doses) have led to the development and use of meningococcal conjugate vaccines, which overcome these limitations. Two quadrivalent conjugated meningococcal vaccines – MenACWY-DT (Menactra®) and MenACWY-CRM197 (Menveo®) – using diphtheria toxoid or a mutant protein, respectively, as carrier proteins have already been licensed in the US. Recently, a quadrivalent meningococcal vaccine conjugated to tetanus toxoid (MenACWY-TT; Nimenrix®) was approved for use in Europe in 2012. The immunogenicity of MenACWY-TT, its reactogenicity and safety profile, as well as its coadministration with other vaccines are discussed in this review. Clinical trials showed that MenACWY-TT was immunogenic in children above the age of 12 months, adolescents, and adults, and has an acceptable reactogenicity and safety profile. Its coadministration with several other vaccines that are commonly used in children, adolescents, and adults did not affect the immunogenicity of MenACWY-TT or the coadministered vaccine, nor did it affect its reactogenicity and safety. Other studies are now ongoing in order to determine the immunogenicity, reactogenicity, and safety of MenACWY-TT in infants from the age of 6 weeks. PMID:24729718

Hedari, Carine P; Khinkarly, Rima W; Dbaibo, Ghassan S

2014-01-01

2

Safety and immunogenicity of a new Neisseria meningitidis serogroup C-tetanus toxoid conjugate vaccine in healthy adults  

Microsoft Academic Search

We evaluated the safety and immunogenicity of a single dose of a new serogroup C O-deacetylated meningococcal polysaccharide–tetanus toxoid conjugate vaccine in 30 healthy adult volunteers. The vaccine was well tolerated with no serious adverse events and minimal local reactions and systemic symptoms. All subjects developed a fourfold or greater increase in serum bactericidal antibody (SBA) to serogroup C meningococcus.

Peter Richmond; David Goldblatt; Peter C Fusco; Joan D. S Fusco; Iver Heron; Sarah Clark; Ray Borrow; Francis Michon

1999-01-01

3

Immune response to type III group B streptococcal polysaccharide-tetanus toxoid conjugate vaccine.  

PubMed Central

Group B Streptococcus (GBS) is an important perinatal pathogen. Because transplacentally acquired maternal antibodies to the GBS capsular polysaccharides (CPS) confer protection, prevention of infant disease may be possible after immunization of women. Unfortunately, the purified CPS of GBS are only variably immunogenic in adults; therefore to enhance immunogenicity we have designed and developed a CPS-protein conjugate vaccine. The lability of a conformationally dependent epitope on the III CPS containing a critical sialic acid residue was important to consider in vaccine design. 100 women were randomized to receive GBS type III CPS-tetanus toxoid conjugate (III-TT) vaccine at one of three doses; unconjugated GBS type III CPS; or saline. Serum samples were obtained before immunization and 2, 4, 8, and 26 wk thereafter, and specific antibody to type III CPS was measured. Vaccines were well tolerated. In sera from recipients of the highest dose of III-TT, CPS-specific IgG levels rose from a geometric mean of 0.09 microg/ml before immunization to 4.53 microg/ml 8 wk later, whereas levels in recipients of unconjugated type III CPS rose from 0.21 microg/ml to 1.41 microg/ml. Lower doses resulted in lower antibody levels. A > or = 4-fold rise in antibody concentration was achieved in 90% of recipients of III-TT compared with 50% of those that received III CPS (P = 0.0015). Antibodies evoked by the conjugate vaccine recognized a conformationally dependent epitope of the III-CPS, promoted opsonophagocytosis and killing of GBS, and, after maternal immunization, protected neonatal mice from lethal challenge with type III GBS. We conclude that directed coupling of type III GBS polysaccharide to a carrier protein yielded a conjugate vaccine with preserved expression of a highly labile conformational epitope involving sialic acid and enhanced immunogenicity compared with uncoupled CPS. PMID:8941648

Kasper, D L; Paoletti, L C; Wessels, M R; Guttormsen, H K; Carey, V J; Jennings, H J; Baker, C J

1996-01-01

4

Group B Streptococcus type II polysaccharide-tetanus toxoid conjugate vaccine.  

PubMed Central

Group B streptococci (GBS) are the most common cause of bacterial sepsis and meningitis in neonates in the United States. Although the capsular polysaccharide of GBS is an important virulence factor, it is variably immunogenic in humans. In this report, we have increased the immunogenicity of GBS type II polysaccharide by coupling it to tetanus toxoid (TT). Like other GBS capsular polysaccharides, the type II polysaccharide has side chains terminating in sialic acid. Controlled periodate oxidation of native II polysaccharide resulted in the conversion of 7% of sialic acid residues to an analog of sialic acid, 5-acetamido-3,5-dideoxy-D-galactosyloctulosonic acid. TT was conjugated to free aldehyde groups created on the oxidized sialic acid residues by reductive amination. Serum from rabbits vaccinated with type II-TT conjugate (II-TT) vaccine contained antibodies specific to type II polysaccharide as well as to TT, whereas rabbits vaccinated with uncoupled native type II polysaccharide failed to produce a type-specific antibody response. Antibodies elicited by II-TT vaccine were serotype specific and mediated phagocytosis and killing in vitro of type II GBS by human peripheral blood leukocytes. Serum from rabbits vaccinated with II-TT vaccine provided 100% protection in a mouse model of GBS type II infection. Antibodies induced by II-TT vaccine were specific for the native but not desialylated type II polysaccharide, suggesting that an important antigenic epitope of II-TT vaccine was dependent on the presence of sialic acid. Therefore, the coupling strategy which selectively modified a portion of the sialic acid residues of types II polysaccharide before coupling the polysaccharide to TT preserved the epitope essential to protective immunity and enhanced the immunogenicity of the polysaccharide. PMID:1398913

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

1992-01-01

5

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

PubMed

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. PMID:21843575

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

6

Combined vaccination with BCG and toxoid antigens*  

PubMed Central

Simultaneous vaccination with different antigens has been widely practised in recent years. A notable example is percutaneous smallpox vaccination together with the intradermal injection of BCG. In contrast, the potentially even more time-saving procedure of combined vaccination (i.e., with vaccines mixed prior to injection) has been tried on only a very limited, experimental scale. Combined vaccination with a mixture of BCG and toxoids has not been suggested before. Such a mixed vaccine, with diphtheria and tetanus toxoids, was used in experiments in vitro and in vivo. No deleterious effect of toxoids on BCG was found in terms of reduction in oxygen uptake, germination rate, or counts of viable particles. The dose—response relationships (delayed hypersensitivity and skin reactivity) for BCG with and without added toxoids were compared in guinea pigs and no differences were found. The antibody response in guinea pigs to toxoids mixed with BCG or with aluminium hydroxide was measured following both primary and booster immunization. The primary response to toxoids was lower with BCG than with aluminium hydroxide. In booster immunization, the response was identical for the two mixtures. It appears that not only is a mixture of toxoids and BCG innocuous (given intradermally) but also BCG may have an adjuvant effect on the production of antibodies to the toxoids. Further experimentation is needed, first in the guinea pig model and later in pilot trials in man, to establish suitable dose levels. Furthermore, since BCG may act as an adjuvant both in producing antibodies and in the cell-mediated response to the toxoids, it would be desirable to clarify the possible interaction of these two immune responses in protection against disease. PMID:310736

Guld, J.; Ladefoged, A.; Ramh?j, W.

1978-01-01

7

Immune response, antibody persistence, and safety of a single dose of the quadrivalent meningococcal serogroups A, C, W-135, and Y tetanus toxoid conjugate vaccine in adolescents and adults: results of an open, randomised, controlled study  

PubMed Central

Background The best strategy to protect individuals against meningococcal disease is to immunize against multiple serogroups. Immunogenicity, antibody persistence, and safety of the EU-licensed meningococcal ACWY-tetanus toxoid conjugate vaccine (MenACWY-TT) were evaluated in healthy participants aged 11–55 years from the Philippines and Saudi Arabia. Methods In this phase IIb, open, controlled study, 500 participants were randomised (3:1) to receive one dose of MenACWY-TT or a licensed meningococcal polysaccharide vaccine (Men-PS). Functional antibody responses against meningococcal serogroups A, C, W-135, and Y were assessed by a serum bactericidal antibody assay using rabbit complement (rSBA) at Month 0, Month 1, Year 1, Year 2, and Year 3. Vaccine response was defined as an rSBA titre ?32 at Month 1 in participants who were seronegative (rSBA titre <8) pre-vaccination and as at least a four-fold increase in titre in participants who were seropositive pre-vaccination. Solicited symptoms were recorded up to Day 4, safety outcomes up to Month 6, and serious adverse events related to vaccination up to Year 3. Results Pre-specified criteria for non-inferiority of MenACWY-TT versus Men-PS were met in terms of rSBA vaccine response and incidence of grade 3 general symptoms. At Month 1, 82.7%–96.3% of MenACWY-TT and 69.7%–91.7% in Men-PS recipients had a vaccine response for each serogroup. At Year 3, ?99.1% and ?92.9% of MenACWY-TT recipients retained rSBA titres ?8 and ?128, respectively, as compared to ?86.7% and ?80.0% in the Men-PS group. Both vaccines had a clinically acceptable safety profile, although injection site redness and swelling were more frequent in MenACWY-TT recipients. Conclusions These results suggest that MenACWY-TT could protect adolescents and adults against meningococcal disease up to three years post-vaccination. Trial registration This study is registered at http://www.clinicaltrials.gov/NCT00356369. PMID:23510357

2013-01-01

8

Meningococcal Polysaccharide A O-Acetylation Levels Do Not Impact the Immunogenicity of the Quadrivalent Meningococcal Tetanus Toxoid Conjugate Vaccine: Results from a Randomized, Controlled Phase III Study of Healthy Adults Aged 18 to 25 Years  

PubMed Central

In this study, we compared the immunogenicities of two lots of meningococcal ACWY-tetanus toxoid conjugate vaccine (MenACWY-TT) that differed in serogroup A polysaccharide (PS) O-acetylation levels and evaluated their immunogenicities and safety in comparison to a licensed ACWY polysaccharide vaccine (Men-PS). In this phase III, partially blinded, controlled study, 1,170 healthy subjects aged 18 to 25 years were randomized (1:1:1) to receive one dose of MenACWY-TT lot A (ACWY-A) (68% O-acetylation), MenACWY-TT lot B (ACWY-B) (92% O-acetylation), or Men-PS (82% O-acetylation). Immunogenicity was evaluated in terms of serum bactericidal activity using rabbit complement (i.e., rabbit serum bactericidal activity [rSBA]). Solicited symptoms, unsolicited adverse events (AEs), and serious AEs (SAEs) were recorded. The immunogenicities, in terms of rSBA geometric mean titers, were comparable for both lots of MenACWY-TT. The vaccine response rates across the serogroups were 79.1 to 97.0% in the two ACWY groups and 73.7 to 94.1% in the Men-PS group. All subjects achieved rSBA titers of ?1:8 for all serogroups. All subjects in the two ACWY groups and 99.5 to 100% in the Men-PS group achieved rSBA titers of ?1:128. Pain was the most common solicited local symptom and was reported more frequently in the ACWY group (53.9 to 54.7%) than in the Men-PS group (36.8%). The most common solicited general symptoms were fatigue and headache, which were reported by 28.6 to 30.3% and 26.9 to 31.0% of subjects, respectively. Two subjects reported SAEs; one SAE was considered to be related to vaccination (blighted ovum; ACWY-B group). The level of serogroup A PS O-acetylation did not affect vaccine immunogenicity. MenACWY-TT (lot A) was not inferior to Men-PS in terms of vaccine response and was well tolerated. PMID:23885033

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

2013-01-01

9

The immunogenicity and safety of an investigational meningococcal serogroups A, C, W-135 and Y tetanus toxoid conjugate vaccine (ACWY-TT) compared with a licensed meningococcal tetravalent polysaccharide vaccine  

PubMed Central

Immunogenicity and safety of ACWY-TT compared with licensed ACWY polysaccharide vaccine (MenPS) in healthy adults, and lot-to-lot consistency of three ACWY-TT lots were evaluated in a phase 3, open, controlled study. Adults aged 18–55 y were randomized to receive ACWY-TT (one of three lots) or MenPS. Serum bactericidal antibodies (rSBA) were measured pre- and 1 mo post-vaccination. Adverse events (AEs) were assessed 4 d (solicited symptoms) and 31 d (unsolicited symptoms) post-vaccination. Serious AEs were reported up to 6 mo after vaccination. The number of vaccinated subjects was 1247 (ACWY-TT, n = 935; MenPS, n = 312). ACWY-TT lot-to-lot consistency and non-inferiority of ACWY-TT as compared with MenPS groups were demonstrated according to pre-specified criteria. The percentages of subjects with a vaccine response (VR = rSBA titer ? 1:32 in initially seronegative; ? 4-fold increase in initially seropositive) to ACWY-TT vs. MenPS were 80.1%/69.8% (serogroup A), 91.5%/ 92.0% (C), 90.2%/85.5% (W-135), 87.0%/78.8% (Y). Exploratory analyses showed that for serogroups A, W-135 and Y, VR rates and GMTs were significantly higher for ACWY-TT compared with MenPS. For each serogroup, ? 98.0% of subjects had rSBA titers ? 1:128. Grade 3 solicited AEs were reported in ? 1.6% of subjects in any group. The immunogenicity of ACWY-TT vaccine was non-inferior to MenPS for all four serogroups in adults, with significantly higher VR rates to serogroups A, W-135 and Y and an acceptable safety profile. Consistency of 3 ACWY-TT production lots was demonstrated. These data suggest that, if licensed, ACWY-TT conjugate vaccine may be used for protection against invasive meningococcal disease in healthy adults.   This study is registered at clinicaltrials.gov NCT00453986 PMID:22485050

Dbaibo, Ghassan; Macalalad, Noel; Reyes, Mari Rose Aplasca-De Los; Dimaano, Efren; Bianco, Veronique; Baine, Yaela; Miller, Jacqueline

2012-01-01

10

Preparation and evaluation of immunogenic conjugates of Salmonella enterica serovar Typhi O-specific polysaccharides with diphtheria toxoid.  

PubMed

Typhoid fever, caused by Salmonella enterica serovar Typhi (S. Typhi), is a major health problem particularly in developing countries. The available vaccines have certain limitations regarding their efficacy, and inability to induce an immune response especially in individuals under 2 years of age. Conjugate vaccines which consist of a bacteria-specific polysaccharide chemically bound to a carrier protein overcome these problems by inducing a T-cell dependent immune response characterized by enhanced immunogenicity in all ages. In this study, O-specific polysaccharides (OSP) of S. Typhi were conjugated to diphtheria toxoid (DT) using adipic acid dihydrazide (ADH) as a linker. These conjugates (OSP-AH-DT) were then evaluated for their immunogenicity using mice as a model and showed significantly higher levels of IgG ELISA titers (P = 0.0241 and 0.0245) than lipopolysaccharides alone. Different immunization  schedules were compared and it was found that schedule-B (three injections with 4-weeks interval) induced higher immune responses than schedule-A (three injections with 2-weeks interval). We showed that diphtheria toxoid can be successfully employed as a carrier protein for conjugation with Salmonella OSP and play an important role in facilitating adequate immune response. PMID:22426380

Ali, Aamir; An, So Jung; Cui, Changfa; Haque, Abdul; Carbis, Rodney

2012-02-01

11

A clinical trial examining the effect of increased total CRM(197) carrier protein dose on the antibody response to Haemophilus influenzae type b CRM(197) conjugate vaccine.  

PubMed

CRM(197) is a carrier protein in certain conjugate vaccines. When multiple conjugate vaccines with the same carrier protein are administered simultaneously, reduced response to vaccines and/or antigens related to the carrier protein may occur. This study examined responses of infants who, in addition to diphtheria toxoid/tetanus toxoid/acellular pertussis vaccine (DTaP) received either diphtheria CRM(197)-based Haemophilus influenzae type b conjugate vaccine (HbOC) or HbOC and a diphtheria CRM(197)-based combination 9-valent pneumococcal conjugate vaccine/meningococcal group C conjugate vaccine. Administration of conjugate vaccines with CRM(197) carrier protein load >50 microg did not reduce response to CRM(197) conjugate vaccines or immunogenicity to immunologically cross-reactive diphtheria toxoid. PMID:18577410

Usonis, Vytautas; Bakasenas, Vytautas; Lockhart, Stephen; Baker, Sherryl; Gruber, William; Laudat, France

2008-08-18

12

Physical and chemical characterization and immunologic properties of Salmonella enterica serovar typhi capsular polysaccharide-diphtheria toxoid conjugates.  

PubMed

Typhoid fever remains a serious public health problem in developing countries, especially among young children. Recent studies showed more than 50% of typhoid cases are in children under 5 years old. Licensed vaccines, such as Salmonella enterica serovar Typhi capsular Vi, did not confer protection against typhoid fever for this age group. Vi conjugate, prepared by binding Vi to Pseudomonas aeruginosa recombinant exoprotein A (rEPA), induces protective levels of antibody at as young as 2 years old. Because of the lack of regulatory precedent for rEPA in licensing vaccines, we employed diphtheria toxoid (DT) as the carrier protein to accommodate accessibility in developing countries. Five lots of Vi-DT conjugates were prepared using adipic acid dihydrazide (ADH) as the linker. All 5 lots showed consistency in their physical and chemical characteristics and final yields. These Vi-DT conjugates elicited levels of IgG anti-Vi in young mice significantly higher than those in mice injected with Vi alone and induced a booster response upon reinjection. This booster effect was absent if the Vi replaced one of the two conjugate injections. Vi-DT was stable under repeated freeze-thaw (20 cycles). We plan to perform clinical evaluation of the safety and immunogenicity of Vi-DT when added to the infant combination vaccines. PMID:19889941

Cui, Changfa; Carbis, Rodney; An, So Jung; Jang, Hyun; Czerkinsky, Cecil; Szu, Shousun C; Clemens, John D

2010-01-01

13

Safety and Immunogenicity of Increasing Doses of a Clostridium difficile Toxoid Vaccine Administered to Healthy Adults  

Microsoft Academic Search

Clostridium difficile is a major cause of nosocomial diarrhea in industrialized countries. Although most ill- nesses respond to available therapy, infection can increase morbidity, prolong hospitalization, and produce life- threatening colitis. Vaccines are being explored as an alternative means for protecting high-risk individuals. We assessed the safety, immunogenicity, and dose response of a parenteral vaccine containing C. difficile toxoids A

KAREN L. KOTLOFF; STEVEN S. WASSERMAN; GENEVIEVE A. LOSONSKY; WILLIAM THOMAS; RICHARD NICHOLS; ROBERT EDELMAN; MARGARET BRIDWELL; THOMAS P. MONATH

2001-01-01

14

Immunogenicity of a Reduced Schedule of Meningococcal Group C Conjugate Vaccine Given Concomitantly with the Prevenar and Pediacel Vaccines in Healthy Infants in the United Kingdom  

Microsoft Academic Search

This study investigated the use of two doses of three different meningococcal group C conjugate (MCC) vaccines when given for primary immunization with a seven-valent pneumococcal conjugate vaccine (PCV7) and Pediacel, a combination product containing five acellular pertussis components, diphtheria and tetanus toxoids, Haemophilus influenzae type b (Hib) conjugate, and inactivated-poliovirus vaccine. The immune response after a single dose of

Ray Borrow; Nick Andrews; Rhonwen Morris; Pauline Waight; Michael Hudson; Paul Balmer; Helen Findlow; Jamie Findlow; Elizabeth Miller

2009-01-01

15

Antibody response to a delayed booster dose of anthrax vaccine and botulinum toxoid  

Microsoft Academic Search

We evaluated the prevalence and concentration of serum antibodies 18–24 months after primary inoculation with anthrax and botulinum vaccines, and assessed the reactogenicity and immunogenicity of a significantly delayed booster dose of these vaccines. Five hundred and eight male active-duty military personnel received one, two or three inoculations with anthrax vaccine and\\/or botulinum toxoid in 1990\\/1991 in preparation for Operations

Phillip R Pittman; Dallas Hack; Joseph Mangiafico; Paul Gibbs; Kelly T McKee; Arthur M Friedlander; Maria H Sjogren

2002-01-01

16

Phase I/II, Open-Label Trial of Safety and Immunogenicity of Meningococcal (Groups A, C, Y, and W-135) Polysaccharide Diphtheria Toxoid Conjugate Vaccine in Human Immunodeficiency Virus-Infected Adolescents  

PubMed Central

Background: Quadrivalent meningococcal polysaccharide conjugate vaccine (MCV4) is routinely recommended for healthy youth in the United States, but there are no data about its use in HIV-infected people. Methods: P1065 is a Phase I/II trial of MCV4 safety and immunogenicity in HIV-infected children and youth performed at 27 US sites of the IMPAACT network. All youth (11–24 years old) received 1 dose of open-label MCV4 at entry. Standardized questionnaires were used to evaluate safety. Baseline protective immunity was defined as rabbit serum bactericidal antibody (rSBA) titer ?1:128. Immunogenic response was defined as a ?4-fold rise in rSBA against each meningococcal serogroup. Multivariable logistic regression analysis was used to evaluate the association of demographic and clinical characteristics on immunogenic response to serogroup C. Results: Among 319 subjects who received MCV4, 10 (3.1%) reported immediate adverse events which were local and mild, and 7 (2.2%) experienced Grade ?3 adverse events, unrelated to vaccine. The 305 subjects with serologic data had a median age of 17 years and were 59% male, 50% Black, and 38% Latino. Subjects were stratified by entry CD4%: 12%, CD4 <15%; 40%, 15% to 24%; and 48%, ?25%. Baseline protective immunity varied by serogroup: A, 41%; C, 11%; W-135, 15%; Y, 35% The immunogenic response rates to serogroups A, C, W-135, and Y were 68%, 52%, 73%, and 63%, respectively. In multivariable logistic regression models, lower entry CD4%, higher entry viral load, and CDC Class B/C diagnosis were associated with significantly lower odds of response to serogroup C. Conclusion: Many HIV-infected youth naturally acquire meningococcal immunity. MCV4 is safe and immunogenic in HIV-infected youth, but response rates are lower than in healthy youth, particularly for those with more advanced HIV clinical, immunologic, and virologic status. PMID:20431379

Siberry, George K.; Williams, Paige L.; Lujan-Zilbermann, Jorge; Warshaw, Meredith G.; Spector, Stephen A.; Decker, Michael D.; Heckman, Barbara E.; Demske, Emily F.; Read, Jennifer S.; Jean-Philippe, Patrick; Kabat, William; Nachman, Sharon

2010-01-01

17

Development of Vi conjugate - a new generation of typhoid vaccine.  

PubMed

Typhoid fever remains to be a serious disease burden worldwide with an estimated annual incidence about 20 million. The licensed vaccines showed moderate protections and have multiple deficiencies. Most important of all, none of the licensed typhoid vaccines demonstrated protection for children under 5 years old. These limitations impeded successful implementation of typhoid vaccination programs. To improve immunogenicity Vi was conjugated to rEPA, a recombinant exoprotein A from Pseudomonas aeruginosa. Vi-rEPA showed higher and longer lasting anti-Vi IgG in adults and children than Vi alone in high endemic areas. In school-age children and adults, the immunity persisted more than 8 years. In a double-blind, placebo-controlled and randomized efficacy trial in 2- to 5-year-old children, Vi-rEPA conferred 89% protective efficacy against typhoid fever and the protection lasted at least 4 years. When given concomitantly with infant routine vaccines, Vi-rEPA was safe, immunogenic and showed no interference with the routine vaccines. Vi conjugate vaccine was also attempted and successfully demonstrated by several other laboratories and manufactures. Using either rEPA or different carrier proteins, such as diphtheria or tetanus toxoid, recombinant diphtheria toxin (CRM197), the Vi conjugates synthesized was significantly more immunogenic than Vi alone. Recently, two Vi-tetanus toxoid conjugates were licensed in India for all ages, starts as young as 3 month old. This new generation of typhoid vaccine opens up a new era for typhoid prevention and elimination. PMID:24156285

Szu, Shousun Chen

2013-11-01

18

Associated or combined vaccination of Brazilian infants with a conjugate Haemophilus influenzae type b (Hib) vaccine, a diphtheria–tetanus–whole-cell pertussis vaccine and IPV or OPV elicits protective levels of antibodies against Hib  

Microsoft Academic Search

This study investigated the immunogenicity and safety of including a Haemophilus influenzae type b vaccine (polyribosylribitol phosphate conjugated to tetanus toxoid, PRP-T) in three different vaccination schemes: (1) PRP-T reconstituted with a combined diphtheria–tetanus–pertussis-inactivated poliovirus vaccine (DTP-IPV\\/\\/PRP-T); (2) PRP-T reconstituted with DTP and administered concomitantly with an oral poliovirus vaccine (DTP\\/\\/PRP-T+OPV); and (3) PRP-T administered concomitantly with DTP at a

Orlei O Araújo; Eduardo Forleo-Neto; Glaucia N. R Vespa; Rosana F Puccini; Lilly W Weckx; Eduardo S Carvalho; Calil K Farhat

2000-01-01

19

Antibody response to a delayed booster dose of anthrax vaccine and botulinum toxoid.  

PubMed

We evaluated the prevalence and concentration of serum antibodies 18-24 months after primary inoculation with anthrax and botulinum vaccines, and assessed the reactogenicity and immunogenicity of a significantly delayed booster dose of these vaccines. Five hundred and eight male active-duty military personnel received one, two or three inoculations with anthrax vaccine and/or botulinum toxoid in 1990/1991 in preparation for Operations Desert Shield/Desert Storm. Subjects were vaccinated with the licensed anthrax vaccine, adsorbed (AVA) and pentavalent (ABCDE) botulinum toxoid (PBT) BB-IND 3723. Anthrax protective antigen (PA) IgG antibody was measured in serum using an immunocapture enzyme-linked immunosorbent assay (ELISA). A mouse neutralization test was used to determine the titer of Clostridium botulinum type A antitoxin in serum samples. The prevalence of anti-PA IgG was 30% in individuals 18-24 months after priming with one, two or three doses of AVA. After boosting, 99% of volunteers had detectable anti-PA IgG; only two individuals failed to respond. The prevalence of antibodies against botulinum toxin type A was 28% 18-24 months after initial priming. Following boosting, 99% of volunteers had serum titers >0.02IU/ml, and 97% responded with titers > or =0.25IU/ml. Systemic reactions to booster vaccinations could not be specifically ascribed to one or the other vaccine, but were generally mild and of brief duration. Forty-five percent of volunteers reported one or more systemic reactions over the course of 7 days. Injection site reactions of any kind occurred in 25% of AVA recipients and in 16% of PBT recipients; persistence of local reactions beyond 7 days was infrequent. While the kinetics and durability of immune responses must be studied, these findings suggest that booster doses of anthrax vaccine and botulinum toxoid sufficient to stimulate a robust anamnestic response may be given at times distant from receipt of the primary inoculations. PMID:11972980

Pittman, Phillip R; Hack, Dallas; Mangiafico, Joseph; Gibbs, Paul; McKee, Kelly T; Friedlander, Arthur M; Sjogren, Maria H

2002-05-15

20

An adult formulation of a five-component acellular pertussis vaccine combined with diphtheria and tetanus toxoids is safe and immunogenic in adolescents and adults  

Microsoft Academic Search

Pertussis is increasingly being recognized as an important cause of cough illness in adolescents and adults. To evaluate the safety and immunogenicity of an adult formulation of a five-component (pertussis toxoid, filamentous hemagglutinin, pertactin, fimbriae 2 and 3) acellular pertussis vaccine combined with diphtheria and tetanus toxoids, we randomly allocated 749 healthy adolescents and adults from 12–54 years of age

Scott A. Halperin; Bruce Smith; Margaret Russell; Paul Hasselback; Roland Guasparini; Danuta Skowronski; William Meekison; Robert Parker; Pierre Lavigne; Luis Barreto

2000-01-01

21

Maternal Tetanus Toxoid Vaccination and Neonatal Mortality in Rural North India  

PubMed Central

Objectives Preventable neonatal mortality due to tetanus infection remains common. We aimed to examine antenatal vaccination impact in a context of continuing high neonatal mortality in rural northern India. Methods and Findings Using the third round of the Indian National Family Health Survey (NFHS) 2005–06, mortality of most recent singleton births was analysed in discrete-time logistic model with maternal tetanus vaccination, together with antenatal care utilisation and supplementation with iron and folic acid. 59% of mothers reported receiving antenatal care, 48% reported receiving iron and folic acid supplementation and 68% reported receiving two or more doses of tetanus toxoid (TT) vaccination. The odds of all-cause neonatal death were reduced following one or more antenatal dose of TT with odds ratios (OR) of 0.46 (95% CI 0.26 to 0.78) after one dose and 0.45 (95% CI 0.31 to 0.66) after two or more doses. Reported utilisation of antenatal care and iron-folic acid supplementation did not influence neonatal mortality. In the statistical model, 16% (95% CI 5% to 27%) of neonatal deaths could be attributed to a lack of at least two doses of TT vaccination during pregnancy, representing an estimated 78,632 neonatal deaths in absolute terms. Conclusions Substantial gains in newborn survival could be achieved in rural North India through increased coverage of antenatal TT vaccination. The apparent substantial protective effect of a single antenatal dose of TT requires further study. It may reflect greater population vaccination coverage and indicates that health programming should prioritise universal antenatal coverage with at least one dose. PMID:23152814

Singh, Abhishek; Pallikadavath, Saseendran; Ogollah, Reuben; Stones, William

2012-01-01

22

Transcriptomic Response of Porcine PBMCs to Vaccination with Tetanus Toxoid as a Model Antigen  

PubMed Central

The aim of the present study was to characterize in vivo genome-wide transcriptional responses to immune stimulation in order to get insight into the resulting changes of allocation of resources. Vaccination with tetanus toxoid was used as a model for a mixed Th1 and Th2 immune response in pig. Expression profiles of PBMCs (peripheral blood mononuclear cells) before and at 12 time points over a period of four weeks after initial and booster vaccination at day 14 were studied by use of Affymetrix GeneChip microarrays and Ingenuity Pathway Analysis (IPA). The transcriptome data in total comprised more than 5000 genes with different transcript abundances (DE-genes). Within the single time stages the numbers of DE-genes were between several hundred and more than 1000. Ingenuity Pathway Analysis mainly revealed canonical pathways of cellular immune response and cytokine signaling as well as a broad range of processes in cellular and organismal growth, proliferation and development, cell signaling, biosynthesis and metabolism. Significant changes in the expression profiles of PBMCs already occurred very early after immune stimulation. At two hours after the first vaccination 679 DE-genes corresponding to 110 canonical pathways of cytokine signaling, cellular immune response and other multiple cellular functions were found. Immune competence and global disease resistance are heritable but difficult to measure and to address by breeding. Besides QTL mapping of immune traits gene expression profiling facilitates the detection of functional gene networks and thus functional candidate genes. PMID:23536793

Adler, Marcel; Murani, Eduard; Brunner, Ronald; Ponsuksili, Siriluck; Wimmers, Klaus

2013-01-01

23

Transcriptomic response of porcine PBMCs to vaccination with tetanus toxoid as a model antigen.  

PubMed

The aim of the present study was to characterize in vivo genome-wide transcriptional responses to immune stimulation in order to get insight into the resulting changes of allocation of resources. Vaccination with tetanus toxoid was used as a model for a mixed Th1 and Th2 immune response in pig. Expression profiles of PBMCs (peripheral blood mononuclear cells) before and at 12 time points over a period of four weeks after initial and booster vaccination at day 14 were studied by use of Affymetrix GeneChip microarrays and Ingenuity Pathway Analysis (IPA). The transcriptome data in total comprised more than 5000 genes with different transcript abundances (DE-genes). Within the single time stages the numbers of DE-genes were between several hundred and more than 1000. Ingenuity Pathway Analysis mainly revealed canonical pathways of cellular immune response and cytokine signaling as well as a broad range of processes in cellular and organismal growth, proliferation and development, cell signaling, biosynthesis and metabolism. Significant changes in the expression profiles of PBMCs already occurred very early after immune stimulation. At two hours after the first vaccination 679 DE-genes corresponding to 110 canonical pathways of cytokine signaling, cellular immune response and other multiple cellular functions were found. Immune competence and global disease resistance are heritable but difficult to measure and to address by breeding. Besides QTL mapping of immune traits gene expression profiling facilitates the detection of functional gene networks and thus functional candidate genes. PMID:23536793

Adler, Marcel; Murani, Eduard; Brunner, Ronald; Ponsuksili, Siriluck; Wimmers, Klaus

2013-01-01

24

A novel approach to generate a recombinant toxoid vaccine against Clostridium difficile  

PubMed Central

The Clostridium difficile toxins A and B are primarily responsible for symptoms of C. difficile associated disease and are prime targets for vaccine development. We describe a plasmid-based system for the production of genetically modified toxins in a non-sporulating strain of C. difficile that lacks the toxin genes tcdA and tcdB. TcdA and TcdB mutations targeting established glucosyltransferase cytotoxicity determinants were introduced into recombinant plasmids and episomally expressed toxin mutants purified from C. difficile transformants. TcdA and TcdB mutants lacking glucosyltransferase and autoproteolytic processing activities were ~10?000-fold less toxic to cultured human IMR-90 cells than corresponding recombinant or native toxins. However, both mutants retained residual cytotoxicity that could be prevented by preincubating the antigens with specific antibodies or by formalin treatment. Such non-toxic formalin-treated mutant antigens were immunogenic and protective in a hamster model of infection. The remaining toxicity of untreated TcdA and TcdB mutant antigens was associated with cellular swelling, a phenotype consistent with pore-induced membrane leakage. TcdB substitution mutations previously shown to block vesicular pore formation and toxin translocation substantially reduced residual toxicity. We discuss the implications of these results for the development of a C. difficile toxoid vaccine. PMID:23629868

Flint, Mike; Kalyan, Narender; Johnson, Erik; Witko, Susan E.; Kotash, Cheryl; Zhao, Ping; Megati, Shakuntala; Yurgelonis, Irina; Lee, Phillip Kwok; Matsuka, Yury V.; Severina, Elena; Deatly, Anne; Sidhu, Mini; Jansen, Kathrin U.; Minton, Nigel P.; Anderson, Annaliesa S.

2013-01-01

25

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)

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.

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

2004-09-01

26

Prophylaxis With Acetaminophen or Ibuprofen for Prevention of Local Reactions to the Fifth Diphtheria-Tetanus Toxoids-Acellular Pertussis Vaccination: A Randomized, Controlled Trial  

Microsoft Academic Search

BACKGROUND.The frequency of local vaccination reactions increases with successive doses of diphtheria-tetanus toxoids-acellular pertussis (DTaP) vaccine, and local reactions occur for the majority of children receiving the fifth DTaP vaccination. It is not known whether these reactions can be prevented with prophylactic use of acetaminophen or ibuprofen. METHODS.In this 3-group, randomized, blinded, controlled trial, 372 children were assigned randomly, in

Lisa A. Jackson; Maya Dunstan; Patty Starkovich; John Dunn; Jennifer C. Nelson; Thom Rees

27

Determination of hydrazine in a meningococcal C conjugate vaccine intermediary product.  

PubMed

In Brazil, polysaccharide-protein conjugate vaccine against Neisseria meningitidis group C (MenCPS-TT) using hydrazine-activated-tetanus toxoid (TT) as a carrier protein has been developed. Because of the toxicity of hydrazine in humans, it is necessary to monitor this substance's process control step during the vaccine production. The electroanalytical methodology was developed and validated for the determination of hydrazine during the process control of MenCPS-TT vaccine production by differential pulse polarography. The reduction potential was -0.95 V in acetone and sulphuric acid solution. The method presented linear range between 30 and 150 microgL(-1)and recovery of 93.5+/-0.8%. PMID:20598406

Bastos, Renata Chagas; de Carvalho, Juliana Machado; da Silveira, Ivna Alana Freitas Brasileiro; do Couto Jacob, Silvana; Leandro, Katia Christina

2010-08-01

28

Safety and immunogenicity of two doses of quadrivalent meningococcal conjugate vaccine or one dose of meningococcal group C conjugate vaccine, both administered concomitantly with routine immunization to 12- to 18-month-old children  

PubMed Central

OBJECTIVES: To describe the immunogenicity and safety of a two-dose series of a quadrivalent meningococcal (serogroups A, C, Y and W) polysaccharide diphtheria toxoid conjugate vaccine (MenACYW-D) administered to toddlers. METHODS: Children were randomly assigned (1:1) at study entry to receive MenACYW-D at 12 and 18 months of age (group 1; n=61) or meningococcal serogroup C conjugate vaccine (MCC) at 12 months of age (group 2; n=62). All received routine childhood immunizations. A, C, Y and W antibody titres were measured in group 1 before and one month after the 18-month MenACYW-D vaccination and were measured in group 2 at one and seven months post-MCC vaccination. Antibodies elicited by diphtheria and tetanus toxoids, and acellular pertussis vaccine adsorbed combined with inactivated poliomyelitis vaccine and Haemophilus influenzae b conjugate (DTaP-IPV-Hib) vaccine coadministered at the 18-month vaccination were measured one month later. Safety data were collected. RESULTS: At 19 months of age, ?96% in group 1 achieved protective titres for the four meningococcal serogroups after dose 2; 67% in group 2 exhibited protective titres against serogroup C 28 days after MCC vaccination at 12 months of age, declining to 27% seven months later. DTaP-IPV-Hib elicited high antibody concentrations/titres in groups 1 and 2, consistent with historical values. The safety profiles after each dose generated no unexpected safety signals; no serious adverse events were related to vaccination. DISCUSSION: A two-dose series of MenACYW-D given concomitantly with a DTaP-IPV-Hib booster dose at 18 months of age demonstrated a good immunogenicity and safety profile. A two-dose series of MenACYW-D can be used as an alternative to one dose of MCC and provides protection against additional serogroups (NCT ID: NCT01359449).

Noya, Francisco; McCormack, Deirdre; Reynolds, Donna L; Neame, Dion; Oster, Philipp

2014-01-01

29

Effect of Spirulina (Arthrospira) supplementation on the immune response to tetanus toxoid vaccination in a mouse model.  

PubMed

The aim of this study was to investigate whether Spirulina (Arthrospira) supplementation could enhance the immune response to tetanus toxoid (TT) vaccine in a mouse model. Vaccination of TT was performed on day 7 and 21 in mice fed daily with Spirulina (50 and 150 mg/kg body weight). Both Spirulina supplementation and TT vaccination did not significantly affect body weight gain of the mice. Supplementation of Spirulina significantly enhanced IgG level (p = .01) after the first but not after the second TT vaccination. The anti-TT IgG levels of the groups that received low dose and high dose of Spirulina were not significantly different. Spirulina supplementation did not show significant effects on in vitro splenocyte proliferation and cytokine (IFN-? and IL-4) production induced by Con A and TT. This study showed that Spirulina supplementation could enhance primary immune response in terms of antibody production, but not secondary immune response following TT vaccination in a mouse model. PMID:23927690

Chu, Wan-Loy; Quynh, Le Van; Radhakrishnan, Ammu Kutty

2013-09-01

30

Immunogenicity of a Reduced Schedule of Meningococcal Group C Conjugate Vaccine Given Concomitantly with the Prevenar and Pediacel Vaccines in Healthy Infants in the United Kingdom?  

PubMed Central

This study investigated the use of two doses of three different meningococcal group C conjugate (MCC) vaccines when given for primary immunization with a seven-valent pneumococcal conjugate vaccine (PCV7) and Pediacel, a combination product containing five acellular pertussis components, diphtheria and tetanus toxoids, Haemophilus influenzae type b (Hib) conjugate, and inactivated-poliovirus vaccine. The immune response after a single dose of MCC is also presented. Infants were randomized to receive two doses of one of the MCC vaccines and PCV7 at 2 and 3 months or at 2 and 4 months of age. Meningococcal group C serum bactericidal antibody (SBA) geometric mean titers, Hib-polyribosylribitol phosphate (PRP) immunoglobulin G (IgG) geometric mean concentrations (GMCs), and diphtheria and tetanus antitoxin GMCs, together with the proportions of infants achieving putative protective levels, were determined. A total of 393 infants were recruited. Following the first dose of NeisVac-C (MCC conjugated to tetanus toxoid), 97% of infants achieved protective levels (SBA titer of ?8), compared with 80% and 53%, respectively, for Menjugate and Meningitec (both of which are conjugated to CRM197). SBA responses to MCC vaccines were not significantly different when administered at 2 and 3 or 2 and 4 months of age. Following two doses of each MCC, 98 to 100% of infants achieved protective levels. Both PRP IgG and tetanus responses were significantly enhanced when Pediacel was coadministered with NeisVac-C. This study demonstrates that NeisVac-C and Menjugate generate good immunogenicity after the first dose at 2 months of age when coadministered with PCV7 and Pediacel and merit further investigation in single-dose priming strategies. PMID:19091990

Southern, Jo; Borrow, Ray; Andrews, Nick; Morris, Rhonwen; Waight, Pauline; Hudson, Michael; Balmer, Paul; Findlow, Helen; Findlow, Jamie; Miller, Elizabeth

2009-01-01

31

Immunogenicity of a reduced schedule of meningococcal group C conjugate vaccine given concomitantly with the Prevenar and Pediacel vaccines in healthy infants in the United Kingdom.  

PubMed

This study investigated the use of two doses of three different meningococcal group C conjugate (MCC) vaccines when given for primary immunization with a seven-valent pneumococcal conjugate vaccine (PCV7) and Pediacel, a combination product containing five acellular pertussis components, diphtheria and tetanus toxoids, Haemophilus influenzae type b (Hib) conjugate, and inactivated-poliovirus vaccine. The immune response after a single dose of MCC is also presented. Infants were randomized to receive two doses of one of the MCC vaccines and PCV7 at 2 and 3 months or at 2 and 4 months of age. Meningococcal group C serum bactericidal antibody (SBA) geometric mean titers, Hib-polyribosylribitol phosphate (PRP) immunoglobulin G (IgG) geometric mean concentrations (GMCs), and diphtheria and tetanus antitoxin GMCs, together with the proportions of infants achieving putative protective levels, were determined. A total of 393 infants were recruited. Following the first dose of NeisVac-C (MCC conjugated to tetanus toxoid), 97% of infants achieved protective levels (SBA titer of >or=8), compared with 80% and 53%, respectively, for Menjugate and Meningitec (both of which are conjugated to CRM(197)). SBA responses to MCC vaccines were not significantly different when administered at 2 and 3 or 2 and 4 months of age. Following two doses of each MCC, 98 to 100% of infants achieved protective levels. Both PRP IgG and tetanus responses were significantly enhanced when Pediacel was coadministered with NeisVac-C. This study demonstrates that NeisVac-C and Menjugate generate good immunogenicity after the first dose at 2 months of age when coadministered with PCV7 and Pediacel and merit further investigation in single-dose priming strategies. PMID:19091990

Southern, Jo; Borrow, Ray; Andrews, Nick; Morris, Rhonwen; Waight, Pauline; Hudson, Michael; Balmer, Paul; Findlow, Helen; Findlow, Jamie; Miller, Elizabeth

2009-02-01

32

Immunogenicity and efficacy against lethal aerosol staphylococcal enterotoxin B challenge in monkeys by intramuscular and respiratory delivery of proteosome-toxoid vaccines.  

PubMed Central

Staphylococcal enterotoxin B (SEB), a primary cause of food poisoning, is also a superantigen that can cause toxic shock after traumatic or surgical staphylococcal wound [correction of would] infections or viral influenza-associated staphylococcal superinfections or when aerosolized for use as a potential biologic warfare threat agent. Intranasal or intramuscular (i.m.) immunization with formalinized SEB toxoid formulated with meningococcal outer membrane protein proteosomes has previously been shown to be immunogenic and protective against lethal respiratory or parenteral SEB challenge in murine models of SEB intoxication. Here, it is demonstrated that immunization of nonhuman primates with the proteosome-SEB toxoid vaccine is safe, immunogenic, and protective against lethal aerosol challenge with 15 50% lethal doses of SEB. Monkeys (10 per group) were primed i.m. and given booster injections by either the i.m. or intratracheal route without adverse side effects. Anamnestic anti-SEB serum immunoglobulin G (IgG) responses were elicited in all monkeys, but strong IgA responses in sera and bronchial secretions were elicited both pre- and post-SEB challenge only in monkeys given booster injections intratracheally. The proteosome-SEB toxoid vaccine was efficacious by both routes in protecting 100% of monkeys against severe symptomatology and death from aerosolized-SEB intoxication. These data confirm the safety, immunogenicity, and efficacy in monkeys of parenteral and respiratory vaccination with the proteosome-SEB toxoid, thereby supporting clinical trials of this vaccine in humans. The safety and enhancement of both bronchial and systemic IgA and IgG responses by the proteosome vaccine delivered by a respiratory route are also encouraging for the development of mucosally delivered proteosome vaccines to protect against SEB and other toxic or infectious respiratory pathogens. PMID:8890226

Lowell, G H; Colleton, C; Frost, D; Kaminski, R W; Hughes, M; Hatch, J; Hooper, C; Estep, J; Pitt, L; Topper, M; Hunt, R E; Baker, W; Baze, W B

1996-01-01

33

Oligosaccharide conjugates of Bordetella pertussis and bronchiseptica induce bactericidal antibodies, an addition to pertussis vaccine.  

PubMed

Pertussis is a highly contagious respiratory disease that is especially dangerous for infants and children. Despite mass vaccination, reported pertussis cases have increased in the United States and other parts of the world, probably because of increased awareness, improved diagnostic means, and waning vaccine-induced immunity among adolescents and adults. Licensed vaccines do not kill the organism directly; the addition of a component inducing bactericidal antibodies would improve vaccine efficacy. We investigated Bordetella pertussis and Bordetella bronchiseptica LPS-derived core oligosaccharide (OS) protein conjugates for their immunogenicity in mice. B. pertussis and B. bronchiseptica core OS were bound to aminooxylated BSA via their terminal Kdo residues. The two conjugates induced similar anti-B. pertussis LPS IgG levels in mice. B. bronchiseptica was investigated because it is easier to grow than B. pertussis. Using B. bronchiseptica genetically modified strains deficient in the O-specific polysaccharide, we isolated fractions of core OS with one to five repeats of the terminal trisaccharide, having at the nonreducing end a GlcNAc or GalNAc, and bound them to BSA at different densities. The highest antibody levels in mice were elicited by conjugates containing an average of 8-17 OS chains per protein and with one repeat of the terminal trisaccharide. Conjugate-induced antisera were bactericidal against B. pertussis, and the titers correlated with ELISA-measured antibody levels (r = 0.74). Such conjugates are easy to prepare and standardize; added to a recombinant pertussis toxoid, they may induce antibacterial and antitoxin immunity. PMID:21367691

Kubler-Kielb, Joanna; Vinogradov, Evgeny; Lagergård, Teresa; Ginzberg, Ariel; King, Jerry D; Preston, Andrew; Maskell, Duncan J; Pozsgay, Vince; Keith, Jerry M; Robbins, John B; Schneerson, Rachel

2011-03-01

34

Dosing Schedules for Pneumococcal Conjugate Vaccine  

PubMed Central

Since second generation pneumococcal conjugate vaccines (PCVs) targeting 10 and 13 serotypes became available in 2010, the number of national policy makers considering these vaccines has steadily increased. An important consideration for a national immunization program is the timing and number of doses—the schedule—that will best prevent disease in the population. Data on disease epidemiology and the efficacy or effectiveness of PCV schedules are typically considered when choosing a schedule. Practical concerns, such as the existing vaccine schedule, and vaccine program performance are also important. In low-income countries, pneumococcal disease and deaths typically peak well before the end of the first year of life, making a schedule that provides PCV doses early in life (eg, a 6-, 10- and 14-week schedule) potentially the best option. In other settings, a schedule including a booster dose may address disease that peaks in the second year of life or may be seen to enhance a schedule already in place. A large and growing body of evidence from immunogenicity studies, as well as clinical trials and observational studies of carriage, pneumonia and invasive disease, has been systematically reviewed; these data indicate that schedules of 3 or 4 doses all work well, and that the differences between these regimens are subtle, especially in a mature program in which coverage is high and indirect (herd) effects help enhance protection provided directly by a vaccine schedule. The recent World Health Organization policy statement on PCVs endorsed a schedule of 3 primary doses without a booster or, as a new alternative, 2 primary doses with a booster dose. While 1 schedule may be preferred in a particular setting based on local epidemiology or practical considerations, achieving high coverage with 3 doses is likely more important than the specific timing of doses. PMID:24336059

2014-01-01

35

Botulinum Toxoids.  

National Technical Information Service (NTIS)

Procedures were developed for preparing purified aluminum-phosphate-absorbed, univalent, bivalent, and pentavalent botulinum toxoids to immunize man. All preparations were well tolerated and elicited satisfactory antitoxin responses in man, whether admini...

M. A. Cardella

1964-01-01

36

Tetanus, Diphtheria, Pertussis (Tdap) Vaccine  

MedlinePLUS

Adacel® (as a combination product containing Diphtheria, Tetanus Toxoids, Acellular Pertussis Vaccine) ... Boostrix® (as a combination product containing Diphtheria, Tetanus Toxoids, Acellular Pertussis Vaccine)

37

Kinetics of Antibody Persistence following Administration of a Combination Meningococcal Serogroup C and Haemophilus influenzae Type b Conjugate Vaccine in Healthy Infants in the United Kingdom Primed with a Monovalent Meningococcal Serogroup C Vaccine ?  

PubMed Central

The kinetics of antibody persistence following the administration of a combination meningococcal serogroup C and Haemophilus influenzae type b (Hib) conjugate vaccine (Menitorix) in the second year of life in children primed with two doses of one of three monovalent meningococcal serogroup C (MCC) vaccines was investigated. The study subjects were administered either Menitorix at 12 to 15 months of age, followed by the seven-valent pneumococcal conjugate vaccine (PCV7) and the measles, mumps, and rubella vaccine 4 to 6 weeks later, or all three vaccines concomitantly at 12 to 15 months of age. Blood samples were collected before and 1, 2, 12, and 24 months after the boosting. Sera were analyzed for meningococcal serogroup C serum bactericidal antibody (SBA) and IgG as well as Hib-polyribosylribitol phosphate (PRP)-specific IgG. The antibody persistence data from this study were compared to those of a prior study of Southern et al. (Clin. Vaccine Immunol. 14:1328-1333, 2007) in which children were given three primary doses of a vaccine containing both the MCC and the Hib vaccines but were boosted only with a Hib conjugate vaccine. The magnitude of the meningococcal SBA geometric mean titer was higher for those subjects primed with the MCC vaccine conjugated to tetanus toxoid (NeisVac-C) than for those primed with one of two MCC vaccines conjugated to CRM197 (Menjugate or Meningitec) up to 1 year following boosting. Two years after boosting, the percentages of subjects with putatively protective SBA titers of ?8 for children primed with NeisVac-C, Menjugate, and Meningitec were 43%, 22%, and 23%, respectively. Additional booster doses of the MCC vaccine may be required in the future to maintain good antibody levels; however, there is no immediate need for a booster during adolescence, as mathematical modeling has shown that persisting herd immunity is likely to control disease for a number of years. PMID:19906895

Borrow, Ray; Andrews, Nick; Findlow, Helen; Waight, Pauline; Southern, Joanna; Crowley-Luke, Annette; Stapley, Lorraine; England, Anna; Findlow, Jamie; Miller, Elizabeth

2010-01-01

38

Persistence of serogroup C antibody responses following quadrivalent meningococcal conjugate vaccination in United States military personnel.  

PubMed

Serogroup C meningococcal (MenC) disease accounts for one-third of all meningococcal cases and causes meningococcal outbreaks in the U.S. Quadrivalent meningococcal vaccine conjugated to diphtheria toxoid (MenACYWD) was recommended in 2005 for adolescents and high risk groups such as military recruits. We evaluated anti-MenC antibody persistence in U.S. military personnel vaccinated with either MenACYWD or meningococcal polysaccharide vaccine (MPSV4). Twelve hundred subjects vaccinated with MenACYWD from 2006 to 2008 or MPSV4 from 2002 to 2004 were randomly selected from the Defense Medical Surveillance System. Baseline serologic responses to MenC were assessed in all subjects; 100 subjects per vaccine group were tested during one of the following six post-vaccination time-points: 5-7, 11-13, 17-19, 23-25, 29-31, or 35-37 months. Anti-MenC geometric mean titers (GMT) were measured by rabbit complement serum bactericidal assay (rSBA) and geometric mean concentrations (GMC) by enzyme-linked immunosorbent assay (ELISA). Continuous variables were compared using the Wilcoxon rank sum test and the proportion of subjects with an rSBA titer ? 8 by chi-square. Pre-vaccination rSBA GMT was <8 for the MenACWYD group. rSBA GMT increased to 703 at 5-7 months post-vaccination and decreased by 94% to 43 at 3 years post-vaccination. GMT was significantly lower in the MenACWYD group at 5-7 months post-vaccination compared to the MPSV4 group. The percentage of MenACWYD recipients achieving an rSBA titer of ? 8 decreased from 87% at 5-7 months to 54% at 3 years. There were no significant differences between vaccine groups in the proportion of subjects with a titer of ? 8 at any time-point. GMC for the MenACWYD group was 0.14 ?g/mL at baseline, 1.07 ?g/mL at 5-7 months, and 0.66 ?g/mL at 3 years, and significantly lower than the MPSV4 group at all time-points. Anti-MenC responses wane following vaccination with MenACYWD; a booster dose is needed to maintain protective levels of circulating antibody. PMID:24837781

Patel, Manisha; Romero-Steiner, Sandra; Broderick, Michael P; Thomas, Cynthia G; Plikaytis, Brian D; Schmidt, Daniel S; Johnson, Scott E; Milton, Andrea S; Carlone, George M; Clark, Thomas A; Messonnier, Nancy E; Cohn, Amanda C; Faix, Dennis J

2014-06-24

39

Protein Conjugate Polysaccharide Vaccines: Challenges in Development and Global Implementation  

PubMed Central

Pneumonia and meningitis caused by Haemophilus influenzae type b, Streptococcus pneumoniae, and Neisseria meningitidis are among the leading causes of under five mortality and morbidity. Polysaccharide vaccines to prevent these infections are available since 1980s, but these are not effective in infants and children who are the common targets; therefore, protein conjugated were developed. The aim of this article is to understand the need for peumococcal protein conjugate vaccines, the challenges related to their development and global implementation, and the impact of these vaccines on global child health. Challenges in development of new vaccines are as follows: While pneumonia is a major threat in developing countries, available vaccine 7-valent pneumococcal conjugate vaccine (PCV7) protects against only 30% of invasive disease.Serogroup B of Neisseria meningitidis causes 32% of the cases in the USA and 45–80% or more in Europe. Due to similarity of its capsular polysaccharide with the cell surface glycoprotein on fetal brain tissue, developing a vaccine against this bacterium remains a challenge. Challenges in implementation are as follows: Replacement by nonvaccine serotypes;capsule switching;time duration of the antibody protective effect following vaccination;costs of the vaccines, programme costs, lack of knowledge of the disease burden, and targeting population groups for vaccination. PMID:22654279

Nair, Manisha

2012-01-01

40

Invasive pneumococcal infection despite 7-valent conjugated vaccine  

PubMed Central

Despite good cover with 7-valent vaccination, invasive pneumococcal infections may still be misdiagnosed and may lead to lifethreatening situations or death in young children. New serotypes are emerging and, therefore, clinicians must keep a high level of suspicion in young children regardless of their vaccination status. We report three cases of invasive pneumococcal infection due to new serotypes not covered by the 7-valent conjugated vaccine, two of which led children to death. PMID:24765491

Joye, Sebastien; Gao, Anja; Kayemba-Kay’s, Simon; Cotting, Jacques; Perez, Marie-Hélène

2013-01-01

41

Hypothesis: conjugate vaccines may predispose children to autism spectrum disorders.  

PubMed

The first conjugate vaccine was approved for use in the US in 1988 to protect infants and young children against the capsular bacteria Haemophilus influenzae type b (Hib). Since its introduction in the US, this vaccine has been approved in most developed countries, including Denmark and Israel where the vaccine was added to their national vaccine programs in 1993 and 1994, respectively. There have been marked increases in the reported prevalence of autism spectrum disorders (ASDs) among children in the US beginning with birth cohorts in the late 1980s and in Denmark and Israel starting approximately 4-5 years later. Although these increases may partly reflect ascertainment biases, an exogenous trigger could explain a significant portion of the reported increases in ASDs. It is hypothesized here that the introduction of the Hib conjugate vaccine in the US in 1988 and its subsequent introduction in Denmark and Israel could explain a substantial portion of the initial increases in ASDs in those countries. The continuation of the trend toward increased rates of ASDs could be further explained by increased usage of the vaccine, a change in 1990 in the recommended age of vaccination in the US from 15 to 2 months, increased immunogenicity of the vaccine through changes in its carrier protein, and the subsequent introduction of the conjugate vaccine for Streptococcus pneumoniae. Although conjugate vaccines have been highly effective in protecting infants and young children from the significant morbidity and mortality caused by Hib and S. pneumoniae, the potential effects of conjugate vaccines on neural development merit close examination. Conjugate vaccines fundamentally change the manner in which the immune systems of infants and young children function by deviating their immune responses to the targeted carbohydrate antigens from a state of hypo-responsiveness to a robust B2 B cell mediated response. This period of hypo-responsiveness to carbohydrate antigens coincides with the intense myelination process in infants and young children, and conjugate vaccines may have disrupted evolutionary forces that favored early brain development over the need to protect infants and young children from capsular bacteria. PMID:21993250

Richmand, Brian J

2011-12-01

42

Safety and preliminary immunogenicity of Cuban pneumococcal conjugate vaccine candidate in healthy children: a randomized phase I clinical trial.  

PubMed

A new heptavalent conjugate vaccine (PCV7-TT) is under development in Cuba. PCV7-TT contains 2 ?g of serotypes 1, 5, 14, 18C, 19F, 23F and 4 ?g of 6B, each one conjugated to tetanus toxoid (TT). This vaccine was designed with the serotypes that cause most invasive pneumococcal diseases (IPD) worldwide. In the present study, we investigated the safety and explored the immunogenicity of PCV7-TT during a controlled, randomized and double blind clinical trial phase I in 4-5-year-old children. PCV7-TT was well tolerated and as safe as Synflorix used as control vaccine. Following a single-dose vaccination, all individual serotypes included in PCV7-TT induced statistically significant increase of IgG GMC and OPA GMT. These are the first clinical results of PCV7-TT in children and they pave the way toward next clinical trials in children and infants. This clinical trial was published in the Cuban Public Register of Clinical Trials with code RPCEC00000173. PMID:25068497

Dotres, Carlos P; Puga, Rinaldo; Ricardo, Yariset; Broño, Carmen R; Paredes, Beatriz; Echemendía, Vladimir; Rosell, Sandra; González, Nadezhda; García-Rivera, Dagmar; Valdés, Yury; Goldblatt, David; Vérez-Bencomo, Vicente

2014-09-15

43

Evaluation of the safety and immunogenicity in United Kingdom laboratory workers of a combined Haemophilus influenzae type b and meningococcal capsular group C conjugate vaccine  

PubMed Central

Background Although a combined Haemophilus influenzae type b (Hib)/meningococcal capsular group C (MenC) conjugate vaccine with a tetanus toxoid carrier protein (Hib/MenC-TT) is not licensed for use in those above 2 years of age due to lack of data on safety and efficacy, certain patient groups at high risk of MenC and/or Hib disease are recommended to receive it. Laboratory workers working with Hib and/or MenC cultures may be at a potentially increased risk of acquiring infectious diseases and vaccination is therefore an important safety consideration. We undertook a clinical trial to investigate the safety and immunogenicity of Hib/MenC-TT vaccine in this cohort. Methods A total of 33 subjects were recruited to the trial, all of whom were vaccinated. Serology was completed on samples taken at baseline and four weeks following vaccination to determine MenC specific IgG, MenC serum bactericidal antibody (SBA), anti-Hib polyribosylribitol phosphate (PRP) IgG and anti-tetanus toxoid IgG responses. Results At baseline, high proportions of subjects had protective antibody concentrations against MenC, Hib and tetanus due to previous vaccination and/or natural exposure. Vaccination induced?>?3, 10 and 220 fold increases in geometric mean concentrations for MenC SBA, anti-tetanus toxoid IgG and anti-Hib PRP IgG, respectively. Following vaccination, 97% of subjects had putative protective SBA titres???8, 100% had short term protective anti-Hib PRP IgG concentrations???0.15 ?g/mL and 97% had protective anti-tetanus toxoid concentrations???0.1 IU/mL. No safety concerns were reported with minor local reactions being reported by 21% of subjects. Conclusions Immunological responses determined in this trial are likely a combination of primary and secondary responses due to previous vaccination and natural exposure. Subjects were a representative cross-section of laboratory workers, enabling us to conclude that a single dose of Hib/MenC-TT was safe and immunogenic in healthy adults providing the evidence that this vaccine may be used for providing protection in an occupational setting. PMID:25071861

2014-01-01

44

Efficacy and effectiveness of extended-valency pneumococcal conjugate vaccines  

PubMed Central

The 7-valent pneumococcal protein conjugate vaccine (PCV7) has been shown to be highly efficacious against invasive pneumococcal diseases and effective against pneumonia and in reducing otitis media. The introduction of PCV7 has resulted in major changes in the epidemiology of pneumococcal diseases. However, pneumococcal vaccines induce serotype-specific immunity, and a relative increase in non-vaccine serotypes has been reported following the widespread use of PCV7, leading to a need for extended serotype coverage for protection. PCV10 and PCV13 have been licensed on the basis of noninferiority of immunogenicity compared to a licensed conjugate vaccine. In this article, we aimed to review important data regarding the efficacy and effectiveness of the extended-coverage PCVs published or reported thus far and to discuss future implications for pneumococcal vaccines in Korea. After the introduction of PCV10 and PCV13, within a short period of time, evidence of protection conferred by these vaccines against invasive and mucosal infections caused by most of the serotypes included in the vaccines is accumulating. The choice of vaccine should be based on the changes in the dynamics of pneumococcal serotype distribution and diseases in the region where the vaccines are to be used. Continuous surveillance is essential for the appropriate use of pneumococcal vaccines and evaluation of the impact of PCVs on pneumococcal diseases. PMID:24678328

Lee, Hyunju; Choi, Eun Hwa

2014-01-01

45

Quantitative and qualitative analyses of serum antibodies elicited in adults by Haemophilus influenzae type b and pneumococcus type 6A capsular polysaccharide-tetanus toxoid conjugates.  

PubMed Central

Covalent binding to immunogenic proteins increases the immunogenicity of the capsular polysaccharides of Haemophilus influenzae type b (Hib) and pneumococcus type 6A (Pn6A). Conjugates composed of Hib, Pn6A, or the cross-reacting Escherichia coli K100 covalently bound to tetanus toxoid (TT) were injected into young adult volunteers. Local reactions were common and were probably due to Arthus reactivity mediated by the preexisting antibodies reacting with the TT component of the conjugates. Fever occurred in about 10% of the volunteers after the first injection; no volunteers had fever after the second injection. Similar levels of Hib or Pn6A antibodies were elicited by either 50- or 100-micrograms doses or by concurrent injection of two different conjugates (Hib-TT and Pn6A-TT or Hib-TT and K100-TT). The Hib-TT elicited about a 180-fold increase in Hib antibodies, and the Pn6A-TT conjugate elicited about an 8-fold increase in Pn6A antibodies after one injection. Booster reactions were not elicited in adults; similar levels of antibodies in the five experimental groups suggested that the responses elicited by the conjugates were maximal. A one-way cross-reaction was noted as Pn6A conjugates elicited rises of Hib antibodies in 13 of 20 volunteers; only 4 of 59 volunteers immunized with Hib-TT had increases in Pn6A antibodies. The preimmunization Hib antibodies were composed of immunoglobulin M (IgM), IgA, and IgG. The postimmunization sera showed an increase in all three isotypes; the elevation of the IgG was the highest of the three isotypes. Conjugate-induced antibodies to both the polysaccharide and TT exerted biological activities that have been correlated with immunity. Adsorption of the Hib-TT onto aluminium hydroxide resulted in higher levels and an earlier Hib antibody response in infant rhesus. These results encourage the evaluation of Hib and Pn6A conjugates in human children and infants. PMID:3516876

Schneerson, R; Robbins, J B; Parke, J C; Bell, C; Schlesselman, J J; Sutton, A; Wang, Z; Schiffman, G; Karpas, A; Shiloach, J

1986-01-01

46

10-Valent pneumococcal non-typeable haemophilus influenzae protein D-conjugate vaccine: a review in infants and children.  

PubMed

The 10-valent pneumococcal non-typeable Haemophilus influenzae protein D-conjugate vaccine (PHiD-CV) (Synflorix™) includes ten serotype-specific polysaccharides of Streptococcus pneumoniae, eight of which are conjugated individually to a nonlipidated cell-surface lipoprotein (protein D) of non-typeable H. influenzae and two of which are conjugated to nontoxic tetanus or diphtheria toxoid carrier proteins. This article provides an overview of the well-established immunogenicity of PHiD-CV, including functional immune responses and immunologic memory, as well as immune responses in preterm infants and HIV-infected children. It also includes a brief discussion of cross-protection against vaccine-related serotypes (6A and 19A) and focuses on labelling in the EU, where PHiD-CV is approved for active immunization against invasive disease, pneumonia, and acute otitis media (AOM) caused by S. pneumoniae in infants and young children up to 5 years of age. Evidence of the protective efficacy and effectiveness of PHiD-CV against pneumococcal diseases is available from several studies, including the randomized, double-blind trials COMPAS (Clinical Otitis Media and Pneumonia Study) and FinIP (Finnish Invasive Pneumococcal disease), as well as postmarketing studies from various countries. As would be expected, protection against pneumonia or AOM is substantially lower than that against invasive pneumococcal disease, as many micro-organisms other than pneumococcal vaccine serotypes can cause pneumonia and AOM, thereby limiting the overall protection of PHiD-CV against these diseases. PHiD-CV has a safety and reactogenicity profile similar to that of other pneumococcal conjugate vaccines. PMID:25192686

Plosker, Greg L

2014-10-01

47

Economic evaluation of pneumococcal conjugate vaccination in The Gambia  

Microsoft Academic Search

BACKGROUND: Gambia is the second GAVI support-eligible country to introduce the 7-valent pneumococcal conjugate vaccine (PCV7), but a country-specific cost-effectiveness analysis of the vaccine is not available. Our objective was to assess the potential impact of PCVs of different valences in The Gambia. METHODS: We synthesized the best available epidemiological and cost data using a state-transition model to simulate the

Sun-Young Kim; Gene Lee; Sue J Goldie

2010-01-01

48

Generation of polyclonal catalytic antibodies against cocaine using transition state analogs of cocaine conjugated to diphtheria toxoid.  

PubMed

Six novel transition state analogs (TSAs) of cocaine (10-14 and 17) and one non-cocaine, p-aminophenylphosphonyl ester of cyclohexanol (19), were synthesized and characterized by 1H- and 13C-NMR and FAB-MS. (1R)-ecgonine methyl ester or cyclohexanol were subjected to phenylphosphonylation in the presence of dicyclohexyl carbodiimde (DCC) and 4-N,N-dimethyl aminopyridine (4-DMAP). TSA-IV (10), however, was synthesized from norcocaine which was protected with dibromoethane to yield 4 before acid hydrolysis, esterification and phenylphosphonylation were carried out. TSA-III (11) TSA-I (12) and (19), using various length spacer arms, were coupled with the immunogenic protein, diphtheria toxoid (DT). The TSAs coupled with DT were used to immunize mice and after appropriate boosts their sera were tested for the presence and titer of anti-TSA polyclonal antibodies using ELISA. Preliminary results show that the mice immunized with these TSAs produced high titers of polyclonal catalytic antibodies, except for (19), with the ability to hydrolyze the substrate 125I-4'-iodococaine in an in vitro assay, even in the presence of noncatalytic anti-TSA antibodies. PMID:8575031

Basmadjian, G P; Singh, S; Sastrodjojo, B; Smith, B T; Avor, K S; Chang, F; Mills, S L; Seale, T W

1995-11-01

49

Vaccination of risk groups in England using the 13 valent pneumococcal conjugate vaccine: economic analysis  

PubMed Central

Objective To estimate the cost effectiveness of vaccinating people with high risk conditions against invasive pneumococcal disease using the 13 valent pneumococcal conjugate vaccine. Design Economic evaluation using a cohort model from the perspective of healthcare providers. Setting England. Participants People aged 2 years and older at increased risk of invasive pneumococcal disease due to chronic kidney disease; splenic dysfunction; HIV infection; a compromised immune system; chronic heart, liver, or respiratory disease; or diabetes. Main outcome measures Costs, gains in life years and quality adjusted life years (QALYs), and incremental cost effectiveness ratios. Results Increasing indirect protection resulting from the vaccination programme of infants using the 13 valent pneumococcal conjugate vaccine means that the burden of disease preventable by targeting high risk groups will diminish in time. Under base case assumptions—that is, no overall impact on non bacteraemic pneumonia in high risk groups and assuming the high risk vaccination programme would be launched two to three years after the infant programme—the incremental cost effectiveness ratio was estimated to be more than £30?000 (€37?216; $48?210) per QALY gained for most risk groups. If, however, the vaccine does not offer protection against non-bacteraemic pneumococcal pneumonia or the vaccine was introduced concomitantly with the infant 13 valent pneumococcal conjugate vaccination programme then vaccinating high risk people would (more) likely be cost effective. Sensitivity analyses showed that the cost effectiveness was particularly sensitive to assumed herd benefits and vaccine efficacy estimates. Conclusion Under base case assumptions it is unlikely that a pneumococcal vaccination programme aimed at risk groups could be considered cost effective. Uncertainty could be substantially reduced by establishing the effectiveness of the 13 valent pneumococcal conjugate vaccine against non-bacteraemic pneumococcal pneumonia, particularly in at risk groups. PMID:23103369

2012-01-01

50

Diphtheria, Tetanus, and Pertussis (DTaP) Vaccine  

MedlinePLUS

Certiva® (as a combination product containing Diphtheria, Tetanus Toxoids, Acellular Pertussis Vaccine) ... Daptacel® (as a combination product containing Diphtheria, Tetanus Toxoids, Acellular Pertussis Vaccine)

51

Systemic antibody responses induced by a two-component Clostridium difficile toxoid vaccine protect against C. difficile-associated disease in hamsters.  

PubMed

Clostridium difficile infection (CDI) has been identified as the leading cause of nosocomial diarrhoea and pseudomembranous colitis associated with antibiotic therapy. Recent epidemiological changes as well as increases in the number of outbreaks of strains associated with increased virulence and higher mortality rates underscore the importance of identifying alternatives to antibiotics to manage this important disease. Animal studies have clearly demonstrated the roles that toxins A and B play in gut inflammation as well as diarrhoea; therefore it is not surprising that serum anti-toxin A and B IgG are associated with protection against recurrent CDI. In humans, strong humoral toxin-specific immune responses elicited by natural C. difficile infection is associated with recovery and lack of disease recurrence, whereas insufficient humoral responses are associated with recurrent CDI. The first generation of C. difficile vaccine that contained inactivated toxin A and B was found to be completely protective against death and diarrhoea in the hamster C. difficile challenge model. When tested in young healthy volunteers in Phase I clinical trials, this investigational vaccine was shown to be safe and immunogenic. Moreover, in a separate study this vaccine was able to prevent further relapses in three out of three patients who had previously suffered from chronic relapsing C. difficile-associated diarrhoea. Herein we examined the immunogenicity and protective activity of a next-generation Sanofi Pasteur two-component highly purified toxoid vaccine in a C. difficile hamster model. This model is widely recognized as a stringent and relevant choice for the evaluation of novel treatment strategies against C. difficile and was used in preclinical testing of the first-generation vaccine candidate. Intramuscular (i.m.) immunizations with increasing doses of this adjuvanted toxoid vaccine protected hamsters from mortality and disease symptoms in a dose-dependent manner. ELISA measurements of pre-challenge sera showed that the median anti-toxin A and anti-toxin B IgG titres in the group of surviving animals were significantly higher than the median values in the group of animals that did not survive challenge. Assessment of the neutralizing activity of these sera revealed a statistically significant difference between the levels of both toxin A and toxin B neutralizing titres in protected versus unprotected animals as the median anti-toxin A and anti-toxin B neutralizing titres from surviving animals were higher than the median values from animals that succumbed to challenge. Statistically significant correlations between the toxin-specific binding titres and toxin neutralizing titres were seen for both toxin A and toxin B responses. The role of circulating anti-toxin antibodies in immunity against disease was evaluated by passive transfer of immune sera against C. difficile toxoids to naïve hamsters. Passively immunized animals were protected against morbidity and mortality associated with C. difficile challenge. Taken together, these results indicate the ability of i.m. immunization with inactivated toxins A and B to induce robust dose-dependent anti-toxin A and anti-toxin B IgG responses, the principal role of circulating anti-toxin antibody in immunity against disease and that antibody toxin binding and neutralization titres can serve as correlates of protection in the hamster challenge model of C. difficile. PMID:23518659

Anosova, Natalie G; Brown, Anna M; Li, Lu; Liu, Nana; Cole, Leah E; Zhang, Jinrong; Mehta, Hersh; Kleanthous, Harry

2013-09-01

52

Immunogenicity and safety of a single intramuscular dose of a diphtheria-tetanus toxoid (Td) vaccine (GC1107) in Korean adults.  

PubMed

The current study aimed to evaluate immunogenicity and safety of a newly developed diphtheria-tetanus toxoid (Td) vaccine, GC1107 (Green Cross Corporation, Yongin, Korea), in comparison with placebo and active comparator (licensed Td vaccine) in healthy Korean adults. A randomized, double-blind, placebo and active comparator-controlled study was conducted. Forty subjects were randomly administered a single intramuscular dose of GC1107, active comparator or placebo in a ratio of 2:1:1. At 2 and 4 weeks after vaccination, anti-diphtheria antibody levels in the GC1107 group increased 9.2 and 9.3 times, respectively, compared to predose titers. The corresponding values were 9.3 and 8.3 times for the active comparator group. Anti-tetanus antibody levels increased 39.0 and 37.9 fold at 2 and 4 weeks, respectively, after GC1107 administration, and 12.2 and 14.7 fold after active comparator administration. No increases in tetanus or diphtheria antibody were observed for the placebo group. Adverse events in the GC1107 and active comparator groups were more frequent than for the placebo group, but there were no significant differences between the two active treatments. In conclusion, GC1107 was well tolerated and provided significant boosts of anti-tetanus and anti-diphtheria antibodies. PMID:21864613

Lee, SeungHwan; Park, Wan Beom; Shin, Kwang-Hee; Ahn, Dong Ho; Yoon, Seo Hyun; Cho, Joo-Youn; Shin, Sang-Goo; Jang, In-Jin; Yu, Kyung-Sang

2011-10-13

53

Transcutaneous immunization with cross-reacting material CRM(197) of diphtheria toxin boosts functional antibody levels in mice primed parenterally with adsorbed diphtheria toxoid vaccine.  

PubMed

Transcutaneous immunization (TCI) capitalizes on the accessibility and immunocompetence of the skin, elicits protective immunity, simplifies vaccine delivery, and may be particularly advantageous when frequent boosting is required. In this study we examined the potential of TCI to boost preexisting immune responses to diphtheria in mice. The cross-reacting material (CRM(197)) of diphtheria toxin was used as the boosting antigen and was administered alone or together with either one of two commonly used mucosal adjuvants, cholera toxin (CT) and a partially detoxified mutant of heat-labile enterotoxin of Escherichia coli (LTR72). We report that TCI with CRM(197) significantly boosted preexisting immune responses elicited after parenteral priming with aluminum hydroxide-adsorbed diphtheria toxoid (DTxd) vaccine. In the presence of LTR72 as an adjuvant, toxin-neutralizing antibody titers were significantly higher than those elicited by CRM(197) alone and were comparable to the functional antibody levels induced after parenteral booster immunization with the adsorbed DTxd vaccine. Time course study showed that high levels of toxin-neutralizing antibodies persisted for at least 14 weeks after the transcutaneous boost. In addition, TCI resulted in a vigorous antigen-specific proliferative response in all groups of mice boosted with the CRM(197) protein. These findings highlight the promising prospect of using booster administrations of CRM(197) via the transcutaneous route to establish good herd immunity against diphtheria. PMID:18227167

Stickings, Paul; Peyre, Marisa; Coombes, Laura; Muller, Sylviane; Rappuoli, Rino; Del Giudice, Giuseppe; Partidos, Charalambos D; Sesardic, Dorothea

2008-04-01

54

Effect of Currently Approved Carriers and Adjuvants on the Pre-Clinical Efficacy of a Conjugate Vaccine against Oxycodone in Mice and Rats  

PubMed Central

Vaccination against the highly abused prescription opioid oxycodone has shown pre-clinical efficacy for blocking oxycodone effects. The current study further evaluated a candidate vaccine composed of oxycodone derivatized at the C6 position (6OXY) conjugated to the native keyhole limpet hemocyanin (nKLH) carrier protein. To provide an oxycodone vaccine formulation suitable for human studies, we studied the effect of alternative carriers and adjuvants on the generation of oxycodone-specific serum antibody and B cell responses, and the effect of immunization on oxycodone distribution and oxycodone-induced antinociception in mice and rats. 6OXY conjugated to tetanus toxoid (TT) or a GMP grade KLH dimer (dKLH) was as effective as 6OXY conjugated to the nKLH decamer in mice and rats, while the 6OXY hapten conjugated to a TT-derived peptide was not effective in preventing oxycodone-induced antinociception in mice. Immunization with 6OXY-TT s.c. absorbed on alum adjuvant provided similar protection to 6OXY-TT administered i.p. with Freund’s adjuvant in rats. The toll-like receptor 4 (TLR4) agonist monophosphoryl lipid A (MPLA) adjuvant, alone or in combination with alum, offered no advantage over alum alone for generating oxycodone-specific serum antibodies or 6OXY-specific antibody secreting B cells in mice vaccinated with 6OXY-nKLH or 6OXY-TT. The immunogenicity of oxycodone vaccines may be modulated by TLR4 signaling since responses to 6OXY-nKLH in alum were decreased in TLR4-deficient mice. These data suggest that TT, nKLH and dKLH carriers provide consistent 6OXY conjugate vaccine immunogenicity across species, strains and via different routes of administration, while adjuvant formulations may need to be tailored to individual immunogens or patient populations. PMID:24797666

Pravetoni, Marco; Vervacke, Jeffrey S.; Distefano, Mark D.; Tucker, Ashli M.; Laudenbach, Megan; Pentel, Paul R.

2014-01-01

55

Impact of conjugation chemistry on the immunogenicity of S. Typhimurium conjugate vaccines.  

PubMed

Salmonella Typhimurium is major cause of invasive nontyphoidal Salmonella disease in Africa. Conjugation of S. Typhimurium O-antigen to an appropriate carrier protein constitutes a possible strategy for the development of a vaccine against this disease, for which no vaccines are currently available. The conjugation chemistry used is one of the parameters that can affect the immunogenicity of glycoconjugate vaccines. Herein different glycoconjugates were synthesized to investigate the impact of this variable on the immunogenicity of S. Typhimurium conjugate vaccines in mice, all with CRM197 as carrier protein. Random derivatization along the O-antigen chain was compared with site-directed activation of the terminal KDO sugar residue of the core oligosaccharide. In particular, two different random approaches were used, based on the oxidation of the polysaccharide, which differently impact the structure and conformation of the O-antigen chain. For the selective conjugation methods, linkers of two different lengths were compared. When tested in mice, all conjugates induced anti-O-antigen IgG antibodies with serum bactericidal activity. Similar anti-O-antigen antibody levels were elicited independent of the chemistry used and a higher degree of saccharide derivatization did not impact negatively on the anti-O-antigen IgG response. Bactericidal activity of serum antibodies induced by selective conjugates was similar independent of the length of the spacer used. Random conjugates elicited antibodies with greater bactericidal activity than selective ones, and an inverse correlation was found between degree of O-antigen modification and antibody functional activity. PMID:25192974

Stefanetti, G; Rondini, S; Lanzilao, L; Saul, A; MacLennan, C A; Micoli, F

2014-10-21

56

Effectiveness of pneumococcal conjugate vaccine and rotavirus vaccine introduction into the South African public immunisation programme.  

PubMed

Immunisation has contributed greatly to the control of vaccine-preventable diseases and therefore to improvements in health and survival, especially among young children, and remains one of the most successful and cost-effective public health interventions. This remains true for many of the newer, more expensive vaccines. Vaccines against invasive pneumococcal disease and rotavirus infection were introduced into the South African Expanded Programme on Immunization in April 2009. This article describes the rationale for and process of the introduction of these two vaccines, pneumococcal conjugate vaccine and rotavirus vaccine. It also aims to evaluate the success of and challenges related to their introduction, in terms of both achieving universal coverage and improving survival and health in South African children. PMID:24893498

Madhi, S A; Bamford, L; Ngcobo, N

2014-03-01

57

Enhancement of immunoglobulin G responses in mice against hepatitis B virus surface antigen, influenza virus hemagglutinin vaccine, and tetanus toxoid by 6-O-acylated muramyl dipeptides.  

PubMed Central

The adjuvant activity of chemically synthesized 6-O-acylated muramyl dipeptides (MDP) was tested in aqueous form. The activity was assessed by determining immunoglobulin G (IgG) titers in sera of mice immunized with hepatitis B virus surface antigen, influenza virus hemagglutinin (HA) vaccine, or tetanus toxoid with an enzyme-linked immunosorbent assay. Administration of 6-O-acyl-MDP analogs with antigens induced marked enhancement of primary and secondary IgG antibody responses and maintained high antibody levels for at least 7 weeks. Among the analogs tested, an MDP methyl ester carrying a 6-O-3-hexadecanoyl-oxytetradecanoyl group (compound 309) exhibited the most intensive adjuvant activity. Its activity was stronger than that of 6-O-2-tetradecylhexadecanoyl (B3O)-MDP used as a positive control. However, accumulation of peritoneal cells and activation of peritoneal macrophages by compound 309 was weaker than that by 6-O-B30-MDP, suggesting that 309 as an immunoadjuvant is more suitable for vaccination in terms of its stronger enhancement of antibody formation and lower induction of inflammatory response than 6-O-B30-MDP. PMID:2722242

Furuya, T.; Kumazawa, Y.; Takimoto, H.; Nagumo, T.; Watanabe, M.; Aizawa, C.; Kiso, M.; Hasegawa, A.; Nomoto, K.

1989-01-01

58

Cancer Vaccine Composed of Oligonucleotides Conjugated to Apoptotic Tumor Cells  

Cancer.gov

NCI Scientists have discovered that conjugating CpG ODNs to apoptotic tumor cells to improve vaccine activity by ensuring that the ODN remains associated with the tumor antigen so that both are internalized by professional antigen presenting cells. The strategy eliminates the need to define specific tumor-associated antigens, substituting instead the entire tumor cell (which in the absence of CpG ODN is poorly immunogenic).

59

Management of Febrile Children in the Conjugate Pneumococcal Vaccine Era  

Microsoft Academic Search

The objective of this study was to evaluate physician attitudes toward the management of young febrile children since the introduction of the conjugate heptavalent pneumococcal vaccine (PCV 7). Seven thousand five hundred pediatricians and 7,500 emergency department (ED) physicians were surveyed with regard to their management of a febrile 7-month-old child and 20-month-old child without an apparent fever focus. Specifically,

Michael E. Gabriel; Leslie Aiuto; Nina Kohn; Stephen R. Barone

2004-01-01

60

Pediatricians' Adherence to Pneumococcal Conjugate Vaccine Shortage Recommendations in 2 National Shortages  

Microsoft Academic Search

OBJECTIVES. The goals were (1) to compare pediatricians' heptavalent pneumococcal conjugate vaccine shortage experience and adherence to shortage recommenda- tions during 2 heptavalent pneumococcal conjugate vaccine shortages, (2) to assess factors associated with nonadherence to second shortage recommendations, and (3) to assess opinions about national immunization policy during vaccine shortages. METHODS. We mailed surveys to all pediatrician immunization providers in

Gerry Fairbrother; Karen Broder; Mary Allen Staat; Benjamin Schwartz; Christine Heubi; Frances J. Walker; Ardythe L. Morrow

2010-01-01

61

Results from a Randomized Clinical Trial of Coadministration of RotaTeq, a Pentavalent Rotavirus Vaccine, and NeisVac-C, a Meningococcal Serogroup C Conjugate Vaccine ? †  

PubMed Central

RotaTeq (Merck & Co. Inc./Sanofi Pasteur MSD) is a three-dose, oral pentavalent rotavirus vaccine for the immunization of infants from 6 weeks of age for the prevention of rotavirus gastroenteritis. The primary objective of the present trial was to demonstrate that RotaTeq can be coadministered with meningococcal serogroup C conjugate vaccine (MenCC; NeisVac-C; Baxter Healthcare) to healthy infants without impairing the protective immune responses to MenCC. This was an open-label, randomized, comparative study conducted in Finland. The study was designed to assess concomitant versus sequential administration of RotaTeq and MenCC on the immune response to both vaccines. Healthy infants (n = 247), aged 6 to 7 weeks, were recruited. Coadministration of MenCC with RotaTeq was noninferior to sequential administration for the seroprotection rate against meningococcal serogroup C (the proportion of infants with a serum bactericidal antibody titer using baby rabbit complement of ?8 was 100% in both groups). The other responses to MenCC (titer of ?1:128, ?4-fold increase in titer, and geometric mean titers [GMTs]) and the responses to RotaTeq (IgA and SNA response to G1 to G4 and P1A[8], GMTs, and ?3-fold increase in titer) were comparable between groups, including a ?3-fold IgA increase in >96% of the infants in both groups. Concomitant administration of the first doses of MenCC, diphtheria and tetanus toxoids and acellular pertussis vaccine, inactivated poliovirus vaccine, and Haemophilus influenzae type b conjugate vaccine (DTaP-IPV-Hib), and RotaTeq was associated with a higher rate of vomiting and diarrhea than concomitant administration of MenCC and DTaP-IPV-Hib, but that was not observed after the second concomitant administration. The convenience of concomitant administration of RotaTeq and MenCC may, however, outweigh the additive effect of mostly mild adverse events reported after the individual administration of each vaccine. These results support the coadministration of RotaTeq and MenCC. PMID:21389149

Vesikari, Timo; Karvonen, Aino; Borrow, Ray; Kitchin, Nick; Baudin, Martine; Thomas, Stephane; Fiquet, Anne

2011-01-01

62

Preparation and testing of a Vi conjugate vaccine using pneumococcal surface protein A (PspA) from Streptococcus pneumoniae as the carrier protein.  

PubMed

In the current study pneumococcal surface protein A (PspA) was conjugated to Vi capsular polysaccharide from Salmonella Typhi to make available a vaccine against typhoid fever that has the potential to also provide broad protection from Streptococcus pneumoniae. High yielding production processes were developed for the purification of PspAs from families 1 and 2. The purified PspAs were conjugated to Vi with high recovery of both Vi and PspA. The processes developed especially for PspA family 2 could readily be adapted for large scale production under cGMP conditions. Previously we have shown that conjugation of diphtheria toxoid (DT) to Vi polysaccharide improves the immune response to Vi but can also enhance the response to DT. In this study it was shown that conjugation of PspA to Vi enhanced the anti-PspA response and that PspA was a suitable carrier protein as demonstrated by the characteristics of a T-cell dependent response to the Vi. We propose that a bivalent vaccine consisting of PspA from families 1 and 2 bound to Vi polysaccharide would protect against typhoid fever and has the potential to also protect against pneumococcal disease and should be considered for use in developing countries. PMID:25171842

Kothari, Neha; Genschmer, Kristopher R; Kothari, Sudeep; Kim, Jeong Ah; Briles, David E; Rhee, Dong Kwon; Carbis, Rodney

2014-09-29

63

Production of tag-free recombinant fusion protein encompassing promiscuous T cell epitope of tetanus toxoid and dog zona pellucida glycoprotein-3 for contraceptive vaccine development.  

PubMed

Affinity tags can interfere in various physicochemical properties and immunogenicity of the recombinant proteins. In the present study, tag-free recombinant fusion protein encompassing promiscuous T cell epitope of tetanus toxoid [TT; amino acid (aa) residues 830-844] followed by dilysine linker and dog zona pellucida glycoprotein-3 (ZP3; aa residues 23-348) (TT-KK-ZP3) was expressed in Escherichia coli. The recombinant protein, expressed as inclusion bodies (IBs), was purified by isolation of IBs, processed to remove host cell proteins, followed by solubilization and refolding. A specific 39 kDa protein including ZP3 was identified by SDS-PAGE. CD spectra showed the presence of ?-helices and ?-sheets, and fluorescent spectroscopy revealed emission maxima of 265 A.U. at 339 nm for refolded protein and showed red shift in the presence of 6 M guanidine hydrochloride. Immunization of inbred FvB/J female mice with purified recombinant TT-KK-ZP3 (25 ?g/animal) led to generation of high antibody titers against the recombinant protein. The antibodies reacted specifically with ZP matrix surrounding mouse oocytes. Immunized mice showed significant reduction in fertility as compared to the control group. The studies described herein provide a simple method to produce and purify tag-free recombinant protein for the development of a contraceptive vaccine. PMID:23242635

Gupta, Neha; Shrestha, Abhinav; Panda, Amulya Kumar; Gupta, Satish Kumar

2013-07-01

64

Impact of State Vaccine Financing Policy on Uptake of Heptavalent Pneumococcal Conjugate Vaccine  

PubMed Central

Objective. We examined heptavalent pneumococcal conjugate vaccine (PCV7) uptake among children aged 19 to 35 months in the United States and determined how uptake rates differed by state vaccine financing policy. Methods. We analyzed data from the 2001–2003 National Immunization Survey. States that changed their vaccine financing policy between 2001 and 2003 (n=17) were excluded from analysis. Logistic regression was performed to identify the association between state vaccine financing policy and receipt of 3 or more doses of PCV7 after control for demographic characteristics. Results. The proportion of children receiving 3 or more doses increased from 6.7% in 2001 to 69.0% in 2003. After controlling for demographic characteristics, children residing in states that provided all vaccines except PCV7 to all children had lower odds of receiving 3 or more doses compared to children residing in states that provided PCV7 only to children eligible for the Vaccines for Children program (odds ratio=0.58; 95% confidence interval=0.51, 0.66). Conclusion. It is essential that we continue to monitor the effect that state vaccine financing policy has on the delivery of PCV7 and future vaccines, which are likely to be increasingly expensive. PMID:16735626

Stokley, Shannon; Shaw, Kate M.; Barker, Lawrence; Santoli, Jeanne M.; Shefer, Abigail

2006-01-01

65

Evaluation of a diphtheria-tetanus-acellular pertussis-inactivated poliovirus-Haemophilus influenzae type b vaccine given concurrently with meningococcal group C conjugate vaccine at 2, 3 and 4 months of age  

PubMed Central

Background and objective In view of the possible introduction of diphtheria–tetanus–acellular pertussis–inactivated poliovirus–Haemophilus influenzae type b (DTaP?IPV?Hib, eg Pediacel) vaccine in the UK, a study of the immunogenicity of Pediacel when given with one of two different meningococcal group C conjugate (MCC) vaccines at 2, 3 and 4?months of age was conducted. Methods Randomised controlled study in 241 infants. Results Post vaccination, the proportion of infants with anti?polyribosylribitol phosphate (PRP) levels ?0.15??g/ml was 93.2% (95% confidence interval (CI) 86.6 to 96.7) in the Pediacel group compared with 100% (95% CI 96.4 to 100) in the diphtheria–tetanus–whole?cell pertussis–Haemophilus influenzae type b (DTwP?Hib) group. The anti?PRP response was lower in infants receiving either Pediacel or DTwP?Hib when these vaccines were given concomitantly with meningococcal group C conjugate with diphtheria?derived protein CRM197 as conjugate protein (MCC?CRM) compared with meningococcal group C conjugate with tetanus toxoid as conjugate protein (MCC?TT). For group C meningococcus, the proportion of infants with serum bactericidal antibody (SBA) titre ?1:8 in the Pediacel group was 99.0% compared with 100% in the DTwP?Hib group. The MCC SBA geometric mean titre (GMT) was lower in those receiving Pediacel with MCC?TT than in those receiving DTwP?Hib with MCC?TT, although all titres were well above the protective threshold. The MCC SBA GMT was similar in those receiving Pediacel and DTwP?Hib and MCC?CRM. Responses to all other vaccine components were equivalent in the two groups. Conclusions Pediacel is immunogenic when given at 2, 3 and 4?months of age. Coadministration of MCC vaccine can influence the Hib response, and the MCC response to a tetanus conjugate can be influenced by the nature of the coadministered DTP?Hib vaccine. PMID:16670121

Kitchin, N R E; Southern, J; Morris, R; Hemme, F; Thomas, S; Watson, M W; Cartwright, K; Miller, E

2007-01-01

66

Dosing schedules for pneumococcal conjugate vaccine: considerations for policy makers.  

PubMed

Since second generation pneumococcal conjugate vaccines (PCVs) targeting 10 and 13 serotypes became available in 2010, the number of national policy makers considering these vaccines has steadily increased. An important consideration for a national immunization program is the timing and number of doses-the schedule-that will best prevent disease in the population. Data on disease epidemiology and the efficacy or effectiveness of PCV schedules are typically considered when choosing a schedule. Practical concerns, such as the existing vaccine schedule, and vaccine program performance are also important. In low-income countries, pneumococcal disease and deaths typically peak well before the end of the first year of life, making a schedule that provides PCV doses early in life (eg, a 6-, 10- and 14-week schedule) potentially the best option. In other settings, a schedule including a booster dose may address disease that peaks in the second year of life or may be seen to enhance a schedule already in place. A large and growing body of evidence from immunogenicity studies, as well as clinical trials and observational studies of carriage, pneumonia and invasive disease, has been systematically reviewed; these data indicate that schedules of 3 or 4 doses all work well, and that the differences between these regimens are subtle, especially in a mature program in which coverage is high and indirect (herd) effects help enhance protection provided directly by a vaccine schedule. The recent World Health Organization policy statement on PCVs endorsed a schedule of 3 primary doses without a booster or, as a new alternative, 2 primary doses with a booster dose. While 1 schedule may be preferred in a particular setting based on local epidemiology or practical considerations, achieving high coverage with 3 doses is likely more important than the specific timing of doses. PMID:24336059

Whitney, Cynthia G; Goldblatt, David; O'Brien, Katherine L

2014-01-01

67

Do pneumococcal conjugate vaccines provide any cross-protection against serotype 19A?  

Microsoft Academic Search

BACKGROUND: Introduction of the 7-valent pneumococcal conjugate vaccine (7vCRM) in several countries has led to a rapid, significant drop in vaccine-type invasive pneumococcal disease (IPD) in immunized children. In the United States and some other countries with high antibiotic use, a subsequent rise in serotype 19A IPD has been taken to indicate that the 19F conjugate in the vaccine provides

William P Hausdorff; Bernard Hoet; Lode Schuerman

2010-01-01

68

Immunization with Haemophilus influenzae (Hib) Conjugate Vaccine following Discharge from Hospital  

Microsoft Academic Search

Background: This study was undertaken to ascertain Haemophilus influenzae type b (Hib) conjugate vaccination status following discharge from hospital and to determine the time taken to vaccinate with Hib conjugate vaccine following hospital discharge of unvaccinated children. Materials and Methods: Population-based cross-sectional survey involving children aged 3–59 months admitted to a hospital with laboratory confirmed invasive H. influenzae disease. Results:

B. Olowokure; N. J. Spencer; J. I. Hawker; I. Blair

2003-01-01

69

Overview of the development and current use of CRM(197) conjugate vaccines for pediatric use.  

PubMed

Glycoconjugate vaccines have been proven safe and effective against various diseases in children. Although these vaccines have a history of effectiveness, there are still many unanswered questions to be addressed, including conjugate interference when multiple vaccines are administered at one time, expansion of serotype coverage, effectiveness in special populations, and issues relating to conjugate vaccine use in the developing world. This paper focuses on the use of CRM(197) as a carrier protein, contrasting it to other carrier proteins used in single-antigen pediatric vaccines as well as identifying areas for future study. PMID:20452430

Shinefield, Henry R

2010-06-17

70

Haemophilus influenzae type b conjugate vaccine trial in Oxford: implications for the United Kingdom  

Microsoft Academic Search

The safety and immunogenicity of a Haemophilus influenzae type b conjugate vaccine was investigated in 103 infants immunised at 3, 5, and 9 months of age; the infants also received diphtheria, pertussis, and tetanus and polio vaccines. Side effects were compared with 99 matched infants receiving diphtheria, pertussis, and tetanus and polio vaccines only. No serious side effects were observed

G Tudor-Williams; J Frankland; D Isaacs; R T Mayon-White; J A MacFarlane; D G Rees; E R Moxon

1989-01-01

71

Immune Response to Meningococcal Serogroup C Conjugate Vaccine in Asplenic Individuals  

Microsoft Academic Search

Asplenic individuals are known to be at increased risk of infection with encapsulated bacteria. Recent United Kingdom recommendations stated that this at-risk group should receive one dose of the meningococcal serogroup C conjugate (MCC) vaccine. However, the immune response of asplenic individuals to MCC vaccine is unknown. The immune response of asplenics (n 130) to immunization with the MCC vaccine

Paul Balmer; Michelle Falconer; Paula McDonald; Nick Andrews; Emily Fuller; Christine Riley; Edward Kaczmarski; Raymond Borrow

2004-01-01

72

Impact of the introduction of pneumococcal conjugate vaccine on immunization coverage among infants  

Microsoft Academic Search

BACKGROUND: The introduction of pneumococcal conjugate vaccine (PCV) to the U.S. recommended childhood immunization schedule in the year 2000 added three injections to the number of vaccinations a child is expected to receive during the first year of life. Surveys have suggested that the addition of PCV has led some immunization providers to move other routine childhood vaccinations to later

Nancy D Lin; Ken Kleinman; K Arnold Chan; Xian-Jie Yu; Eric K France; Stanley Xu; Feifei Wei; John Mullooly; Jeanne Santoli; Tracy A Lieu

2005-01-01

73

Efficacy, safety and immunogenicity of heptavalent pneumococcal conjugate vaccine in children  

Microsoft Academic Search

Objective: To determine the effica- cy, safety, and immunogenicity of the heptavalent CRM197 pneumococcal conjugate vaccine (PCV) against inva- sive disease caused by vaccine serotypes and to determine the effec- tiveness of this vaccine against clinical episodes of otitis media. Methods: The Wyeth Lederle heptavalent CRM197 PCV was given to infants at 2, 4, 6 and 12 to 15 months

STEVEN BLACK; HENRY SHINEFIELD; BRUCE FIREMAN; EDWIN LEWIS; PAULA RAY; JOHN R. HANSEN; LAURA ELVIN; KATHY M. ENSOR; JILL HACKELL; GEORGE SIBER; FRANK MALINOSKI; DACE MADORE; IH CHANG; ROBERT KOHBERGER; WENDY WATSON; ROBERT AUSTRIAN; KATHY EDWARDS

2000-01-01

74

Cost Effectiveness of Pneumococcal Conjugate Vaccination against Acute Otitis Media in Children: A Review  

Microsoft Academic Search

While pneumococcal conjugate vaccines have shown to be highly effective against invasive pneumococcal disease, their potential effectiveness against acute otitis media (AOM) might become a major economic driver for implementing these vaccines in national immunization programmes. However, the relationship between the costs and benefits of available vaccines remains a controversial topic. Our objective is to systematically review the literature on

Chantal W. B. Boonacker; Pieter H. Broos; Elisabeth A. M. Sanders; Anne G. M. Schilder; Maroeska M. Rovers

2011-01-01

75

The Vi Conjugate Typhoid Vaccine Is Safe, Elicits Protective Levels of IgG Anti-Vi, and Is Compatible with Routine Infant Vaccines ? †  

PubMed Central

Typhoid fever remains a serious problem in developing countries. Current vaccines are licensed for individuals who are 5 years old or older. A conjugate of the capsular polysaccharide (CP) of Salmonella enterica serovar Typhi (Vi) bound to recombinant exoprotein A of Pseudomonas aeruginosa (Vi-rEPA) enhanced Vi immunogenicity and protected 2- to 5-year-olds in Vietnam. In this study, Vi-rEPA was evaluated for use in infants. A total of 301 full-term Vietnamese infants received Expanded Program on Immunization (EPI) vaccines alone or with Vi-rEPA or Haemophilus influenzae type b-tetanus toxoid conjugate (Hib-TT) at 2, 4, and 6 months and Vi-rEPA or Hib-TT alone at 12 months. Infants were visited 6, 24, and 48 h after each injection to monitor adverse reactions. Maternal, cord, and infant sera were assayed for IgG anti-Vi and for IgG antibodies to Hib CP and the diphtheria, tetanus, and pertussis toxins at 7, 12, and 13 months. No vaccine-related serious adverse reactions occurred. In the Vi-rEPA group, the IgG anti-Vi geometric mean (GM) increased from the cord level of 0.66 to 17.4 enzyme-linked immunosorbent assay units (EU) at 7 months, declined to 4.76 EU at 12 months, and increased to 50.1 EU 1 month after the 4th dose (95% of infants had levels of ?3.5 EU, the estimated protective level). Controls had no increase of the IgG anti-Vi GM. Infants with cord anti-Vi levels of <3.5 EU responded with significantly higher IgG anti-Vi levels than those with levels of ?3.5 EU. Anti-diphtheria, -tetanus, and -pertussis toxin levels were similar in all groups. Vi-rEPA was safe, induced protective anti-Vi levels, and was compatible with EPI vaccines, and it can be used in infants. High cord IgG anti-Vi levels partially suppressed infant responses to Vi-rEPA. PMID:21411598

Thiem, Vu Dinh; Lin, Feng-Ying C.; Canh, Do Gia; Son, Nguyen Hong; Anh, Dang Duc; Mao, Nguyen Duc; Chu, Chiayung; Hunt, Steven W.; Robbins, John B.; Schneerson, Rachel; Szu, Shousun C.

2011-01-01

76

Otitis media in children vaccinated during consecutive 7-valent or 10-valent pneumococcal conjugate vaccination schedules  

PubMed Central

Background In 2001 when 7-valent pneumococcal conjugate vaccine (PCV7) was introduced, almost all (90%) young Australian Indigenous children living in remote communities had some form of otitis media (OM), including 24% with tympanic membrane perforation (TMP). In late 2009, the Northern Territory childhood vaccination schedule replaced PCV7 with 10-valent pneumococcal Haemophilus influenzae protein D conjugate vaccine (PHiD-CV10). Methods We conducted regular surveillance of all forms of OM in children in remote Indigenous communities between September 2008 and December 2012. This analysis compares children less than 36 months of age who received a primary course of at least two doses of PCV7 or PHiD-CV10, and not more than one dose of another pneumococcal vaccine. Results Mean ages of 444 PCV7- and 451 PHiD-CV10-vaccinated children were 20 and 18 months, respectively. Bilaterally normal middle ears were detected in 7% and 9% respectively. OM with effusion was diagnosed in 41% and 51% (Risk Difference 10% [95% Confidence Interval 3 to 17] p?=?0.002), any suppurative OM (acute OM or any TMP) in 51% versus 39% (RD ?12% [95% CI ?19 to ?5] p?=?0.0004], and TMP in 17% versus 14% (RD ?3% [95% CI ?8 to 2] p?=?0.2), respectively. Multivariate analyses described a similar independent negative association between suppurative OM and PHiD-CV10 compared to PCV7 (Odds Ratio?=?0.6 [95% CI 0.4 to 0.8] p?=?0.001). Additional children in the household were a risk factor for OM (OR?=?2.4 [95% CI 2 to 4] p?=?0.001 for the third additional child), and older age and male gender were associated with less disease. Other measured risk factors were non-significant. Similar clinical results were found for children who had received non-mixed PCV schedules. Conclusions Otitis media remains a significant health and social issue for Australian Indigenous children despite PCV vaccination. Around 90% of young children have some form of OM. Children vaccinated in with PHiD-CV10 had less suppurative OM than children vaccinated with PCV7. Ongoing surveillance during the PCV13 era, and trials of early intervention including earlier and mixed vaccine schedules are warranted. PMID:25109288

2014-01-01

77

Clinical experience of a tricomponent acellular pertussis vaccine combined with diphtheria and tetanus toxoids for primary vaccination in 22,505 infants  

Microsoft Academic Search

OBJECTIVES: To assess the safety and tolerability of 12 lots of SmithKline Beecham Biologicals' diphtheria-tetanus-tricomponent acellular pertussis vaccine (DTaP) in a large cohort of 22,000 vaccinees, with detailed analyses of reactivity, immunogenicity, and immune response to pertussis toxin in subsets. METHODS: In a prospective, double-blind, multicenter trial in Germany, 22,505 healthy infants received three vaccinations of DTaP at age 3,

Heinz J. Schmitt; Anne Schuind; Markus Knuf; Karin Beutel; Hermann Schulte-Wissermann; Manfred Gahr; Rainer Schult; Jens Folkens; Wolfgang Rauh; Hugues Bogaerts; Hans L. Bork; Ralf Clemens

1996-01-01

78

Benefits and costs of immunization of children with pneumococcal conjugate vaccine in Canada  

Microsoft Academic Search

To estimate cost-effectiveness of routine and catch-up vaccination of Canadian children with seven-valent pneumococcal conjugate vaccine, a simulation model was constructed. In base scenario (vaccination coverage: 80%, and vaccine price: $58 per dose), pneumococcal disease incidence reduction would be superior to 60% for invasive infections, and to 30% for non-invasive infections, but the number of deaths prevented would be small.

Philippe De Wals; Geneviève Petit; Lonny James Erickson; Maryse Guay; Theresa Tam; Barbara Law; Alicia Framarin

2003-01-01

79

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

PubMed Central

Background: Antipneumococcal capsular polysaccharide antibody concentrations are used as predictors of vaccine efficacy against vaccine serotype (ST) pneumococcal disease among infants. While pneumococcal conjugate vaccines (PCV) are recommended globally, factors associated with optimal PCV immune response are not well described. We aimed to systematically assess local setting factors, beyond dosing schedule, which may affect PCV antibody levels. Methods: We conducted a literature review of PCV immunogenicity, abstracting data from published reports, unpublished sources, and conference abstracts from 1994 to 2010 (and ad hoc 2011 reports). Studies included in this analysis evaluated ? 2 primary doses of PCV before 6 months of age in non–high-risk populations, used 7-valent or higher PCV products (excluding Aventis-Pasteur and Merck products) and provided information on geometric mean concentration (GMC) for STs 1, 5, 6B, 14, 19F or 23F. Using random effects meta-regression, we assessed the impact of geographic region, coadministered vaccines and PCV product on postprimary GMC, adjusting for dosing schedule and ELISA laboratory method. Results: Of 12,980 citations reviewed, we identified 103 vaccine study arms for this analysis. Children in studies from Asia, Africa and Latin America had significantly higher GMC responses compared with those in studies from Europe and North America. Coadministration with acellular pertussis DTP compared with whole-cell DTP had no effect on PCV immunogenicity except for ST14, where GMCs were higher when coadministered with acellular pertussis DTP. Vaccine product, number of PCV doses, dosing interval, age at first dose and ELISA laboratory method also affected the GMC. Conclusions: PCV immunogenicity is associated with geographic region and vaccine product; however, the associations and magnitude varied by ST. Consideration of these factors is essential when comparing PCV immunogenicity results between groups and should be included in the evidence base when selecting optimal PCV vaccine schedules in specific settings. PMID:24336055

2014-01-01

80

Complex cytokine responses to hepatitis B surface antigen and tetanus toxoid in responders, nonresponders and subjects naive to  

E-print Network

Complex cytokine responses to hepatitis B surface antigen and tetanus toxoid in responders of cytokine secretion in response to HBsAg and tetanus toxoid (TT) by peripheral blood mononuclear cells (PBMC Elsevier Science Ltd. All rights reserved. Keywords: Hepatitis B vaccine; Tetanus toxoid; Cytokines 1

Alper, Chester A.

81

Immunity against Neisseria meningitidis Serogroup C in the Dutch Population before and after Introduction of the Meningococcal C Conjugate Vaccine  

PubMed Central

Background In 2002 a Meningococcal serogroup C (MenC) conjugate vaccine, with tetanus toxoid as carrier protein, was introduced in the Netherlands as a single-dose at 14 months of age. A catch-up campaign was performed targeting all individuals aged 14 months to 18 years. We determined the MenC-specific immunity before and after introduction of the MenC conjugate (MenCC) vaccine. Methods and Findings Two cross-sectional population-based serum banks, collected in 1995/1996 (n?=?8539) and in 2006/2007 (n?=?6386), were used for this study. The main outcome measurements were the levels of MenC polysaccharide(PS)-specific IgG and serum bactericidal antibodies (SBA) after routine immunization, 4–5 years after catch-up immunization or by natural immunity. There was an increasing persistence of PS-specific IgG and SBA with age in the catch-up immunized cohorts 4–5 years after their MenCC immunization (MenC PS-specific IgG, 0.25 µg/ml (95%CI: 0.19–0.31 µg/ml) at age 6 years, gradually increasing to 2.34 µg/ml,(95%CI: 1.70–3.32 µg/ml) at age 21–22 years). A comparable pattern was found for antibodies against the carrier protein in children immunized above 9 years of age. In case of vaccination before the age of 5 years, PS-specific IgG was rapidly lost. For all age-cohorts together, SBA seroprevalence (?8) increased from 19.7% to 43.0% in the pre- and post-MenC introduction eras, respectively. In non-immunized adults the SBA seroprevalence was not significantly different between the pre- and post-MenC introduction periods, whereas PS-specific IgG was significantly lower in the post-MenC vaccination (GMT, age ?25 years, 0.10 µg/ml) era compared to the pre-vaccination (GMT, age ?25 years, 0.43 µg/ml) era. Conclusion MenCC vaccination administered above 5 years of age induced high IgG levels compared to natural exposure, increasing with age. In children below 14 months of age and non-immunized cohorts lower IgG levels were observed compared to the pre-vaccination era, whereas functional levels remained similar in adults. Whether the lower IgG poses individuals at increased risk for MenC disease should be carefully monitored. Large-scale introduction of a MenCC vaccine has led to improved protection in adolescents, but in infants a single-dose schedule may not provide sufficient protection on the long-term and therefore a booster-dose early in adolescence should be considered. PMID:20730091

de Voer, Richarda M.; Mollema, Liesbeth; Schepp, Rutger M.; de Greeff, Sabine C.; van Gageldonk, Pieter G. M.; de Melker, Hester E.; Sanders, Elisabeth A. M.; Berbers, Guy A. M.; van der Klis, Fiona R. M.

2010-01-01

82

Maleimide conjugation markedly enhances the immunogenicity of both human and murine idiotype-KLH vaccines  

PubMed Central

The collection of epitopes present within the variable regions of the tumor-specific clonal immunoglobulin expressed by B cell lymphomas (idiotype, Id) can serve as a target for active immunotherapy. Traditionally, tumor-derived Id protein is chemically-conjugated to the immunogenic foreign carrier protein keyhole limpet hemocyanin (KLH) using glutaraldehyde to serve as a therapeutic vaccine. While this approach offered promising results for some patients treated in early clinical trials, glutaraldehyde Id-KLH vaccines have failed to induce immune and clinical responses in many vaccinated subjects. We recently described an alternative conjugation method employing maleimide-sulfhydryl chemistry that significantly increased the therapeutic efficacy of Id-KLH vaccines in three different murine B cell lymphoma models, with protection mediated by either CD8+ T cells or antibodies. We now define in detail the methods and parameters critical for enhancing the in vivo immunogenicity of human as well as murine Id-KLH conjugate vaccines. Optimal conditions for Id sulfhydryl pre-reduction were determined, and maleimide Id-KLH conjugates maintained stability and potency even after prolonged storage. Field flow fractionation analysis of Id-KLH particle size revealed that maleimide conjugates were far more uniform in size than glutaraldehyde conjugates. Under increasingly stringent conditions, maleimide Id-KLH vaccines maintained superior efficacy over glutaraldehyde Id-KLH in treating established, disseminated murine lymphoma. More importantly, human maleimide Id-KLH conjugates were consistently superior to glutaraldehyde Id-KLH conjugates in inducing Id-specific antibody and T cell responses. The described methods should be easily adaptable to the production of clinical grade vaccines for human trials in B cell malignancies. PMID:19046770

Kafi, Kamran; Betting, David J.; Yamada, Reiko E.; Bacica, Michael; Steward, Kristopher K.; Timmerman, John M.

2009-01-01

83

Randomized clinical trial to evaluate the immunogenicity of quadrivalent meningococcal conjugate and polysaccharide vaccines in adults in the United kingdom.  

PubMed

Meningococcal conjugate vaccines are today successfully deployed in universal programs for children and adolescents in different geographic regions to control meningitis and septicemia. However, in adults, the advantages of these conjugates over the older polysaccharide vaccines are less clear. In this randomized clinical trial, we demonstrated that both conjugate and polysaccharide quadrivalent meningococcal vaccines elicit protective antibody responses in adults aged 18 to 70. (This study has been registered at www.clinicaltrials.gov under registration no. NCT00901940.). PMID:24964805

Ramasamy, Maheshi N; Clutterbuck, Elizabeth A; Haworth, Kathryn; Bowman, Jaclyn; Omar, Omar; Thompson, Amber J; Blanchard-Rohner, Geraldine; Yu, Ly-Mee; Snape, Matthew D; Pollard, Andrew J

2014-08-01

84

Immunogenicity and Efficacy against Lethal Aerosol Staphylococcal Enterotoxin B Challenge in Monkeys by Intramuscular and Respiratory Delivery of Proteosome-Toxoid Vaccines  

Microsoft Academic Search

StaphylococcalenterotoxinB(SEB),aprimarycauseoffoodpoisoning,isalsoasuperantigenthatcancause toxic shock after traumatic or surgical staphylococcal would infections or viral influenza-associated staphy- lococcal superinfections or when aerosolized for use as a potential biologic warfare threat agent. Intranasal or intramuscular (i.m.) immunization with formalinized SEB toxoid formulated with meningococcal outer mem- brane protein proteosomes has previously been shown to be immunogenic and protective against lethal respiratory or parenteral SEB

GEORGE H. LOWELL; CURTIS COLLETON; DENZIL FROST; ROBERT W. KAMINSKI; MICHAEL HUGHES; JENNIFER HATCH; CHARLES HOOPER; JAMES ESTEP; LOUISE PITT; MICHAEL TOPPER; ROBERT E. HUNT; WILLIAM BAKER; ANDWALLACE B. BAZE

1996-01-01

85

Induction of potential protective immunity against enterotoxemia in calves by single or multiple recombinant Clostridium perfringens toxoids.  

PubMed

Cattle enterotoxemia caused by Clostridium perfringens toxins is a noncontagious, sporadic, and fatal disease characterized by sudden death. Strategies for controlling and preventing cattle enterotoxemia are based on systematic vaccination of herds with toxoids. Because the process of producing conventional clostridial vaccines is dangerous, expensive, and time-consuming, the prospect of recombinant toxoid vaccines against diseases caused by C. perfringens toxins is promising. In this study, nontoxic recombinant toxoids derived from ?-, ?- and ?-toxins of C. perfringens, namely, rCPA247-370 , rCPB and rEtxHP, respectively, were expressed in Escherichia coli. High levels of specific IgG antibodies and neutralizing antibodies against the toxins were detected in sera from calves vaccinated with either a single recombinant toxoid or a mixed cocktail of all three recombinant toxoids, indicating the potential of these recombinant toxoids to provide calves with protective immunity against enterotoxemia caused by C. perfringens. PMID:25197030

Jiang, Zhigang; De, Yanyan; Chang, Jitao; Wang, Fang; Yu, Li

2014-11-01

86

Phase 1 and phase 2 studies of Salmonella enterica serovar paratyphi A O-specific polysaccharide-tetanus toxoid conjugates in adults, teenagers, and 2- to 4-year-old children in Vietnam.  

PubMed

Salmonella enterica serovar Paratyphi A O-specific polysaccharide (O-SP) was activated with 1-cyano-4-dimethylaminopyridinium tetrafluoroborate (CDAP) and bound to tetanus toxoid (TT) with adipic acid dihydrazide as a linker (SPA-TT(1)) or directly (SPA-TT(2)). In mice, these two conjugates elicited high levels of immunoglobulin G (IgG) anti-lipopolysaccharide (LPS) in serum with bactericidal activity (E. Konadu, J. Shiloach, D. A. Bryla, J. B. Robbins, and S. C. Szu, Infect. Immun. 64:2709-2715, 1996). The safety and immunogenicity of the two conjugates were then evaluated sequentially in Vietnamese adults, teenagers, and 2- to 4-year-old children. None of the vaccinees experienced significant side effects, and all had preexisting LPS antibodies. At 4 weeks after injection, there were significant increases of the geometric mean IgG and IgM anti-LPS levels in the adults and teenagers: both conjugates elicited a greater than fourfold rise in the IgG anti-LPS level in serum in >/=80% of the volunteers. SPA-TT(2) elicited slightly higher, though not statistically significantly, levels of IgG anti-LPS than did SPA-TT(1) in these age groups. Accordingly, only SPA-TT(2) was evaluated in the 2- to 4-year-old children. On a random basis, one or two injections were administered 6 weeks apart to the children. No significant side effects were observed, and the levels of preexisting anti-LPS in serum were similar in children of all ages. A significant rise in the IgG anti-LPS titer was elicited by the first injection (P = 0.0001); a second injection did not elicit a booster response. Representative sera from all groups had bactericidal activity that could be adsorbed by S. enterica serovar Paratyphi A LPS. PMID:10678970

Konadu, E Y; Lin, F Y; Hó, V A; Thuy, N T; Van Bay, P; Thanh, T C; Khiem, H B; Trach, D D; Karpas, A B; Li, J; Bryla, D A; Robbins, J B; Szu, S C

2000-03-01

87

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

PubMed

The induction of persistent protective levels of pathogen-specific antibody is an important goal of immunization against childhood infections. However, antibody persistence is poor after immunization in infancy versus later in life. Serogroup C meningococci (MenC) are an important cause of bacteraemia and meningitis in children. The use of protein-polysaccharide conjugate vaccines against MenC has been associated with a significant decline in the incidence of invasive disease. However, vaccine effectiveness is negligible by more than 1 year after a three-dose priming series in infancy and corresponds to a rapid decline in antibody following an initial immune response. The cellular mechanisms underlying the generation of persistent antibody in this age group are unclear. An essential prelude to larger studies of peripheral blood B cells is an understanding of B-cell kinetics following immunization. We measured MenC- and diphtheria-specific plasma and memory B-cell kinetics in infants receiving a CRM(197) (cross-reactive material; mutant diphtheria toxoid)-conjugated MenC vaccine at 2, 3 and 4 months of age. Plasma cell responses were more delayed after the first dose when compared with the rapid appearance of plasma cells after the third dose. Memory B cells were detectable at all time-points following the third dose as opposed to the low frequency seen following a first dose. This study provides data on B-cell kinetics following a primary schedule of immunization in young infants upon which to base further studies of the underlying cellular mechanism of humoral immunity. PMID:19175802

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

2009-05-01

88

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

PubMed Central

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

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

89

Safety and immunogenicity of 13-valent pneumococcal conjugate vaccine in infants: a meta-analysis.  

PubMed

Pneumococcal infections are a major cause of morbidity and mortality worldwide. Pneumococcal conjugate vaccines represent major progress in the prevention of invasive pneumococcal disease in the paediatric population. We performed a meta-analysis, in accordance with the PRISMA statement, in order to assess the immunogenicity and safety of 13-valent pneumococcal conjugate vaccines in infants. A literary search was conducted using electronic databases and specialized journals were searched manually. Inclusion criteria were: clinical trials with infants vaccinated with 13-valent pneumococcal conjugate, compared to 7-valent vaccine. We recorded the results in terms of the immunogenicity and safety of the vaccines. The quality of the studies included was assessed using the CASP and Jadad checklists. We included nine randomized clinical trials of 258 potentially relevant references in the meta-analysis. The studies included had high-moderate quality. Both vaccines were well tolerated in all groups of infants, and most local reactions and systemic events were of mild or medium intensity and typical of any injected vaccine. All studies included in the meta-analysis showed high immunogenicity for both pneumococcal vaccines in all tested serotypes. An anti-polysaccharide antibody concentration of ?0.35 ?g/mL was achieved in at least 89% of the infants. Our results suggest that the 13-valent pneumococcal conjugate vaccine has a similar safety profile, and is as effective as, the 7-valent vaccine in the prevention of invasive pneumococcal disease caused by the seven common serotypes, and could provide expanded protection against the six additional serotypes. PMID:24055349

Ruiz-Aragón, J; Márquez Peláez, S; Molina-Linde, J M; Grande-Tejada, A M

2013-11-01

90

Seven-valent pneumococcal conjugate vaccine and nasopharyngeal microbiota in healthy children.  

PubMed

Seven-valent pneumococcal conjugate vaccine (PCV-7) is effective against vaccine serotype disease and carriage. Nevertheless, shifts in colonization and disease toward nonvaccine serotypes and other potential pathogens have been described. To understand the extent of these shifts, we analyzed nasopharyngeal microbial profiles of 97 PCV-7-vaccinated infants and 103 control infants participating in a randomized controlled trial in the Netherlands. PCV-7 immunization resulted in a temporary shift in microbial community composition and increased bacterial diversity. Immunization also resulted in decreased presence of the pneumococcal vaccine serotype and an increase in the relative abundance and presence of nonpneumococcal streptococci and anaerobic bacteria. Furthermore, the abundance of Haemophilus and Staphylococcus bacteria in vaccinees was increased over that in controls. This study illustrates the much broader effect of vaccination with PCV-7 on the microbial community than currently assumed, and highlights the need for careful monitoring when implementing vaccines directed against common colonizers. PMID:24447437

Biesbroek, Giske; Wang, Xinhui; Keijser, Bart J F; Eijkemans, Rene M J; Trzci?ski, Krzysztof; Rots, Nynke Y; Veenhoven, Reinier H; Sanders, Elisabeth A M; Bogaert, Debby

2014-02-01

91

Seven-Valent Pneumococcal Conjugate Vaccine and Nasopharyngeal Microbiota in Healthy Children  

PubMed Central

Seven-valent pneumococcal conjugate vaccine (PCV-7) is effective against vaccine serotype disease and carriage. Nevertheless, shifts in colonization and disease toward nonvaccine serotypes and other potential pathogens have been described. To understand the extent of these shifts, we analyzed nasopharyngeal microbial profiles of 97 PCV-7–vaccinated infants and 103 control infants participating in a randomized controlled trial in the Netherlands. PCV-7 immunization resulted in a temporary shift in microbial community composition and increased bacterial diversity. Immunization also resulted in decreased presence of the pneumococcal vaccine serotype and an increase in the relative abundance and presence of nonpneumococcal streptococci and anaerobic bacteria. Furthermore, the abundance of Haemophilus and Staphylococcus bacteria in vaccinees was increased over that in controls. This study illustrates the much broader effect of vaccination with PCV-7 on the microbial community than currently assumed, and highlights the need for careful monitoring when implementing vaccines directed against common colonizers. PMID:24447437

Biesbroek, Giske; Wang, Xinhui; Keijser, Bart J.F.; Eijkemans, Rene M.J.; Trzcinski, Krzysztof; Rots, Nynke Y.; Veenhoven, Reinier H.; Sanders, Elisabeth A.M.

2014-01-01

92

Introduction of Hib conjugate vaccines in the non-industrialized world: experience in four ‘newly adopting’ countries  

Microsoft Academic Search

Hib conjugate vaccines are widely used in the industrialized world, but are just now beginning to be introduced into other countries. To identify factors facilitating rapid global introduction, we evaluated the decision-making process, mode of introduction, effectiveness, and impact on the immunization program of Hib conjugate vaccine introduction in four non- industrialized countries through site visits and use of a

Jay D Wenger; Jose-Luis DiFabio; Jose Mauricio Landaverde; Orin S Levine; Taki Gaafar

1999-01-01

93

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

PubMed

An efficacious, low cost vaccine against typhoid fever, especially for young children, would make a major impact on disease burden in developing countries. The virulence capsular polysaccharide of Salmonella Typhi (Vi) coupled to recombinant mutant Pseudomonas aeruginosa exoprotein A (Vi-rEPA) has been shown to be highly efficacious. We investigated the use of carrier proteins included in infant vaccines, standardized the conjugation process and developed key assays required for routine lot release at production scale. Vi from a BSL1 organism, Citrobacter freundii, strain WR7011, was used as an alternative to Vi from S. Typhi. We showed that Vi conjugated to CRM(197), a non-toxic mutant of diphtheria toxin, widely used in commercial vaccines, was produced at high yield. Vi-CRM(197) proved immunogenic in animal studies, even without adjuvant. Thus, Vi-CRM(197) appears to be a suitable candidate for the development of a commercially viable, effective typhoid vaccine for developing countries. PMID:21115057

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

2011-01-17

94

[Conjugate pneumococcal vaccines and influence on the ear, nose and throat area].  

PubMed

The importance of anti-pneumococcal vaccines has increased due to the gradually increasing incidence rate of pneumococcal infections and their antibiotic resistance. Conjugate pneumococcal vaccine began to be used routinely in the USA in 2000. An important property of this conjugate vaccine is the ability to create immunity in infants after two months. Thus, conjugate vaccines allow us to protect children below the age of two years against to invasive and mortal pneumococcal infections. The first pneumococcal conjugate vaccine (PCV7) contains the seven most common pneumococcal serotypes in the USA. Pneumococci are also the most important bacterial agents in acute otitis media (AOM) and recurrent acute otitis media. Acute otitis media is the most common infectious disease in childhood and resistance to treatment has rapidly increased over the last decade. The incidence of AOM and applications of tympanostomy tubes saw statistically significant decreases in the USA after implementation of PCV7 in national immunization programs. PCV7 was implemented in the national immunization program in Turkey in 2008. For this reason, reductions in the incidence of upper respiratory tract infectious diseases and especially AOM should be expected in our country. PMID:22014302

Almaç, Ahmet; Kuru, F Demir

2011-01-01

95

Safety and Immunogenicity of Coadministering a Combined Meningococcal Serogroup C and Haemophilus influenzae Type b Conjugate Vaccine with 7-Valent Pneumococcal Conjugate Vaccine and Measles, Mumps, and Rubella Vaccine at 12 Months of Age ?  

PubMed Central

The coadministration of the combined meningococcal serogroup C conjugate (MCC)/Haemophilus influenzae type b (Hib) vaccine with pneumococcal conjugate vaccine (PCV7) and measles, mumps, and rubella (MMR) vaccine at 12 months of age was investigated to assess the safety and immunogenicity of this regimen compared with separate administration of the conjugate vaccines. Children were randomized to receive MCC/Hib vaccine alone followed 1 month later by PCV7 with MMR vaccine or to receive all three vaccines concomitantly. Immunogenicity endpoints were MCC serum bactericidal antibody (SBA) titers of ?8, Hib-polyribosylribitol phosphate (PRP) IgG antibody concentrations of ?0.15 ?g/ml, PCV serotype-specific IgG concentrations of ?0.35 ?g/ml, measles and mumps IgG concentrations of >120 arbitrary units (AU)/ml, and rubella IgG concentrations of ?11 AU/ml. For safety assessment, the proportions of children with erythema, swelling, or tenderness at site of injection or fever or other systemic symptoms for 7 days after immunization were compared between regimens. No adverse consequences for either safety or immunogenicity were demonstrated when MCC/Hib vaccine was given concomitantly with PCV and MMR vaccine at 12 months of age or separately at 12 and 13 months of age. Any small differences in immunogenicity were largely in the direction of a higher response when all three vaccines were given concomitantly. For systemic symptoms, there was no evidence of an additive effect; rather, any differences between schedules showed benefit from the concomitant administration of all three vaccines, such as lower overall proportions with postvaccination fevers. The United Kingdom infant immunization schedule now recommends that these three vaccines may be offered at one visit at between 12 and 13 months of age. PMID:21191076

Miller, Elizabeth; Andrews, Nick; Waight, Pauline; Findlow, Helen; Ashton, Lindsey; England, Anna; Stanford, Elaine; Matheson, Mary; Southern, Joanna; Sheasby, Elizabeth; Goldblatt, David; Borrow, Ray

2011-01-01

96

Proportion of Invasive Pneumococcal Infections in German Children Preventable by Pneumococcal Conjugate Vaccines  

Microsoft Academic Search

different age groups were as follows: children aged !1 year, 18.9 (9.7 for meningitis); children aged !2 years, 16.0 (7.2 for meningitis); for children aged !5 years, 8.9 (3.9 for meningitis); and for children aged !16 years, 3.2 (1.4 for meningitis). The proportions of cases involving strains (304 serotyped) included in conjugate vaccines were as follows: for the 7-valent vaccine,

Rudiger von Kries; Anette Siedler; Heinz J. Schmitt; Ralf Rene Reinert

2000-01-01

97

Evaluation of antibody response to the heptavalent pneumococcal conjugate vaccine in pediatric chronic kidney disease  

Microsoft Academic Search

Pneumococcal vaccination has been recommended for immunocompromised children, including patients with chronic kidney disease.\\u000a We determined pneumococcal immunoglobulin (Ig)G antibodies to serotypes 4, 6B, 9V, 14, 18C, 19F, and 23F before and after\\u000a 48 pediatric patients with chronic renal failure were administered heptavalent conjugated pneumococcal vaccine. The patients\\u000a were between 1 and 9 years of age and were separated into a

Simone Vieira; Evandro Roberto Baldacci; Magda Carneiro-Sampaio; Ulysses Doria Filho; Vera Hermina Koch

2009-01-01

98

Phase I study of a lipooligosaccharide-based conjugate vaccine against nontypeable Haemophilus influenzae.  

PubMed

Nontypeable Haemophilus influenzae (NTHi) accounts for about one-third of purulent otitis media (OM) in children and is a common cause of pulmonary infection in adults with decreased resistance. Based upon sero-epidemiological data in humans and immunochemical data in laboratory animals, a lipooligosaccharide (LOS)-tetanus toxoid (TT) conjugate was prepared and evaluated for its safety and immunogenicity in a Phase I study of 40 healthy adults. The conjugate was injected intramuscularly into all volunteers: 28 of them received a second injection 14 weeks later. Local and systemic reactions were monitored and sera, taken before and 2, 6, 14, 16, and 38 weeks after injection, were assayed for IgG, IgA, and IgM antibodies to the LOS by ELISA and for bactericidal activity. The results indicate that there were no significant local or systemic reactions after either injection. All volunteers had pre-existing IgG anti-LOS. The geometric mean (GM) level rose from 14 to 40 at 2 weeks, remained at 35 at 6 weeks (40 or 35 versus 14, P<0.01) and dropped to 27 at 14 weeks after the first injection. There was also a rise 2 weeks after the second injection (27 versus 37, P<0.05). A total of 52.5% of subjects showed serum-conversion (greater than four-fold increase) after one and two injections. At 38 weeks, the GM IgG anti-LOS was still higher than before initial injection (20 versus 14, P<0.05). A similar pattern of reactivity was observed for IgA and IgM anti-LOS. Similar to that observed in mice, but not in rabbits, the conjugate-induced antibodies did not yield significant bactericidal activity in vitro. The LOS-TT conjugate is well tolerant in adults and a Phase II evaluation of the conjugate in children is planned. PMID:12706701

Gu, Xin-Xing; Rudy, Susan F; Chu, Chiayung; McCullagh, Linda; Kim, Hung N; Chen, Jing; Li, Jianping; Robbins, John B; Van Waes, Carter; Battey, James F

2003-05-16

99

Haemophilus influenzae type b conjugate vaccines - a South African perspective.  

PubMed

Introduction of Hib vaccine is known to positively impact on reduction of both morbidity and mortality in children less than 5 years of age. Incorporation of this vaccine into a National EPI, however, does come at a significant cost, which is especially important in non-GAVI funded countries. Compounded reduction in response in certain patient populations and possible indication of booster doses further impacts on cost-benefit analyses. Despite these issues, South Africa has supplied Hib vaccine as part of the National EPI in the form of a combination vaccine, Pentaxim, which combines Hib with Diphtheria, Tetanus, acellular Pertussis (DTP) and Poliomyelitis since 2009. Prior to this, another combination vaccine was utilized containing Hib and DTP. This has subsequently lead to a significant reduction in invasive Hib disease post-introduction, therefore largely justifying utilization. PMID:22939022

Visser, Adele; Hoosen, Anwar

2012-09-01

100

Effects of Pneumococcal Conjugate Vaccine 2 Years after Its Introduction, the Netherlands  

PubMed Central

In the Netherlands, the 7-valent pneumococcal conjugate vaccine (PCV-7) was implemented in a 3+1-dose schedule in the national immunization program for infants born after April 1, 2006. To assess the vaccine’s effectiveness, we compared disease incidence before and after vaccine implementation (June 2004–June 2006 and June 2006–June 2008, respectively). We serotyped 2,552 invasive pneumococcal isolates from throughout the Netherlands, covering 25% of the country’s population. Clinical characteristics were extracted from hospital records. After June 2006, vaccine-serotype invasive pneumococcal disease (IPD) decreased 90% (95% confidence interval [CI] 68%–97%) in children age eligible for PCV-7; simultaneously, however, non–vaccine-serotype IPD increased by 71% (not significant), resulting in a 44% total net IPD reduction (95% CI 7%–66%). IPD rates did not change for other age groups. In the Netherlands, PCV-7 offered high protection against vaccine-serotype IPD in vaccinated children, but increases of non–vaccine-serotype IPD reduced net vaccine benefits. PMID:20409372

de Greeff, Sabine C.; Jansen, Angelique G.C.S.; de Melker, Hester E.; Schouls, Leo M.; Hak, Eelko; Spanjaard, Lodewijk; Sanders, Elisabeth A.M.; van der Ende, Arie

2010-01-01

101

Reduced Response to Multiple Vaccines Sharing Common Protein Epitopes That Are Administered Simultaneously to Infants  

PubMed Central

The plethora of newly discovered vaccines implies that, in the future, many vaccines will have to be administered simultaneously to infants. We examined the potential interference with the immune response of several coadministered vaccines containing the same protein component, namely, tetanus toxoid (TT). Infants simultaneously receiving a tetravalent pneumococcal vaccine conjugated to TT (PncT) and a diphtheria-tetanus-pertussis–poliovirus–Haemophilus influenzae type b-tetanus conjugate vaccine showed significantly lower anti-H. influenzae type b polysaccharide (polyribosylribitol phosphate [PRP]) antibody concentrations than those receiving either a tetravalent pneumococcal vaccine conjugated to diphtheria toxoid or placebo. A dose range study showed that anti-PRP antibody concentrations were inversely related to the TT content of the PncT vaccines administered in infancy. Postimmunization antitetanus antibody concentrations were also affected adversely as the TT content of the coadministered vaccines was increased. This phenomenon, which we believe derives from interference by a common protein carrier, should be taken into account when the introduction of an immunization program including multiple conjugate vaccines is considered. PMID:9573094

Dagan, Ron; Eskola, Juhani; Leclerc, Claude; Leroy, Odile

1998-01-01

102

9 CFR 113.114 - Tetanus Toxoid.  

Code of Federal Regulations, 2011 CFR

...Products 1 2011-01-01 2011-01-01 false Tetanus Toxoid. 113.114 Section 113.114 Animals... Inactivated Bacterial Products § 113.114 Tetanus Toxoid. Tetanus Toxoid shall be produced from a culture of...

2011-01-01

103

9 CFR 113.114 - Tetanus Toxoid.  

...Products 1 2014-01-01 2014-01-01 false Tetanus Toxoid. 113.114 Section 113.114 Animals... Inactivated Bacterial Products § 113.114 Tetanus Toxoid. Tetanus Toxoid shall be produced from a culture of...

2014-01-01

104

9 CFR 113.114 - Tetanus Toxoid.  

Code of Federal Regulations, 2012 CFR

...Products 1 2012-01-01 2012-01-01 false Tetanus Toxoid. 113.114 Section 113.114 Animals... Inactivated Bacterial Products § 113.114 Tetanus Toxoid. Tetanus Toxoid shall be produced from a culture of...

2012-01-01

105

9 CFR 113.114 - Tetanus Toxoid.  

Code of Federal Regulations, 2013 CFR

...Products 1 2013-01-01 2013-01-01 false Tetanus Toxoid. 113.114 Section 113.114 Animals... Inactivated Bacterial Products § 113.114 Tetanus Toxoid. Tetanus Toxoid shall be produced from a culture of...

2013-01-01

106

75 FR 48707 - Proposed Vaccine Information Materials for Pneumococcal Conjugate Vaccine and Human...  

Federal Register 2010, 2011, 2012, 2013

...People who are mildly ill when a dose of HPV vaccine is planned can still be vaccinated. People...screening. Women should still get regular Pap tests...People who are mildly ill when a dose of HPV vaccine is planned can still be vaccinated....

2010-08-11

107

The effect of a pneumococcal conjugate vaccine on the risk of otitis media with effusion at 7 and 24 months of age  

Microsoft Academic Search

Objective: To explore the effect of a pneumococcal conjugate vaccine on the risk of otitis media with effusion and to search for subgroups in which the vaccine had a higher or lower effect. Methods: Analyses were performed on data from the Finnish Otitis Media Vaccine Trial, a randomised controlled double-blind trial to evaluate the efficacy of pneumococcal conjugate vaccination against

M. Straetemans; A. Palmu; K. Auranen; G. A. Zielhuis; T. Kilpi

2003-01-01

108

The evidence for using conjugate vaccines to protect HIV-infected children against pneumococcal disease  

Microsoft Academic Search

Pneumococcal conjugate vaccines (PCVs) are a potentially useful complement to existing treatment strategies in HIV-infected children, for whom pneumococcal infections are common and serious. This Review summarises available data on the burden of pneumococcal disease and the safety and effi cacy of PCVs in HIV-infected children. The data demonstrate that children with HIV have signifi cantly increased risk of pneumococcal

Sandra J Bliss; Katherine L O'Brien; Edward N Janoff; Mark F Cotton; Philippa Musoke; Hoosen Coovadia; Orin S Levine

2008-01-01

109

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

PubMed Central

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

2014-01-01

110

Effects of pneumococcal conjugate vaccine 2 years after its introduction, the Netherlands.  

PubMed

In the Netherlands, the 7-valent pneumococcal conjugate vaccine (PCV-7) was implemented in a 3+1-dose schedule in the national immunization program for infants born after April 1, 2006. To assess the vaccine's effectiveness, we compared disease incidence before and after vaccine implementation (June 2004-June 2006 and June 2006-June 2008, respectively). We serotyped 2,552 invasive pneumococcal isolates from throughout the Netherlands, covering 25% of the country's population. Clinical characteristics were extracted from hospital records. After June 2006, vaccine-serotype invasive pneumococcal disease (IPD) decreased 90% (95% confidence interval [CI] 68%-97%) in children age eligible for PCV-7; simultaneously, however, non-vaccine-serotype IPD increased by 71% (not significant), resulting in a 44% total net IPD reduction (95% CI 7%-66%). IPD rates did not change for other age groups. In the Netherlands, PCV-7 offered high protection against vaccine-serotype IPD in vaccinated children, but increases of non-vaccine-serotype IPD reduced net vaccine benefits. PMID:20409372

Rodenburg, Gerwin D; de Greeff, Sabine C; Jansen, Angelique G C S; de Melker, Hester E; Schouls, Leo M; Hak, Eelko; Spanjaard, Lodewijk; Sanders, Elisabeth A M; van der Ende, Arie

2010-05-01

111

Epidemiology of vaccine-preventable invasive diseases in Catalonia in the era of conjugate vaccines  

PubMed Central

We investigated the incidence and distribution of cases of invasive pneumococcal disease (IPD), invasive meningococcal disease (IMD) and invasive Hemophilus influenzae disease (IHiD) notified by hospital laboratories to the Microbiological Reporting System of Catalonia between 2005 and 2009. Incidence rates were compared using the rate ratio (RR) and 95% CI were calculated. A value of p < 0.05 was considered statistically significant. Of the 6,661 cases, 6,012 were IPD, 436 IMD and 213 IHiD. The global annual incidence per 105 inhabitants was 16.62 (95% CI 16.20–17.04) for IPD, 1.21 (95% CI 1.09–1.32) for IMD and 0.59 (95% CI 0.51–0.67) for IHiD. IPD increased in 2009 compared with 2005 (RR:1.55, 95%CI: 1.43–1.70) and IMD and IHiD remained stable. Pneumonia was the most-frequent clinical manifestation of IPD (75.6%) and IHiD (44.1%) and meningoencephalitis with or without sepsis for IMD (70.6%). The male:female ratio was 1.37 for IPD, 1.0 for IMD and 1.15 for IHiD. The age groups with the highest incidence were the ? 2 y and 2–4 y groups for IPD (66.40 and 50.66/100,000 persons-year) and IMD (14.88 and 7.26/100,000 persons-year) and the ? 2 y and ? 65 y groups for IHiD (1.88 and 1.89/100,000 persons-year). The most-frequent serotypes were serotype 1 (19.0%) in IPD and untypeable serotypes (60.8%) in IHiD. Serogroup B (78.3%) was the most frequent in IMD. S. pneumoniae is the most-frequent agent causing invasive disease in Catalonia. The main clinical manifestations were pneumonia in IPD and IHiD and meningitis in IMD. The main causative agent of meningitis was N. meningitidis in people aged < 20 y and S. pneumoniae in people aged ? 20 y. Vaccination with conjugate vaccines may reduce the risk of infectious disease in our setting. PMID:23303166

Ciruela, Pilar; Martinez, Ana; Izquierdo, Conchita; Hernandez, Sergi; Broner, Sonia; Munoz-Almagro, Carmen; Dominguez, Angela; of Catalonia Study Group, the Microbiological Reporting System

2013-01-01

112

A Second Generation Pneumococcal Conjugate Vaccine for Prevention of Pneumococcal Diseases in Children  

PubMed Central

Purpose A second generation 13 valent pneumococcal conjugate vaccine (PCV13) was licensed and recommended for universal immunization of children through age five years in 2010. Its introduction is intended to address the residual burden of pneumococcal diseases that persists a decade after the introduction of PCV7. Recent Findings Immunization with PCV7 has resulted in a substantial decline in pneumococcal diseases caused by vaccine serotypes in both vaccinated and unvaccinated persons in the US. However an increase in disease due to non vaccine serotypes, including empyema; the emergence of multidrug, including ceftriaxone, resistant serotype 19A strains; and the need for broader serotype coverage to address the global disease burden provides a rationale for a second generation conjugate vaccine that includes serotypes 1, 3, 5, 6A, 7F and 19A. Summary This article reviews the lessons learned from a decade of experience with PCV7, the increasing problem of disease due to non-vaccine serotypes, and the likelihood of PCV13 to impact the residual disease burden. We contrast the potential differences in prevention of invasive pneumococcal disease (IPD) compared to nonbacteremic pneumonia and acute otitis media. We conclude with the current recommendations for PCV13 providing a rationale for immunization through age 5 years to create both direct and indirect protection in the population. PMID:21191300

Grijalva, Carlos G.; Pelton, Stephen I.

2012-01-01

113

Physicochemical and immunochemical assays for monitoring consistent production of tetanus toxoid.  

PubMed

The detoxification of tetanus toxin by formaldehyde is a crucial step in the production of tetanus toxoid. The inactivation results in chemically modified proteins and it determines largely the ultimate efficacy and safety of the vaccine. Currently, the quality of tetanus toxoid lots is evaluated in potency and safety tests performed in animals. As a possible alternative, this article describes a panel of in vitro methods, which provides detailed information about the quality of tetanus toxoid. Ten experimental lots of tetanus toxoid were prepared using increasing concentrations of formaldehyde and glycine to obtain tetanus toxoids having differences in antigenicity, immunogenicity, residual toxicity and protein structure. The structural properties of each individual toxoid were determined using immunochemical and physicochemical methods, including biosensor analysis, ELISA, circular dichroism, TNBS assay, differential scanning calorimetry, fluorescence and SDS-PAGE. The quality of a tetanus toxoid lot can be assessed by these set of analytical techniques. Based on antigenicity, immunogenicity and residual toxicity data, criteria are formulated that tetanus toxoids lot have to meet in order to have a high quality. The in vitro methods are a valuable selection of techniques for monitoring consistency of production of tetanus toxoid, especially for the detoxification process of tetanus toxin. PMID:23726755

Metz, Bernard; Tilstra, Wichard; van der Put, Robert; Spruit, Nanda; van den Ijssel, Jan; Robert, Jolanda; Hendriksen, Coenraad; Kersten, Gideon

2013-07-01

114

A morphine conjugate vaccine attenuates the behavioral effects of morphine in rats  

PubMed Central

Vaccines for opioid dependence may provide a treatment that would reduce or slow the distribution of the drug to brain, thus reducing the drug's reinforcing effects. We tested whether a conjugate vaccine against morphine (keyhole limpet hemocyanin-6-succinylmorphine; KLH-6-SM) administered to rats would produce antibodies and show specificity for morphine or other heroin metabolites. The functional effects of the vaccine were tested with antinociceptive and conditioned place preference (CPP) tests. Rats were either vaccinated with KLH-6-SM and received two boosts 3 and 16 weeks later or served as controls and received KLH alone. Anti-morphine antibodies were produced in vaccinated rats; levels increased and were sustained at moderate levels through 24 weeks. Antibody binding was inhibited by free morphine and other heroin metabolites as demonstrated by competitive inhibition ELISA. Vaccinated rats showed reduced morphine CPP, tested during weeks 4 to 6, and decreased antinociceptive responses to morphine, tested at week 7. Brain morphine levels, assessed using gas-chromatography coupled to mass spectrometry (GC–MS) on samples obtained at 26 weeks, were significantly lower in vaccinated rats. This suggests that morphine entry into the brain was reduced or slowed. These results provide support for KLH-6-SM as a candidate vaccine for opioid dependence. PMID:23739535

Kosten, Therese A.; Shen, Xiaoyun Y.; O'Malley, Patrick W.; Kinsey, Berma M.; Lykissa, Ernest D.; Orson, Frank M.; Kosten, Thomas R.

2013-01-01

115

Overview and outlook of Toll-like receptor ligand-antigen conjugate vaccines.  

PubMed

The discovery of Toll-like receptors (TLRs) facilitated our understanding of the innate and adaptive immune systems, and has raised the potential to develop novel methods of vaccine and immunotherapy. For effective vaccination, antigens and adjuvants must be administered simultaneously via the same route. Many studies have demonstrated that TLR ligands covalently coupled to the antigens have several benefits over nonconjugated antigens. This review introduces the applications of TLR ligands as vaccine adjuvants, focusing on the development of vaccines composed of antigen and TLR ligand in single molecules (TLR ligand-antigen conjugates) using Pam3/2Cys, lipid A analogues, recombinant flagellin, imidazoquinoline analogues and unmethylated CpG motifs to activate immune systems through TLR2, TLR4, TLR5, TLR7/8 and TLR9, respectively. PMID:22838070

Fujita, Yoshio; Taguchi, Hiroaki

2012-06-01

116

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

PubMed

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-CRM??? 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-?), and gamma interferon (IFN-?) 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-CRM??? 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. PMID:21450979

Lai, Zengzu; Schreiber, John R

2011-05-01

117

A preclinical study comparing approaches for augmenting the immunogenicity of a heptavalent KLH-conjugate vaccine against epithelial cancers  

Microsoft Academic Search

Previously using a series of monovalent vaccines, we demonstrated that the optimal method for inducing an antibody response against cancer cell-surface antigens is covalent conjugation of the antigens to keyhole limpet hemocyanin (KLH) and the use of a saponin adjuvant. We have prepared a heptavalent-KLH conjugate vaccine containing the seven epithelial cancer antigens GM2, Globo H, Lewis y, TF(c), Tn(c),

Govind Ragupathi; Fusataka Koide; Natarajan Sathyan; Ella Kagan; Maria Spassova; William Bornmann; Polly Gregor; Celso A. Reis; Henrik Clausen; Samuel J. Danishefsky; Philip O. Livingston

2003-01-01

118

Immunogenicity and safety of CRM??? conjugated 9-valent pneumococcal and meningococcal C combination vaccine in healthy infants.  

PubMed

Streptococcus pneumoniae and Neisseria meningitidis cause invasive disease in children aged <2 years. While individual conjugate vaccines are available to protect this age group against these pathogens, availability of a vaccine combining these antigens into a single injection is desirable. This study randomized 467 healthy infants to receive 4 doses of combination 9-valent pneumococcal and meningococcal serogroup C conjugate vaccine (9vPnC-MnCC) or 9-valent pneumococcal conjugate vaccine (9vPnC). Percentages of subjects achieving immunoglobulin G (IgG) antibody concentrations ?0.35?g/mL and geometric mean IgG concentrations for each pneumococcal serotype in the 9vPnC-MnCC group were noninferior compared to the 9vPnC group. Both vaccines were well-tolerated. PMID:21296118

Mallet, Eric; Brachet, Elisabeth; Fernsten, Philip; Laudat, France; Razmpour, Ahmad; Gruber, William C

2011-08-01

119

Saccharide/protein conjugate vaccines for Bordetella species: preparation of saccharide, development of new conjugation procedures, and physico-chemical and immunological characterization of the conjugates  

PubMed Central

Bordetellae are Gram-negative bacilli causing respiratory tract infections of mammals and birds. Clinically important are B. pertussis, B. parapertussis and B. bronchiseptica. B. pertussis vaccines have been successful in preventing pertussis in infants and children. Veterinary vaccines against B. bronchiseptica are available, but their efficacy and mode of action are not established. There is no vaccine against B. parapertussis. Based on the concept that immunity to non-capsulated Gram-negative bacteria may be conferred by serum IgG anti-LPS we studied chemical, serological and immunological properties of the O-specific polysaccharides (O-SP) of B. bronchiseptica and B. parapertussis obtained by different degradation procedures. One type of the B. parapertussis and two types of B. bronchiseptica O-SP were recognized based on the structure of their non-reducing end saccharide; no cross-reaction between the two B. bronchiseptica types was observed. Competitive inhibition assays showed the immunodominance of the non-reducing end of these O-SP. Conjugates of B. bronchiseptica and B. parapertussis O-SP were prepared by two methods: using the Kdo residue exposed by mild acid hydrolysis of the LPS or the core glucosamine residue exposed by deamination of the LPS, for binding to an aminooxylated protein. Both coupling methods were carried out at a neutral pH, room temperature, and in a short time. All conjugates, injected as saline solutions at a fraction of an estimated human dose, induced antibodies in mice to the homologous O-SP. These methodologies can be applied to prepare O-SP-based vaccines against other Gram-negative bacteria. PMID:18539367

Kubler-Kielb, Joanna; Vinogradov, Evgeny; Ben-Menachem, Gil; Pozsgay, Vince; Robbins, John B.; Schneerson, Rachel

2008-01-01

120

N19 Polyepitope as a Carrier for Enhanced Immunogenicity and Protective Efficacy of Meningococcal Conjugate Vaccines  

Microsoft Academic Search

N19, a string of human universal CD4 T-cell epitopes from various pathogen-derived antigens, was shown to exert a stronger carrier effect than CRM197 for the induction of anti-group C Neisseria meningitidis capsular polysaccharide (MenC), after immunization of mice with various dosages of N19-MenC or CRM-MenC conjugate vaccines. After two immunizations, the N19-based construct induced anti-MenC antibody and protective bactericidal antibody

Karin Baraldo; Elena Mori; Antonella Bartoloni; Roberto Petracca; Aldo Giannozzi; Francesco Norelli; Rino Rappuoli; Guido Grandi; Giuseppe Del Giudice

2004-01-01

121

Cost effectiveness of pediatric pneumococcal conjugate vaccines: a comparative assessment of decision-making tools  

Microsoft Academic Search

Background  Several decision support tools have been developed to aid policymaking regarding the adoption of pneumococcal conjugate vaccine\\u000a (PCV) into national pediatric immunization programs. The lack of critical appraisal of these tools makes it difficult for\\u000a decision makers to understand and choose between them. With the aim to guide policymakers on their optimal use, we compared\\u000a publicly available decision-making tools in

Nathorn Chaiyakunapruk; Ratchadaporn Somkrua; Raymond Hutubessy; Ana Maria Henao; Joachim Hombach; Alessia Melegaro; John W Edmunds; Philippe Beutels

2011-01-01

122

Construction and Characterization of a Pseudomonas aeruginosa Mucoid Exopolysaccharide-Alginate Conjugate Vaccine  

PubMed Central

Deterioration of lung function in patients with cystic fibrosis (CF) is closely associated with chronic pulmonary infection with mucoid Pseudomonas aeruginosa. The mucoid exopolysaccharide (MEP) from P. aeruginosa has been shown to induce opsonic antibodies in mice that are protective against this chronic infection. MEP-specific opsonic antibodies are also commonly found in the sera of older CF patients lacking detectable P. aeruginosa infection. When used in a human vaccine trial, however, MEP only minimally induced opsonic antibodies. To evaluate whether conjugation of MEP to a carrier protein could improve its immunogenicity, we bound thiolated MEP to keyhole limpet hemocyanin (KLH) by using succinimidyl-4-(N-maleimidomethyl)cyclohexane-1-carboxylate (SMCC) as a linker. In contrast to the native MEP polymer, the MEP-KLH conjugate vaccine induced high titers of MEP-specific immunoglobulin G (IgG) in C3H-HeN mice and in a rabbit. Sera from mice immunized with MEP-KLH conjugate, but not from animals immunized with comparable doses of native MEP, demonstrated opsonic killing activity. Vaccination with MEP-KLH conjugate induced opsonic antibodies broadly cross-reactive to heterologous mucoid strains of P. aeruginosa. Preexisting nonopsonic antibodies to MEP are found in normal human sera, including young CF patients, and their presence impedes the induction of opsonic antibodies. Induction of nonopsonic antibodies by either intraperitoneal injection of MEP or injection or feeding of the cross-reactive antigen, seaweed alginate, reduced the level of overall IgG elicited by follow-up immunization with the MEP-KLH conjugate. However, the opsonic activity was lower only in the sera of MEP-KLH conjugate-immunized mice with preexisting antibodies induced by MEP but not with antibodies induced by seaweed alginate. Immunization with MEP-KLH elicited a significant proportion of antibodies specific to epitopes involving O-acetate residues, and this subpopulation of antibodies mediated opsonic killing of mucoid P. aeruginosa in vitro. These results indicate that conjugation of MEP to KLH significantly enhances its immunogenicity and the elicitation of opsonic antibodies in mice and rabbits, that the conjugate induces opsonic antibodies in the presence of preexisting nonopsonic antibodies, and that opsonic antibodies to MEP are directed at epitopes that include acetate residues on the uronic acid polymer. PMID:12819072

Theilacker, Christian; Coleman, Fadie T.; Mueschenborn, Simone; Llosa, Nicolas; Grout, Martha; Pier, Gerald B.

2003-01-01

123

Sortase-conjugation generates a capsule vaccine that protects guinea pigs against Bacillus anthracis  

PubMed Central

Capsules protect bacteria against phagocytic clearance. Capsular polysaccharides or polyglutamates have evolved also to resist antigen presentation by immune cells, thereby interfering with the production of opsonophagocytic antibodies. Linking capsular material to a carrier protein stimulates its presentation to the immune system. For many conjugate vaccines this is achieved by a process of random chemical cross-linking. Here we describe a new technology, designated sortase-conjugation, which generates a single amide bond between the C-terminal end of a carrier protein and the capsular material. Sortase-conjugation was used to link the poly-D-?-glutamic acid (PDGA) capsule of Bacillus anthracis to the receptor binding domain (D4) of protective antigen (PagA). When used as a vaccine, PDGA-D4 conjugate elicited robust antibody responses against both capsule and D4. Immunization with PDGA-D4 afforded guinea pigs complete protection against anthrax challenge with wild-type or pagA mutant B. anthracis Ames. PMID:22449424

Garufi, Gabriella; Wang, Ya-Ting; Oh, So-Young; Maier, Hannah; Missiakas, Dominique M.; Schneewind, Olaf

2012-01-01

124

Efficacy and safety of a Haemophilus influenzae type b capsular polysaccharide-tetanus protein conjugate vaccine.  

PubMed

A polyribosylribitol phosphate (polysaccharide)-tetanus protein conjugate vaccine (PRP-T) against Haemophilus influenzae type b (Hib) was evaluated for safety and efficacy after vaccination of more than 100,000 infants. No major side effects were attributed to the vaccine. Immunogenicity studies showed an antibody response in 70% to 100% of infants after two doses, and in 98% to 100% of infants after three doses, within the first 6 months of life. Antibodies persisted in 90% of recipients, in whom significant anamnestic responses developed after a booster dose at 18 months of age. In comparison with other available Hib vaccines, PRP-T induces equal or higher mean titers after three doses. Although licensure of other vaccines interrupted controlled efficacy trials, up to that point five cases of Hib disease in those trials had occurred in placebo recipients, and no Hib disease has been reported in the more than 100,000 vaccinated infants who have received more than one dose of PRP-T. Thus PRP-T combined immunogenicity early in life with induction of immunologic memory. PMID:1517908

Fritzell, B; Plotkin, S

1992-09-01

125

Impact of Pneumococcal Conjugate Vaccination on Otitis Media: A Systematic Review  

PubMed Central

Acute otitis media (AOM) is a leading cause of visits to physicians and of antibiotic prescriptions for young children. We systematically reviewed studies on all-cause AOM episodes and physician visits in which impact was attributed to pneumococcal conjugate vaccines, either as efficacy or effectiveness. Of 18 relevant publications found, most used the 7-valent pneumococcal conjugate vaccine (7vCRM). The efficacy of 7vCRM against all-cause AOM episodes or visits was 0%–9% in randomized trials and 17%–23% in nonrandomized trials. In observational database studies, physician visits for AOM were already declining in the 3–5 years before 7vCRM introduction (mean change, ?15%; range, +14% to ?24%) and continued to decline afterward (mean, ?19%; range, +7% to ?48%). This vaccine provides some protection against OM, but other factors have also contributed to the recent decline in OM incidence. Future effectiveness studies should thus use better-controlled methods to estimate the true impact of vaccination on AOM. PMID:22423134

Taylor, Sylvia; Marchisio, Paola; Vergison, Anne; Harriague, Julie; Hausdorff, William P.; Haggard, Mark

2012-01-01

126

Effect of Pneumococcal Conjugate Vaccination in Uruguay, a Middle-Income Country  

PubMed Central

Background In 2008, a 7-valent pneumococcal conjugate vaccine (PCV7) was introduced into the routine childhood immunization program in Uruguay, with a 2+1 schedule. In 2010, PCV13 replaced PCV7, and the same 2+1 schedule was used. The effect of these pneumococcal vaccines on the incidence of invasive pneumococcal infections (IPD) and on serotype distribution was analyzed retrospectively, based on passive national laboratory surveillance. Methods Data from 1,887 IPD isolates from 5 years before and 5 years after PCV7 introduction (7 before and 3 after PCV13 introduction) was examined to assess the incidence rate per 100,000 age-specific population of all IPD, PCV7-serotypes, and PCV13-serotypes associated IPD among children <2 years and 2 to 4 years old, and patients ?5 years old. Trends of frequency for each serotype were also analyzed. Results Comparison of pre-vaccination (2003–2007) and post-vaccination (2008–2012) periods showed a significant decrease in IPD incidence among children <2 years old (IR 68.7 to IR 29.6, p<0.001) and children 2 to 4 years (p<0.04). IPD caused by serotypes in PCV7 was reduced by 95.6% and IPD caused by 6 serotypes added in PCV13 was reduced by 83.9% in children <5 years old. Indirect effects of both conjugate vaccines were observed among patients ?5 years old one year after the introduction of each vaccine, in 2010 for PCV7 and in 2012 for PCV13. Nevertheless, for reasons that still need to be explained, perhaps due to ascertainment bias, total IPD in this group increased after 2007. In 2012, the relative frequency of vaccine serotypes among vaccinated and unvaccinated population declined, except for serotype 3. Non vaccine serotypes with increasing frequency were identified, in rank order: 12F, 8, 24F, 22F, 24A, 15C, 9N, 10A and 33. Conclusion Consecutive immunization with PCV7 and PCV13 has significantly reduced IPD in children <5 years of age in Uruguay. PMID:25375647

Garcia Gabarrot, Gabriela; Lopez Vega, Mariana; Perez Giffoni, Gabriel; Hernandez, Silvia; Cardinal, Pablo; Felix, Viviana; Gabastou, Jean Marc; Camou, Teresa

2014-01-01

127

Modeling the impact of the 7-valent pneumococcal conjugate vaccine in Chinese infants: an economic analysis of a compulsory vaccination  

PubMed Central

Background The purpose of this study was to compare, from a Chinese societal perspective, the projected health benefits, costs, and cost-effectiveness of adding pneumococcal conjugate heptavalent vaccine (PCV-7) to the routine compulsory child immunization schedule. Methods A decision-tree model, with data and assumptions adapted for relevance to China, was developed to project the health outcomes of PCV-7 vaccination (compared with no vaccination) over a 5-year period as well as a lifetime. The vaccinated birth cohort included 16,000,000 children in China. A 2?+?1 dose schedule at US$136.51 per vaccine dose was used in the base-case analysis. One-way sensitivity analysis was used to test the robustness of the model. The impact of a net indirect effect (herd immunity) was evaluated. Outcomes are presented in terms of the saved disease burden, costs, quality-adjusted life years (QALYs) and incremental cost-effectiveness ratio. Results In a Chinese birth cohort, a PCV-7 vaccination program would reduce the number of pneumococcus-related infections by at least 32% and would prevent 2,682 deaths in the first 5 years of life, saving $1,190 million in total costs and gaining an additional 9,895 QALYs (discounted by 3%). The incremental cost per QALY was estimated to be $530,354. When herd immunity was taken into account, the cost per QALY was estimated to be $95,319. The robustness of the model was influenced mainly by the PCV-7 cost per dose, effectiveness herd immunity and incidence of pneumococcal diseases. With and without herd immunity, the break-even costs in China were $29.05 and $25.87, respectively. Conclusions Compulsory routine infant vaccination with PCV-7 is projected to substantially reduce pneumococcal disease morbidity, mortality, and related costs in China. However, a universal vaccination program with PCV-7 is not cost-effective at the willingness-to-pay threshold that is currently recommended for China by the World Health Organization. PMID:24507480

2014-01-01

128

Pneumococcal serotypes before and after introduction of conjugate vaccines, United States, 1999-2011(1.).  

PubMed

Serotyping data for pneumococci causing invasive and noninvasive disease in 2008-2009 and 2010-2011 from >43 US centers were compared with data from preconjugate vaccine (1999-2000) and postconjugate vaccine (2004-2005) periods. Prevalence of 7-valent pneumococcal conjugate vaccine serotypes decreased from 64% of invasive and 50% of noninvasive isolates in 1999-2000 to 3.8% and 4.2%, respectively, in 2010-2011. Increases in serotype 19A stopped after introduction of 13-valent pneumococcal vaccine (PCV13) in 2010. Prevalences of other predominant serotypes included in or related to PCV13 (3, 6C, 7F) also remained similar for 2008-2009 and 2010-2011. The only major serotype that increased from 2008-2009 to 2010-2011 was nonvaccine serotype 35B. These data show that introduction of the 7-valent vaccine has dramatically decreased prevalence of its serotypes and that addition of serotypes in PCV13 could provide coverage of 39% of isolates that continue to cause disease. PMID:23763847

Richter, Sandra S; Heilmann, Kristopher P; Dohrn, Cassie L; Riahi, Fathollah; Diekema, Daniel J; Doern, Gary V

2013-07-01

129

Direct Effect of 10-Valent Conjugate Pneumococcal Vaccination on Pneumococcal Carriage in Children Brazil  

PubMed Central

Background 10-valent conjugate pneumococcal vaccine/PCV10 was introduced in the Brazilian National Immunization Program along the year of 2010. We assessed the direct effectiveness of PCV10 vaccination in preventing nasopharyngeal/NP pneumococcal carriage in infants. Methods A cross-sectional population-based household survey was conducted in Goiania Brazil, from December/2010-February/2011 targeting children aged 7–11 m and 15–18 m. Participants were selected using a systematic sampling. NP swabs, demographic data, and vaccination status were collected from 1,287 children during home visits. Main outcome and exposure of interest were PCV10 vaccine-type carriage and dosing schedules (3p+0, 2p+0, and one catch-up dose), respectively. Pneumococcal carriage was defined by a positive culture and serotyping was performed by Quellung reaction. Rate ratio/RR was calculated as the ratio between the prevalence of vaccine-types carriage in children exposed to different schedules and unvaccinated for PCV10. Adjusted RR was estimated using Poisson regression. PCV10 effectiveness/VE on vaccine-type carriage was calculated as 1-RR*100. Results The prevalence of pneumococcal carriage was 41.0% (95%CI: 38.4–43.7). Serotypes covered by PCV10 and PCV13 were 35.2% and 53.0%, respectively. Vaccine serotypes 6B (11.6%), 23F (7.8%), 14 (6.8%), and 19F (6.6%) were the most frequently observed. After adjusted for confounders, children who had received 2p+0 or 3p+0 dosing schedule presented a significant reduction in pneumococcal vaccine-type carriage, with PCV10 VE equal to 35.9% (95%CI: 4.2–57.1; p?=?0.030) and 44.0% (95%CI: 14.–63.5; p?=?0.008), respectively, when compared with unvaccinated children. For children who received one catch-up dose, no significant VE was detected (p?=?0.905). Conclusion PCV10 was associated with high protection against vaccine-type carriage with 2p+0 and 3p+0 doses for children vaccinated before the second semester of life. The continuous evaluation of carriage serotypes distribution is likely to be useful for evaluating the long-term effectiveness and impact of pneumococcal vaccination on serotypes reduction. PMID:24892409

Andrade, Ana Lucia; Ternes, Yves Mauro; Vieira, Maria Aparecida; Moreira, Weslley Garcia; Lamaro-Cardoso, Juliana; Kipnis, Andre; Cardoso, Maria Regina; Brandileone, Maria Cristina; Moura, Iaci; Pimenta, Fabiana C.; da Gloria Carvalho, Maria; Saraiva, Fabricia Oliveira; Toscano, Cristiana Maria; Minamisava, Ruth

2014-01-01

130

Quadrivalent meningococcal vaccination of adults: phase III comparison of an investigational conjugate vaccine, MenACWY-CRM, with the licensed vaccine, Menactra.  

PubMed

Neisseria meningitidis is a leading cause of bacterial meningitis in the United States, with the highest case fatality rates reported for individuals > or = 15 years of age. This study compares the safety and immunogenicity of the Novartis Vaccines investigational quadrivalent meningococcal CRM(197) conjugate vaccine, MenACWY-CRM, to those of the licensed meningococcal conjugate vaccine, Menactra, when administered to healthy adults. In this phase III multicenter study, 1,359 adults 19 to 55 years of age were randomly assigned to one of four groups (1:1:1:1 ratio) to receive a single dose of one of three lots of MenACWY-CRM or a single dose of Menactra. Serum samples obtained at baseline and 1 month postvaccination were tested for serogroup-specific serum bactericidal activity using human complement (hSBA). The hSBA titers following vaccination with MenACWY-CRM and Menactra were compared in noninferiority and prespecified superiority analyses. Reactogenicity was similar in the MenACWY-CRM and Menactra groups, and neither vaccine was associated with a serious adverse event. When compared with Menactra, MenACWY-CRM met the superiority criteria for the proportions of recipients achieving a seroresponse against serogroups C, W-135, and Y and the proportion of subjects achieving postvaccination titers of > or = 1:8 for serogroups C and Y. MenACWY-CRM's immunogenicity was statistically noninferior (the lower limit of the two-sided 95% confidence interval was more than -10%) to that of Menactra for all four serogroups, with the postvaccination hSBA geometric mean titers being consistently higher for MenACWY-CRM than for Menactra. MenACWY-CRM is well tolerated in adults 19 to 55 years of age, with immune responses to each of the serogroups noninferior and, in some cases, statistically superior to those to Menactra. PMID:19812260

Reisinger, Keith S; Baxter, Roger; Block, Stanley L; Shah, Jina; Bedell, Lisa; Dull, Peter M

2009-12-01

131

Quadrivalent Meningococcal Vaccination of Adults: Phase III Comparison of an Investigational Conjugate Vaccine, MenACWY-CRM, with the Licensed Vaccine, Menactra?  

PubMed Central

Neisseria meningitidis is a leading cause of bacterial meningitis in the United States, with the highest case fatality rates reported for individuals ?15 years of age. This study compares the safety and immunogenicity of the Novartis Vaccines investigational quadrivalent meningococcal CRM197 conjugate vaccine, MenACWY-CRM, to those of the licensed meningococcal conjugate vaccine, Menactra, when administered to healthy adults. In this phase III multicenter study, 1,359 adults 19 to 55 years of age were randomly assigned to one of four groups (1:1:1:1 ratio) to receive a single dose of one of three lots of MenACWY-CRM or a single dose of Menactra. Serum samples obtained at baseline and 1 month postvaccination were tested for serogroup-specific serum bactericidal activity using human complement (hSBA). The hSBA titers following vaccination with MenACWY-CRM and Menactra were compared in noninferiority and prespecified superiority analyses. Reactogenicity was similar in the MenACWY-CRM and Menactra groups, and neither vaccine was associated with a serious adverse event. When compared with Menactra, MenACWY-CRM met the superiority criteria for the proportions of recipients achieving a seroresponse against serogroups C, W-135, and Y and the proportion of subjects achieving postvaccination titers of ?1:8 for serogroups C and Y. MenACWY-CRM's immunogenicity was statistically noninferior (the lower limit of the two-sided 95% confidence interval was more than ?10%) to that of Menactra for all four serogroups, with the postvaccination hSBA geometric mean titers being consistently higher for MenACWY-CRM than for Menactra. MenACWY-CRM is well tolerated in adults 19 to 55 years of age, with immune responses to each of the serogroups noninferior and, in some cases, statistically superior to those to Menactra. PMID:19812260

Reisinger, Keith S.; Baxter, Roger; Block, Stanley L.; Shah, Jina; Bedell, Lisa; Dull, Peter M.

2009-01-01

132

Selective Effects of a Morphine Conjugate Vaccine on Heroin and Metabolite Distribution and Heroin-Induced Behaviors in Rats  

PubMed Central

Morphine conjugate vaccines have effectively reduced behavioral effects of heroin in rodents and primates. To better understand how these effects are mediated, heroin and metabolite distribution studies were performed in rats in the presence and absence of vaccination. In non-vaccinated rats 6-monoacetylmorphine (6-MAM) was the predominant opioid in plasma and brain as early as 1 minute after i.v. administration of heroin and for up to 14 minutes. Vaccination with morphine conjugated to keyhole limpet hemocyanin (M-KLH) elicited high titers and concentrations of antibodies with high affinity for heroin, 6-MAM, and morphine. Four minutes after heroin administration vaccinated rats showed substantial retention of all three opioids in plasma compared to controls and reduced 6-MAM and morphine, but not heroin, distribution to brain. Administration of 6-MAM rather than heroin in M-KLH vaccinated rats showed a similar drug distribution pattern. Vaccination reduced heroin-induced analgesia and blocked heroin-induced locomotor activity throughout 2 weeks of repeated testing. Higher serum opioid-specific antibody concentrations were associated with higher plasma opioid concentrations, lower brain 6-MAM and morphine concentrations, and lower heroin-induced locomotor activity. Serum antibody concentrations over 0.2 mg/ml were associated with substantial effects on these measures. These data support a critical role for 6-MAM in mediating the early effects of i.v. heroin and suggest that reducing 6-MAM concentration in brain is essential to the efficacy of morphine conjugate vaccines. PMID:23220743

Pravetoni, M.; Harris, A.C.; Birnbaum, A.K.; Pentel, P.R.

2013-01-01

133

Synthetic Teichoic Acid Conjugate Vaccine against Nosocomial Gram-Positive Bacteria  

PubMed Central

Lipoteichoic acids (LTA) are amphiphilic polymers that are important constituents of the cell wall of many Gram-positive bacteria. The chemical structures of LTA vary among organisms, albeit in the majority of Gram-positive bacteria the LTAs feature a common poly-1,3-(glycerolphosphate) backbone. Previously, the specificity of opsonic antibodies for this backbone present in some Gram-positive bacteria has been demonstrated, suggesting that this minimal structure may be sufficient for vaccine development. In the present work, we studied a well-defined synthetic LTA-fragment, which is able to inhibit opsonic killing of polyclonal rabbit sera raised against native LTA from Enterococcus faecalis 12030. This promising compound was conjugated with BSA and used to raise rabbit polyclonal antibodies. Subsequently, the opsonic activity of this serum was tested in an opsonophagocytic assay and specificity was confirmed by an opsonophagocytic inhibition assay. The conjugated LTA-fragment was able to induce specific opsonic antibodies that mediate killing of the clinical strains E. faecalis 12030, Enterococcus faecium E1162, and community-acquired Staphylococcus aureus strain MW2 (USA400). Prophylactic immunization with the teichoic acid conjugate and with the rabbit serum raised against this compound was evaluated in active and passive immunization studies in mice, and in an enterococcal endocarditis rat model. In all animal models, a statistically significant reduction of colony counts was observed indicating that the novel synthetic LTA-fragment conjugate is a promising vaccine candidate for active or passive immunotherapy against E. faecalis and other Gram-positive bacteria. PMID:25333799

Laverde, Diana; Wobser, Dominique; Romero-Saavedra, Felipe; Hogendorf, Wouter; van der Marel, Gijsbert; Berthold, Martin; Kropec, Andrea; Codee, Jeroen; Huebner, Johannes

2014-01-01

134

Evolving Role of 13-valent Pneumococcal Conjugate Vaccine in Clinical Practice.  

PubMed

Since the introduction of 7-valent pneumococcal conjugate vaccine (PCV7), PCVs with extended coverage have become available, and there is emerging global evidence that these vaccines, in particular PCV13, have further reduced rates of invasive pneumococcal disease compared with PCV7. The present article aims to address emerging topics related to PCV13 use in routine clinical practice; specifically: (1) the potential role of high-valent PCVs in reducing pneumococcal disease burden; (2) the impact of PCVs on nasopharyngeal carriage and how this may contribute to reductions in otitis media and pneumonia, as well as the prevalence of resistant pneumococcal strains; (3) new PCV13 indications and (4) importance of schedule adherence for PCV in the prevention of cases of vaccine serotype-specific invasive pneumococcal disease. The beneficial effects of PCVs in protecting individuals from a wide spectrum of pneumococcal diseases can be increased by improving the vaccine coverage and adhering to the recommended vaccination schedules. There is increasing evidence that PCV13 has reduced much of the post-PCV7 burden of pneumococcal diseases in the pediatric community, including reducing pneumococcal colonization and the incidence of invasive pneumococcal disease and mucosal diseases. This has also led to a reduction in antibiotic-resistant pneumococcal diseases. The role of PCV13 in clinical practice is evolving, with PCV13 now available for children and adolescents between the ages of 6 weeks and 17 years, thus ensuring that children in all age groups can be protected against vaccine-serotype pneumococcal diseases. Continued surveillance is warranted to monitor the impact of PCV13 on disease burden. PMID:24618937

Azzari, Chiara; Martinón-Torres, Federico; Schmitt, Heinz-Josef; Dagan, Ron

2014-08-01

135

Safety, immunogenicity and efficacy of pneumococcal conjugate vaccine in HIV-infected individuals  

PubMed Central

Streptococcus pneumoniae is the leading bacterial opportunistic infection in HIV-infected individuals. Anti-retroviral treatment (ART) of HIV-infected individuals reduces their risk of invasive pneumococcal disease (IPD), however, it remains 20- to 40-fold greater compared with age-matched general population. This review summarizes the available published data on the immunogenicity, safety and efficacy of pneumococcal polysaccharide-protein conjugate vaccines (PCV) in HIV-infected children and adults.   Several studies have demonstrated that PCV are safe in the HIV-infected persons. Although PCV are immunogenic in HIV-infected infants, the antibodies produced are functionally impaired, there is possibly a lack or loss of anamnestic responses and immunity declines in later life However, quantitative and qualitative antibody responses to PCV in HIV-infected infants are enhanced when vaccination occurs whilst on ART, as well as if vaccination occurs when the CD4+ cell percentage is ? 25% and if the nadir CD4+ is >15%. Although the efficacy of PCV was lower, the vaccine preventable burden of hospitalization for IPD and clinical pneumonia were 18-fold and 9-fold greater, respectively, in HIV-infected children compared with –uninfected children. In HIV-infected adults, PCV vaccination induces more durable and functional antibody responses in individuals on ART at the time of vaccination than in ART-naive adults, independently of baseline CD4+ cell count, although there does not appear to be much benefit from a second-dose of PCV. PCV has also been shown to reduce the risk of recurrent IPD by 74% in HIV-infected adults not on ART, albeit, also with subsequent decline in immunity and protection. PMID:22426374

Nunes, Marta C.; Madhi, Shabir A.

2012-01-01

136

[Pneumococcal conjugate vaccine failure in HIV-infected child. Clinical case].  

PubMed

Despite appropriate antimicrobial therapy and vaccination, invasive pneumococcal infections remain associated with significant mortality, especially in selected high-risk groups (asplenic, humoral immunity deficient patients, etc.). We present a 13-year-old caucasian boy with HIV infection (vertical transmission). He received treatment with highly-active antiretroviral therapy (amprenavir, lamivudine and zidovudine) and vaccination with 23-valent vaccine (6 years old) and 7-valent pneumococcal conjugate vaccine (10 years old). His CD4 count and his viral load at these times were 2,063/microl and 13461 cop/ml, when he was 6 years old and 1,315/microl and 32400 cop/ml when he was 10 years old, respectively. The latest CD4 count (1,000/microl) and his viral load (3800 cop/ml) confirmed satisfactory control of the disease. He was referred to our emergency department presenting with fever, head and stomach-ache and vomiting. In the following hours his condition continued to deteriorate and depressed level of consciousness and meningismus were observed. Streptococcus pneumoniae, serotype 18 C, was detected in blood and cerebrospinal fluid cultures. Despite appropriate treatment with antibiotics (cefotaxime and vancomycin) and anti-oedema medications, brain-death was confirmed 24 hours after his admittance. PMID:18620680

Rives Ferreiro, M T; Menéndez Suso, J J; Calderón Llopis, B; De José Gómez, M I; Alvarado Ortega, F; Ruza Tarrio, F J

2008-07-01

137

Cost-effectiveness and cost utility analysis of three pneumococcal conjugate vaccines in children of Peru  

PubMed Central

Background The clinical and economic burden associated with invasive and non-invasive pneumococcal and non-typeable Haemophilus influenzae (NTHi) diseases is substantial in the Latin America and Caribbean region, where pneumococcal vaccines have only been introduced to a few countries. This study analyzed the cost-effectiveness and cost utility of three different pneumococcal conjugate vaccines (PCVs) for Peru. Methods A Markov model that simulated the disease processes in a birth cohort over a lifetime, within 1,128 month cycles was used to evaluate the cost-effectiveness of 10-valent pneumococcal NTHi protein D conjugate vaccine (PHiD-CV) and 7- and 13-valent PCVs (PCV-7 and PCV-13). Expected quality-adjusted life years (QALYs), cost-savings and incremental cost-effectiveness ratios (ICERs) were calculated. Results Without vaccination, pneumonia was associated with the greatest health economic burden (90% of QALYs lost and 63% of lifetime direct medical costs); while acute otitis media (AOM) was responsible for 1% of QALYs lost and 25% of direct medical costs. All vaccines were predicted to be cost-effective for Peru, with PHiD-CV being most cost-effective. PHiD-CV was predicted to generate 50 more QALYs gained and required a reduced investment (?US$ 3.4 million) versus PCV-13 (discounted data), and was therefore dominant and cost saving. The probabilistic sensitivity analysis showed that PHiD-CV generated more QALYs gained at a reduced cost than PCV-13 in 84% of the simulations and less QALYs gains at a reduced cost in 16%. Additional scenarios using different assumptions on vaccine efficacies based on previous evidence were explored, but no significant change in the overall cost-effective results were observed. Conclusions The results of this modeling study predict that PCVs are likely to be a cost-effective strategy to help relieve the epidemiological and economic burden associated with pediatric pneumococcal and NTHi diseases for Peru. PHiD-CV is likely to be a dominant (better health gains at a reduced net cost) intervention compared to PCV-13 or PCV-7. The most significant drivers for these results are the better health and economic profile of PHiD-CV against AOM and its reduced cost per dose available through the PAHO Revolving Fund in the LAC region. PMID:24171921

2013-01-01

138

Randomized, Controlled, Multicenter Study of the Immunogenicity and Safety of a Fully Liquid Combination Diphtheria-Tetanus Toxoid-Five-Component Acellular Pertussis (DTaP5), Inactivated Poliovirus (IPV), and Haemophilus influenzae Type b (Hib) Vaccine Compared with a DTaP3-IPV/Hib Vaccine Administered at 3, 5, and 12 Months of Age  

PubMed Central

This study compared the levels of immunogenicity and safety of diphtheria–tetanus toxoid–five-component acellular pertussis (DTaP5), inactivated poliovirus (IPV), and Haemophilus influenzae type b (Hib) (DTaP5-IPV-Hib) and DTaP3-IPV/Hib vaccines for study participants 3, 5, and 12 months of age. Post-dose 3 noninferiority criteria comparing DTaP5-IPV-Hib to DTaP3-IPV/Hib using rates of seroprotection were demonstrated against diphtheria, tetanus, and polio types 1 to 3, but not for polyribosylribitol phosphate (PRP). While PRP did not meet noninferiority criteria, the seroprotection rate and geometric mean concentration (GMC) were high, indicating a clinically robust immune response. GMCs or titers for other antigens (including pertussis) and the safety profiles were generally similar between groups. Fully liquid DTaP5-IPV-Hib can be administered using the 3-, 5-, and 12-month vaccination schedule. (This study has been registered at ClinicalTrials.gov under registration no. NCT00287092.) PMID:23966556

Silfverdal, Sven Arne; Boisnard, Florence; Thomas, Stephane; Mwawasi, Grace; Reynolds, Donna

2013-01-01

139

Immunogenicity and safety of pneumococcal 7-valent conjugate vaccine (diphtheria CRM(197) protein conjugate; Prevenar ) in Korean infants: differences that are found in Asian children.  

PubMed

This study was conducted to determine the immunogenicity and safety of a 7-valent CRM197 protein conjugated pneumococcal vaccine (PCV7) in Korean infants immunized at 2, 4 and 6 months. A total of 202 infants were enrolled and 146 and 141 infants were, respectively, included in post-2nd dose and post-3rd dose immunogenicity evaluations conducted on a per protocol basis. After two and three PCV7 vaccinations, 63.0-98.0 and 97.2-100% of infants achieved an antibody level of >or=0.35microg/mL, respectively, with a lowest against serotype 6B. No vaccination-related serious adverse reactions were observed. Thus, PCV7 appears safe and highly immunogenic in Korean infants, and adopting two doses for a primary series could be a feasible option for facilitating vaccine coverage rate. PMID:17931753

Kim, Nam-Hee; Lee, Jina; Lee, Sang Jeong; Lee, Hyunju; Kim, Kyung-Hyo; Park, Su-Eun; Lee, Hoan-Jong

2007-11-01

140

Cost-effectiveness of new pneumococcal conjugate vaccines in Turkey: a decision analytical model  

PubMed Central

Background Streptococcus pneumoniae infections, which place a considerable burden on healthcare resources, can be reduced in a cost-effective manner using a 7-valent pneumococcal conjugate vaccine (PCV-7). We compare the cost effectiveness of a 13-valent PCV (PCV-13) and a 10-valent pneumococcal non-typeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV) with that of PCV-7 in Turkey. Methods A cost-utility analysis was conducted and a decision analytical model was used to estimate the proportion of the Turkish population <10 years old that would experience 10 mutually exclusive outcomes over the course of 1 year from a perspective of a healthcare system. Model outcomes were adjusted according to the population demographics and region-specific serotype distribution in Turkey. Health outcomes and direct healthcare costs were simulated for PCV-7, PCV-13 and PHiD-CV. Results PCV-13 and PHiD-CV are projected to have a substantial impact on pneumococcal disease in Turkey versus PCV-7, with 2,223 and 3,156 quality-adjusted life years (QALYs) and 2,146 and 2,081 life years, respectively, being saved under a 3+1 schedule. Projections of direct medical costs showed that a PHiD-CV vaccination programme would provide the greatest cost savings, offering additional savings of US$11,718,813 versus PCV-7 and US$8,235,010 versus PCV-13. Probabilistic sensitivity analysis showed that PHiD-CV dominated PCV-13 in terms of QALYs gained and cost savings in 58.3% of simulations. Conclusion Under the modeled conditions, PHiD-CV would provide the most cost-effective intervention for reducing pneumococcal disease in Turkish children. PMID:23137037

2012-01-01

141

Pediatric Invasive Pneumococcal Disease in the United States in the Era of Pneumococcal Conjugate Vaccines  

PubMed Central

Summary: Invasive infections caused by Streptococcus pneumoniae continue to be a major cause of morbidity and mortality worldwide, especially in children under 5 years of age. In the United States, 90% of invasive pneumococcal infections in children are caused by 13 serotypes of S. pneumoniae. The licensure (in 2000) and subsequent widespread use of a heptavalent pneumococcal conjugate vaccine (PCV7) have had a significant impact on decreasing the incidence of serious invasive pneumococcal disease (IPD) in all age groups, especially in children under 2 years of age. However, the emergence of replacement non-PCV7 serotypes, especially serotype 19A, has resulted in an increase in the incidence of serious and invasive infections. In 2010, a 13-valent PCV was licensed in the United States. However, the impact that this vaccine will have on IPD remains to be seen. The objectives of this review are to discuss the epidemiology of serious and invasive pneumococcal infections in the United States in the PCV era and to review some of the pneumococcal vaccines that are in development. PMID:22763632

2012-01-01

142

Invasive Pneumococcal Disease after Routine Pneumococcal Conjugate Vaccination in Children, England and Wales  

PubMed Central

We assessed known risk factors, clinical presentation, and outcome of invasive pneumococcal disease (IPD) in children 3–59 months of age after introduction of the 7-valent pneumococcal conjugate vaccine (PCV7) in England and Wales. During September 2006–March 2010, a total of 1,342 IPD episodes occurred in 1,332 children; 14.9% (198/1,332) had comorbidities. Compared with IPD caused by PCV7 serotypes (44/248; 17.7%), comorbidities were less common for the extra 3 serotypes in the 10-valent vaccine (15/299; 5.0%) but similar to the 3 additional PCV13 serotypes (45/336; 13.4%) and increased for the 11 extra serotypes in 23-valent polysaccharide vaccine (PPV23) (39/186; 21.0%) and non-PPV23 serotypes (38/138; 27.5%). Fifty-two (3.9%) cases resulted from PCV7 failure; 9 (0.7%) case-patients had recurrent IPD. Case-fatality rate was 4.4% (58/1,332) but higher for meningitis (11.0%) and children with comorbidities (9.1%). Thus, comorbidities were more prevalent in children with IPD caused by non-PCV13 serotypes and were associated with increased case fatality. PMID:23259937

Slack, Mary P.E.; Andrews, Nick J.; Waight, Pauline A.; Borrow, Ray; Miller, Elizabeth

2013-01-01

143

Piliation of Invasive Streptococcus pneumoniae Isolates in the Era before Pneumococcal Conjugate Vaccine Introduction in Malawi  

PubMed Central

The pneumococcal pilus has been shown to be an important determinant of adhesion and virulence in mouse models of colonization, pneumonia, and bacteremia. A pilus is capable of inducing protective immunity, supporting its inclusion in next-generation pneumococcal protein vaccine formulations. Whether this vaccine target is common among pneumococci in sub-Saharan Africa is uncertain. To define the prevalence and genetic diversity of type I and II pili among invasive pneumococci in Malawi prior to the introduction of the 13-valent pneumococcal conjugate vaccine (PCV13) into routine childhood immunization, we examined 188 Streptococcus pneumoniae isolates collected between 2002 and 2008 (17% serotype 1). In this region of high disease burden, we found a low frequency of invasive piliated pneumococci (14%) and pilus gene sequence diversity similar to that seen previously in multiple global pneumococcal lineages. All common serotypes with pilus were covered by PCV13 and so we predict that pilus prevalence will be reduced in the Malawian pneumococcal population after PCV13 introduction. PMID:24027261

Gray, Katherine; Kamng'ona, Arox; Cornick, Jennifer; Bentley, Stephen D.; Heyderman, Robert S.; Everett, Dean B.

2013-01-01

144

Efficacy of a Conjugate Vaccine Containing Polymannuronic Acid and Flagellin against Experimental Pseudomonas aeruginosa Lung Infection in Mice?  

PubMed Central

Vaccines that could effectively prevent Pseudomonas aeruginosa pulmonary infections in the settings of cystic fibrosis (CF) and nosocomial pneumonia could be exceedingly useful, but to date no effective immunotherapy targeting this pathogen has been successfully developed for routine use in humans. Evaluations using animals and limited human trials of vaccines and their associated immune effectors against different P. aeruginosa antigens have suggested that antibody to the conserved surface polysaccharide alginate, as well as the flagellar proteins, often give high levels of protection. However, alginate itself does not elicit protective antibody in humans, and flagellar vaccines containing the two predominant serotypes of this antigen may not provide sufficient coverage against variant flagellar types. To evaluate if combining these antigens in a conjugate vaccine would be potentially efficacious, we conjugated polymannuronic acid (PMA), containing the blocks of mannuronic acid conserved in all P. aeruginosa alginates, to type a flagellin (FLA) and evaluated immunogenicity, opsonic killing activity, and passive protective efficacy in mice. The PMA-FLA conjugate was highly immunogenic in mice and rabbits and elicited opsonic antibodies against mucoid but not nonmucoid P. aeruginosa, but nonetheless rabbit antibody to PMA-FLA showed evidence of protective efficacy against both types of this organism in a mouse lung infection model. Importantly, the PMA-FLA conjugate vaccine did not elicit antibodies that neutralized the Toll-like receptor 5 (TLR5)-activating activity of flagellin, an important part of innate immunity to flagellated microbial pathogens. Conjugation of PMA to FLA appears to be a promising path for developing a broadly protective vaccine against P. aeruginosa. PMID:21628521

Campodonico, Victoria L.; Llosa, Nicolas J.; Bentancor, Leticia V.; Maira-Litran, Tomas; Pier, Gerald B.

2011-01-01

145

The effect of Haemophilus influenzae type B and pneumococcal conjugate vaccines on childhood meningitis mortality: a systematic review  

PubMed Central

Background Two of the most prevalent causes of severe bacterial meningitis in children, Haemophilus influenzae type B (Hib) and Streptococcus pneumoniae, are preventable by existing vaccines increasingly available in developing countries. Our objective was to estimate the dose-specific effect of Hib and pneumococcal conjugate vaccines (PCV) on childhood meningitis mortality in low-income countries for use in the Lives Saved Tool (LiST). Methods We systematically searched and reviewed published vaccine efficacy trials and observational studies reporting the effect of Hib or PCV vaccines on organism-specific meningitis, bacterial meningitis and all-cause meningitis incidence and mortality among children less than five years old in low- and middle-income countries. Data collection and quality assessments were performed using standardized guidelines. For outcomes available across multiple studies (?2) and approximating meningitis mortality, we pooled estimates reporting dose-specific effects using random effects meta-analytic methods, then combined these with meningitis etiology data to determine the preventable fraction of childhood meningitis mortality for inclusion in LiST. Results We identified 18 studies of Hib conjugate vaccines reporting relevant meningitis morbidity and mortality outcomes (2 randomized controlled trials [RCTs], 16 observational studies) but few provided dose-specific effects. A meta-analysis of four case-control studies examined the dose-specific effect of Hib conjugate vaccines on Hib meningitis morbidity (1 dose: RR=0.64, 95% CI 0.38-1.06; 2 doses: RR=0.09, 95% CI 0.03-0.27; 3 doses: RR=0.06, 95% CI 0.02-0.22), consistent with results from single RCTs. Pooled estimates of two RCTs provided evidence for the effect of three doses of PCV on vaccine-serotype meningitis morbidity (RR=0.16, 95% CI 0.02-1.20). We considered these outcomes of severe disease as proxy estimates for meningitis mortality and combined the estimates of protective effects with meningitis etiology data to provide an estimate of the preventable fraction of childhood meningitis mortality with three doses of Hib (38-43%) and pneumococcal conjugate vaccines (28-35%) for use in LiST. Conclusions Few RCTs or vaccine effectiveness studies evaluated the dose-specific impact of Hib and PCV vaccines on childhood meningitis mortality, necessitating use of proxy measures to estimate population impact in LiST. Our analysis indicates that approximately three-quarters of meningitis deaths are preventable with existing Hib and PCV vaccines. PMID:24564188

2013-01-01

146

Concentration and High Avidity of Pneumococcal Antibodies Persist at Least 4 Years after Immunization with Pneumococcal Conjugate Vaccine in Infancy  

PubMed Central

To provide more extensive evidence of long-term effects of vaccination on immunity against Streptococcus pneumoniae, a follow-up study of the Finnish Otitis Media (FinOM) Vaccine Trial was conducted. One of the objectives was to assess the persistence and avidity of pneumococcal antibodies 4 years after pneumococcal vaccination given in infancy. Children with complete follow-up in the FinOM trial up to 24 months of age were invited to a single visit in their fifth year of life. A blood sample was taken from all children for determination of anticapsular antibody concentrations to vaccine serotypes and avidity of antibodies to three serotypes. Children had been vaccinated at 2, 4, 6, and 12 months of age with 7-valent pneumococcal capsular polysaccharide, CRM197 conjugate vaccine (PCV7), or a control vaccine. Serum IgG antibody concentrations to vaccine serotypes remained significantly higher in children who had received PCV7 than in control children for 4 years after the fourth PCV7 dose. Concentrations of antibodies to frequently carried serotypes (6B and 19F) declined less than those of antibodies to a rarely carried serotype (4), suggesting that natural boosting contributed to antibody persistence. Furthermore, antibody avidity was significantly higher in PCV7 than control vaccine recipients. Four doses of PCV7 given in infancy elicit long-lasting antibody responses with high avidity. (This study has been registered at ClinicalTrials.gov under registration no. NCT00378417.) PMID:23658394

Ahman, Heidi; Palmu, Arto; Gronholm, Sinikka; Kilpi, Terhi

2013-01-01

147

Cost effectiveness of pediatric pneumococcal conjugate vaccines: a comparative assessment of decision-making tools  

PubMed Central

Background Several decision support tools have been developed to aid policymaking regarding the adoption of pneumococcal conjugate vaccine (PCV) into national pediatric immunization programs. The lack of critical appraisal of these tools makes it difficult for decision makers to understand and choose between them. With the aim to guide policymakers on their optimal use, we compared publicly available decision-making tools in relation to their methods, influential parameters and results. Methods The World Health Organization (WHO) requested access to several publicly available cost-effectiveness (CE) tools for PCV from both public and private provenance. All tools were critically assessed according to the WHO's guide for economic evaluations of immunization programs. Key attributes and characteristics were compared and a series of sensitivity analyses was performed to determine the main drivers of the results. The results were compared based on a standardized set of input parameters and assumptions. Results Three cost-effectiveness modeling tools were provided, including two cohort-based (Pan-American Health Organization (PAHO) ProVac Initiative TriVac, and PneumoADIP) and one population-based model (GlaxoSmithKline's SUPREMES). They all compared the introduction of PCV into national pediatric immunization program with no PCV use. The models were different in terms of model attributes, structure, and data requirement, but captured a similar range of diseases. Herd effects were estimated using different approaches in each model. The main driving parameters were vaccine efficacy against pneumococcal pneumonia, vaccine price, vaccine coverage, serotype coverage and disease burden. With a standardized set of input parameters developed for cohort modeling, TriVac and PneumoADIP produced similar incremental costs and health outcomes, and incremental cost-effectiveness ratios. Conclusions Vaccine cost (dose price and number of doses), vaccine efficacy and epidemiology of critical endpoint (for example, incidence of pneumonia, distribution of serotypes causing pneumonia) were influential parameters in the models we compared. Understanding the differences and similarities of such CE tools through regular comparisons could render decision-making processes in different countries more efficient, as well as providing guiding information for further clinical and epidemiological research. A tool comparison exercise using standardized data sets can help model developers to be more transparent about their model structure and assumptions and provide analysts and decision makers with a more in-depth view behind the disease dynamics. Adherence to the WHO guide of economic evaluations of immunization programs may also facilitate this process. Please see related article: http://www.biomedcentral.com/1741-7007/9/55 PMID:21569402

2011-01-01

148

Meningococcal Serogroup A, C, W135 and Y Conjugated Vaccine: A Cost-Effectiveness Analysis in the Netherlands  

PubMed Central

Background In 2002, vaccination with a serogroup C meningococcal conjugate vaccine (MenC) was introduced in the Netherlands for all children aged 14 months. Despite its success, herd immunity may wane over time. Recently, a serogroup A,C,W135,Y meningococcal conjugate vaccine (MenACWY) was licensed for use in subjects of 12 months of age and above. Objectives To evaluate the cost-effectiveness of meningococcal vaccination at 14 months and an additional vaccination at the age of 12 years, both with the MenACWY vaccine. Methods A decision analysis cohort model, with 185,000 Dutch newborns, was used to evaluate the cost-effectiveness of different immunization strategies. For strategies including a vaccination at 12 years of age, an additional cohort with adolescents aged 12 years was followed. The incremental cost-effectiveness ratio (ICER) was estimated for the current disease incidence and for a scenario when herd immunity is lost. Results Vaccination with MenACWY at 14 months is cost-saving. Vaccinating with MenACWY at 14 months and at 12 years would prevent 7 additional cases of meningococcal serogroup A,C,W135,Y disease in the birth cohort and adolescent cohort followed for 99 years compared to the current vaccine schedule of a single vaccination with MenC at 14 months. With the current incidence, this strategy resulted in an ICER of €635,334 per quality adjusted life year. When serogroup C disease incidence returns to pre-vaccination levels due to a loss of vaccine-induced herd-immunity, vaccination with MenACWY at 14 months and at 12 years would be cost-saving. Conclusions Routine vaccination with MenACWY is cost-saving. With the current epidemiology, a booster-dose with MenACWY is not likely cost-effective. When herd immunity is lost, a booster-dose has the potential of being cost-effective. A dynamic model should be developed for more precise estimation of the cost-effectiveness of the prevention of disappearance of herd immunity. PMID:23741448

van der Ende, Arie; Westra, Tjalke A.; Postma, Maarten J.

2013-01-01

149

Tetanus, Diphtheria (Td) Vaccine  

MedlinePLUS

Tenivac® (as a combination product containing Diphtheria, Tetanus Toxoids) ... Why get vaccinated?Tetanus and diphtheria are very serious diseases. They are rare in the United States today, but people who do become ...

150

Immunogenicity and safety of a meningococcal serogroup A, C, Y and W glycoconjugate vaccine, ACWY-TT.  

PubMed

A quadrivalent meningococcal serogroup A, C, W and Y conjugate vaccine (ACWY), utilising tetanus toxoid (TT) as its carrier protein (ACWY-TT; Nimenrix™, GlaxoSmithKline Vaccines, Rixensart, Belgium) has been demonstrated to be safe and immunogenic when administered to young children from 12 months of age, older children, adolescents, and adults. Administration of a single dose of ACWY-TT induces protective serum bactericidal antibodies against all four serogroups as well as good antibody persistence. Coadministration studies have demonstrated that ACWY-TT can be administered with diphtheria, tetanus, three-component acellular pertussis, hepatitis B, inactivated polio virus and Haemophilus influenzae type b conjugate vaccine (DTaP3-IPV-HBV/Hib, Infanrix™ hexa; GlaxoSmithKline Vaccines, Rixensart, Belgium); measles, mumps, rubella, varicella vaccine (Priorix-Tetra™; GlaxoSmithKline Vaccines, Rixensart, Belgium); 10-valent pneumococcal conjugate vaccine (Synflorix(®); GlaxoSmithKline Vaccines, Rixensart, Belgium); hepatitis A and B vaccine (Twinrix(®); GlaxoSmithKline Vaccines, Rixensart, Belgium); and seasonal influenza vaccine (Fluarix™; GlaxoSmithKline Vaccines, Rixensart, Belgium). Studies in young infants from 2 months of age have now commenced but immunisation with a single dose of ACWY-TT from 12 months of age is a safe and immunogenic option in the prevention of meningococcal disease. PMID:23712402

Findlow, Helen; Borrow, Ray

2013-05-01

151

Combined effects of antenatal receipt of influenza vaccine by mothers and pneumococcal conjugate vaccine receipt by infants: results from a randomized, blinded, controlled trial.  

PubMed

A 2 × 2 factorial trial was performed to determine the efficacy of antennal influenza vaccination of mothers plus pneumococcal conjugate vaccination of their infants against respiratory illness during early infancy. The efficacy of trivalent inactivated influenza vaccine (TIV; delivered to mothers) plus 7-valent pneumococcal vaccine (PCV7; delivered to infants) was higher than the efficacy of TIV alone or PCV7 alone. During the period of the study in which influenza was circulating, the efficacy of TIV plus PCV7 was 72.4% (95% confidence interval, 30.2%-89.1%) against febrile respiratory illness and 66.4% (95% CI, 14.3%-86.9%) against medically attended acute respiratory illness. PMID:23300160

Omer, Saad B; Zaman, Khalequ; Roy, Eliza; Arifeen, Shams E; Raqib, Rubhana; Noory, Laila; Seib, Katherine; Breiman, Robert F; Steinhoff, Mark C

2013-04-01

152

Licensure of a Haemophilus influenzae type b (Hib) vaccine (Hiberix) and updated recommendations for use of Hib vaccine.  

PubMed

On August 19, 2009, the Food and Drug Administration (FDA) licensed Hiberix (GlaxoSmithKline Biologicals, Rixensart, Belgium), a Haemophilus influenzae type b (Hib) conjugate vaccine composed of H. influenzae type b capsular polysaccharide (polyribosyl-ribitol-phosphate [PRP]) conjugated to inactivated tetanus toxoid (PRP-T). Hiberix is licensed for use as the booster (final) dose of the Hib vaccine series for children aged 15 months through 4 years (before the 5th birthday) who have received previously the primary series of Hib vaccination (consisting of 2 or 3 doses, depending on the formulation). The Advisory Committee on Immunization Practices (ACIP) recommends Hib booster vaccination for children at ages 12 through 15 months; however, because of the recent shortage of Hib vaccines, many children have deferred the booster dose and therefore require catch-up vaccination. This report summarizes the indications for Hiberix use and provides guidance on Hib booster dose administration based on increasing vaccine supplies. Vaccination recommendations in this report update the previous advisory on Hib booster administration (June 26, 2009), which advised that children with deferred booster doses receive it at the next regularly scheduled visit. Vaccination providers are now recommended to begin recall of children in need of the booster dose when feasible and monovalent Hib vaccine supply in the office is adequate. PMID:19763078

2009-09-18

153

Effects of an Oxycodone Conjugate Vaccine on Oxycodone Self-Administration and Oxycodone-Induced Brain Gene Expression in Rats  

PubMed Central

Prescription opioid abuse is an increasing public health concern in the USA. A vaccine comprising a hapten (OXY) conjugated to the carrier protein keyhole limpet hemocyanin (OXY-KLH) has been shown to attenuate the antinociceptive effects of oxycodone. Here, the vaccine's ability to prevent acquisition of intravenous (i.v.) oxycodone self-administration was studied in rats. Effects of vaccination on oxycodone-induced changes in the expression of several genes within the mesolimbic system, which are regulated by chronic opiate use, were also examined. Vaccination with OXY-KLH reduced the proportion of rats acquiring i.v. self-administration of oxycodone under a fixed ratio (FR) 3 schedule of reinforcement compared to control rats immunized with the unconjugated KLH carrier protein. Vaccination significantly reduced the mean number of infusions at FR3, total number of infusions, and total oxycodone intake during the entire protocol. Compared to oxycodone self-administering control rats immunized with the carrier alone, rats vaccinated with the OXY-KLH immunogen showed increased levels of adenylate cyclase 5 (Adcy5) and decreased levels of early growth response protein 2 (Egr2) and the early immediate gene c-Fos in the striatum. These data suggest that vaccination with OXY-KLH can attenuate the reinforcing effects of oxycodone at a clinically-relevant exposure level. Analysis of mRNA expression identified some addiction-relevant markers that may be of interest in understanding oxycodone effects or the protection provided by vaccination. PMID:25025380

Pravetoni, Marco; Pentel, Paul R.; Potter, David N.; Chartoff, Elena H.; Tally, Laura; LeSage, Mark G.

2014-01-01

154

Characterization of Heat-Stable (STa) Toxoids of Enterotoxigenic Escherichia coli Fused to Double Mutant Heat-Labile Toxin Peptide in Inducing Neutralizing Anti-STa Antibodies  

PubMed Central

A long-standing challenge in developing vaccines against enterotoxigenic Escherichia coli (ETEC), the most common bacteria causing diarrhea in children of developing countries and travelers to these countries, is to protect against heat-stable toxin type Ib (STa or hSTa). STa and heat-labile toxin (LT) are virulence determinants in ETEC diarrhea. LT antigens are often used in vaccine development, but STa has not been included because of its poor immunogenicity and potent toxicity. Toxic STa is not safe for vaccines, but only STa possessing toxicity is believed to be able to induce neutralizing antibodies. However, recent studies demonstrated that nontoxic STa derivatives (toxoids), after being fused to an LT protein, induced neutralizing antibodies and suggested that different STa toxoids fused to an LT protein might exhibit different STa antigenic propensity. In this study, we selected 14 STa toxoids from a mini-STa toxoid library based on toxicity reduction and reactivity to anti-native STa antibodies, and genetically fused each toxoid to a monomeric double mutant LT (dmLT) peptide for 14 STa-toxoid-dmLT toxoid fusions. These toxoid fusions were used to immunize mice and were characterized for induction of anti-STa antibody response. The results showed that different STa toxoids (in fusions) varied greatly in anti-STa antigenicity. Among them, STaN12S, STaN12T, and STaA14H were the top toxoids in inducing anti-STa antibodies. In vitro neutralization assays indicated that antibodies induced by the 3×STaN12S-dmLT fusion antigen exhibited the greatest neutralizing activity against STa toxin. These results suggested 3×STaN12S-dmLT is a preferred fusion antigen to induce an anti-STa antibody response and provided long-awaited information for effective ETEC vaccine development. PMID:24549325

Ruan, Xiaosai; Robertson, Donald C.; Nataro, James P.; Clements, John D.

2014-01-01

155

Cost-effectiveness of 2 + 1 dosing of 13-valent and 10-valent pneumococcal conjugate vaccines in Canada  

PubMed Central

Background Thirteen-valent pneumococcal conjugate vaccine (PCV13) and 10-valent pneumococcal conjugate vaccine (PCV10) are two recently approved vaccines for the active immunization against Streptococcus pneumoniae causing invasive pneumococcal disease in infants and children. PCV13 offers broader protection against Streptococcus pneumoniae; however, PCV10 offers potential protection against non-typeable Haemophilus influenza (NTHi). We examined public health and economic impacts of a PCV10 and PCV13 pediatric national immunization programs (NIPs) in Canada. Methods A decision-analytic model was developed to examine the costs and outcomes associated with PCV10 and PCV13 pediatric NIPs. The model followed individuals over the remainder of their lifetime. Recent disease incidence, serotype coverage, population data, percent vaccinated, costs, and utilities were obtained from the published literature. Direct and indirect effects were derived from 7-valent pneumococcal vaccine. Additional direct effect of 4% was attributed to PCV10 for moderate to severe acute otitis media to account for potential NTHi benefit. Annual number of disease cases and costs (2010 Canadian dollars) were presented. Results In Canada, PCV13 was estimated to prevent more cases of disease (49,340 when considering both direct and indirect effects and 7,466 when considering direct effects only) than PCV10. This translated to population gains of 258 to 13,828 more quality-adjusted life-years when vaccinating with PCV13 versus PCV10. Annual direct medical costs (including the cost of vaccination) were estimated to be reduced by $5.7 million to $132.8 million when vaccinating with PCV13. Thus, PCV13 dominated PCV10, and sensitivity analyses showed PCV13 to always be dominant or cost-effective versus PCV10. Conclusions Considering the epidemiology of pneumococcal disease in Canada, PCV13 is shown to be a cost-saving immunization program because it provides substantial public health and economic benefits relative to PCV10. PMID:22530841

2012-01-01

156

Characterization and optimization of heroin hapten-BSA conjugates: method development for the synthesis of reproducible hapten-based vaccines.  

PubMed

A potential new treatment for drug addiction is immunization with vaccines that induce antibodies that can abrogate the addictive effects of the drug of abuse. One of the challenges in the development of a vaccine against drugs of abuse is the availability of an optimum procedure that gives reproducible and high yielding hapten-protein conjugates. In this study, a heroin/morphine surrogate hapten (MorHap) was coupled to bovine serum albumin (BSA) using maleimide-thiol chemistry. MorHap-BSA conjugates with 3, 5, 10, 15, 22, 28, and 34 haptens were obtained using different linker and hapten ratios. Using this optimized procedure, MorHap-BSA conjugates were synthesized with highly reproducible results and in high yields. The number of haptens attached to BSA was compared by 2,4,6-trinitrobenzenesulfonic acid (TNBS) assay, modified Ellman's test and matrix assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS). Among the three methods, MALDI-TOF MS discriminated subtle differences in hapten density. The effect of hapten density on enzyme-linked immunosorbent assay (ELISA) performance was evaluated with seven MorHap-BSA conjugates of varying hapten densities, which were used as coating antigens. The highest antibody binding was obtained with MorHap-BSA conjugates containing 3-5 haptens. This is the first report that rigorously analyzes, optimizes and characterizes the conjugation of haptens to proteins that can be used for vaccines against drugs of abuse. The effect of hapten density on the ELISA detection of antibodies against haptens demonstrates the importance of careful characterization of the hapten density by the analytical techniques described. PMID:25084736

Torres, Oscar B; Jalah, Rashmi; Rice, Kenner C; Li, Fuying; Antoline, Joshua F G; Iyer, Malliga R; Jacobson, Arthur E; Boutaghou, Mohamed Nazim; Alving, Carl R; Matyas, Gary R

2014-09-01

157

Bactericidal antibody responses of juvenile rhesus monkeys immunized with group B Neisseria meningitidis capsular polysaccharide-protein conjugate vaccines.  

PubMed Central

Reports on the bactericidal activities of antibodies to group B Neisseria meningitidis capsular polysaccharide (B PS) are conflicting. Using three different complement sources, we analyzed the bactericidal activities of sera of juvenile rhesus monkeys immunized with five conjugate vaccines of B PS synthesized by different schemes, an Escherichia coli K92 conjugate, and a noncovalent complex of B PS with group B meningococcal outer membrane vesicles (B+OMV) (S. J. N. Devi, W. D. Zollinger, P. J. Snoy, J. Y. Tai, P. Costantini, F. Norelli, R. Rappuoli, and C. E. Frasch, Infect. Immun. 65:1045-1052, 1997). With rabbit complement, nearly all preimmune sera showed relatively high bactericidal titers, and all vaccines, except the K92 conjugate, induced a fourfold or greater increase in bactericidal titers in most of the monkeys vaccinated. In contrast, with human complement, most prevaccination sera showed no bactericidal activity and in most of the vaccine groups, little or no increase in bactericidal titer was observed. However, the covalent conjugation of P BS and OMV (B-OMV) administered with and without the Ribi adjuvant induced relatively high bactericidal titers which persisted up to 30 weeks. An analysis of the specificities of bactericidal antibodies revealed that absorption with E. coli K1 cells did not change the bactericidal titer with human complement but reduced the titers observed with the rabbit and monkey complements. A significant increase in anti-lipopolysaccharide (LPS) antibodies was elicited by the B-OMV conjugates, and nearly all of the bactericidal activity with human complement could be inhibited with the purified group B meningococcal L3,7,8 LPS. B-OMV covalently coupled via adipic acid dihydrazide elicited significantly elevated levels (P < or = 0.02) of anti-OMV antibodies compared to those of the noncovalently complexed B+OMV. An initial small-scale evaluation of B PS conjugates in adult human males appears feasible, with careful monitoring, to settle the inconsistent reports of the importance of source of complement in eliciting bacteriolysis. Subsequent analysis of resultant human antibodies for bacteriolysis, opsonophagocytosis, and protective efficacy in animal models may be the first step toward answering safety- and efficacy-related concerns about B PS conjugate vaccines. PMID:9038315

Zollinger, W D; Moran, E E; Devi, S J; Frasch, C E

1997-01-01

158

75 FR 7281 - Pediatric Advisory Committee; Notice of Meeting  

Federal Register 2010, 2011, 2012, 2013

...live, oral), Kinrix (Diphtheria and Tetanus Toxoids and Acellular Pertussis Adsorbed...Vaccine), Pentacel [Diphtheria and Tetanus Toxoids and Acellular Pertussis Adsorbed...Poliovirus and Haemophilus b Conjugate (Tetanus Toxoid Conjugate) Vaccine], and...

2010-02-18

159

Safety and Immunogenicity of Vi Conjugate Vaccines for Typhoid Fever in Adults, Teenagers, and 2- to 4YearOld Children in Vietnam  

Microsoft Academic Search

The capsular polysaccharide of Salmonella typhi, Vi, is an essential virulence factor and a protective vaccine for people older than 5 years. The safety and immunogenicity of two investigational Vi conjugate vaccines were evaluated in adults, 5- to 14-year-old children, and 2- to 4-year-old children in Vietnam. The conjugates were prepared with Pseudomonas aeruginosa recombinant exoprotein A (rEPA) as the

ZUZANA KOSSACZKA; FENG-YING C. LIN; VOANH HO; NGUYEN THI THANH THUY; PHAN VAN BAY; TRAN CONG THANH; DANG DUC TRACH; ARTHUR KARPAS; STEVEN HUNT; DOLORES A. BRYLA; RACHEL SCHNEERSON; JOHN B. ROBBINS; SHOUSUN C. SZU

1999-01-01

160

Mice vaccinated with the O-antigen of Francisella tularensis LVS lipopolysaccharide conjugated to bovine serum albumin develop varying degrees of protective immunity against systemic or aerosol challenge with virulent type A and type B strains of the pathogen  

Microsoft Academic Search

The purpose of this study was to evaluate the efficacy of a vaccine consisting of the O-polysaccharide of the lipopolysaccharide (LPS) of Francisella tularensis chemically conjugated to bovine serum albumin. The results show that conjugation preserved both the antigenicity and immunogenicity of the polysaccharide moiety. Mice vaccinated with the glyco-conjugate, but not with BSA alone, were completely protected against an

J. Wayne Conlan; Hua Shen; Ann Webb; Malcolm B Perry

2002-01-01

161

The potential of dextran-based glycoconjugates for development of Helicobacter pylori vaccine.  

PubMed

We have recently demonstrated that synthetic glycoconjugates based on delipidated lipopolysaccharide (LPS) of Helicobacter pylori and containing an ?(1-6)-glucan chain induced broadly cross-reactive functional antibodies in immunized animals. To investigate the candidacy of ?(1-6)-glucan as an alternative vaccine strategy we prepared glycoconjugates based on dextrans produced by lactic acid bacteria Leuconostoc mesenteroides B512F and consisting of linear ?(1-6)-glucan chains with limited branching. Three dextrans with averaged molecular masses of 5,000 Da, 3,500 Da and 1,500 Da, respectively, were modified with a diamino group-containing linker and conjugated to a carrier protein, tetanus toxoid (TT) or diphtheria toxoid (DT), and their immunological properties investigated. The conjugates were immunogenic in both rabbits and mice and induced specific IgG responses against ?(1-6)-glucan-expressing H. pylori LPS. Studies performed with post-immune sera of mice and rabbits immunized with dextran-based conjugates demonstrated cross-reactivity with LPS from typeable and non-typeable strains of H. pylori and selected mutants. The post-immune sera from rabbits that received the conjugates exhibited functional activity against ?(1-6)-glucan-positive strains of H. pylori. These data provide evidence that dextran-based conjugates may offer a simplified approach to the development of carbohydrate-based vaccines against H. pylori. PMID:23990317

Altman, Eleonora; Chandan, Vandana; Harrison, Blair

2014-01-01

162

Indirect Effect of 7-Valent Pneumococcal Conjugate Vaccine on Pneumococcal Carriage in Newborns in Rural Gambia: A Randomised Controlled Trial  

PubMed Central

Background Gambian infants frequently acquire Streptococcus pneumoniae soon after birth. We investigated the indirect effect of 7-valent pneumococcal conjugate vaccine (PCV-7) on pneumococcal acquisition in newborn Gambian babies. Methods Twenty-one villages were randomised to receive PCV-7 to all subjects (11 vaccinated villages) or to infants aged 2–30 months (10 control villages). Other control villagers received Meningococcal C conjugate vaccine. From 328 babies born during the trial, nasopharyngeal swabs were collected after birth, then weekly until 8 weeks of age when they received their first dose of PCV-7. Pneumococcal carriage and acquisition rates were compared between the study arms and with a baseline study. Results 57.4% of 2245 swabs were positive for S. pneumoniae. Overall carriage was similar in both arms. In vaccinated villages fewer infants carried pneumococci of vaccine serotypes (VT) (16.9% [31/184] vs. 37.5% [54/144], p<0.001) and more carried pneumococci of non-vaccine serotypes (NVT) (80.9% [149/184] vs. 75.7% [109/144], p?=?0.246). Infants from vaccinated villages had a significantly lower acquisition rate of VT (HR 0.39 [0.26–0.58], p<0.001) and increased acquisition of NVT (HR 1.16 [0.87–1.56], p?=?0.312). VT carriage (51.6% vs. 37.5%, p?=?031 in control and 46.1% vs. 16.8%, p<0.001 in vaccinated villages) and acquisition rates (HR 0.68 [0.50–0.92], p?=?0.013 in control villages and HR 0.31 [0.19–0.50], p<.001 in vaccinated villages) were significantly lower in both study arms than in the baseline study. NVT carriage (63.2% vs. 75.7%, p?=?0.037 in control and 67.2% vs. 75.3%, p?=?0.005 in vaccinated villages) and acquisition rates (HR 1.48 [1.06–2.06], p?=?0.022) and (HR 1.52 [1.11–2.10], p?=?0.010 respectively) were significantly higher. Conclusion PCV-7 significantly reduced carriage of VT pneumococci in unvaccinated infants. This indirect effect likely originated from both the child and adult vaccinated populations. Increased carriage of NVT pneumococci needs ongoing monitoring. Trial Registration ISRCTN Register 51695599 PMID:23185303

Egere, Uzochukwu; Townend, John; Roca, Anna; Akinsanya, Abiodun; Bojang, Abdoulie; Nsekpong, David; Greenwood, Brian; Adegbola, Richard A.; Hill, Philip C.

2012-01-01

163

DTaP(5)-IPV-Hib vaccine (Pediacel®).  

PubMed

Pediacel® is a fully liquid formulation of a diphtheria, tetanus, five-component acellular pertussis, inactivated poliovirus and Haemophilus influenzae type b combination vaccine, which does not require reconstitution. Both vial and prefilled syringe presentations of Pediacel® are available for use in the EU. In active-controlled clinical trials, primary and/or booster vaccination with Pediacel® was highly immunogenic, eliciting strong and sustained serologic responses against all its component toxoids/antigens when administered according to a variety of different schedules. In particular, pivotal studies showed that Pediacel® was generally similar and/or noninferior to reconstituted pentavalent and hexavalent diphtheria, tetanus, and acellular pertussis-based combination vaccines in terms of the seroprotection rates elicited against the diphtheria, tetanus, poliovirus, and Haemophilus influenzae type b components that these products have in common, as well as in terms of the seroresponse/booster response rates elicited against the acellular pertussis components that these products have in common. Differences in immune responses between Pediacel® and these vaccines were considered unlikely to be clinically significant. There was no clear evidence of clinically relevant changes in the immunogenicity of Pediacel® (or the coadministered vaccine) when given concomitantly with meningococcal group C conjugate, pneumococcal conjugate, or hepatitis B vaccines in clinical studies. Pediacel® was generally well tolerated and demonstrated low reactogenicity in clinical trials. It had an adverse event profile generally similar to that of other combination vaccines based on diphtheria, tetanus and acellular pertussis vaccine, including Infanrix®-IPV+Hib and Infanrix® hexa. PMID:21999652

Frampton, James E

2011-12-01

164

PspA Family Distribution, unlike Capsular Serotype, Remains Unaltered following Introduction of the Heptavalent Pneumococcal Conjugate Vaccine  

PubMed Central

Pneumococcal conjugate vaccines (PCVs) are recommended for the prevention of invasive pneumococcal disease (IPD) in young children. Since the introduction of the heptavalent pneumococcal vaccine (PCV7) in 2000, IPD caused by serotypes in the vaccine has almost been eliminated, and previously uncommon capsular serotypes now cause most cases of pediatric IPD in the United States. One way to protect against these strains would be to add cross-reactive protein antigens to new vaccines. One such protein is pneumococcal surface protein A (PspA). Prior to 2000, PspA families 1 and 2 were expressed by 94% of isolates. Because PCV7 vaccine pressure has resulted in IPD caused by capsular serotypes that were previously uncommon and unstudied for PspA expression, it was possible that many of the new strains expressed different PspA antigens or even lacked PspA. Of 157 pediatric invasive pneumococcal isolates collected at a large pediatric hospital in Alabama between 2002 and 2010, only 60.5% had capsular serotypes included in PCV13, which came into general use in Alabama after our strains were collected. These isolates included 17 serotypes that were not covered by PCV13. Nonetheless, pneumococcal capsular serotype replacement was not associated with changes in PspA expression; 96% of strains in this collection expressed PspA family 1 or 2. Continued surveillance will be critical to vaccine strategies to further reduce IPD. PMID:22539473

Croney, Christina M.; Coats, Mamie T.; Nahm, Moon H.; Briles, David E.

2012-01-01

165

Invasive pneumococcal disease and 7-valent pneumococcal conjugate vaccine, the Netherlands.  

PubMed

In the Netherlands, the national immunization program includes 7-valent pneumococcal conjugate vaccine (PCV7) for all newborns born after April 1, 2006. We compared the incidence of invasive pneumococcal disease (IPD) and patient and disease characteristics before PCV7 introduction (June 2004-June 2006) with those after PCV7 introduction (June 2008-June 2010). Culture-confirmed IPD cases were identified by 9 sentinel laboratories covering ?25% of the Dutch population. Significant declines in overall IPD incidence were observed in children <2 (60%) and in persons >65 (13%) years of age. A trend toward gradual increases in non-PCV7 serotype IPD infections was observed in all age groups; the largest increases were among persons 50-64 (37%) and >65 (25%) years of age. In adults, the proportion of immunocompromised persons increased among IPD patients. Overall, deaths from IPD decreased from 16% to 12% because of a lower case-fatality rate for persons with non-PCV7 serotype IPD. PMID:23092683

van Deursen, Anna M M; van Mens, Suzan P; Sanders, Elisabeth A M; Vlaminckx, Bart J M; de Melker, Hester E; Schouls, Leo M; de Greeff, Sabine C; van der Ende, Arie

2012-11-01

166

Methods for a Systematic Review of Pneumococcal Conjugate Vaccine Dosing Schedules  

PubMed Central

Background: Streptococcus pneumoniae causes a considerable amount of morbidity and mortality in children <5. However, pneumococcal conjugate vaccines (PCVs) can prevent much of this burden. Until recently, PCVs were mostly available only in developed countries using a variety of dosing schedules. As more lower income countries make decisions to introduce PCV into their national immunization programs, an optimal schedule with which to administer PCV has become a key policy question. Methods: We performed a systematic review of English literature published from 1994 to 2010 on the effects of PCV dosing schedules on immunogenicity, nasopharyngeal carriage, invasive pneumococcal disease and pneumonia. Data were independently double abstracted and cleaned for analysis. Descriptive analyses were performed. Results: We identified 12,980 citations from the literature search (12,976) and secondary means (44). Double review of titles and abstracts yielded 769 articles that underwent full data abstraction. Of these, 350 were further analyzed and are presented in separate reports in this supplement. Conclusions: This article presents the methods utilized in our systematic review. Because of the heterogenity of the study methods of the reports identified by this review, we did not conduct formal meta-analyses. However, these methods allow us to present a full landscape of the literature on PCV dosing schedules. PMID:24336060

2014-01-01

167

Effectiveness of Haemophilus influenzae type b vaccines.  

PubMed Central

PURPOSE: To determine the clinical effectiveness of Haemophilus influenzae type b (Hib) vaccines. STUDY IDENTIFICATION AND SELECTION: Computerized searches of MEDLINE, EMBASE and SCISEARCH databases were performed, and the reference list of each retrieved article was reviewed. Two prospective clinical trials of Hib polyribosyl ribitol phosphate conjugated with diphtheria toxoid (PRP-D) were identified. In addition, one cohort study of the PRP-D vaccine, two trials of the PRP vaccine, five case-control studies of the PRP vaccine and 10 randomized controlled trials of the immunogenicity of the PRP-D vaccine were identified. DATA EXTRACTION: Study quality was assessed and descriptive information concerning the study populations, the interventions and the outcome measurements was extracted. RESULTS: The difference in the effectiveness of the PRP-D vaccine between the prospective trials, in which a three-dose schedule had been used beginning at 2 to 3 months of age, was clinically important (37% v. 83%) but not statistically significant. The PRP vaccine, which induces lower antibody responses than the PRP-D vaccine does, was clinically effective only in a subgroup of one prospective trial; 90% effectiveness was reported among children 18 to 60 months of age. CONCLUSIONS: Hib vaccine appears to be less effective in high-risk populations. None the less, because of the large variation in baseline risk, the number of children who would have to be vaccinated to prevent one case of invasive Hib disease is substantially less for high-risk than for low-risk populations. The vaccination of children at high risk, such as native children, with the PRP-D vaccine using a four-dose schedule (at 2, 4, 6 and 14 months of age) seems warranted. The currently available evidence does not strongly support a policy of universal vaccination with either a one-dose or a four-dose schedule. PMID:2107962

Stieb, D M; Frayha, H H; Oxman, A D; Shannon, H S; Hutchison, B G; Crombie, F S

1990-01-01

168

Immunization of Aged Mice with a Pneumococcal Conjugate Vaccine Combined with an Unmethylated CpG-Containing Oligodeoxynucleotide Restores Defective Immunoglobulin G Antipolysaccharide Responses and Specific CD4+-T-Cell Priming to Young Adult Levels  

Microsoft Academic Search

Polysaccharide (PS)-protein conjugate vaccines, in contrast to purified PS vaccines, recruit CD4-T-cell help and restore defective PS-specific humoral immunity in the immature host. Surprisingly, in the immunocompromised, aged host, anti-PS responses to conjugate vaccines are typically no better than those elicited by purified PS vaccines. Although aging leads to defects in multiple immune cell types, diminished CD4-T-cell helper function has

Goutam Sen; Quanyi Chen; Clifford M. Snapper

2006-01-01

169

An Assessment of the Screening Method to Evaluate Vaccine Effectiveness: The Case of 7-Valent Pneumococcal Conjugate Vaccine in the United States  

PubMed Central

The screening method, which employs readily available data, is an inexpensive and quick means of estimating vaccine effectiveness (VE). We compared estimates of effectiveness of heptavalent pneumococcal conjugate vaccine (PCV7) against invasive pneumococcal disease (IPD) using the screening and case-control methods. Cases were children aged 19–35 months with pneumococcus isolated from normally sterile sites residing in Active Bacterial Core surveillance areas in the United States. Case-control VE was estimated for 2001–2004 by comparing the odds of vaccination among cases and community controls. Screening-method VE for 2001–2009 was estimated by comparing the proportion of cases vaccinated to National Immunization Survey-derived coverage among the general population. To evaluate the plausibility of screening-method VE findings, we estimated attack rates among vaccinated and unvaccinated persons. We identified 1,154 children with IPD. Annual population PCV7 coverage with ?1 dose increased from 38% to 97%. Case-control VE for ?1 dose was estimated as 75% against all-serotype IPD (annual range: 35–83%) and 91% for PCV7-type IPD (annual range: 65–100%). By the screening method, the overall VE was 86% for ?1 dose (annual range: ?240–70%) against all-serotype IPD and 94% (annual range: 62–97%) against PCV7-type IPD. As cases of PCV7-type IPD declined during 2001–2005, estimated attack rates for all-serotype IPD among vaccinated and unvaccinated individuals became less consistent than what would be expected with the estimated effectiveness of PCV7. The screening method yields estimates of VE that are highly dependent on the time period during which it is used and the choice of outcome. The method should be used cautiously to evaluate VE of PCVs. PMID:22870248

Cohen, Adam L.; Taylor, Thomas; Farley, Monica M.; Schaffner, William; Lesher, Lindsey J.; Gershman, Kenneth A.; Bennett, Nancy M.; Reingold, Arthur; Thomas, Ann; Baumbach, Joan; Harrison, Lee H.; Petit, Susan; Beall, Bernard; Zell, Elizabeth; Moore, Matthew

2012-01-01

170

Use of 13-valent pneumococcal conjugate vaccine and 23-valent pneumococcal polysaccharide vaccine for adults with immunocompromising conditions: recommendations of the Advisory Committee on Immunization Practices (ACIP).  

PubMed

On June 20, 2012, 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.) for adults aged ?19 years with immunocompromising conditions, functional or anatomic asplenia, cerebrospinal fluid (CSF) leaks, or cochlear implants. PCV13 should be administered to eligible adults in addition to the 23-valent pneumococcal polysaccharide vaccine (PPSV23; Pneumovax 23, Merck & Co. Inc.), the vaccine currently recommended for these groups of adults. The evidence for the benefits and risk of PCV13 vaccination of adults with immunocompromising conditions was evaluated using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) framework and designated as a Category A recommendation. This report outlines the new ACIP recommendations for PCV13 use; explains the recommendations for the use of PCV13 and PPSV23 among adults with immunocompromising conditions, functional or anatomic asplenia, CSF leaks, or cochlear implants; and summarizes the evidence considered by ACIP to make its recommendations. PMID:23051612

2012-10-12

171

Sentinel versus population-based surveillance of pneumococcal conjugate vaccine effectiveness  

PubMed Central

Abstract Objective To compare sentinel and population-based surveillance of the effect of seven-valent pneumococcal conjugate vaccine (PCV7), introduced in 2000, on the hospitalization of children aged under 5 years with invasive pneumococcal disease (IPD) in the United States of America. Methods Population surveillance data were used to identify children hospitalized between 1998 and 2006 with IPD caused by Streptococcus pneumoniae serotypes. The change from 1998 and 1999 (baseline) to 2006 in the number of hospitalized IPD cases recorded by sentinel surveillance systems involving single hospitals or groups of hospitals was compared with the change in the incidence of hospitalized IPD cases measured by population-based surveillance. Findings The change in incidence in the eight surveillance areas varied from ?37 to ?82% for IPD caused by any serotype and from ?96 to ?100% for IPD caused by serotypes contained in PCV7. All individual sentinel hospitals with more than three cases annually at baseline reported a decrease in cases by 2006. In addition, over 95% of sentinel systems with an average of more than 30 cases annually at baseline recorded a change by 2006 in the number of cases caused by any serotype that fell within the 95% confidence interval for the change in the incidence of hospitalized cases in the corresponding population surveillance area. The change in cases caused by PCV7 serotypes was accurately measured by 93% and 100% of sentinel systems with ??20 and >?20 cases annually at baseline, respectively. Conclusion Sentinel surveillance can accurately measure the effect of PCV7 on the number of children hospitalized with IPD, provided sufficient cases are detected at baseline. Serotyping increases accuracy. PMID:22893740

Zell, Elizabeth R; Schrag, Stephanie; Cohen, Adam L

2012-01-01

172

Immunogenicity of a Heptavalent Conjugate Pneumococcal Vaccine Administered Concurrently with a Combination Diphtheria, Tetanus, Five-Component Acellular Pertussis, Inactivated Polio, and Haemophilus influenzae Type b Vaccine and a Meningococcal Group C Conjugate Vaccine at 2, 3, and 4 Months of Age ?  

PubMed Central

The immunogenicities of conjugate pneumococcal vaccines have been demonstrated when they are administered at 2, 3, and 4 months of age. There is a paucity of data on the immunogenicity of this vaccine when it is administered concurrently with other vaccines in the primary immunization schedule of the United Kingdom. We immunized 55 term infants at 2, 3, and 4 months of age with the seven-valent pneumococcal conjugate vaccine (PCV7), the meningococcal group C conjugate (MCC) vaccine, and the diphtheria, tetanus, five-component acellular pertussis, inactivated polio, and Haemophilus influenzae type b (DTaP5/IPV/Hib-TT) vaccine. The immune responses to the H. influenzae type b (Hib), MCC, and tetanus vaccines were measured at 2, 5, and 12 months of age; and the immune responses to PCV7 were measured at 2 and 5 months and then either at 12 months or following a 4th dose of PCV7. There were increases in the geometric mean concentrations (GMCs) of all antigens postimmunization. Greater than or equal to 90% of the infants achieved putatively protective levels postimmunization for all vaccine antigens except pneumococcal serotype 6B and Hib. The GMCs of the PCV7 serotypes increased following a 4th dose, although one infant had not reached putative levels of protection against serotype 6B. In conclusion, when infants were vaccinated according to the schedule described above, they had lower postprimary immunization responses to Hib, meningococcus group C capsular polysaccharide, and pneumococcal serotype 6B than the responses demonstrated by use of the other schedules. Despite this finding, there was a good response following a 4th dose of PCV7. PMID:20042517

Moss, S. J.; Fenton, A. C.; Toomey, J.; Grainger, A.; Borrow, R.; Balmer, P.; Smith, J.; Gennery, A. R.

2010-01-01

173

A cost-effectiveness analysis of a 10-valent pneumococcal conjugate vaccine in children in six Latin American countries  

PubMed Central

Background A recently developed 10-valent pneumococcal non-typeable H influenzae protein D-conjugate vaccine (PHiD-CV) is expected to afford protection against more than two thirds of isolates causing IPD in children in Latin America, and also against acute otitis media caused by both Spn and NTHi. The objective of this study is to assess the cost-effectiveness of PHiD-CV in comparison to non-vaccination in children under 10 years of age in Argentina, Brazil, Chile, Colombia, Mexico and Peru. Methods We used a static, deterministic, compartmental simulation model. The dosing regimen considered included three vaccine doses (at 2 months, 4 months and 6 months) and a booster dose (at 13 months) (3?+?1 schedule). Model outcomes included number of cases prevented, deaths averted, quality-adjusted life-years (QALYs) gained and costs. Discount for costs and benefits of long term sequelae was done at 3.5%, and currency reported in 2008-2009 U$S varying between countries. Results The largest effect in case prevention was observed in pneumococcal meningitis (from 27% in Peru to 47% in Colombia), neurologic sequelae after meningitis (from 38% in Peru to 65% in Brazil) and bacteremia (from 42% in Argentina to 49% in Colombia). The proportion of predicted deaths averted annually ranged from 18% in Peru to 33% in Brazil. Overall, the health benefits achieved with PHiD-CV vaccination resulted in a lower QALY loss (from 15% lower in Peru to 26% in Brazil). At a cost of USD 20 per vaccine dose, vaccination was cost-effective in all countries, from being cost saving in Chile to a maximum Incremental Cost-effectiveness Ratio of 7,088 US$ Dollars per QALY gained. Results were robust in the sensitivity analysis, and scenarios with indirect costs affected results more than those with herd immunity. Conclusions The incorporation of the 10-valent pneumococcal conjugate vaccine into routine infant immunization programs in Latin American countries could be a cost-effective strategy to improve infant population health in the region. PMID:24004943

2013-01-01

174

Immunogenicity of conjugate vaccines consisting of pneumococcal capsular polysaccharide types 6B, 14, 19F, and 23F and a meningococcal outer membrane protein complex.  

PubMed Central

In an effort to prepare pneumococcal (Pn) capsular polysaccharide (Ps) vaccines that would be immunogenic in infants, covalent conjugates were prepared for Pn types 6B, 14, 19F, and 23F. Each Ps type was covalently bound to an outer membrane protein complex from Neisseria meningitidis serogroup B and evaluated for immunogenicity in mice and infant monkeys. The conjugates induced specific anti-Ps antibody responses in mice and in infant rhesus and African green monkeys; a conjugate of 6B and outer membrane protein complex was immunogenic at Ps doses as low as 20 ng. Although low levels of the Pn group-common cell wall polysaccharide were present in all type-specific Ps preparations, anti-cell wall polysaccharide responses induced by covalent conjugates were < 1% of the total anti-Ps response after two doses of vaccine. In contrast, the anti-cell wall polysaccharide response of a noncovalent conjugate represented 41% of the anti-Ps response after two doses. Relative T-cell dependence, a requirement for the human target population of infants less than 18 months old, was demonstrated for all four Pn Ps conjugates in an athymic mouse model. Therefore, these Pn Ps-outer membrane protein complex conjugate vaccines are excellent candidates for evaluation in human infants. PMID:1452327

Vella, P P; Marburg, S; Staub, J M; Kniskern, P J; Miller, W; Hagopian, A; Ip, C; Tolman, R L; Rusk, C M; Chupak, L S

1992-01-01

175

Assessment of Health Benefits and Cost-Effectiveness of 10-Valent and 13-Valent Pneumococcal Conjugate Vaccination in Kenyan Children  

PubMed Central

Background The GAVI Alliance supported10-valent pneumococcal conjugate vaccine (PCV10) introduction in Kenya. We estimated the cost-effectiveness of introducing either PCV10 or the13-valent vaccine (PCV13) from a societal perspective and explored the incremental impact of including indirect vaccine effects. Methods The costs and effects of pneumococcal vaccination among infants born in Kenya in 2010 were assessed using a decision analytic model comparing PCV10 or PCV13, in turn, with no vaccination. Direct vaccine effects were estimated as a reduction in the incidence of pneumococcal meningitis, sepsis, bacteraemic pneumonia and non-bacteraemic pneumonia. Pneumococcal disease incidence was extrapolated from a population-based hospital surveillance system in Kilifi and adjustments were made for variable access to care across Kenya. We used vaccine efficacy estimates from a trial in The Gambia and accounted for serotype distribution in Kilifi. We estimated indirect vaccine protection and serotype replacement by extrapolating from the USA. Multivariable sensitivity analysis was conducted using Monte Carlo simulation. We assumed a vaccine price of US$ 3.50 per dose. Findings The annual cost of delivering PCV10 was approximately US$14 million. We projected a 42.7% reduction in pneumococcal disease episodes leading to a US$1.97 million reduction in treatment costs and a 6.1% reduction in childhood mortality annually. In the base case analysis, costs per discounted DALY and per death averted by PCV10, amounted to US$ 59 (95% CI 26–103) and US$ 1,958 (95% CI 866–3,425), respectively. PCV13 introduction improved the cost-effectiveness ratios by approximately 20% and inclusion of indirect effects improved cost-effectiveness ratios by 43–56%. The break-even prices for introduction of PCV10 and PCV13 are US$ 0.41 and 0.51, respectively. Conclusions Introducing either PCV10 or PCV13 in Kenya is highly cost-effective from a societal perspective. Indirect effects, if they occur, would significantly improve the cost-effectiveness. PMID:23826268

Ayieko, Philip; Griffiths, Ulla K.; Ndiritu, Moses; Moisi, Jennifer; Mugoya, Isaac K.; Kamau, Tatu; English, Mike; Scott, J. Anthony G.

2013-01-01

176

Systematic Review of the Effect of Pneumococcal Conjugate Vaccine Dosing Schedules on Immunogenicity  

PubMed Central

Background: Despite the breadth of studies demonstrating benefits of pneumococcal conjugate vaccine (PCV), uncertainty remains regarding the optimal PCV dosing schedule in infants. Methods: We conducted a systematic literature review of PCV immunogenicity published from 1994 to 2010 (supplemented post hoc with studies from 2011). Studies included for analysis evaluated ?2 doses of 7-valent or higher product (excluding Aventis-Pasteur PCV11) administered to nonhigh-risk infants ?6 months of age. Impact of PCV schedule on geometric mean antibody concentration (GMC) and proportion of subjects over 0.35 mcg/mL were assessed at various time points; the GMC 1 month postdose 3 (for various dosing regimens) for serotypes 1, 5, 6B, 14, 19F and 23F was assessed in detail using random effects linear regression, adjusted for product, acellular diphtheria-tetanus-pertussis/whole-cell diphtheria- tetanus-pertussis coadministration, laboratory method, age at first dose and geographic region. Results: From 61 studies, we evaluated 13 two-dose (2+0) and 65 three-dose primary schedules (3+0) without a booster dose, 11 “2+1” (2 primary plus booster) and 42 “3+1” schedules. The GMC after the primary series was higher following 3-dose schedules compared with 2-dose schedules for all serotypes except for serotype 1. Pre- and postbooster GMCs were generally similar regardless of whether 2 or 3 primary doses were given. GMCs were significantly higher for all serotypes when dose 3 was administered in the second year (2+1) compared with ?6 months of age (3+0). Conclusions: While giving the third dose in the second year of life produces a higher antibody response than when given as part of the primary series in the first 6 months, the lower GMC between the 2-dose primary series and booster may result in less disease protection for infants in that interval than those who completed the 3-dose primary series. Theoretical advantages of higher antibodies induced by giving the third dose in the second year of life, such as increased protection against serotype 1 disease, longer duration of protection or more rapid induction of herd effects, need to be evaluated in practice. PMID:24336054

2014-01-01

177

Antibody persistence in UK pre-school children following primary series with an acellular pertussis-containing pentavalent vaccine given concomitantly with meningococcal group C conjugate vaccine, and response to a booster dose of an acellular pertussis-containing quadrivalent vaccine  

Microsoft Academic Search

This open-label, randomised, controlled study examined antibody persistence following infant vaccination at 2, 3 and 4 months of age with either an acellular pertussis, diphtheria, tetanus, inactivated poliovirus, Haemophilus influenzae type b (DT5aP-IPV-Hib; Pediacel®) or a whole-cell pertussis (DTwP\\/\\/Hib+oral poliomyelitis vaccine [OPV]) combination vaccine, given concomitantly with meningococcal serogroup C conjugate (MCC) vaccine, followed by a Hib booster at approximately

Nicholas Kitchin; Rhonwen Morris; Ray Borrow; Anne Fiquet; Florence Boisnard; Stéphane Thomas; Elizabeth Miller

2009-01-01

178

Safety and reactogenicity of primary vaccination with the 10-valent pneumococcal non-typeable Haemophilus influenzae protein D conjugate vaccine in Vietnamese infants: a randomised, controlled trial  

PubMed Central

Background Pneumococcal infections are major causes of child mortality and morbidity worldwide and antibiotic resistance of Streptococcus pneumoniae is a major concern, especially in Asian countries. The present study was designed to evaluate the reactogenicity and safety of the 10-valent pneumococcal non-typeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV) when co-administered with the licensed diphtheria, tetanus, acellular pertussis, hepatitis B virus, inactivated poliovirus and H. influenzae type b vaccine (DTPa-HBV-IPV/Hib) in a 3-dose primary vaccination course in Vietnamese infants. Methods This phase III, open, randomised study was conducted in one centre in Ho Chi Minh City between February and July 2011. Healthy infants (N=300) were randomised (2:1) to receive either PHiD-CV co-administered with DTPa-HBV-IPV/Hib (PHiD-CV group) or DTPa-HBV-IPV/Hib alone (Control group) at 2, 3, and 4 months of age. Results Within 31 days post-vaccination, 8.2% of overall doses in the PHiD-CV group and 3.0% of overall doses in the Control group were followed by at least one solicited and/or unsolicited, local and/or general adverse event of grade 3 intensity. Pain at injection site was the most common grade 3 solicited symptom, which was reported following 6.5% and 1.0% of overall doses in the PHiD-CV and Control groups, respectively. Within 4 days post-vaccination, the most common solicited local and general symptoms reported with any intensity were pain (48.9% and 31.0% of doses in the PHiD-CV and Control groups) and irritability (58.0% and 40.4% of doses in the PHiD-CV and Control groups). Within 31 days post-vaccination, the incidence of unsolicited symptoms was comparable in both groups (following 12.3% and 14.8% of doses in the PHiD-CV and Control groups, respectively). Throughout the study, 13 serious adverse events (SAEs) were reported in 9 infants in the PHiD-CV group and 11 SAEs in 6 infants in the Control group. None of them were fatal or considered causally related to vaccination. Conclusions PHiD-CV had a clinically acceptable safety profile when co-administered with DTPa-HBV-IPV/Hib in Vietnamese infants. The reactogenicity of PHiD-CV was comparable to that observed in other South-East Asian populations. Trial registration ClinicalTrials.gov: http://NCT01153841 PMID:23432812

2013-01-01

179

Synthesis of Mercapto (+) methamphetamine Haptens and Their Use for Obtaining Improved Epitope Density on (+) Methamphetamine Conjugate Vaccines  

PubMed Central

This study reports the synthesis of the mercapto hapten (S)-N-(2-(mercaptoethyl)-6-(3-(2-(methylamino)propyl)phenoxy)hexanamide [3, (+)-METH HSMO9] and its use to prepare METH-conjugated vaccines (MCV) from maleimide activated proteins. MALDI-TOF mass spectrometry analysis of the MCV synthesized using 3 showed there was a high and controllable epitope density on two different carrier proteins. In addition, the MCV produced a substantially greater immunological response in mice than previous METH haptens, and a monoclonal antibody generated from this MCV in mice showed a very high affinity for (+)-METH (KD = 6.8 nM). The efficient covalent coupling of (+)-METH HSMO9 to the activated carrier proteins suggests this approach could be cost effective for large-scale production of MCV. In addition, the general methods described for the synthesis of (+) METH HSMO9 (3) and its use to synthesize MCV will be applicable for conjugated vaccines of small molecules and other substances of abuse such as morphine, nicotine, and cocaine. PMID:21682289

Carroll, F. Ivy; Blough, Bruce E.; Pidaparthi, Ramakrishna R.; Abraham, Philip; Gong, Paul K.; Deng, Liu; Huang, Xiaodong; Gunnell, Melinda; Lay, Jackson O.; Peterson, Eric C.; Owens, S. Michael

2011-01-01

180

Responses to a Conjugate Pneumococcal Vaccine in Preterm Infants Immunized at 2, 3, and 4 Months of Age?  

PubMed Central

Preterm infants are at an increased risk of invasive pneumococcal disease infection and, additionally, have a diminished response to Haemophilus influenzae type b (Hib) conjugate vaccines. There are little data examining the response of preterm infants to a seven-valent pneumococcal conjugate vaccine (PCV7). We examined the responses of preterm infants immunized at 2, 3, and 4 months of age to PCV7. A total of 133 preterm and 54 term infants were immunized with PCV7 and the Neisseria meningitidis group C (MCC), diphtheria, tetanus, pertussis, polio, and Hib vaccines. Pneumococcal serotype-specific IgG was measured by enzyme-linked immunosorbent assay (ELISA) pre- and postimmunization and at 12 months or following a booster of PCV7. Term and preterm responses were compared using linear and logistic regression analyses. Term infants had higher preimmunization geometric mean concentrations (GMCs) for all serotypes. Preterm infants had lower postimmunization GMCs for serotype 23F. Gestational age affected postimmunization GMCs for serotypes 4, 6B, and 23F. Preterm infants were as likely to have levels of ?0.35 ?g/ml as term infants for all serotypes except 23F. The proportions of infants with titers of ?0.35 ?g/ml for all 7 serotypes were comparable between groups. A total of 28 of 29 term infants who received a booster had levels of ?0.35 ?g/ml for all serotypes. One infant had undetectable levels for serotype 6B. Of the 32 preterm infants boosted, 9 had levels of <0.35 ?g/ml for 1 serotype, and 1 had levels of <0.35 ?g/ml for 2 serotypes. In nonboosted infants, GMCs for all serotypes except 6B had fallen by 12 months of age. These results support the need for a booster dose in the second year of life. PMID:20861323

Moss, S. J.; Fenton, A. C.; Toomey, J. A.; Grainger, A. J.; Smith, J.; Gennery, A. R.

2010-01-01

181

Evaluation of a diphtheria–tetanus–acellular pertussis–inactivated poliovirus–Haemophilus influenzae type b vaccine given concurrently with meningococcal group C conjugate vaccine at 2, 3 and 4 months of age  

Microsoft Academic Search

Background and objective: In view of the possible introduction of diphtheria–tetanus–acellular pertussis–inactivated poliovirus–Haemophilus influenzae type b (DTaP-IPV-Hib, eg Pediacel) vaccine in the UK, a study of the immunogenicity of Pediacel when given with one of two different meningococcal group C conjugate (MCC) vaccines at 2, 3 and 4 months of age was conducted.Methods: Randomised controlled study in 241 infants.Results: Post

N R E Kitchin; R Morris; F Hemme; S Thomas; M W Watson; K Cartwright; E Miller

2007-01-01

182

Impact of More Than a Decade of Pneumococcal Conjugate Vaccine Use on Carriage and Invasive Potential in Native American Communities  

PubMed Central

Background.?We assessed the impact of 12 years of pneumococcal conjugate vaccine (PCV7) use on pneumococcal nasopharyngeal carriage and serotype-specific invasive disease potential among Native Americans. Methods.?Families were enrolled in a carriage study from 2006 to 2008; nasopharyngeal specimens and risk factor information were collected monthly for 7 visits. Pneumococcal carriage prevalence was compared with that before (1998–2000) and during (2001–2002) PCV7 introduction. We compared invasive disease incidence and carriage prevalence before and after PCV7 introduction to estimate changes in serotype-specific invasive potential. Results.?We enrolled 1077 subjects from 302 households. There was an absolute reduction in carriage prevalence of 8.0% (95% confidence interval [CI], 4.5%–11.4%) in children aged <5 years and 3.1% (95% CI, 1.1%–5.1%) in adults. In children aged <5 years, vaccine-serotype carriage prevalence decreased by 22.8% (95% CI, 20.1%–25.3%), and nonvaccine serotype (NVT) increased by 15.9% (95% CI, 12.4%–19.3%). No significant change was detected in serotype-specific invasive potential after PCV7 introduction. Conclusions.?Pneumococcal carriage prevalence decreased in all ages since PCV7 introduction; vaccine-serotype carriage has been nearly eliminated, whereas the prevalence of NVT carriage has increased. The increase in the NVT invasive disease rate seems to be proportional to the increase in colonization prevalence. PMID:22128315

Scott, Jennifer R.; Millar, Eugene V.; Lipsitch, Marc; Moulton, Lawrence H.; Weatherholtz, Robert; Perilla, Mindy J.; Jackson, Delois M.; Beall, Bernard; Craig, Mariddie J.; Reid, Raymond; Santosham, Mathuram

2012-01-01

183

Enhancement of Serum and Mucosal Immune Responses to a Haemophilus influenzae Type B Vaccine by Intranasal Delivery  

PubMed Central

Intranasal (i.n.) vaccination is potentially the most direct method for conveying upper respiratory and mucosal immunity to respiratory pathogens. However, for unclear reasons, vaccines introduced into the nasal sinuses often have lower efficacy than vaccines administered by the more frequently used parenteral routes. We examined i.n. vaccination in a mouse immune-response model with a commonly used Haemophilus influenzae type B vaccine (Hibv) composed of the polyribosylribitol phosphate (PRP) capsule antigen conjugated to tetanus toxoid. Intranasal vaccination with Hibv using a Toll-like receptor 4 (TLR4) agonist as an adjuvant significantly increased the levels of IgA specific for the PRP capsule antigen in blood serum, saliva, and mucosal secretion specimens. In contrast, control mice vaccinated transdermally (t.d.) with Hibv did not produce significant levels of PRP-specific IgA in the blood serum and saliva, and anti-PRP IgG was increased only in serum. The i.n. and t.d. vaccinations resulted in equivalent bactericidal antibody responses in blood serum, suggesting that vaccine-derived IgG is protective against infection. Elevated levels of IgG specific for the tetanus toxoid carrier protein were measured in nasal sinuses and vaginal secretions in mice vaccinated by either the t.d. or i.n. route. Tissue culture studies confirmed that the nasopharynx-associated lymphoid tissue (NALT) was at least one of the sources of PRP-specific IgA and carrier-specific IgG within the nasal sinuses. We conclude that i.n. vaccination aided by a TLR4 agonist results in robust immune responses to both the carrier protein and bacterial polysaccharide components of the Hibv. PMID:23986319

Cisney, Emily D.

2013-01-01

184

Levels and functionality of antibodies after pneumococcal conjugate vaccine in schedules with different timing of the booster dose.  

PubMed

The seven-valent pneumococcal conjugate vaccine (PCV7) has been introduced in most high-income countries, although with differences in age, timing and number of primary doses before 6 months of age and presence and timing of a booster vaccination. The objective was to determine and compare the IgG antibody levels and functionality of IgG responses (avidity and opsonophagocytoses) at 1 and 2 years of age following 2 primary doses with a booster at 11 or 24 months of age. Children received PCV7 at 2 and 4 months (2-dose group), or at 2, 4 and 11 months (2+1-dose group), or no PCV7 (controls) before 1 year of age. All children received a PCV7 dose at 24 months of age. At the age of 12 months, the 2+1-dose group had higher IgG levels and functional antibody levels, compared to the 2-dose group for all serotypes, but at 25 months the difference between the 2-dose and 2+1-dose groups had disappeared for most serotypes. The kinetics of opsonophagocytic antibodies were in line with the specific IgG antibody levels for most serotypes, although differences between the 2-dose and the 2+1-dose group were more pronounced in OPA activity as compared to the IgG levels especially at the age of 24 months. Delaying the booster dose from 11 months to 24 months after 2 primary doses resulted in significantly higher OPA GMTs one month after the booster dose. This must, however, be balanced against the risk of leaving children unboosted between the age of 11 and 24 months at a time when disease risk is still high. Local decisions about the timing of a booster dose should also take into account vaccine coverage and the indirect herd effect in a well vaccinated population. Trial registration clinicaltrials.gov Identifier: NCT00189020. PMID:24120678

van Westen, Els; Rodenburg, Gerwin D; van Gils, Elske J M; Tcherniaeva, Irina; Berbers, Guy A M; Cowell, Lucy; Goldblatt, David; Rots, Nynke Y; van den Dobbelsteen, Germie P J M; Sanders, Elisabeth A M

2013-12-01

185

Pneumonia hospitalizations among young children before and after introduction of pneumococcal conjugate vaccine--United States, 1997-2006.  

PubMed

Streptococcus pneumoniae is the leading bacterial cause of community-acquired pneumonia hospitalizations and an important cause of bacteremia and meningitis, especially among young children and older adults. A 7-valent pneumococcal conjugate vaccine (PCV7) was licensed and the Advisory Committee on Immunization Practices formulated recommendations for its use in infants and children in February 2000. Vaccination coverage rapidly increased during the second half of 2000, in part through funding by CDC's Vaccines for Children program. Subsequently, active population- and laboratory-based surveillance demonstrated substantial reductions in invasive pneumococcal disease (IPD) among children and adults. In addition, decreases in hospitalizations and ambulatory-care visits for all-cause pneumonia also were reported. To gauge whether the effects of PCV7 on reducing pneumonia continue, CDC is monitoring pneumonia hospitalizations by using data from the Nationwide Inpatient Sample. This report provides an update for 2005 and 2006, the most recent years for which information is available. In 2005 and 2006, the incidence rates for all-cause pneumonia hospitalizations among children aged <2 years were 9.1 per 1,000 and 8.1 per 1,000, respectively. In 2006, the rate for all-cause pneumonia among children aged <2 years was approximately 35% lower than during 1997--1999. Most of this decrease occurred soon after the vaccine was licensed in 2000, and the rates have remained relatively stable since then. The rate for all-cause pneumonia among children aged 2--4 years did not change after PCV7 licensure and has remained stable. Continued monitoring of pneumonia-related hospitalizations among children is needed to track the effects of pneumococcal immunization programs. PMID:19145219

2009-01-16

186

Effect of Seven-Valent Pneumococcal Conjugate Vaccine on Staphylococcus aureus Colonisation in a Randomised Controlled Trial  

PubMed Central

Background Heptavalent pneumococcal conjugate vaccine (PCV7) shifts nasopharyngeal colonisation with vaccine serotype pneumococci towards nonvaccine serotypes. Because of the reported negative association of vaccine serotype pneumococci and Staphylococcus aureus in the nasopharynx, we explored the effect of PCV7 on nasopharyngeal colonisation with S. aureus in children and parents. Methodology/Principal Findings This study was part of a randomised controlled trial on the effect of PCV7 on pneumococcal carriage, enrolling healthy newborns who were randomly assigned (1?1?1) to receive PCV7 (1) at 2 and 4 months of age (2) at 2, 4 and 11 months or (3) no PCV7 (controls). Nasopharyngeal colonisation of S. aureus was a planned secondary outcome. Nasopharyngeal swabs were obtained from all children over a 2-year period with 6-months interval and from one parent at the child's age of 12 and 24 months and cultured for Streptococcus pneumoniae and S. aureus. Between July 2005 and February 2006, 1005 children were enrolled and received either 2-doses of PCV7 (n?=?336), 2+1-doses (336) or no dose (n?=?333) before PCV7 implementation in the Dutch national immunization program. S. aureus colonisation had doubled in children in the 2+1-dose group at 12 months of age compared with unvaccinated controls (10.1% versus 5.0%; p?=?0.019). A negative association for co-colonisation of S. pneumoniae and S. aureus was observed for both vaccine serotype (adjusted odds ratio (aOR) 0.53, 95% confidence interval (CI) 0.38–0.74) and nonvaccine serotype pneumococci (aOR 0.67, 95% CI 0.52–0.88). Conclusions/Significance PCV7 induces a temporary increase in S. aureus colonisation in children around 12 months of age after a 2+1-dose PCV7 schedule. The potential clinical consequences are unknown and monitoring is warranted. Trial Registration ClinicalTrials.gov NCT00189020 PMID:21695210

van Gils, Elske J. M.; Hak, Eelko; Veenhoven, Reinier H.; Rodenburg, Gerwin D.; Bogaert, Debby; Bruin, Jacob P.; van Alphen, Loek; Sanders, Elisabeth A. M.

2011-01-01

187

Depressive symptoms and immune response to meningococcal conjugate vaccine in early adolescence.  

PubMed

Research findings in psychoneuroimmunology document reliable, bidirectional linkages among psychological processes, the nervous system, and the immune system. However, available data are based almost entirely on animal and adult human studies; the application to children and adolescents is uncertain. We capitalized on the experimental leverage provided by a routine vaccination to examine the link between mood symptoms and the immune response to a vaccine challenge in early adolescence. One hundred twenty-six 11-year-olds for whom vaccine response data were available were assessed at prevaccination and 4 weeks, 3 months, and 6 months following vaccination; self-report ratings of depression and anxiety as well as measures of psychosocial and somatic risk were assessed prior to vaccine response. Analyses indicated that children's internalizing mood symptoms were associated with elevated and persistently higher antibody responses, with evidence extending to two of the four serogroups. The associations remained after controlling for multiple possible confounders (social class, body mass index, sleep, psychosocial risk, and pubertal status). The observed enhanced vaccine response associated with depressive and anxious symptoms in early adolescence may reflect an important developmental difference in immune system-brain interplay between adults and children, and it underscores the need for further developmental studies of psychoneuroimmunology. PMID:25422979

O'Connor, Thomas G; Moynihan, Jan A; Wyman, Peter A; Carnahan, Jennifer; Lofthus, Gerry; Quataert, Sally A; Bowman, Melissa; Caserta, Mary T

2014-11-01

188

Nasopharyngeal Carriage Rate and Serotypes of Streptococcus pneumoniae and Antimicrobial Susceptibility in Healthy Korean Children Younger than 5 Years Old: Focus on Influence of Pneumococcal Conjugate Vaccination  

PubMed Central

Background Even after pneumococcal vaccination introduction, Streptococcus pneumoniae (pneumoccocus) is still an important cause of respiratory and invasive severe infection. Pneumococcus is resided in nasal mucosa and local or systemic infection begins with the nasal mucosa damage. We studied the indirect effect of pneumococcal conjugate vaccine (PCV) on pneumococcal nasopharyngeal carriage rates, serotypes and antimicrobial susceptibility between vaccinate and non-vaccinated children. Materials and Methods From January 2010 to October 2010, 379 healthy children under 5 years old from three university hospitals were recruited. Fully vaccinated children over 3 time doses of PCV and children with no vaccination history of PCV were enrolled, and nasopharyngeal aspirations were obtained from these children. Serotypes using multibead serotyping assay with multiplex PCR and antimicrobial susceptibility was analyzed. Antimicrobial susceptibilities were determined by the CLIS guideline. Results Two hundred seventy six children were received pneumococcal vaccination while 103 were not. 137 pneumococci were isolated from nasopharyngeal aspiration specimens. Nasal carriage rate was significantly low in vaccinated group (P-value; 0.001). Nasopharyngeal carriage rate was 28.6% (79/276) in vaccinate group and 56.3% (58/103) in non-vaccinated group. Among those vaccinated group, 13.0% (36/276) of the serotypes were vaccine or vaccine related type with the most common type 19F. In contrast, 31.1% (32/103) of the serotypes in non vaccinated group were vaccine or vaccine related type with the most common type 6A. The resistant rate of penicillin was 90.5%. For antimicrobial susceptibility, amoxicillin and amoxicillin/clavulanate showed high susceptibility (73.0%), but 19F and 19A serotypes were all resistant against amoxicillin. Conclusions High nasopharyngeal carriage rate in non vaccinated group corresponded to the result of past study. However, 19F and 19A still came up as problematic serotypes with a high carriage rate and antimicrobial resistance in both vaccinated and non vaccinated groups. Also, this study showed that the resistance rate of primary oral antimicrobial agents was increased in compared to past. For solving these problems, the selective antimicrobial use with establishment of high dose amoxicillin/clavulanate regimen and active PCV immunization should be needed. Furthermore, pneumococcal carriage and serotype study concerning with antimicrobial susceptibility should be conducted in the future in 10 or 13-valent PCV received children. PMID:24265953

Lee, Eu Kyoung; Jun, Ja Kyung; Choi, Ui Yoon; Kwon, Hyo-Jin; Kim, Kyung-Hyo

2013-01-01

189

Protective effect of acellular pertussis vaccines  

Microsoft Academic Search

Two acellular pertussis vaccines, a mono-component toxoid of pertussis toxin and a two-component vaccine containing both the toxoid and filamentous haemagglutinin, were used for primary immunization of infants 5 1\\/2 to 10 months of age in two clinical trials in Sweden. Over a follow-up period of 12 to 17 months, 37 children were exposed to pertussis in the household or

M. Blennow; S. Hedenskog; M. Granström

1988-01-01

190

Nasopharyngeal flora in children with acute otitis media before and after implementation of 7 valent pneumococcal conjugate vaccine in France  

PubMed Central

Background Several studies have investigated the impact of 7-valent pneumococcal conjugate vaccine (PCV7) on pneumococcal (Sp) and staphylococcal (Sa) nasopharyngeal (NP) carriage. Few have investigated the impact on Haemophilus influenzae (Hi) and Moraxella catarrhalis (Mc) carriage. We aimed to compare the NP carriage rates in young children with acute otitis media (AOM) before and after PCV7 implementation in France. Methods Prior to PCV7 implementation, we performed 4 successive randomized trials with NP samples. These studies compared several antibiotic regimens for treating AOM in young children (6 to 30 months). After PCV7 implementation, to assess the impact of the vaccination program on NP flora, young children with AOM were enrolled in a prospective surveillance study. In each study, we obtained an NP sample to analyze the carriage rates of Sp, Hi, Mc and Sa and the factors influencing the carriage. Standardized history and physical examination findings were recorded; the methods used for NP swabs (sampling and cultures) were the same in all studies. Results We enrolled 4,405 children (mean age 13.9 months, median 12.8). Among the 2,598 children enrolled after PCV7 implementation, 98.3% were vaccinated with PCV7. In comparing the pre- and post-PCV7 periods, we found a slight but non-significant decrease in carriage rates of pneumococcus (AOR = 0.85 [0.69;1.05]), H. influenzae (AOR = 0.89 [0.73;1.09]) and S. aureus (AOR = 0.92 [0.70;1.19]). By contrast, the carriage rate of M. catarrhalis increased slightly but not significantly between the 2 periods (AOR = 1.08 [0.95;1.2]). Among Sp carriers, the proportion of PCV7 vaccine types decreased from 66.6% to 10.7% (P < 0.001), penicillin intermediate-resistant strains increased from 30.3% to 43.4% (P < 0.001), and penicillin-resistant strains decreased greatly from 22.8% to 3.8% (P < 0.001). The proportion of Hi ß-lactamase-producing strains decreased from 38.6% to 17.1% (P < 0.001). Conclusion The carriage rates of otopathogen species (Sp, Hi, Mc) and Sa did not significantly change in children with AOM after PCV7 implementation in France. However, we observed significant changes in carriage rates of PCV7 vaccine serotypes and penicillin non-susceptible Sp. PMID:22397629

2012-01-01

191

Do community-level predictors of pneumococcal carriage continue to play a role in the conjugate vaccine era?  

PubMed

This paper examined whether previously identified community-level factors (high proportion of crowded households and/or persons below the poverty level) remained associated with childhood pneumococcal carriage in the heptavalent pneumococcal conjugate vaccine (PCV7) era. Using logistic regression, individual factors were used to develop base models to which community-level factors were added to evaluate impact on pneumococcal carriage within two paediatric study cohorts from Massachusetts (urban Boston, outside Boston). Six years after introduction of universal childhood PCV7 vaccination, we found no consistent evidence that census tract characteristics (e.g. population size and density, age and race distribution, percent participating in group childcare, parental education, percent lacking in-unit plumbing, poverty, and community stability) affected odds of pneumococcal carriage when added to individual predictors (e.g. younger age, current respiratory tract infections, and attendance in group childcare). How community-level factors influence pneumococcal carriage continues to change in the era of increasing immunization coverage. PMID:23731707

Hsu, K K; Rifas-Shiman, S L; Shea, K M; Kleinman, K P; Lee, G M; Lakoma, M; Pelton, S I; Finkelstein, J A; Huang, S S

2014-02-01

192

Population-based seroprevalence of Neisseria meningitidis serogroup C capsular antibody before the introduction of conjugate vaccine, in Australia.  

PubMed

Neisseria meningitidis serogroup C (NMC) conjugate vaccine was introduced, in Australia, in 2003. Our aims were to determine pre-immunisation IgG NMC seroprevalence and evaluate an enzyme-linked immunosorbent assay (ELISA), previously validated against the serum bactericidal assay (SBA). 2409 sera, collected in 2002, from subjects aged 2-34 years, were tested. The geometric mean concentration (GMC) of NMC anticapsular IgG was 0.38 U/mL in subjects under 19 years and it increased to 0.67 U/mL for those aged 30-34 years. Variation in GMC correlated with reported NMC disease incidence and was higher in males than females (0.52 U/mL versus 0.41 U/mL; p=0.005). The ELISA appears suitable for serosurveillance but the IgG level that correlates with protection needs further investigation. Serosurveys will be repeated to monitor the impact of vaccination. PMID:17069937

Backhouse, J L; Gidding, H F; MacIntyre, C R; McIntyre, P B; Gilbert, G L

2007-01-26

193

Population Genetic Structure of Streptococcus pneumoniae in Kilifi, Kenya, Prior to the Introduction of Pneumococcal Conjugate Vaccine  

PubMed Central

Background The 10-valent pneumococcal conjugate vaccine (PCV10) was introduced in Kenya in 2011. Introduction of any PCV will perturb the existing pneumococcal population structure, thus the aim was to genotype pneumococci collected in Kilifi before PCV10. Methods and Findings Using multilocus sequence typing (MLST), we genotyped >1100 invasive and carriage pneumococci from children, the largest collection genotyped from a single resource-poor country and reported to date. Serotype 1 was the most common serotype causing invasive disease and was rarely detected in carriage; all serotype 1 isolates were members of clonal complex (CC) 217. There were temporal fluctuations in the major circulating sequence types (STs); and although 1-3 major serotype 1, 14 or 23F STs co-circulated annually, the two major serotype 5 STs mainly circulated independently. Major STs/CCs also included isolates of serotypes 3, 12F, 18C and 19A and each shared ?2 MLST alleles with STs that circulate widely elsewhere. Major CCs associated with non-PCV10 serotypes were predominantly represented by carriage isolates, although serotype 19A and 12F CCs were largely invasive and a serotype 10A CC was equally represented by invasive and carriage isolates. Conclusions Understanding the pre-PCV10 population genetic structure in Kilifi will allow for the detection of changes in prevalence of the circulating genotypes and evidence for capsular switching post-vaccine implementation. PMID:24282605

Brueggemann, Angela B.; Muroki, Beth Mbesu; Kulohoma, Benard W.; Karani, Angela; Wanjiru, Eva; Morpeth, Susan; Kamau, Tatu; Sharif, Shahnaaz; Scott, J. Anthony G.

2013-01-01

194

Safety and immunogenicity of the tetravalent protein-conjugated meningococcal vaccine (MCV4) in recipients of related and unrelated allogeneic hematopoietic stem cell transplantation.  

PubMed

Given the high morbidity and mortality associated with meningococcal disease, in 2007 the Advisory Committee of Immunization Practices recommended immunization of all children ages 11-18 with a protein-conjugated meningococcal vaccine. There are limited data on the immunogenicity of this vaccine after allogeneic hematopoietic stem cell transplantation (allo-HCT). Since 2007, we have immunized 48 patients with the MCV4 vaccine. Two vaccinated patients who lacked follow-up titers were excluded from this analysis. Stem cells were derived from an HLA-identical sibling (n = 17) or an alternative donor (n = 29). The median time to vaccination was 2.34 years after allo-HCT. Only 7 patients responded to all 4 serogroups, and 16 patients responded to none of the serogroups. The response to serogroups A, C, Y, and W-135 was 52%, 30%, 46%, and 33%, respectively. The ability to respond to 2 or more serogroups was not affected by age, diagnosis, time to vaccination, or history of graft-versus-host disease. Receipt of a T cell-depleted graft was associated with a poorer response (P = .044). Eight of 16 patients who received a second MCV4 vaccination responded to all 4 serogroups. This retrospective study suggests that response to a single MCV4 vaccination is poor after allo-HCT. Administration of a 2-dose series, as currently recommended for patients with asplenia, complement deficiency, and HIV infection, should be evaluated in this patient population. PMID:21820392

Mahler, Michelle B; Taur, Ying; Jean, Raymond; Kernan, Nancy A; Prockop, Susan E; Small, Trudy N

2012-01-01

195

Invasive and Noninvasive Streptococcus pneumoniae Capsule and Surface Protein Diversity following the Use of a Conjugate Vaccine  

PubMed Central

The 13-valent pneumococcal conjugate vaccine (PCV13) was introduced in the United States in 2010 for the prevention of invasive pneumococcal disease (IPD) and otitis media. While many studies have reported its potential efficacy for IPD, not much is known about the epidemiology of noninvasive disease following its introduction. We characterized the capsular types and surface protein genes of noninvasive pediatric pneumococcal isolates collected between 2002 and 2010 (n = 1,058) at Children's of Alabama following the introduction of PCV7 and tested a subset of noninvasive and previously characterized IPD isolates for the presence of the pspA, pspC, and rrgC genes, which encode protection-eliciting proteins. PCV7 serotypes had dramatically decreased by 2010 (P < 0.0001), and only 50% of all noninvasive infections were caused by the PCV13 capsular serotypes. Serotype 19A accounted for 32% of the noninvasive isolates, followed by serotypes 35B (9%), 19F (7%), and 6C (6%). After 7 years of PCV7 usage, there were no changes in the frequencies of the pspA or pspC genes; 96% of the strains were positive for family 1 or 2 pspA genes, and 81% were also positive for pspC. Unexpectedly, more noninvasive than invasive strains were positive for rrgC (P < 0.0001), and the proportion of rrgC-positive strains in 2008 to 2010 was greater than that in 2002 to 2008 (IPD, P < 0.02; noninvasive, P < 0.001). Serotypes 19F, 19A, and 35B were more frequently rrgC positive (P < 0.005) than other serotypes. A vaccine containing antigens, such as PspA, PspC, and/or RrgC, can provide coverage against most non-PCV13-type pneumococci. Continued surveillance is critical for optimal future vaccine development. PMID:24006139

Croney, Christina M.; Nahm, Moon H.; Juhn, Steven K.; Briles, David E.

2013-01-01

196

Immunogenicity following the first and second doses of 7-valent pneumococcal conjugate vaccine in HIV-infected and -uninfected infants?,??  

PubMed Central

Background The immunogenicity of pneumococcal conjugate vaccine (PCV) has not been evaluated in HIV-infected infants following the first and second PCV-doses. We studied antibody kinetics of serotypes included in 7-valent PCV in HIV-infected and HIV-uninfected infants prior to and following each of three PCV-doses. Methods HIV-uninfected infants born to HIV-uninfected (HUU) and HIV-infected mothers (HEU); and perinatal HIV-infected children with CD4+ < 25% randomized to initiate antiretroviral treatment (ART) when clinically and/or immunologically indicated (ART?) or immediately (ART+) were enrolled. Vaccination occurred at approximately 7.4, 11.5 and 15.5 weeks of age. Serotype-specific antibody was measured by ELISA following each PCV-dose and opsonophagocytic activity (OPA) to three serotypes following the second and third doses. Results Pre-vaccination, antibody geometric mean concentrations (GMCs) were higher in HUU compared to HIV-exposed groups for most serotypes. GMCs and proportion of infants with antibody ?0.35 ?g/ml were similar in HUU compared to other groups following the second PCV-dose. In all groups, GMCs were greater following the third compared to post-second dose; and a higher proportion within each group had antibody ?0.35 ?g/ml to 6B and 23F. OPA GMTs increased after the third compared to post-second dose for studied-serotypes; as did the proportion with OPA ?8 to 23F. Conclusion A two-dose primary-series of PCV probably confers similar protection against invasive pneumococcal disease in HIV-infected compared to HUU children. The inferior response to serotypes 6B and 23F, and lower GMCs and OPA GMTs, following two compared to after three PCV-doses may have implications in the prevention of pneumococcal disease in high-burden countries. PMID:23228814

Madhi, Shabir A.; Izu, Alane; Violari, Avye; Cotton, Mark F.; Panchia, Ravindre; Dobbels, Els; Sewraj, Poonam; van Niekerk, Nadia; Jean-Philippe, Patrick; Adrian, Peter V.

2013-01-01

197

Evaluation of the immunogenicity and biological activity of the Citrobacter freundii Vi-CRM197 conjugate as a vaccine for Salmonella enterica serovar Typhi.  

PubMed

Typhoid fever remains a major health problem in developing countries. Young children are at high risk, and a vaccine effective for this age group is urgently needed. Purified capsular polysaccharide from Salmonella enterica serovar Typhi (Vi) is licensed as a vaccine, providing 50 to 70% protection in individuals older than 5 years. However, this vaccine is ineffective in infants. Vi conjugated to a carrier protein (i.e., an exoprotein A mutant from Pseudomonas aeruginosa [rEPA]) is highly immunogenic, provides long-term protection, and shows more than 90% protective efficacy in children 2 to 5 years old. Here, we describe an alternative glycoconjugate vaccine for S. Typhi, Vi-CRM(197), where Vi was obtained from Citrobacter freundii WR7011 and CRM(197), the mutant diphtheria toxin protein, was used as the carrier. We investigated the optimization of growth conditions for Vi production from C. freundii WR7011 and the immunogenicity of Vi-CRM(197) conjugates in mice. The optimal saccharide/protein ratio of the glycoconjugates was identified for the best antibody production. We also demonstrated the ability of this new vaccine to protect mice against challenge with Vi-positive Salmonella enterica serovar Typhimurium. PMID:21248155

Rondini, Simona; Micoli, Francesca; Lanzilao, Luisa; Hale, Christine; Saul, Allan J; Martin, Laura B

2011-03-01

198

Serotype-Specific Changes in Invasive Pneumococcal Disease after Pneumococcal Conjugate Vaccine Introduction: A Pooled Analysis of Multiple Surveillance Sites  

PubMed Central

Background Vaccine-serotype (VT) invasive pneumococcal disease (IPD) rates declined substantially following introduction of 7-valent pneumococcal conjugate vaccine (PCV7) into national immunization programs. Increases in non-vaccine-serotype (NVT) IPD rates occurred in some sites, presumably representing serotype replacement. We used a standardized approach to describe serotype-specific IPD changes among multiple sites after PCV7 introduction. Methods and Findings Of 32 IPD surveillance datasets received, we identified 21 eligible databases with rate data ?2 years before and ?1 year after PCV7 introduction. Expected annual rates of IPD absent PCV7 introduction were estimated by extrapolation using either Poisson regression modeling of pre-PCV7 rates or averaging pre-PCV7 rates. To estimate whether changes in rates had occurred following PCV7 introduction, we calculated site specific rate ratios by dividing observed by expected IPD rates for each post-PCV7 year. We calculated summary rate ratios (RRs) using random effects meta-analysis. For children <5 years old, overall IPD decreased by year 1 post-PCV7 (RR 0·55, 95% CI 0·46–0·65) and remained relatively stable through year 7 (RR 0·49, 95% CI 0·35–0·68). Point estimates for VT IPD decreased annually through year 7 (RR 0·03, 95% CI 0·01–0·10), while NVT IPD increased (year 7 RR 2·81, 95% CI 2·12–3·71). Among adults, decreases in overall IPD also occurred but were smaller and more variable by site than among children. At year 7 after introduction, significant reductions were observed (18–49 year-olds [RR 0·52, 95% CI 0·29–0·91], 50–64 year-olds [RR 0·84, 95% CI 0·77–0·93], and ?65 year-olds [RR 0·74, 95% CI 0·58–0·95]). Conclusions Consistent and significant decreases in both overall and VT IPD in children occurred quickly and were sustained for 7 years after PCV7 introduction, supporting use of PCVs. Increases in NVT IPD occurred in most sites, with variable magnitude. These findings may not represent the experience in low-income countries or the effects after introduction of higher valency PCVs. High-quality, population-based surveillance of serotype-specific IPD rates is needed to monitor vaccine impact as more countries, including low-income countries, introduce PCVs and as higher valency PCVs are used. Please see later in the article for the Editors' Summary PMID:24086113

Feikin, Daniel R.; Kagucia, Eunice W.; Loo, Jennifer D.; Link-Gelles, Ruth; Puhan, Milo A.; Cherian, Thomas; Levine, Orin S.; Whitney, Cynthia G.; O'Brien, Katherine L.; Moore, Matthew R.

2013-01-01

199

Early trends in invasive pneumococcal disease in children following the introduction of 13-valent pneumococcal conjugate vaccine: results from eight years of active surveillance in a Mexican hospital  

PubMed Central

Background: In May 2012, universal vaccination with the 13-valent pneumococcal conjugate vaccine (PCV-13) was introduced for all children in the Tijuana region of Mexico, with a coverage of 80%. Method: Between October 2005 and September 2013 active surveillance was undertaken for all invasive pneumococcal diseases (IPDs) in children admitted to the Tijuana General Hospital. Results: Following PCV-13 implementation, there was a 75% reduction in overall IPD, and no cases of serotype 19A, pneumococcal meningitis, and pneumococcal-associated deaths. Conclusions: These results are the first to show the effectiveness of PCV-13 in Mexico. PMID:25364508

Rivas-Landeros, R.M.; Volker-Soberanes, M.L.

2014-01-01

200

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

PubMed

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. PMID:23933367

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

2013-09-23

201

Children's vaccine initiative.  

PubMed

The Consultative Group of the Children's Vaccine Initiative (CVI) held its annual meeting at WHO headquarters in Geneva in November 1992. The CVI meeting provided evidence of solid progress in development of a thermostable oral poliomyelitis vaccine and a single-dose tetanus toxoid vaccine. Researchers were able to stabilize the vaccine for several days at 37 degrees Celsius; this could make a more thermostable oral poliomyelitis vaccine available to the public before the end of the decade. One research project had solved the problem of stability of microencapsulated tetanus toxoid at 37 degrees Celsius. Based on recent research, it appears that microspheres for delivery of tetanus toxoid vaccines (of different sizes and/or compositions) can induce long-lasting immunity. The Consultative Group hopes that experts will conduct the industrial development of these vaccines within 3 years. A comprehensive database of the world's capacity to produce children's vaccines is being compiled, and investment strategies will assure that affordable vaccines are available for all children of the world. For the past 13 years, WHO has supported research at the Mahidol University in Bangkok, Thailand, to develop a safe, immunogenic, live, attenuated, tetravalent vaccine against the 4 strains of dengue virus. Formal Phase 1 and Phase 2 clinical trials have proved the vaccine to be safe and immunogenic in humans, thus bringing the Dengue Vaccine Development Project to a successful conclusion. Researchers are preparing to test the vaccine under actual field conditions for its efficacy in preventing dengue and dengue hemorrhagic fever among children in endemic communities. Participants in the Ministerial Conference on Malaria held in Amsterdam, the Netherlands, in October 1992 adopted a World Declaration on the control of malaria which will serve as a blueprint for action in the 1990s for a partnership of malaria-endemic and malaria-free countries. PMID:8185773

1993-01-01

202

Efficacy of nine-valent pneumococcal conjugate vaccine against pneumonia and invasive pneumococcal disease in The Gambia: randomised, double-blind, placebo-controlled trial  

Microsoft Academic Search

Methods We undertook a randomised, placebo-controlled, double-blind trial in eastern Gambia. Children age 6-51 weeks were randomly allocated three doses of either pneumococcal conjugate vaccine (n=8718) or placebo (8719), with intervals of at least 25 days between doses. Our primary outcome was first episode of radiological pneumonia. Secondary endpoints were clinical or severe clinical pneumonia, invasive pneumococcal disease, and all-cause

FT Cutts; SMA Zaman; G Enwere; S Jaffar; OS Levine; JB Okoko; C Oluwalana; A Vaughan; SK Obaro; A Leach; KP McAdam; E Biney; M Saaka; U Onwuchekwa; F Yallop; NF Pierce; BM Greenwood; RA Adegbola

2005-01-01

203

Invasive Streptococcus pneumoniae infections in children in Kamikawa and Soya subprefecture, Hokkaido, Japan, 2000–2010, before the introduction of the 7-valent pneumococcal conjugate vaccine  

Microsoft Academic Search

We evaluated 103 cases of invasive pneumococcal disease (IPD) encountered in 99 children (two developed the disease twice\\u000a and one, three times) treated in the northern district of Hokkaido (Kamikawa and Soya subprefecture) from April 2000 until\\u000a March 2010, before the introduction of the 7-valent pneumococcal conjugate vaccine. The main diseases were as follows: pneumonia,\\u000a 54 cases (52.9%); occult bacteremia,

Hiroshi Sakata

204

Characteristics of Memory B Cells Elicited by a Highly Efficacious HPV Vaccine in Subjects with No Pre-existing Immunity.  

PubMed

Licensed human papillomavirus (HPV) vaccines provide near complete protection against the types of HPV that most commonly cause anogenital and oropharyngeal cancers (HPV 16 and 18) when administered to individuals naive to these types. These vaccines, like most other prophylactic vaccines, appear to protect by generating antibodies. However, almost nothing is known about the immunological memory that forms following HPV vaccination, which is required for long-term immunity. Here, we have identified and isolated HPV 16-specific memory B cells from female adolescents and young women who received the quadrivalent HPV vaccine in the absence of pre-existing immunity, using fluorescently conjugated HPV 16 pseudoviruses to label antigen receptors on the surface of memory B cells. Antibodies cloned and expressed from these singly sorted HPV 16-pseudovirus labeled memory B cells were predominantly IgG (>IgA>IgM), utilized diverse variable genes, and potently neutralized HPV 16 pseudoviruses in vitro despite possessing only average levels of somatic mutation. These findings suggest that the quadrivalent HPV vaccine provides an excellent model for studying the development of B cell memory; and, in the context of what is known about memory B cells elicited by influenza vaccination/infection, HIV-1 infection, or tetanus toxoid vaccination, indicates that extensive somatic hypermutation is not required to achieve potent vaccine-specific neutralizing antibody responses. PMID:25330199

Scherer, Erin M; Smith, Robin A; Simonich, Cassandra A; Niyonzima, Nixon; Carter, Joseph J; Galloway, Denise A

2014-10-01

205

Characteristics of Memory B Cells Elicited by a Highly Efficacious HPV Vaccine in Subjects with No Pre-existing Immunity  

PubMed Central

Licensed human papillomavirus (HPV) vaccines provide near complete protection against the types of HPV that most commonly cause anogenital and oropharyngeal cancers (HPV 16 and 18) when administered to individuals naive to these types. These vaccines, like most other prophylactic vaccines, appear to protect by generating antibodies. However, almost nothing is known about the immunological memory that forms following HPV vaccination, which is required for long-term immunity. Here, we have identified and isolated HPV 16-specific memory B cells from female adolescents and young women who received the quadrivalent HPV vaccine in the absence of pre-existing immunity, using fluorescently conjugated HPV 16 pseudoviruses to label antigen receptors on the surface of memory B cells. Antibodies cloned and expressed from these singly sorted HPV 16-pseudovirus labeled memory B cells were predominantly IgG (>IgA>IgM), utilized diverse variable genes, and potently neutralized HPV 16 pseudoviruses in vitro despite possessing only average levels of somatic mutation. These findings suggest that the quadrivalent HPV vaccine provides an excellent model for studying the development of B cell memory; and, in the context of what is known about memory B cells elicited by influenza vaccination/infection, HIV-1 infection, or tetanus toxoid vaccination, indicates that extensive somatic hypermutation is not required to achieve potent vaccine-specific neutralizing antibody responses. PMID:25330199

Scherer, Erin M.; Smith, Robin A.; Simonich, Cassandra A.; Niyonzima, Nixon; Carter, Joseph J.; Galloway, Denise A.

2014-01-01

206

Duration of protective immunity conferred by maternal tetanus toxoid immunization: further evidence from Matlab, Bangladesh.  

PubMed Central

OBJECTIVES: Although maternal tetanus immunization has been shown to be highly effective in the prevention of neonatal tetanus, unresolved questions remain concerning the required minimum number of doses and the resulting duration of effective immunity. This study examined the duration of effective immunity against neonatal tetanus provided by maternal tetanus immunization. METHODS: A randomized, double-blind cholera vaccine trial of 41,571 children and nonpregnant adult women carried out in 1974 in the Matlab comparison area of rural Bangladesh provided a unique opportunity to address dose and immunity issues. RESULTS: Children of women who received either 1 or 2 injections of tetanus toxoid experienced 4- to 14-day mortality levels consistently lower than those of children of unimmunized mothers. Analysis of neonatal-tetanus-related mortality showed that 2 injections of tetanus toxoid provided significant protection for subsequent durations of up to 12 or 13 years. CONCLUSIONS: The data demonstrate that a limited-dose regimen of maternal tetanus toxoid provides significant and extended protection against the risk of neonatal tetanus death. PMID:9618617

Koenig, M A; Roy, N C; McElrath, T; Shahidullah, M; Wojtyniak, B

1998-01-01

207

Declines in pneumonia hospitalizations of children aged <2 years associated with the use of pneumococcal conjugate vaccines - tennessee, 1998-2012.  

PubMed

The 7-valent pneumococcal conjugate vaccine (PCV7) was added to the U.S. infant immunization schedule in the year 2000. By 2009, PCV7 introduction was associated with a 43% decline in all-cause pneumonia among U.S. children aged <2 years. In 2010, a new 13-valent pneumococcal conjugate vaccine (PCV13) replaced PCV7 in the infant immunization schedule, expanding protection from seven to 13 pneumococcal serotypes. To examine changes in all-cause pneumonia hospitalizations among children aged <2 years after the switch to PCV13, Tennessee hospital discharge data for 1998-2012 were analyzed. By 2012, all-cause pneumonia hospitalizations in children aged <2 years had declined an additional 27%, relative to the PCV7 years. Pneumonia hospitalizations were estimated to be 4.1 per 1,000 population in 2012, a historically low rate that represents a 72% decline from the rate before PCV7 introduction. Tennessee children aged <2 years experienced about 1,300 fewer pneumonia hospitalizations annually in 2011 and 2012 than in the years before pneumococcal conjugate vaccine (PCV) use. These data attest to the powerful impact of the PCV program on pneumonia in Tennessee children. The observed trend likely represents a major decline in pneumococcal pneumonia, which should stimulate a reassessment of current causes and appropriate management of pneumonia in children. PMID:25375070

Griffin, Marie R; Mitchel, Edward; Moore, Matthew R; Whitney, Cynthia G; Grijalva, Carlos G

2014-11-01

208

Effectiveness of 7-Valent Pneumococcal Conjugate Vaccine Against Invasive Pneumococcal Disease in HIV-Infected and -Uninfected Children in South Africa: A Matched Case-Control Study  

PubMed Central

Background.?South Africa introduced 7-valent pneumococcal conjugate vaccine (PCV7) in April 2009 using a 2 + 1 schedule (6 and 14 weeks and 9 months). We estimated the effectiveness of ?2 PCV7 doses against invasive pneumococcal disease (IPD) in human immunodeficiency virus (HIV)–infected and -uninfected children. Methods.?IPD (pneumococcus identified from a normally sterile site) cases were identified through national laboratory-based surveillance. Specimens were serotyped by Quellung or polymerase chain reaction. Four controls, matched for age, HIV status, and hospital were sought for each case. Using conditional logistic regression, we calculated vaccine effectiveness (VE) as 1 minus the adjusted odds ratio for vaccination. Results.?From March 2010 through November 2012, we enrolled 187 HIV-uninfected (48 [26%] vaccine serotype) and 109 HIV-infected (43 [39%] vaccine serotype) cases and 752 HIV-uninfected and 347 HIV-infected controls aged ?16 weeks. Effectiveness of ?2 PCV7 doses against vaccine-serotype IPD was 74% (95% confidence interval [CI], 25%–91%) among HIV-uninfected and ?12% (95% CI, ?449% to 77%) among HIV-infected children. Effectiveness of ?3 doses against vaccine-serotype IPD was 90% (95% CI, 14%–99%) among HIV-uninfected and 57% (95% CI, ?371% to 96%) among HIV-infected children. Among HIV-exposed but -uninfected children, effectiveness of ?2 doses was 92% (95% CI, 47%–99%) against vaccine-serotype IPD. Effectiveness of ?2 doses against all-serotype multidrug-resistant IPD was 96% (95% CI, 62%–100%) among HIV-uninfected children. Conclusions.?A 2 + 1 PCV7 schedule was effective in preventing vaccine-serotype IPD in HIV-uninfected and HIV-exposed, uninfected children. This finding supports the World Health Organization recommendation for this schedule as an alternative to a 3-dose primary series among HIV-uninfected individuals. PMID:24917657

Cohen, Cheryl; von Mollendorf, Claire; de Gouveia, Linda; Naidoo, Nireshni; Meiring, Susan; Quan, Vanessa; Nokeri, Vusi; Fortuin-de Smit, Melony; Malope-Kgokong, Babatyi; Moore, David; Reubenson, Gary; Moshe, Mamokgethi; Madhi, Shabir A.; Eley, Brian; Hallbauer, Ute; Kularatne, Ranmini; Conklin, Laura; O'Brien, Katherine L.; Zell, Elizabeth R.; Klugman, Keith; Whitney, Cynthia G.; von Gottberg, Anne; Moore, David; Verwey, Charl; Varughese, Sheeba; Archary, Moherndran; Naby, Fathima; Dawood, Khathija; Naidoo, Ramola; Elliott, Gene; Hallbauer, Ute; Eley, Brian; Nuttall, James; Cooke, Louise; Finlayson, Heather; Rabie, Helena; Whitelaw, Andrew; Perez, Dania; Jooste, Pieter; Naidoo, Dhamiran; Kularatne, Ranmini; Reubenson, Gary; Cohen, Cheryl; de Gouveia, Linda; du Plessis, Mignon; Govender, Nevashan; Meiring, Susan; Quan, Vanessa; von Mollendorf, Claire; Fortuin-de Smidt, Melony; Naidoo, Nireshni; Malope-Kgokong, Babatyi; Nokeri, Vusi; Ncha, Relebohile; Lindani, Sonwabo; von Gottberg, Anne; Spies, Barry; Sono, Lino; Maredi, Phasweni; Hamese, Ken; Moshe, Mamokgethi; Nchabeleng, Maphosane; Ngcobo, Ntombenhle; van den Heever, Johann; Madhi, Shabir; Conklin, Laura; Verani, Jennifer; Whitney, Cynthia; Zell, Elizabeth; Loo, Jennifer; Nelson, George; Klugman, Keith; O'Brien, Katherine

2014-01-01

209

Antibody response to Haemophilus influenzae type-b conjugate vaccine in children and young adults with congenital asplenia or after undergoing splenectomy.  

PubMed

Absence of the spleen constitutes a risk of infection caused by encapsulated bacteria. The aim of our study was to determine the immune response to Haemophilus influenzae type-b (Hib) conjugate vaccine (HibCV) in asplenic individuals, considering the cause of asplenia, the age when splenectomy was carried out, and previous Hib vaccinations. Twenty asplenic patients, aged five to 25 years, were immunized with a single dose of HibCV. The specific antibody concentrations against HibCV were measured by enzyme-linked immunosorbent assay. Before vaccinations, the geometric mean antibody concentration (GMC) had an average value of 3.21 ?g/ml and was comparable for all of the patients, regardless of the causes of asplenia. After vaccinations, the GMC was significantly higher, with an average of 6.78 ?g/ml. Further, 4.5 years after vaccinations, the GMC was comparable to that of previously unvaccinated children. Moreover, 17/20 patients had GMC???1.0 ?g/ml, which included all of the children with congenital asplenia, children splenectomized before the age of six years, and only 57% of children splenectomized after that age. HibCV gives asplenic patients long-term protection. Hence, HibCV should be administered regardless of previous vaccinations and time from splenectomy, even if antibody evaluation is not available. PMID:21874399

Mikoluc, B; Motkowski, R; Käyhty, H; Heropolitanska-Pliszka, E; Pietrucha, B; Bernatowska, E

2012-05-01

210

P5 HER2/neu-derived peptide conjugated to liposomes containing MPL adjuvant as an effective prophylactic vaccine formulation for breast cancer.  

PubMed

Vaccines containing synthetic peptides derived from tumor-associated antigens (TAA) can elicit potent cytotoxic T lymphocyte (CTL) response if they are formulated in an optimal vaccine delivery system. The aim of this study was to develop a simple and effective lipid-based vaccine delivery system using P5 HER2/neu-derived peptide conjugated to Maleimide-PEG2000-DSPE. The conjugated lipid was then incorporated into liposomes composed of DMPC:DMPG:Chol:DOPE containing Monophosphoryl lipid A (MPL) (Lip-DOPE-P5-MPL). Different liposome formulations were prepared and characterized for their physicochemical properties. To evaluate anti-tumoral efficacy, BALB/c mice were immunized subcutaneously 3 times in two-week intervals and the generated immune response was studied. The results demonstrated that Lip-DOPE-P5-MPL induced a significantly higher IFN-? production by CD8+ T cells intracellularly which represents higher CTL response in comparison with other control formulations. CTL response induced by this formulation caused the lowest tumor size and the longest survival time in a mice model of TUBO tumor. The encouraging results achieved by Lip-DOPE-P5-MPL formulation could make it a promising candidate in developing effective vaccines against Her2 positive breast cancers. PMID:25224570

Shariat, Sheida; Badiee, Ali; Jalali, Seyed Amir; Mansourian, Mercedeh; Yazdani, Mona; Mortazavi, Seyed Alireza; Jaafari, Mahmoud Reza

2014-12-01

211

Microneedle-Based Transcutaneous Immunisation in Mice with N-Trimethyl Chitosan Adjuvanted Diphtheria Toxoid Formulations  

Microsoft Academic Search

Purpose  The purpose of this study was to gain insight into the delivery and immunogenicity of N-trimethyl chitosan (TMC) adjuvanted\\u000a diphtheria toxoid (DT) formulations applied transcutaneously with microneedles.\\u000a \\u000a \\u000a \\u000a \\u000a Methods  Mice were vaccinated with DT-loaded TMC nanoparticles, a solution of TMC and DT (TMC\\/DT) or DT alone. The formulations were\\u000a applied onto the skin before or after microneedle treatment with two different 300-µm-long

Suzanne M. Bal; Zhi Ding; Gideon F. A. Kersten; Wim Jiskoot; Joke A. Bouwstra

2010-01-01

212

Antibody persistence in UK pre-school children following primary series with an acellular pertussis-containing pentavalent vaccine given concomitantly with meningococcal group C conjugate vaccine, and response to a booster dose of an acellular pertussis-containing quadrivalent vaccine.  

PubMed

This open-label, randomised, controlled study examined antibody persistence following infant vaccination at 2, 3 and 4 months of age with either an acellular pertussis, diphtheria, tetanus, inactivated poliovirus, Haemophilus influenzae type b (DT(5)aP-IPV-Hib; Pediacel) or a whole-cell pertussis (DTwP//Hib+oral poliomyelitis vaccine [OPV]) combination vaccine, given concomitantly with meningococcal serogroup C conjugate (MCC) vaccine, followed by a Hib booster at approximately 15 months of age. Immune responses were sustained to 3.5-4.5 years of age for all antigens contained in Pediacel. Administration of an acellular pertussis-containing quadrivalent pre-school booster (Td(5)ap-IPV; Repevax), with or without measles, mumps and rubella (M-M-RII) vaccine, induced robust antibody responses indicative of protection, regardless of the vaccine used for the primary series. Reactogenicity of Repevax was acceptable and consistent with previous experience. PMID:19573637

Kitchin, Nicholas; Southern, Joanna; Morris, Rhonwen; Borrow, Ray; Fiquet, Anne; Boisnard, Florence; Thomas, Stéphane; Miller, Elizabeth

2009-08-13

213

Towards the 13-valent pneumococcal conjugate universal vaccination: effectiveness in the transition era between PCV7 and PCV13 in Italy, 2010-2013.  

PubMed

Pneumococcal disease epidemiology has changed after introduction of pneumococcal conjugate vaccines. Seven-valent vaccine (PCV7) has been effective in reducing invasive pneumococcal disease (IPD). In Europe, PCV13 effectiveness was estimated at 78% (95% CI: -18-96%) for 2-priming doses. In Italy, PCV7 was introduced in 2006 in the childhood immunization schedule and replaced with PCV13 in 2010. In Apulia, vaccination coverage has reached 95.1% (birth-cohort 2010). We estimated PCV program effectiveness and its impact on S. pneumoniae diseases. PCV EFFECTIVENESS: We used the screening method. We calculated the Proportion of Population Vaccinated from immunization registries and detected cases through a laboratory-confirmed surveillance among hospitalized children?60 months. A confirmed IPD case was a child with PCR positive for S. pneumoniae. Differences among children were assessed with the Chi-square or the Fisher exact test (P value<0.05). PCV IMPACT: We constructed time series using outcome-specific Poisson regression models: hospitalization rate in pre-PCV era and hospitalization risk ratios (RRs) with 95% CIs for both PCV7 and PCV7/PCV13 shifting era. We calculated hospitalization RR with 95% CIs comparing pre-PCV years with vaccination period. The PCV effectiveness was 84.3% (95% CI: 84.0-84.6%). In May 2010-January 2013, we enrolled 159 suspected IPD of whom 4 were confirmed. Two (fully vaccinated) were caused by serotype 9V, 1 (not vaccinated) by serotype 3, 1 (vaccinated with 2 PCV13 doses) by 15B/C. The most important reduction was for pneumococcal pneumonia (RR: 0.43, 95% CI: 0.21-0.90). The PCV program show promising results in terms of both PCV13 effectiveness and its impact in reducing IPD in children<5 years. PMID:24096297

Martinelli, Domenico; Pedalino, Biagio; Cappelli, Maria Giovanna; Caputi, Giovanni; Sallustio, Anna; Fortunato, Francesca; Tafuri, Silvio; Cozza, Vanessa; Germinario, Cinzia; Chironna, Maria; Prato, Rosa

2014-01-01

214

Use of 13-valent pneumococcal conjugate vaccine and 23-valent pneumococcal polysaccharide vaccine among children aged 6-18 years with immunocompromising conditions: recommendations of the Advisory Committee on Immunization Practices (ACIP).  

PubMed

On February 20, 2013, 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.) for children aged 6-18 years with immunocompromising conditions, functional or anatomic asplenia, cerebrospinal fluid (CSF) leaks, or cochlear implants who have not previously received PCV13. PCV13 should be administered to these children regardless of whether they received the 7-valent pneumococcal conjugate vaccine (PCV7) or the 23-valent pneumococcal polysaccharide vaccine (PPSV23). Recommendations for PPSV23 use for children in this age group remain unchanged. The evidence for the benefits and risks associated with PCV13 vaccination of children with immunocompromising conditions was evaluated using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) framework. This recommendation reflects a policy change from permissive and off-label recommendation of PCV13 in the pediatric immunocompromised population to a category A recommendation. This report summarizes the evidence considered by ACIP to make this recommendation and reviews the recommendations for use of PCV13 and PPSV23 for children aged 6-18 years. PMID:23803961

2013-06-28

215

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 Central

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 R2 values ranging from 0.84 to 0.91 for all serotypes except serotype 19F, for which R2 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 ?g/ml should be reevaluated for use in the MIA and may need to be amended separately for each serotype. PMID:20130129

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

2010-01-01

216

Engineering, conjugation, and immunogenicity assessment of Escherichia coli O121 O antigen for its potential use as a typhoid vaccine component.  

PubMed

State-of-the-art production technologies for conjugate vaccines are complex, multi-step processes. An alternative approach to produce glycoconjugates is based on the bacterial N-linked protein glycosylation system first described in Campylobacter jejuni. The C. jejuni N-glycosylation system has been successfully transferred into Escherichia coli, enabling in vivo production of customized recombinant glycoproteins. However, some antigenic bacterial cell surface polysaccharides, like the Vi antigen of Salmonella enterica serovar Typhi, have not been reported to be accessible to the bacterial oligosaccharyltransferase PglB, hence hamper development of novel conjugate vaccines against typhoid fever. In this report, Vi-like polysaccharide structures that can be transferred by PglB were evaluated as typhoid vaccine components. A polysaccharide fulfilling these requirements was found in Escherichia coli serovar O121. Inactivation of the E. coli O121 O antigen cluster encoded gene wbqG resulted in expression of O polysaccharides reactive with antibodies raised against the Vi antigen. The structure of the recombinantly expressed mutant O polysaccharide was elucidated using a novel HPLC and mass spectrometry based method for purified undecaprenyl pyrophosphate (Und-PP) linked glycans, and the presence of epitopes also found in the Vi antigen was confirmed. The mutant O antigen structure was transferred to acceptor proteins using the bacterial N-glycosylation system, and immunogenicity of the resulting conjugates was evaluated in mice. The conjugate-induced antibodies reacted in an enzyme-linked immunosorbent assay with E. coli O121 LPS. One animal developed a significant rise in serum immunoglobulin anti-Vi titer upon immunization. PMID:23053636

Wetter, Michael; Kowarik, Michael; Steffen, Michael; Carranza, Paula; Corradin, Giampietro; Wacker, Michael

2013-07-01

217

Inferior quantitative and qualitative immune responses to pneumococcal conjugate vaccine in infants with nasopharyngeal colonization by Streptococcus pneumoniae during the primary series of immunization  

PubMed Central

Background Heightened immunogenicity, measured one month after the primary series of pneumococcal conjugate vaccine (PCV), in African children was previously hypothesized to be due to increased rates of nasopharyngeal pneumococcal colonization during early infancy. Methods We analyzed the effect of selected vaccine-serotype (6B, 19F and 23F) nasopharyngeal colonization prior to the first PCV dose or when colonized for the first time prior to the second or third (2nd/3rd) PCV dose on serotype quantitative and qualitative antibody responses. Results Colonization prior to receiving the first PCV was associated with lower geometric mean antibody concentrations (GMCs) one month after the third dose of PCV and six months later to the colonizing-serotype. Colonized infants also had lower geometric mean titers (GMTs) on opsonophagocytosis activity assay (OPA) and a lower proportion had titers ?8 against the colonizing serotypes (19F and 23F) post vaccination. Colonization occurring only prior to the 2nd/3rd PCV dose was also associated with lower GMCs and OPA GMTs to the colonizing-serotype. The effect of colonization with serotypes 19F and 23F prior to PCV vaccination had a greater effect on a lower proportion of colonized infants having OPA titers ?8 than the effect of colonization on the lower proportion with antibody ?0.35 ?g/ml. Conclusion Infant nasopharyngeal colonization at any stage before completing the primary series of PCV vaccination was associated with inferior quantitative and qualitative antibody responses to the colonizing-serotype. PMID:21787822

Madhi, Shabir A.; Violari, Avy; Klugman, Keith P.; Lin, Gina; McIntyre, James A.; von Gottberg, Anne; Jean-Philippe, Patrick; Cotton, Mark F.; Adrian, Peter

2011-01-01

218

Use of Prior Vaccinations for the Development of New Vaccines  

NASA Astrophysics Data System (ADS)

There is currently a need for vaccine development to improve the immunogenicity of protective epitopes, which themselves are often poorly immunogenic. Although the immunogenicity of these epitopes can be enhanced by linking them to highly immunogenic carriers, such carriers derived from current vaccines have not proven to be generally effective. One reason may be related to epitope-specific suppression, in which prior vaccination with a protein can inhibit the antibody response to new epitopes linked to the protein. To circumvent such inhibition, a peptide from tetanus toxoid was identified that, when linked to a B cell epitope and injected into tetanus toxoid-primed recipients, retained sequences for carrier but not suppressor function. The antibody response to the B cell epitope was enhanced. This may be a general method for taking advantage of previous vaccinations in the development of new vaccines.

Etlinger, H. M.; Gillessen, D.; Lahm, H.-W.; Matile, H.; Schonfeld, H.-J.; Trzeciak, A.

1990-07-01

219

Toxicity and Immunogenicity of Enterotoxigenic Escherichia coli Heat-Labile and Heat-Stable Toxoid Fusion 3xSTaA14Q-LTS63K/R192G/L211A in a Murine Model  

PubMed Central

Diarrhea is the second leading cause of death to young children. Enterotoxigenic Escherichia coli (ETEC) are the most common bacteria causing diarrhea. Adhesins and enterotoxins are the virulence determinants in ETEC diarrhea. Adhesins mediate bacterial attachment and colonization, and enterotoxins including heat-labile (LT) and heat-stable type Ib toxin (STa) disrupt fluid homeostasis in host cells that leads to fluid hyper-secretion and diarrhea. Thus, adhesins and enterotoxins have been primarily targeted in ETEC vaccine development. A recent study reported toxoid fusions with STa toxoid (STaP13F) fused at the N- or C-terminus, or inside the A subunit of LTR192G elicited neutralizing antitoxin antibodies, and suggested application of toxoid fusions in ETEC vaccine development (Liu et al., Infect. Immun. 79:4002-4009, 2011). In this study, we generated a different STa toxoid (STaA14Q) and a triple-mutant LT toxoid (LTS63K/R192G/L211A, tmLT), constructed a toxoid fusion (3xSTaA14Q-tmLT) that carried 3 copies of STaA14Q for further facilitation of anti-STa immunogenicity, and assessed antigen safety and immunogenicity in a murine model to explore its potential for ETEC vaccine development. Mice immunized with this fusion antigen showed no adverse effects, and developed antitoxin antibodies particularly through the IP route. Anti-LT antibodies were detected and were shown neutralizing against CT in vitro. Anti-STa antibodies were also detected in the immunized mice, and serum from the IP immunized mice neutralized STa toxin in vitro. Data from this study indicated that toxoid fusion 3xSTaA14Q-tmLT is safe and can induce neutralizing antitoxin antibodies, and provided helpful information for vaccine development against ETEC diarrhea. PMID:24146989

Zhang, Chengxian; Knudsen, David E.; Liu, Mei; Robertson, Donald C.; Zhang, Weiping

2013-01-01

220

Age-Dependent Prevalence of Nasopharyngeal Carriage of Streptococcus pneumoniae before Conjugate Vaccine Introduction: A Prediction Model Based on a Meta-Analysis  

PubMed Central

Introduction Data on the prevalence of nasopharyngeal carriage of S.pneumoniae in all age groups are important to help predict the impact of introducing pneumococcal conjugate vaccines (PCV) into routine infant immunization, given the important indirect effect of the vaccine. Yet most carriage studies are limited to children under five years of age. We here explore the association between carriage prevalence and serotype distribution in children aged ?5 years and in adults compared to children. Methods We conducted a systematic review of studies providing carriage estimates across age groups in healthy populations not previously exposed to PCV, using MEDLINE and Embase. We used Bayesian linear meta-regression models to predict the overall carriage prevalence as well as the prevalence and distribution of vaccine and nonvaccine type (VT and NVT) serotypes in older age groups as a function of that in <5 y olds. Results Twenty-nine studies compromising of 20,391 individuals were included in the analysis. In all studies nasopharyngeal carriage decreased with increasing age. We found a strong positive linear association between the carriage prevalence in pre-school childen (<5 y) and both that in school aged children (5–17 y olds) and in adults. The proportion of VT serotypes isolated from carriers was consistently lower in older age groups and on average about 73% that of children <5 y among 5–17 y olds and adults respectively. We provide a prediction model to infer the carriage prevalence and serotype distribution in 5–17 y olds and adults as a function of that in children <5 years of age. Conclusion Such predictions are helpful for assessing the potential population-wide effects of vaccination programmes, e.g. via transmission models, and thus assist in the design of future pneumococcal conjugate vaccination strategies. PMID:24465920

Le Polain de Waroux, Olivier; Flasche, Stefan; Prieto-Merino, David; Edmunds, W. John

2014-01-01

221

Immunogenicity and Safety of One versus Two Doses of Quadrivalent Meningococcal Conjugate Vaccine in Youth Infected with HIV  

PubMed Central

Objective To compare the immunogenicity of one vs. two doses of meningococcal conjugate vaccine (MCV4) in youth infected with HIV. Study design P1065 was a Phase I/II immunogenicity and safety trial of MCV4 in 324 youth infected with HIV performed at 27 sites of the IMPAACT network in the U.S. At entry subjects received one dose of MCV4. At 24 weeks, those with screening CD4% ?15 were randomized to receive a second dose or not, and all with screening CD4% <15 received a second dose. Immunogenicity was evaluated as the proportion of subjects with a ?4-fold rise from entry in serum bactericidal antibody against each meningococcal serogroup at weeks 28 and 72. Logistic regression models adjusting for HIV disease severity were used to evaluate the effect of one vs. two MCV4 doses among those with screening CD4% ?15. Results Subjects randomized to receive two vs. one MCV4 dose had significantly higher response rates to all serogroups at week 28 and to all except N meningitidis serogroupY at week 72, with adjusted ORs of 2.5–5.6. In 31 subjects with screening CD4% <15 who received two MCV4 doses, response rates ranged from 22–55% at week 28 and 6–28% at week 72. Conclusion In youth infected with HIV with a CD4% ?15, a second dose of MCV4 given six months after the initial dose significantly improves response rates at 28 and 72 weeks. Subjects with CD4% <15 at entry had lower response rates despite 2 doses of MCV4. PMID:22622049

Lujan-Zilbermann, Jorge; Warshaw, Meredith G.; Williams, Paige L.; Spector, Stephen A.; Decker, Michael D.; Abzug, Mark J.; Heckman, Barb; Manzella, Adam; Kabat, Bill; Jean-Philippe, Patrick; Nachman, Sharon; Siberry, George K

2012-01-01

222

Population Snapshot of Streptococcus pneumoniae Causing Invasive Disease in South Africa Prior to Introduction of Pneumococcal Conjugate Vaccines  

PubMed Central

We determined the sequence types of isolates that caused invasive pneumococcal disease (IPD) prior to routine use of pneumococcal conjugate vaccines (PCV) in South Africa. PCV-13 serotypes and 6C isolates collected in 2007 (1 461/2 437, 60%) from patients of all ages as part of on-going, national, laboratory-based surveillance for IPD, were selected for genetic characterization. In addition, all 134 non-PCV isolates from children <2 years were selected for characterization. Sequence type diversity by serotype and age category (children <5 years vs. individuals ?5 years) was assessed for PCV serotypes using Simpson’s index of diversity. Similar genotypes circulated among isolates from children and adults and the majority of serotypes were heterogeneous. While globally disseminated clones were common among some serotypes (e.g., serotype 1 [clonal complex (CC) 217, 98% of all serotype 1] and 14 [CC230, 43%)]), some were represented mainly by clonal complexes rarely reported elsewhere (e.g., serotype 3 [CC458, 60%] and 19A [CC2062, 83%]). In children <2 years, serotype 15B and 8 were the most common serotypes among non-PCV isolates (16% [22/134] and 15% [20/134] isolates, respectively). Sequence type 7052 and 53 were most common among serotypes 15B and 8 isolates and accounted for 58% (7/12) and 64% (9/14) of the isolates, respectively. Serotype 19F, 14, 19A and 15B had the highest proportions of penicillin non-susceptible isolates. Genotypes rarely reported in other parts of the world but common among some of our serotypes highlight the importance of our data as these genotypes may emerge post PCV introduction. PMID:25233455

Ndlangisa, Kedibone M.; du Plessis, Mignon; Wolter, Nicole; de Gouveia, Linda; Klugman, Keith P.; von Gottberg, Anne; GERMS-SA, for

2014-01-01

223

Comparative Immunogenicity of 7 and 13-Valent Pneumococcal Conjugate Vaccines and the Development of Functional Antibodies to Cross-Reactive Serotypes  

PubMed Central

Background Protection against disease or colonization from serotypes related to those in pneumococcal conjugate vaccines (i.e. cross-protection) vary by serotype; the basis for this variation is not understood. The 13-valent pneumococcal conjugate vaccine (PCV13) replaced 7-valent conjugate (PCV7) in the USA in 2010 allowing assessment of PCV7 and PCV13 immunogenicity and functional cross-protection in vitro. Methods Post-primary, pre-booster and post-booster sera from American Indian children receiving exclusively PCV7 or PCV13 were collected. IgG was measured by ELISA for 13 vaccine serotypes; functional antibody was assessed by opsonophagocytic killing assays for serotypes 6A/B/C and 19A/F. Results Post-primary IgG geometric mean concentrations (GMC) for serotypes 4 and 9V were lower in PCV13 recipients while 19F GMCs were higher. Only 19F differences persisted after receipt of the booster dose. Functional antibody activity was higher among PCV13 recipients for 6A, 6C, 19A and 19F (p<0.04), and among PCV7 recipients for 6B (p?=?0.01). Following PCV7, functional antibodies to 6A but not 19A were observed. High levels of 6C functional activity were seen after PCV13 but not PCV7. Conclusions Functional antibody activity against 6A/B/C and 19A/F suggest that PCV13 is likely to control the 19A disease and 6C disease remaining despite widespread use of PCV7. PMID:24086394

Grant, Lindsay R.; O'Brien, Sarah E.; Burbidge, Polly; Haston, Mitch; Zancolli, Marta; Cowell, Lucy; Johnson, Marina; Weatherholtz, Robert C.; Reid, Raymond; Santosham, Mathuram; O'Brien, Katherine L.; Goldblatt, David

2013-01-01

224

pertussis vaccines that induce antitoxin immunity and that are widely used in  

E-print Network

pertussis vaccines that induce antitoxin immunity and that are widely used in human populations . A similar mechanism could explain the impact of the pertussis-vaccination pro- gramme implemented in Sweden with a vaccine containing only pertussis toxoid, which also induces antitoxin immunity. This vaccine

Read, Andrew

225

Randomized trial on the safety, tolerability, and immunogenicity of MenACWY-CRM, an investigational quadrivalent meningococcal glycoconjugate vaccine, administered concomitantly with a combined tetanus, reduced diphtheria, and acellular pertussis vaccine in adolescents and young adults.  

PubMed

This study evaluated the safety, tolerability, and immunogenicity of an investigational quadrivalent meningococcal conjugate vaccine, MenACWY-CRM, when administered concomitantly with a combined tetanus, reduced diphtheria, and acellular pertussis (Tdap) vaccine, in subjects aged 11 to 25 years. Subjects received either MenACWY-CRM and Tdap, MenACWY-CRM and saline placebo, or Tdap and saline placebo. No significant increase in reactogenicity and no clinically significant vaccine-related adverse events (AEs) occurred when MenACWY-CRM and Tdap were administered concomitantly. Similar immunogenic responses to diphtheria, tetanus, and meningococcal (serogroups A, C, W-135, and Y) antigens were observed, regardless of concomitant vaccine administration. Antipertussis antibody responses were comparable between vaccine groups for filamentous hemagglutinin and were slightly lower, although not clinically significantly, for pertussis toxoid and pertactin when the two vaccines were administered concomitantly. These results indicate that the investigational MenACWY-CRM vaccine is well tolerated and immunogenic and that it can be coadministered with Tdap to adolescents and young adults. PMID:20164251

Gasparini, Roberto; Conversano, Michele; Bona, Gianni; Gabutti, Giovanni; Anemona, Alessandra; Dull, Peter M; Ceddia, Francesca

2010-04-01

226

Randomized Trial on the Safety, Tolerability, and Immunogenicity of MenACWY-CRM, an Investigational Quadrivalent Meningococcal Glycoconjugate Vaccine, Administered Concomitantly with a Combined Tetanus, Reduced Diphtheria, and Acellular Pertussis Vaccine in Adolescents and Young Adults? †  

PubMed Central

This study evaluated the safety, tolerability, and immunogenicity of an investigational quadrivalent meningococcal conjugate vaccine, MenACWY-CRM, when administered concomitantly with a combined tetanus, reduced diphtheria, and acellular pertussis (Tdap) vaccine, in subjects aged 11 to 25 years. Subjects received either MenACWY-CRM and Tdap, MenACWY-CRM and saline placebo, or Tdap and saline placebo. No significant increase in reactogenicity and no clinically significant vaccine-related adverse events (AEs) occurred when MenACWY-CRM and Tdap were administered concomitantly. Similar immunogenic responses to diphtheria, tetanus, and meningococcal (serogroups A, C, W-135, and Y) antigens were observed, regardless of concomitant vaccine administration. Antipertussis antibody responses were comparable between vaccine groups for filamentous hemagglutinin and were slightly lower, although not clinically significantly, for pertussis toxoid and pertactin when the two vaccines were administered concomitantly. These results indicate that the investigational MenACWY-CRM vaccine is well tolerated and immunogenic and that it can be coadministered with Tdap to adolescents and young adults. PMID:20164251

Gasparini, Roberto; Conversano, Michele; Bona, Gianni; Gabutti, Giovanni; Anemona, Alessandra; Dull, Peter M.; Ceddia, Francesca

2010-01-01

227

Human vaccines & immunotherapeutics: news.  

PubMed

Vaccinating boys against HPV to reduce cancer rates across the sexes: New melanoma vaccine contains natural product from marine sponges: Impact of Hib conjugate vaccines in developing countries: Electronic Health Records to keep track of immunization status: Pregnant women urged to get whooping cough vaccination: New nano-coating developed to preserve vaccines: Alternative approach to creating a universal flu vaccine: New modular vaccine design: MAPS technology. PMID:24051387

Riedmann, Eva M

2013-09-01

228

Human Vaccines & Immunotherapeutics: News  

PubMed Central

Vaccinating boys against HPV to reduce cancer rates across the sexes New melanoma vaccine contains natural product from marine sponges Impact of Hib conjugate vaccines in developing countries Electronic Health Records to keep track of immunization status Pregnant women urged to get whooping cough vaccination New nano-coating developed to preserve vaccines Alternative approach to creating a universal flu vaccine New modular vaccine design: MAPS technology PMID:24051387

Riedmann, Eva M

2013-01-01

229

Serotype distribution of Streptococcus pneumoniae isolated from patients with invasive pneumococcal disease in Brazil before and after ten-pneumococcal conjugate vaccine implementation.  

PubMed

The ten-pneumococcal conjugate vaccine (PCV10) was introduced into the national immunization program for childhood vaccination schedules by the Brazilian Health Public Service in March 2010. The aim of this study was to compare Streptococcus pneumoniae serotype distribution, antibiotic resistance patterns, and potential coverage before (January 2006-June 2010) and after (July 2010-September 2012) PCV10 introduction. The incidence of invasive pneumococcal disease (IPD), patient demographics, and disease characteristics were recorded. This study was conducted at the University Hospital of Sao Paulo University in Brazil from January 2006 to September 2012. Serotyping was performed using multiplex PCR typing, and antimicrobial sensitivity by Clinical and Laboratory Standards Institute (CLSI). A total of 259 S. pneumoniae strains were isolated from patients with IPD. The ages of the patients ranged from 3 months to 95 years old. The strains were isolated from cerebrospinal fluid, pleural fluid, and blood. The incidence of IPD among patients at HU-USP changed after the introduction of PCV10. The overall incidence of IPD was 3.42 cases per 1000 admissions in the vaccine pre- implementation period and of 2.99 cases per 1000 admissions in the vaccine post-implementation period. The incidence of IPD among children<2 y.o. attended at HU-USP changed significantly after the introduction of PCV10, from 20.30 to 3.97 of incidence. The incidence of PCV10- serotypes decrease from 16.47 to 0.44 in the same age, before and after PC10 implementation, respectively. Moreover, it was possible to realize the sensitivity to penicillin among isolates increased significantly in the post-vaccine period. Data from this study suggest that PCV10 contributed to decrease with PID rate among children less than 2 y.o. The resistance rate among pneumococcal isolates also could be observed since serotypes with greater resistance to beta lactam antibiotics were not easily isolated after vaccination. PMID:23747454

dos Santos, Silvia R; Passadore, Lilian F; Takagi, Elizabeth H; Fujii, Cristiane M; Yoshioka, Cristina R M; Gilio, Alfredo E; Martinez, Marina B

2013-12-01

230

Changes in pneumococcal serotypes and antimicrobial resistance after introduction of the 13-valent conjugate vaccine in the United States.  

PubMed

Ongoing surveillance for Streptococcus pneumoniae is needed to assess the impact of the pneumococcal conjugate vaccine introduced in 2010 (PCV13). Forty-two U.S. centers submitted S. pneumoniae isolates between 1 October 2012 and 31 March 2013. Susceptibility testing was performed by use of a broth dilution method as recommended by the Clinical and Laboratory Standards Institute. Serotyping was performed by multiplex PCR and the Quellung reaction. Multidrug resistance (MDR) was defined as nonsusceptibility to penicillin (PNSP; MIC ? 0.12 ?g/ml) combined with resistance to ?2 non-?-lactam antimicrobials. Penicillin-resistant S. pneumoniae (PRSP) was defined as a penicillin MIC of ?2 ?g/ml. For the 1,498 isolates collected during 2012-13, the PRSP and MDR rates were 14.2 and 21.0%, respectively. These percentages were lower than rates obtained in a surveillance study conducted 4 years earlier in 2008-09 (17.0 and 26.6%, respectively). The most common serotypes identified in 2012-13 were 3, 35B, and 19A, each representing 9 to 10% of all isolates. The largest percentage of PNSP in 2012-13 were found in serotypes 35B (24.8%), 19A (23.5%), and 15A (10.3%). Predominant PRSP serotypes were 19A (54.5%), 35B (28.2%), and 19F (7.0%). Major MDR serotypes were 19A (38.5%), 15A (16.9%), 6C (8.3%), and 35B (6.4%). The change in prevalence of PCV13 serotypes (43.4 to 27.1%) was primarily due to a decrease in serotype 19A strains, i.e., 22% of all strains in 2008-09 to 10% of all strains in 2012-13. Among the PNSP subset, serotypes showing a proportional increase were 35B, 15B, and 23B. Among MDR strains, the largest proportional increases were observed in serotypes 35B, 15B, and 23A. PMID:25136018

Richter, Sandra S; Diekema, Daniel J; Heilmann, Kristopher P; Dohrn, Cassie L; Riahi, Fathollah; Doern, Gary V

2014-11-01

231

Induction of Protective Serum Meningococcal Bactericidal and Diphtheria-Neutralizing Antibodies and Mucosal Immunoglobulin A in Volunteers by Nasal Insufflations of the Neisseria meningitidis Serogroup C Polysaccharide-CRM197 Conjugate Vaccine Mixed with Chitosan  

Microsoft Academic Search

Thirty-six healthy volunteers received either a single intramuscular injection of Neisseria meningitidis sero- group C polysaccharide (MCP)-CRM197 conjugate vaccine in alum or two nasal insufflations 28 days apart of the same vaccine powder, without alum, mixed with chitosan. Nasal immunization was well tolerated, with fewer symptoms reported than after intramuscular injection. The geometric mean concentrations of MCP- specific immunoglobulin G

Zhiming Huo; Ruchi Sinha; Edel A. McNeela; Ray Borrow; Rafaela Giemza; Catherine Cosgrove; Paul T. Heath; Kingston H. G. Mills; Rino Rappuoli; George E. Griffin; David J. M. Lewis

2005-01-01

232

Predictors to parental knowledge about childhood immunisation/EPI vaccines in two health districts in Cameroon prior to the introduction of 13-valent Pneumococcal Conjugate Vaccines (PCV-13)  

PubMed Central

Introduction Pneumonia is vaccine-preventable, but the increasing death toll resulting from the disease in Sub-Saharan Africa is alarming. Several factors account for vaccine failing to reach every child, besides incomplete vaccine coverage. Most of these include the perceptions of parents/guardians and healthcare providers. Previous studies on the introduction of new vaccines have focused on experimental trials, coverage figures and vaccine efficacy in developed countries. Little is known on the factors which may hinder the implementation process despite the huge challenges this may encounter in developing countries. This study described the knowledge, attitude and practices (KAP) of parents/guardians on pneumonia and immunisations/EPI vaccines; identify predictive parental socio-economic/demographic characteristics that of good knowledge on pneumonia infections, routine EPI vaccines and the PCV-13. Finally, the study described health center personnel perceptions about immunisations. Methods The WHO's immunisation coverage cluster survey design was used, involving parents/guardians (n = 205) of children aged 0-59 months and health centre personnel (n = 13) directly concerned with vaccination activities between July-September 2010 in two health districts in Yaounde, Cameroon. Descriptive statistics and multivariate logistic models were used to analyse the parental/guardian data while the health personnel data was only analysed descriptively using SPSS version 17.0. Results Only 19% of the parents/guardians were aware of the availability of the PCV-13. Logistic modelling identified important associations between parental socio-economic/demographic factors and good knowledge on pneumonia disease burden and prevention. Conclusion According to parents/guardians a short and clear message on the dangers of pneumonia and the need for prevention provided to parents/guardians during sensitisation/out-reach campaigns and use of social network avenues would be primordial, if the PCV-13 is to reach every child.

Libwea, John Njuma; Kobela, Marie; Ollgren, Jukka; Emah, Irene; Tchio, Robert; Nohynek, Hanna

2014-01-01

233

Primary vaccination with the 10-valent pneumococcal non-typeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV) in infants in Mali and Nigeria: a randomized controlled trial  

PubMed Central

Background Pneumonia is still the leading cause of death among children in Africa, and pneumococcal serotypes 1 and 5 are frequently isolated from African children with invasive pneumococcal disease below the age of 5 years. The immunogenicity, safety and reactogenicity of 3-dose primary vaccination with the 10-valent pneumococcal non-typeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV) were evaluated in infants in Mali and Nigeria. Methods In an open, randomized, controlled study, 357 infants received DTPw-HBV/Hib and OPV primary vaccination with (PHiD-CV group) or without (control group) PHiD-CV co-administration at 6, 10 and 14 weeks of age. Pneumococcal antibody responses and opsonophagocytic activity (OPA) were measured and adverse events (AEs) recorded. Results One month post-dose 3, ? 97.2% of PHiD-CV-vaccinated infants had an antibody concentration ? 0.2 ?g/mL for each vaccine pneumococcal serotype except for 6B (82.0%) and 23F (87.6%) versus < 10% in the control group except for serotypes 14 (35.7%) and 19F (22.5%). For each vaccine serotype, ? 93.3% of PHiD-CV recipients had an OPA titre ? 8, except for serotypes 1 (87.6%) and 6B (85.4%), compared to < 10% in the control group, except for serotypes 7F (42.9%), 9V (24.1%) and 14 (24.5%). Anti-protein D geometric mean antibody concentrations were 3791.8 and 85.4 EL.U/mL in the PHiD-CV and control groups, respectively. Overall incidences of solicited and unsolicited AEs were similar between groups. Conclusions In sub-Saharan African infants, PHiD-CV was immunogenic for all vaccine pneumococcal serotypes and protein D. Vaccine tolerability was generally comparable between the PHiD-CV and control groups. Trial Registration ClinicalTrials.gov identifier: NCT00678301. PMID:22112189

2011-01-01

234

Effects of the 10-Valent Pneumococcal Nontypeable Haemophilus influenzae Protein D-Conjugate Vaccine on Nasopharyngeal Bacterial Colonization in Young Children: A Randomized Controlled Trial  

PubMed Central

Background.?This study evaluated the effects of the 10-valent pneumococcal nontypeable Haemophilus influenzae protein D–conjugate vaccine (PHiD-CV) on nasopharyngeal bacterial colonization compared with the 7-valent pneumococcal conjugate vaccine (7vCRM) in young children. Methods.?A randomized controlled trial in the Netherlands, initiated 2 years after 7vCRM introduction, was conducted between 1 April 2008 and 1 December 2010. Infants (N = 780) received either PHiD-CV or 7vCRM (2:1) at 2, 3, 4, and 11–13 months of age. Nasopharyngeal samples taken at 5, 11, 14, 18, and 24 months of age were cultured to detect Haemophilus influenzae, Streptococcus pneumoniae, Moraxella catarrhalis, and Staphylococcus aureus. Polymerase chain reaction assays quantified H. influenzae and S. pneumoniae and confirmed H. influenzae as nontypeable (NTHi). Primary outcome measure was vaccine efficacy (VE) against NTHi colonization. Results.?In both groups, NTHi colonization increased with age from 33% in 5-month-olds to 65% in 24-month-olds. Three months postbooster, VE against colonization was 0.5% (95% confidence interval [CI], ?21.8% to 18.4%) and VE against acquisition 10.9% (95% CI, ?31.3% to 38.9%). At each sampling moment, no differences between groups in either NTHi prevalence or H. influenzae density were detected. Streptococcus pneumoniae (range, 39%–57%), M. catarrhalis (range, 63%­–69%), and S. aureus (range, 9%–30%) colonization patterns were similar between groups. Conclusions.?PHiD-CV had no differential effect on nasopharyngeal NTHi colonization or H. influenzae density in healthy Dutch children up to 2 years of age, implying that herd effects for NTHi are not to be expected. Other bacterial colonization patterns were also similar. Clinical Trials Registration?NCT00652951. PMID:23118268

van den Bergh, Menno R.; Spijkerman, Judith; Swinnen, Kristien M.; Francois, Nancy A.; Pascal, Thierry G.; Borys, Dorota; Schuerman, Lode; IJzerman, Ed P. F.; Bruin, Jacob P.; van der Ende, Arie; Veenhoven, Reinier H.; Sanders, Elisabeth A. M.

2013-01-01

235

Immunization with the conjugate vaccine Vi-CRM??? against Salmonella typhi induces Vi-specific mucosal and systemic immune responses in mice.  

PubMed

Typhoid fever is a public health problem, especially among young children in developing countries. To address this need, a glycoconjugate vaccine Vi-CRM???, composed of the polysaccharide antigen Vi covalently conjugated to the non-toxic mutant of diphtheria toxin CRM???, is under development. Here, we assessed the antibody and cellular responses, both local and systemic, following subcutaneous injection of Vi-CRM???. The glycoconjugate elicited Vi-specific serum IgG titers significantly higher than unconjugated Vi, with prevalence of IgG1 that persisted for at least 60 days after immunization. Vi-specific IgG, but not IgA, were present in intestinal washes. Lymphocytes proliferation after restimulation with Vi-CRM??? was observed in spleen and mesenteric lymph nodes. These data confirm the immunogenicity of Vi-CRM??? and demonstrate that the vaccine-specific antibody and cellular immune responses are present also in the intestinal tract, thus strengthening the suitability of Vi-CRM??? as a promising candidate vaccine against Salmonella Typhi. PMID:22705173

Fiorino, Fabio; Ciabattini, Annalisa; Rondini, Simona; Pozzi, Gianni; Martin, Laura B; Medaglini, Donata

2012-09-21

236

Prevalent Multidrug-resistant Nonvaccine Serotypes in Pneumococcal Carriage of Healthy Korean Children Associated with the Low Coverage of the Seven-valent Pneumococcal Conjugate Vaccine  

PubMed Central

Objectives Our previous longitudinal multicenter-based carriage study showed that the average carriage rate of Streptococcus pneumoniae was 16.8% in 582 healthy children attending kindergarten or elementary school in Seoul, Korea. We assessed serotype-specific prevalence and antimicrobial resistance among colonizing pneumococcal isolates from young children in the era of low use of the seven-valent pneumococcal conjugate vaccine (PCV7). Methods Serotypes were determined by an agglutination test with specific antisera or by a multiplex polymerase chain reaction (PCR) assay. An antimicrobial susceptibility test was performed with broth microdilution in Korean 96-well panels from Dade-MicroScan (Sacramento, CA, USA). Results Pneumococcal colonization patterns were dynamic and longterm persistent carriage was rare, which indicated a sequential turnover of pneumococcal strains. Of the 369 pneumococci (except for 23 killed isolates), 129 (34.9%) isolates were PCV7 vaccine serotypes (VTs); 213 (57.8%) isolates were nonvaccine serotypes (NVTs); and the remaining 27 (7.2%) isolates were nontypable (NT). The highest rates of multidrug resistance (MDR) were observed in VTs (86.0%; 111/129 isolates) and NVTs (70.0%; 149/213 isolates). Conclusion This study overall showed the frequent carriage of VTs and NVTs with MDR in healthy children attending kindergarten or elementary school. Efforts should be directed toward reducing the extensive prescription of antibiotics and using new broader vaccines to reduce the expansion of MDR strains of NVTs in our community. PMID:24524020

Lee, Sungkyoung; Kim, Ji-Hye; Kim, Seong-Han; Park, Misun; Bae, Songmee

2013-01-01

237

A single administration of tetanus toxoid in biodegradable microspheres elicits T cell and antibody responses similar or superior to those obtained with aluminum hydroxide  

Microsoft Academic Search

The use of biodegradable polymer microspheres as a single dose vaccine delivery system was investigated by using tetanus toxoid (TT). In order to compare the immunogenicity of TT-microspheres (TT-MS) with aluminum hydroxide (alum)-based TT, BALBc mice were immunized with TT in different formulations including individual or mixtures of MS and TT-alum. All TT-MS formulations elicited high proliferative and antibody responses

Ying Men; Claudio Thomasin; Hans P. Merkle; Bruno Gander; Giampietro Corradin

1995-01-01

238

Impact of Pneumococcal Conjugate Vaccination of Infants on Pneumonia and Influenza Hospitalization and Mortality in All Age Groups in the United States  

PubMed Central

A seven-valent pneumococcal conjugate vaccine (PCV7) introduced in the United States in 2000 has been shown to reduce invasive pneumococcal disease (IPD) in both vaccinated children and adults through induction of herd immunity. We assessed the impact of infant immunization on pneumococcal pneumonia hospitalizations and mortality in all age groups using Health Care Utilization Project State Inpatient Databases (SID) for 1996 to 2006 from 10 states; SID contain 100% samples of ICD9-coded hospitalization data for the selected states. Compared to a 1996–1997 through 1998–1999 baseline, by the 2005–2006 season, both IPD and pneumococcal pneumonia hospitalizations and deaths had decreased substantially in all age groups, including a 47% (95% confidence interval [CI], 38 to 54%) reduction in nonbacteremic pneumococcal pneumonia (ICD9 code 481 with no codes indicating IPD) in infants <2 years old and a 54% reduction (CI, 53 to 56%) in adults ?65 years of age. A model developed to calculate the total burden of pneumococcal pneumonia prevented by infant PCV7 vaccination in the United States from 2000 to 2006 estimated a reduction of 788,838 (CI, 695,406 to 875,476) hospitalizations for pneumococcal pneumonia. Ninety percent of the reduction in model-attributed pneumococcal pneumonia hospitalizations occurred through herd immunity among adults 18 years old and older; similar proportions were found in pneumococcal disease mortality prevented by the vaccine. In the first seasons after PCV introduction, when there were substantial state differences in coverage among <5-year-olds, states with greater coverage had significantly fewer influenza-associated pneumonia hospitalizations among children, suggesting that PCV7 use also reduces influenza-attributable pneumonia hospitalizations. PMID:21264063

Simonsen, Lone; Taylor, Robert J.; Young-Xu, Yinong; Haber, Michael; May, Larissa; Klugman, Keith P.

2011-01-01

239

Poly(?-d-glutamic acid) protein conjugates induce IgG antibodies in mice to the capsule of Bacillus anthracis: A potential addition to the anthrax vaccine  

PubMed Central

Both the protective antigen (PA) and the poly(?-d-glutamic acid) capsule (?dPGA) are essential for the virulence of Bacillus anthracis. A critical level of vaccine-induced IgG anti-PA confers immunity to anthrax, but there is no information about the protective action of IgG anti-?dPGA. Because the number of spores presented by bioterrorists might be greater than encountered in nature, we sought to induce capsular antibodies to expand the immunity conferred by available anthrax vaccines. The nonimmunogenic ?dPGA or corresponding synthetic peptides were bound to BSA, recombinant B. anthracis PA (rPA), or recombinant Pseudomonas aeruginosa exotoxin A (rEPA). To identify the optimal construct, conjugates of B. anthracis ?dPGA, Bacillus pumilus ?dLPGA, and peptides of varying lengths (5-, 10-, or 20-mers), of the d or l configuration with active groups at the N or C termini, were bound at 5–32 mol per protein. The conjugates were characterized by physico-chemical and immunological assays, including GLC-MS and matrix-assisted laser desorption ionization time-of-flight spectrometry, and immunogenicity in 5- to 6-week-old mice. IgG anti-?dPGA and antiprotein were measured by ELISA. The highest levels of IgG anti-?dPGA were elicited by decamers of ?dPGA at 10 –20 mol per protein bound to the N- or C-terminal end. High IgG anti-?dPGA levels were elicited by two injections of 2.5 ?g of ?dPGA per mouse, whereas three injections were needed to achieve high levels of protein antibodies. rPA was the most effective carrier. Anti-?dPGA induced opsonophagocytic killing of B. anthracis tox–, cap+. ?dPGA conjugates may enhance the protection conferred by PA alone. ?dPGA-rPA conjugates induced both anti-PA and anti-?dPGA. PMID:12857944

Schneerson, Rachel; Kubler-Kielb, Joanna; Liu, Teh-Yung; Dai, Zhong-Dong; Leppla, Stephen H.; Yergey, Alfred; Backlund, Peter; Shiloach, Joseph; Majadly, Fathy; Robbins, John B.

2003-01-01

240

All-Cause Pneumonia Hospitalizations in Children <2 Years Old in Sweden, 1998 to 2012: Impact of Pneumococcal Conjugate Vaccine Introduction  

PubMed Central

Background In late 2007, some Swedish County Councils started 7-valent pneumococcal conjugate vaccine (PCV7) implementation for children, and PCV7 was included in the national immunization program in 2009. By 2010, both PCV10 and PCV13 were licensed, and the selection of vaccine was subject to County Councils tenders. This study investigated the impact of the order of PCV introduction into vaccination programs on the incidence of all-cause pneumonia hospitalizations in children <2 years-old. Methods Using population-based data from the publicly available National Inpatient Registry, the incidence of inpatient pneumonia (ICD-10 J12-J18) hospitalizations by County Councils among children <2 years old was identified between 1998 and 2012. Incidence rate ratios (IRR; 95% CI) were calculated during the nationwide implementation of PCV7 and then between County Councils, as based on the higher-valent vaccine chosen for a program. Results There was a lower risk of all-cause pneumonia hospitalization among <2 year-old children following the introduction of PCV7, as compared to the pre-PCV7 period (0.77; 0.63–0.93). A decreased risk of all-cause pneumonia was also observed in the County Councils that followed the order PCV7 then PCV13 (0.82; 0.66–1.01), while no trend was observed in County Councils with a program in the order PCV7 then PCV10 (1.03; 0.82–1.30). When comparing the higher-valent vaccines, there was a 21% (0.79; 0.66–0.96) lower risk for childhood pneumonia hospitalization in County Councils finally using PCV13 as compared to the experience in County Councils that ultimately adopted PCV10. Conclusions Among children <2 years-old, all-cause pneumonia hospitalizations were significantly reduced by 23% one to two years after introduction of PCV7 vaccination in Sweden. In those County Councils that next introduced PCV13, a further decline in all-cause pneumonia hospitalization was observed, in contrast to those County Councils that followed with PCV10; this 21% lower risk for childhood pneumonia hospitalization was statistically significant. PMID:25379659

Berglund, Anders; Ekelund, Mats; Fletcher, Mark A.; Nyman, Lars

2014-01-01

241

Adjuvanticity of pGPL-Mc and LRS in the immune responses of monkeys to oral immunization with diphtheria and tetanus toxoids.  

PubMed

Experiments were carried out to examine the adjuvanticity of polar glycopeptidolipids of Mycobacterium chelonae (pGPL-Mc) or the London rocket seed (LRS) when combined with diphtheria and tetanus toxoids in an oral immunization of the African green monkey. The results showed that none of the monkeys receiving diphtheria and tetanus toxoids combined with 25 mg/kg of pGPL-Mc showed an increase in the the level of diphtheria antitoxin (DA) on the third and sixth weeks following the first and the second immunizations. One monkey from this group responded with increased seroneutralizing antibodies 3 weeks after the third feeding. On the other hand, one monkey, 3 weeks after the first immunization, and three monkeys, 3 weeks after the second and third oral vaccinations, showed an increase in specific anti-diphtheria antibody responses when the toxoids were combined with 25 mg/kg of LRS. The anti-diphtheria antitoxin responses of monkeys receiving diphtheria and tetanus toxoids combined with 50 mg/kg of pGPL-Mc or 50 mg/kg of LRS were significantly enhanced compared to the groups administered 25 mg/kg of the two adjuvants. The increase was observed in four out of five pGPL-Mc administered and in three out of five LRS-receiving monkeys. The results show that pGPL-Mc induced the highest titres of anti-diphtheria antitoxin compared to LRS, whereas the level of anti-diphtheria antitoxin titre of the two monkeys receiving the toxoids alone was less than 0.1 i.u./ml of serum throughout the experiment. According to the statistical analyses, no significant differences were recorded between the diphtheria antitoxin responses of monkeys following the first, second or third administration of LRS-adjuvated diphtheria and tetanus toxoids. However, a significant difference (P < or = 0.05) was observed in the diphtheria antitoxin response between the first and the second immunization of monkeys administered with toxoids adjuvated with 50 mg/kg of pGPL-Mc. The tetanus antitoxin responses of all monkeys were less than 0.1 i.u. of antitoxin per millilitre of serum throughout the study, which is considered not to be protective. However, we have recorded an anti-tetanus antitoxin titre of more than 0.2 i.u./ml of serum in one monkey that received diphtheria and tetanus toxoids combined with 50 mg/kg of pGPL-Mc. PMID:9023036

Mirchamsy, H; Neway, T; Hamedi, M; Pilet, C

1997-01-01

242

Evaluation of a LPS-based glycoconjugate vaccine against bovine Escherichia coli mastitis: Formation of LPS Abs in cows after immunization with E. coli core oligosaccharides conjugated to hemocyanine.  

PubMed

The immune response of cows against the core oligosaccharide of Escherichia coli rough mutants (core types R1-R4, K-12 and J-5) was investigated after immunization with a synthetic glycoconjugate composed of deacylated LPS conjugated to hemocyanine (22 animals). Ab formation was measured by ELISA using LPS or deacylated LPS conjugated to BSA as an Ag. The glycoconjugate immunogens were used to vaccinate cows (36 animals), which were then challenged intramammarily with E. coli O 157 (K1 negative, R1 core type). Compared with control groups no protection was observed, although high titers against the R1 core type were detected in vaccinated animals. Western blots using the immune sera showed that the Ab response was directed against the core region and not against the O-antigen, which may explain the failure of the vaccine. PMID:23112009

Brade, Lore; Hensen, Selma; Brade, Helmut

2013-01-01

243

Efficacy of Pneumococcal Nontypable Haemophilus influenzae Protein D Conjugate Vaccine (PHiD-CV) in Young Latin American Children: A Double-Blind Randomized Controlled Trial  

PubMed Central

Background The relationship between pneumococcal conjugate vaccine–induced antibody responses and protection against community-acquired pneumonia (CAP) and acute otitis media (AOM) is unclear. This study assessed the impact of the ten-valent pneumococcal nontypable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV) on these end points. The primary objective was to demonstrate vaccine efficacy (VE) in a per-protocol analysis against likely bacterial CAP (B-CAP: radiologically confirmed CAP with alveolar consolidation/pleural effusion on chest X-ray, or non-alveolar infiltrates and C-reactive protein ? 40 µg/ml); other protocol-specified outcomes were also assessed. Methods and Findings This phase III double-blind randomized controlled study was conducted between 28 June 2007 and 28 July 2011 in Argentine, Panamanian, and Colombian populations with good access to health care. Approximately 24,000 infants received PHiD-CV or hepatitis control vaccine (hepatitis B for primary vaccination, hepatitis A at booster) at 2, 4, 6, and 15–18 mo of age. Interim analysis of the primary end point was planned when 535 first B-CAP episodes, occurring ?2 wk after dose 3, were identified in the per-protocol cohort. After a mean follow-up of 23 mo (PHiD-CV, n?=?10,295; control, n?=?10,201), per-protocol VE was 22.0% (95% CI: 7.7, 34.2; one-sided p?=?0.002) against B-CAP (conclusive for primary objective) and 25.7% (95% CI: 8.4%, 39.6%) against World Health Organization–defined consolidated CAP. Intent-to-treat VE was 18.2% (95% CI: 5.5%, 29.1%) against B-CAP and 23.4% (95% CI: 8.8%, 35.7%) against consolidated CAP. End-of-study per-protocol analyses were performed after a mean follow-up of 28–30 mo for CAP and invasive pneumococcal disease (IPD) (PHiD-CV, n?=?10,211; control, n?=?10,140) and AOM (n?=?3,010 and 2,979, respectively). Per-protocol VE was 16.1% (95% CI: ?1.1%, 30.4%; one-sided p?=?0.032) against clinically confirmed AOM, 67.1% (95% CI: 17.0%, 86.9%) against vaccine serotype clinically confirmed AOM, 100% (95% CI: 74.3%, 100%) against vaccine serotype IPD, and 65.0% (95% CI: 11.1%, 86.2%) against any IPD. Results were consistent between intent-to-treat and per-protocol analyses. Serious adverse events were reported for 21.5% (95% CI: 20.7%, 22.2%) and 22.6% (95% CI: 21.9%, 23.4%) of PHiD-CV and control recipients, respectively. There were 19 deaths (n?=?11,798; 0.16%) in the PHiD-CV group and 26 deaths (n?=?11,799; 0.22%) in the control group. A significant study limitation was the lower than expected number of captured AOM cases. Conclusions Efficacy was demonstrated against a broad range of pneumococcal diseases commonly encountered in young children in clinical practice. Trial registration www.ClinicalTrials.gov NCT00466947 Please see later in the article for the Editors' Summary PMID:24892763

Tregnaghi, Miguel W.; Saez-Llorens, Xavier; Lopez, Pio; Abate, Hector; Smith, Enrique; Posleman, Adriana; Calvo, Arlene; Wong, Digna; Cortes-Barbosa, Carlos; Ceballos, Ana; Tregnaghi, Marcelo; Sierra, Alexandra; Rodriguez, Mirna; Troitino, Marisol; Carabajal, Carlos; Falaschi, Andrea; Leandro, Ana; Castrejon, Maria Mercedes; Lepetic, Alejandro; Lommel, Patricia; Hausdorff, William P.; Borys, Dorota; Guinazu, Javier Ruiz; Ortega-Barria, Eduardo; Yarzabal, Juan P.; Schuerman, Lode

2014-01-01

244

Effect of HIV infection status and anti-retroviral treatment on quantitative and qualitative antibody responses to pneumococcal conjugate vaccine in infants.  

PubMed

Serotype-specific antibody concentration and opsonophagocytic activity (OPA) were evaluated after 3 doses of pneumococcal conjugate vaccine. Groups included human immunodeficiency virus (HIV)-positive infants with CD4(+) cell percentages > or =25% who initiated immediate antiretroviral treatment (the HIV+/ART+ group) or whose antiretroviral treatment was deferred until clinically or immunologically indicated (the HIV+/ART- group). Immune responses were also evaluated in HIV-noninfected infants born to HIV-seronegative (M-/I-) or HIV-positive mothers (M+/I-). Antibody concentrations were similar between HIV+/ART+ and HIV+/ART- infants. However, antibody concentrations were lower in M-/I- infants than in M+/I- infants. Nevertheless, M-/I- infants had superior OPA responses, compared with those in HIV+/ART+ infants, who in turn had better OPA responses, compared with those in HIV+/ART- infants. PMID:20583920

Madhi, Shabir A; Adrian, Peter; Cotton, Mark F; McIntyre, James A; Jean-Philippe, Patrick; Meadows, Shawn; Nachman, Sharon; Käyhty, Helena; Klugman, Keith P; Violari, Avye

2010-08-15

245

The data management of a phase III efficacy trial of an 11-valent pneumococcal conjugate vaccine and related satellite studies conducted in the Philippines  

PubMed Central

Background A large phase III placebo-controlled, randomized efficacy trial of an investigational 11-valent pneumococcal conjugate vaccine against pneumonia in children less than 2 years of age was conducted in the Philippines from July 2000 to December 2004. Clinical data from 12,194 children who were given either study vaccine or placebo was collected from birth up to two years of age for the occurrence of radiologically proven pneumonia as the primary endpoint, and for clinical pneumonia and invasive pneumococcal disease as the secondary endpoints. Several tertiary endpoints were also explored. Along the core trial, several satellite studies on herd immunity, cost-effectiveness of the study vaccine, acute otitis media, and wheezing were conducted. Results We describe here in detail how the relevant clinical records were managed and how quality control procedures were implemented to ensure that valid data were obtained respectively for the core trial and for the satellite studies. We discuss how the task was achieved, what the challenges were and what might have been done differently. Conclusions There were several factors that made the task of data management doable and efficient. First, a pre-trial data management system was available. Secondly, local committed statisticians, programmers and support staff were available and partly familiar to clinical trials. Thirdly, the personnel had undergone training during trial and grew with the task they were supposed to do. Thus the knowledge needed to develop and operate clinical data system was fully transferred to local staff. Trial registration Current Controlled Trials ISRCTN62323832 PMID:22676626

2012-01-01

246

Safety and immunogenicity of Vi conjugate vaccines for typhoid fever in adults, teenagers, and 2- to 4-year-old children in Vietnam.  

PubMed

The capsular polysaccharide of Salmonella typhi, Vi, is an essential virulence factor and a protective vaccine for people older than 5 years. The safety and immunogenicity of two investigational Vi conjugate vaccines were evaluated in adults, 5- to 14-year-old children, and 2- to 4-year-old children in Vietnam. The conjugates were prepared with Pseudomonas aeruginosa recombinant exoprotein A (rEPA) as the carrier, using either N-succinimidyl-3-(2-pyridyldithio)-propionate (SPDP; Vi-rEPA(1)) or adipic acid dihydrazide (ADH; Vi-rEPA(2)) as linkers. None of the recipients experienced a temperature of >38.5 degrees C or significant local reactions. One injection of Vi-rEPA(2) into adults elicited a geometric mean (GM) increase in anti-Vi immunoglobulin G (IgG) from 9.62 enzyme-linked immunosorbent assay units/ml (EU) to 465 EU at 6 weeks; this level fell to 119 EU after 26 weeks. In the 5- to 14-year-old children, anti-Vi IgG levels at 6 weeks elicited by Vi-rEPA(2), Vi-rEPA(1), and Vi were 169, 22.8, and 18.9 EU, respectively (P = 0.0001 for Vi-rEPA(1) and Vi with respect to Vi-rEPA(2)). At 26 weeks, the anti-Vi IgG levels for recipients of Vi-rEPA(2), Vi-rEPA(1), and Vi were 30.0, 10.8, and 13.4 EU, respectively (P < 0.001 for Vi-rEPA(1) and Vi with respect to Vi-rEPA(2)); all were higher than the preinjection levels (P = 0. 0001). Vi-rEPA(2) also elicited the highest anti-Vi IgM and IgA levels of the three vaccines. In the 2- to 4-year-old children at 6 weeks following the first injection, Vi-rEPA(2) elicited an anti-Vi IgG level of 69.9 EU compared to 28.9 EU for Vi-rEPA(1) (P = 0.0001). Reinjection increased Vi antibody levels from 69.9 to 95.4 EU for Vi-rEPA(2) and from 28.9 to 83.0 EU for Vi-rEPA(1). At 26 weeks, anti-Vi IgG levels remained higher than those at preinjection (30.6 versus 0.18 for Vi-rEPA(2) and 12.8 versus 0.33 for Vi-rEPA(1); P = 0.0001 for both). Vi vaccine is recommended for individuals of 5 years of age or older. In the present study, the GM level of anti-Vi IgG elicited by two injections of Vi-rEPA(2) in the 2- to 4-year-old children was higher than that elicited by Vi in the 5- to 14-year-old children (30.6 versus 13.4; P = 0.0001). The safety and immunogenicity of the Vi-rEPA(2) conjugate warrant further investigation. PMID:10531232

Kossaczka, Z; Lin, F Y; Ho, V A; Thuy, N T; Van Bay, P; Thanh, T C; Khiem, H B; Trach, D D; Karpas, A; Hunt, S; Bryla, D A; Schneerson, R; Robbins, J B; Szu, S C

1999-11-01

247

Empiric First-line Antibiotic Treatment of Acute Otitis in the Era of the Heptavalent Pneumococcal Conjugate Vaccine  

Microsoft Academic Search

OBJECTIVES.Our goal was to estimate the local prevalence of Streptococcus pneumoniae nonsusceptible to penicillin and amoxicillin after widespread use of the heptava- lent pneumococcal vaccine and to revise community-specific recommendations for first-line antibiotic treatment of acute otitis media. METHODS.We conducted serial prevalence surveys between 2000 and 2004 in the offices of community pediatricians in St Louis, Missouri. Study participants were

Jane Garbutt; Isabel Rosenbloom; Jenny Wua; Gregory A. Storch

248

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

PubMed

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

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

2011-01-01

249

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

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 microg/mL) in >90% of infants after 3 doses given at 2, 4, and 6 months of age. After priming doses, significant booster responses (ie, immunologic memory) are apparent when additional doses are given at 12 to 15 months of age. In efficacy trials, infant immunization with Prevnar decreased invasive infections by >93% and consolidative pneumonia by 73%, and it was associated with a 7% decrease in otitis media and a 20% decrease in tympanostomy tube placement. Adverse events after the administration of Prevnar have been limited to areas of local swelling or erythema of 1 to 2 cm and some increase in the incidence of postimmunization fever when it is given with other childhood vaccines. Based on data in phase 3 efficacy and safety trials, the US Food and Drug Administration has provided an indication for the use of Prevnar in children younger than 24 months. PMID:10920170

Overturf, G D

2000-08-01

250

Safety and immunogenicity of 10-valent pneumococcal nontypeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV) in Nigerian children: Booster dose and 2-dose catch-up regimens in the second year of life.  

PubMed

In a previous study, 3-dose primary vaccination of Nigerian infants with the 10-valent pneumococcal nontypeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV) was immunogenic for vaccine pneumococcal serotypes, with comparable tolerability between PHiD-CV and control groups. In an open-label study (ClinicalTrials.gov, NCT01153893), 68 primed children received a PHiD-CV booster dose co-administered with a diphtheria-tetanus-acellular pertussis (DTPa) booster dose at 15-21 months and 36 children unprimed for pneumococcal vaccination received two PHiD-CV catch-up doses (first dose co-administered with DTPa booster dose) at 15-21 and 17-23 months. Adverse events were recorded and immune responses were measured before and one month after vaccination. In both groups, pain was the most frequent solicited local symptom and fever was the most frequent solicited general symptom after the booster dose and each catch-up dose. Few grade 3 solicited symptoms and no vaccine-related serious adverse events were reported. After booster vaccination, for each vaccine serotype, at least 98.5% of children had an antibody concentration ? 0.2 µg/ml and at least 94.0% had an opsonophagocytic activity (OPA) titer ? 8. After 2-dose catch-up, for each vaccine serotype, at least 97.1% had an antibody concentration ? 0.2 µg/ml, except for serotypes 6B (82.9%) and 23F (88.6%), and at least 91.4% had an OPA titer ?8, except for serotypes 6B (77.4%) and 19F (85.3%). PHiD-CV induced antibody responses against protein D in both groups. In conclusion, PHiD-CV administered to Nigerian toddlers as a booster dose or 2-dose catch-up was well tolerated and immunogenic for vaccine pneumococcal serotypes and protein D. PMID:24356787

Odusanya, Olumuyiwa O; Kuyinu, Yetunde A; Kehinde, Omolara A; Shafi, Fakrudeen; François, Nancy; Yarzabal, Juan Pablo; Dobbelaere, Kurt; Rüggeberg, Jens U; Borys, Dorota; Schuerman, Lode

2014-03-01

251

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

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. PMID:19446183

Lai, Zengzu; Schreiber, John R

2009-05-21

252

Heterosubtypic protection against influenza A induced by adenylate cyclase toxoids delivering conserved HA2 subunit of hemagglutinin.  

PubMed

The protective efficacy of currently available influenza vaccines is restricted to vaccine strains and their close antigenic variants. A new strategy to obtain cross-protection against influenza is based on conserved antigens of influenza A viruses (IAV), which are able to elicit a protective immune response. Here we describe a vaccination approach involving the conserved stem part of hemagglutinin, the HA2 subunit, shared by different HA subtypes of IAV. To increase its immunogenicity, a novel strategy of antigen delivery to antigen presenting cells (APCs) has been used. The HA2 segment (residues 23-185) was inserted into a genetically detoxified adenylate cyclase toxoid (CyaA-E5) which specifically targets and penetrates CD11b-expressing dendritic cells. The CyaA-E5-HA2 toxoid induced HA2(93-102), HA2(96-104) and HA2(170-178)-specific and Th1 polarized T-cell responses, and also elicited strong broadly cross-reactive HA2-specific antibody response. BALB/c mice immunized with three doses of purified CyaA-E5-HA2 without any adjuvant recovered from influenza infection 2days earlier than the control mock-immunized mice. More importantly, immunized mice were protected against a lethal challenge with 2LD(50) dose of a homologous virus (H3 subtype), as well as against the infection with a heterologous (H7 subtype) influenza A virus. This is the first report on heterosubtypic protection against influenza A infection mediated by an HA2-based vaccine that can induce both humoral and cellular immune responses without the need of adjuvant. PMID:23036818

Staneková, Zuzana; Adkins, Irena; Kosová, Martina; Janulíková, Jana; Sebo, Peter; Vare?ková, Eva

2013-01-01

253

Immunogenicity of Seven-Valent Pneumococcal Conjugate Vaccine Administered at 6, 14 and 40 Weeks of Age in South African Infants  

PubMed Central

Background The high cost of pneumococcal conjugate vaccine (PCV) and local epidemiological factors contributed to evaluating different PCV dosing-schedules. This study evaluated the immunogenicity of seven-valent PCV (PCV7) administered at 6-weeks; 14-weeks and 9-months of age. Methods 250 healthy, HIV-unexposed infants were immunized with PCV7 concurrently with other childhood vaccines. Serotype-specific anti-capsular IgG concentrations were measured one-month following the 1st and 2nd PCV-doses, prior to and two-weeks following the 3rd dose. Opsonophagocytic killing assay (OPA) was measured for three serotypes following the 2nd and 3rd PCV7-doses. Immunogenicity of the current schedule was compared to a historical cohort of infants who received PCV7 at 6, 10 and 14 weeks of age. Results The proportion of infants with serotype-specific antibody ?0.35 µg/ml following the 2nd PCV7-dose ranged from 84% for 6B to ?89% for other serotypes. Robust antibody responses were observed following the 3rd dose. The proportion of children with OPA ?8 for serotypes 9V, 19F and 23F increased significantly following the 3rd PCV7-dose to 93.6%; 86.0% and 89.7% respectively. The quantitative antibody concentrations following the 2nd PCV7-dose were comparable to that after the 3rd -dose in the 6-10-14 week schedule. Geometric mean concentrations (GMCs) following the 3rd PCV7-dose were higher for all serotypes in this study compared to the historical cohort. Conclusions The studied PCV7 dosing schedule induced good immune responses, including higher GMCs following the 3rd-dose at 9-months compared to when given at 14-weeks of age. This may confer longer persistence of antibodies and duration of protection against pneumococcal disease. PMID:24015277

Jones, Stephanie A.; Groome, Michelle; Koen, Anthonet; Van Niekerk, Nadia; Sewraj, Poonam; Kuwanda, Locadiah; Izu, Alane; Adrian, Peter V.; Madhi, Shabir A.

2013-01-01

254

Poly-gamma-d-glutamic acid and protective antigen conjugate vaccines induce functional antibodies against the protective antigen and capsule of Bacillus anthracis in guinea-pigs and rabbits.  

PubMed

Anthrax is a lethal infectious disease caused by the spore-forming Bacillus anthracis. The two major virulence factors of B. anthracis are exotoxin and the poly-gamma-d-glutamic acid (PGA) capsule. The three components of the exotoxin, protective antigen (PA), lethal factor and edema factor act in a binary combination, which results in massive edema and organ failure in the progress of anthrax disease. The antiphagocytic PGA capsule disguises the bacilli from immune surveillance and allows unimpeded growth of bacilli in the host. Because PA can elicit a protective immune response, it has been a target of the anthrax vaccine. In addition to PA, efforts have been made to include PGA as a component of the anthrax vaccine. In this study, we report that PA-PGA conjugates induce expressions of anti-PA, anti-PGA and toxin-neutralizing antibodies in guinea-pigs and completely protect guinea-pigs against a 50 x LD(50) challenge with fully virulent B. anthracis spores. Polyclonal rabbit antisera produced against either PA or ovalbumin conjugated to a PGA-15mer offer a partial passive protection to guinea-pigs against B. anthracis infection, indicating that anti-PGA antibodies play a protective role. Our results demonstrate that PA-PGA conjugate vaccines are effective in the guinea-pig model, in addition to the previously reported mouse model. PMID:19732139

Lee, Deog-Yong; Chun, Jeong-Hoon; Ha, Hyun-Joon; Park, Jungchan; Kim, Bong-Su; Oh, Hee-Bok; Rhie, Gi-Eun

2009-11-01

255

Adapting group sequential methods to observational postlicensure vaccine safety surveillance: results of a pentavalent combination DTaP-IPV-Hib vaccine safety study.  

PubMed

To address gaps in traditional postlicensure vaccine safety surveillance and to promote rapid signal identification, new prospective monitoring systems using large health-care database cohorts have been developed. We newly adapted clinical trial group sequential methods to this observational setting in an original safety study of a combination diphtheria and tetanus toxoids and acellular pertussis adsorbed (DTaP), inactivated poliovirus (IPV), and Haemophilus influenzae type b (Hib) conjugate vaccine (DTaP-IPV-Hib) among children within the Vaccine Safety Datalink population. For each prespecified outcome, we conducted 11 sequential Poisson-based likelihood ratio tests during September 2008-January 2011 to compare DTaP-IPV-Hib vaccinees with historical recipients of other DTaP-containing vaccines. No increased risk was detected among 149,337 DTaP-IPV-Hib vaccinees versus historical comparators for any outcome, including medically attended fever, seizure, meningitis/encephalitis/myelitis, nonanaphylactic serious allergic reaction, anaphylaxis, Guillain-Barré syndrome, or invasive Hib disease. In end-of-study prespecified subgroup analyses, risk of medically attended fever was elevated among 1- to 2-year-olds who received DTaP-IPV-Hib vaccine versus historical comparators (relative risk = 1.83, 95% confidence interval: 1.34, 2.50) but not among infants under 1 year old (relative risk = 0.83, 95% confidence interval: 0.73, 0.94). Findings were similar in analyses with concurrent comparators who received other DTaP-containing vaccines during the study period. Although lack of a controlled experiment presents numerous challenges, implementation of group sequential monitoring methods in observational safety surveillance studies is promising and warrants further investigation. PMID:23292957

Nelson, Jennifer C; Yu, Onchee; Dominguez-Islas, Clara P; Cook, Andrea J; Peterson, Do; Greene, Sharon K; Yih, W Katherine; Daley, Matthew F; Jacobsen, Steven J; Klein, Nicola P; Weintraub, Eric S; Broder, Karen R; Jackson, Lisa A

2013-01-15

256

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

PubMed Central

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

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

2013-01-01

257

Impact of 13-valent pneumococcal conjugate vaccine (PCV13) in a pandemic similar to the 2009 H1N1 in the United States  

PubMed Central

Background High rates of bacterial coinfection in autopsy data from the 2009 H1N1 influenza (“flu”) pandemic suggest synergies between flu and pneumococcal disease (PD) during pandemic conditions, and highlight the importance of interventions like the 13-valent pneumococcal conjugate vaccine (PCV13) that may mitigate the impact of a pandemic. Methods We used a decision-analytic model, estimated from published sources, to assess the impact of pediatric vaccination with PCV13 versus the 7-valent vaccine (PCV7) on PD incidence and mortality in a normal flu season (10% flu incidence) and in a pandemic similar to 2009-2010 H1N1 (20% flu incidence, mild virulence, high impact in children). Both direct and indirect (herd) effects against PD were considered. Effectiveness of PCV13 was extrapolated from observed PCV7 data, using assumptions of serotype prevalence and PCV13 protection against the 6 serotypes not in PCV7. To simulate 2009–2010 H1N1, autopsy data were used to estimate the overall proportion of flu deaths with bacterial coinfections. By assuming that increased risk of death during the pandemic occurred among those with comorbidity (using obesity as proxy) and bacterial coinfections primarily due to S. pneumoniae or S. aureus, we estimated the proportion co-infected among all (fatal and non-fatal) flu cases (7.6% co-infected with any organism; 2.2% with S. pneumoniae). PD incidence, mortality, and total healthcare costs were evaluated over a 1-year horizon. Results In a normal flu season, compared to PCV7, PCV13 is expected to prevent an additional 13,400 invasive PD (IPD) cases, 399,000 pneumonia cases, and 2,900 deaths, leading to cost savings of $472 M. In a pandemic similar to 2009–2010 H1N1, PCV13 would prevent 22,800 IPD cases, 872,000 pneumonia cases, and 3,700 deaths, resulting in cost savings of $1.0 B compared to PCV7. Conclusions In a flu pandemic similar to the 2009–2010 H1N1, protection against the 6 additional serotypes in PCV13 would likely be effective in preventing pandemic-related PD cases, mortality, and associated costs. PMID:23687999

2013-01-01

258

Immunogenicity, Impact on Carriage and Reactogenicity of 10-Valent Pneumococcal Non-Typeable Haemophilus influenzae Protein D Conjugate Vaccine in Kenyan Children Aged 1-4 Years: A Randomized Controlled Trial  

PubMed Central

Background The impact on carriage and optimal schedule for primary vaccination of older children with 10-valent pneumococcal non-typeable Haemophilus influenzae protein-D conjugate vaccine (PHiD-CV) are unknown. Methods 600 Kenyan children aged 12–59 months were vaccinated at days 0, 60 and 180 in a double-blind randomized controlled trial according to the following vaccine sequence: Group A: PHiD-CV, PHiD-CV, diphtheria/tetanus/acellular pertussis vaccine (DTaP); Group B: PHiD-CV, DTaP, PHiD-CV; Group C: hepatitis A vaccine (HAV), DTaP, HAV. Nasopharyngeal carriage of Streptococcus pneumoniae was measured at five timepoints. In 375 subjects, serotype-specific responses were measured by 22F-inhibition ELISA and opsonophagocytic killing assays (OPA) one month after vaccination. Results Following one dose of PHiD-CV, >90% of recipients developed IgG?0.35 µg/mL to serotypes 1, 4, 5, 7F, 9V and 18C and OPA?8 to serotypes 4, 7F, 9V, 18C, 23F. After a second dose >90% of recipients had IgG?0.35 µg/mL to all vaccine serotypes and OPA?8 to all vaccine serotypes except 1 and 6B. At day 180, carriage of vaccine-type pneumococci was 21% in recipients of two doses of PHiD-CV (Group A) compared to 31% in controls (p?=?0.04). Fever after dose 1 was reported by 41% of PHiD-CV recipients compared to 26% of HAV recipients (p<0.001). Other local and systemic adverse experiences were similar between groups. Conclusions Vaccination of children aged 12–59 months with two doses of PHiD-CV two to six months apart was immunogenic, reduced vaccine-type pneumococcal carriage and was well-tolerated. Administration of PHiD-CV would be expected to provide effective protection against vaccine-type disease. Trial Registration ClinicalTrials.gov NCT01028326 PMID:24465570

Hammitt, Laura L.; Ojal, John; Bashraheil, Mahfudh; Morpeth, Susan C.; Karani, Angela; Habib, Ahsan; Borys, Dorota; Goldblatt, David; Scott, J. Anthony G

2014-01-01

259

[Anti-meningococcal vaccines: diversity of vaccination policies and recommendations].  

PubMed

In European Country, Canada, Australia and Brazil immunization program with conjugate meningococcal C, including universal vaccination of infants or toddlers, with a catch-up program up to 19 y in several areas, have been successful in reducing disease incidence through direct and indirect protection. In USA, quadrivalent conjugate vaccines targeting serogroups ACYW135 are used in programs of adolescent immunization at 10 and 15 years because serotype Y is frequent. A mass immunization campaign against serogroupe A disease with a conjugate vaccine is beginning in African belt of meningitis. Polysaccharide vaccines A, C or ACYW135 are used in travelers but quadrivalent conjugate vaccine, with larger targets, gives higher titers after booster and must be preferred. Some questions are pending: immunize before or after one year of age, a booster dose in adolescence and the routine use of quadrivalent conjugate vaccine in Europe if the incidence of serotype Y is growing. PMID:22883370

Gendrel, D

2012-09-01

260

Assessment in mice of a synthetic peptide-based vaccine against the sporozoite stage of the human malaria parasite, P. falciparum.  

PubMed Central

The anti-P. falciparum sporozoite vaccine consisting of the synthetic peptide, Ac-Cys-(NANP)3, conjugated to the protein tetanus toxoid (TT), [Ac-Cys-(NANP)3]25-TT, is currently undergoing human trials. The purpose of the present study was to assess various immunological parameters of this vaccine in mice, which have practical implications in humans. Two injections of [Ac-Cys-(NANP)3]25-TT adsorbed to Al(OH)3 were required to elicit a high antibody response against both Ac-Cys-(NANP)3 and TT. The vaccine initiated equivalent Ac-Cys-(NANP)3 priming for a secondary IgG response in 1-week-old and adult mice. Immunization of female mice with TT or [Ac-Cys-(NANP)3]23-TT prior to mating resulted in offspring that passively received anti-Ac-Cys-(NANP)3 and/or anti-TT antibody and that had reduced secondary responses to Ac-Cys-(NANP)3 and TT. Tertiary challenge with vaccine could substantially overcome such inhibition. Preimmunization of adult mice with TT resulted in a specific inhibition of the anti-Ac-Cys-(NANP)3 antibody response that disappeared following tertiary challenge with the vaccine. The conjugate initiated an antibody response against Ac-Cys-(NANP)3 and TT in mice of 16 different genotypes; only very low T-cell proliferative responses to (NANP)3 were observed for some of these strains. Mice injected with (NANP)3 coupled to protein demonstrated a secondary response to Ac-Cys-(NANP)3 when challenged with (NANP)3 on a heterologous carrier, indicating that B-cell priming alone may be sufficient for a secondary antibody response. These results demonstrate that the vaccine has favourable and unfavourable characteristics in mice; the potential for both exists in humans. PMID:3044983

Etlinger, H M; Heimer, E P; Trzeciak, A; Felix, A M; Gillessen, D

1988-01-01

261

[Surveillance of Haemophilus influenzae serotypes in Argentina from 2005 to 2010 during the Haemophilus influenzae type b conjugate vaccine era].  

PubMed

The introduction of the Haemophilus influenzae type b vaccine in the immunization programs of many countries has greatly reduced this invasive disease and the carriage caused by this serotype, also increasing other capsular types and non-capsular isolations. There were 313 isolations of H. influenzae under study, which were recovered from a sterile site coming from pediatric and adult patients carrying the invasive disease. Patients were treated at 90 different hospitals belonging to the Red Nacional de Laboratorios para Meningitis e Infecciones Respiratorias Agudas Bacterianas (National Lab Network for Meningitis and Acute Bacterial Respiratory Infections) from 2005 to 2010 for the following disorders: pneumonia, 40.3% (n=126), meningitis, 30.0% (n=94) and bacteremia, 26.5% (n=83). In pediatric patients (n=279), the highest frequency of isolations corresponded to children under the age of 2 years, 74.5% (n=208). Regarding type distribution, 61.3% corresponded to non-capsular H. influenzae (n=192), 20.1% to type b (n=63), 11.2% to type a (n=35), 4.8% to type f, and 2.6% to other types. Capsular H. influenzae was predominant in meningitis whereas non-capsular H. influenzae in pneumonia and bacteremia. The biotype was determined in 306 isolations. The totality (100%) of type a (n=35) was biotype II whereas 66.7% of type b (n=63) was biotype I. Slide agglutination and PCR tests were used in 220 isolations. There was a match of 0.982 (IC: 0.92-1.00) between them. During the last year, there was a great increase in type b, showing the importance of clinical and laboratory-based surveillance of the invasive disease caused by H. influenzae. PMID:24401777

Efron, Adriana M; Moscoloni, María A; Reijtman, Vanesa R; Regueira, Mabel

2013-01-01

262

Pseudomonas exotoxin A: toxoid preparation by photoaffinity inactivation.  

PubMed Central

A method for toxoid preparation has been developed in which toxins expressing enzymatic activity can be detoxified by photoaffinity labeling techniques. In the case of Pseudomonas aeruginosa exotoxin A, the method relies on the affinity of azido-substituted analogs of the substrate (NAD) for the proenzyme form of the toxin. Photolysis of the putative toxin-analog complex results in irreversible inactivation of the toxin without loss of antigenic character. It is proposed that this occurs by nitrene insertion into a chemical bond on the toxin molecule. This affinity photoinactivation process should be applicable to other ADP-ribosylating toxins. PMID:6407002

Marburg, S; Tolman, R L; Callahan, L T

1983-01-01

263

Enhanced immune response against pertussis toxoid by IgA-loaded chitosan-dextran sulfate nanoparticles.  

PubMed

The objective of the present study was to evaluate immunological activities of chitosan-dextran sulfate (CS-DS) nanoparticle formulation of pertussis toxoid (PTXd) and its combination with a potential immunological adjuvant, immunoglobulin A (IgA). CS-DS nanoparticles were prepared using a complex coacervation (polyelectrolyte complexation) technique. CS-DS nanoparticle formulations with size and zeta potential in a range of 300-350 nm and +40-+55 mV, respectively, were obtained. An entrapment efficiency of more than 90% was obtained for pertussis toxin and IgA in CS-DS nanoparticles. All loaded nanoparticle formulations showed less than 20% of release within 24 h in in vitro release studies. The immunological evaluation of developed formulations in female Balb/c mice groups showed that the CS-DS nanoparticles formulations induced significantly higher serum IgG and IgG1 titers (p < 0.05) as compared with conventional alum-adjuvanted PTXd formulation administered by subcutaneous route. This study indicated the potential of CS-DS nanoparticles to be a simple and effective particulate delivery system with in-built immunological adjuvant property for acellular protein antigens. The study also revealed the potential important role of IgA-loaded CS-DS nanoparticles as a novel immunological adjuvant for vaccine delivery. PMID:21953499

Sharma, Sameer; Mukkur, Trilochan Ks; Benson, Heather Ae; Chen, Yan

2012-01-01

264

The Impact of Making Vaccines Thermostable in Niger’s Vaccine Supply Chain  

PubMed Central

Objective Determine the effects on the vaccine cold chain of making different types of World Health Organization (WHO) Expanded Program on Immunizations (EPI) vaccines thermostable. Methods Utilizing a detailed computational, discrete-event simulation model of the Niger vaccine supply chain, we simulated the impact of making different combinations of the six current EPI vaccines thermostable. Findings Making any EPI vaccine thermostable relieved existing supply chain bottlenecks (especially at the lowest levels), increased vaccine availability of all EPI vaccines, and decreased cold storage and transport capacity utilization. By far, the most substantial impact came from making the pentavalent vaccine thermostable, increasing its own vaccine availability from 87% to 97% and the vaccine availabilities of all other remaining non-thermostable EPI vaccines to over 93%. By contrast, making each of the other vaccines thermostable had considerably less effect on the remaining vaccines, failing to increase the vaccine availabilities of other vaccines to more than 89%. Making tetanus toxoid vaccine along with the pentavalent thermostable further increased the vaccine availability of all EPI vaccines by at least 1–2%. Conclusion Our study shows the potential benefits of making any of Niger’s EPI vaccines thermostable and therefore supports further development of thermostable vaccines. Eliminating the need for refrigerators and freezers should not necessarily be the only benefit and goal of vaccine thermostability. Rather, making even a single vaccine (or some subset of the vaccines) thermostable could free up significant cold storage space for other vaccines, and thereby help alleviate supply chain bottlenecks that occur throughout the world. PMID:22789507

Lee, Bruce Y.; Cakouros, Brigid E.; Assi, Tina-Marie; Connor, Diana L.; Welling, Joel; Kone, Souleymane; Djibo, Ali; Wateska, Angela R.; Pierre, Lionel; Brown, Shawn T.

2012-01-01

265

Guidelines on Vaccinations in Paediatric Haematology and Oncology Patients  

PubMed Central

Objective. Vaccinations are the most important tool to prevent infectious diseases. Chemotherapy-induced immune depression may impact the efficacy of vaccinations in children. Patients and Methods. A panel of experts of the supportive care working group of the Italian Association Paediatric Haematology Oncology (AIEOP) addressed this issue by guidelines on vaccinations in paediatric cancer patients. The literature published between 1980 and 2013 was reviewed. Results and Conclusion. During intensive chemotherapy, vaccination turned out to be effective for hepatitis A and B, whilst vaccinations with toxoid, protein subunits, or bacterial antigens should be postponed to the less intensive phases, to achieve an adequate immune response. Apart from varicella, the administration of live-attenuated-virus vaccines is not recommended during this phase. Family members should remain on recommended vaccination schedules, including toxoid, inactivated vaccine (also poliomyelitis), and live-attenuated vaccines (varicella, measles, mumps, and rubella). By the time of completion of chemotherapy, insufficient serum antibody levels for vaccine-preventable diseases have been reported, while immunological memory appears to be preserved. Once immunological recovery is completed, usually after 6 months, response to booster or vaccination is generally good and allows patients to be protected and also to contribute to herd immunity. PMID:24868544

Cesaro, Simone; Giacchino, Mareva; Fioredda, Francesca; Barone, Angelica; Battisti, Laura; Bezzio, Stefania; Frenos, Stefano; De Santis, Raffaella; Livadiotti, Susanna; Marinello, Serena; Zanazzo, Andrea Giulio; Caselli, Desiree

2014-01-01

266

Nanoparticle-detained toxins for safe and effective vaccination  

NASA Astrophysics Data System (ADS)

Toxoid vaccines--vaccines based on inactivated bacterial toxins--are routinely used to promote antitoxin immunity for the treatment and prevention of bacterial infections. Following chemical or heat denaturation, inactivated toxins can be administered to mount toxin-specific immune responses. However, retaining faithful antigenic presentation while removing toxin virulence remains a major challenge and presents a trade-off between efficacy and safety in toxoid development. Here, we show a nanoparticle-based toxin-detainment strategy that safely delivers non-disrupted pore-forming toxins for immune processing. Using erythrocyte membrane-coated nanoparticles and staphylococcal ?-haemolysin, we demonstrate effective virulence neutralization via spontaneous particle entrapment. Compared with vaccination with heat-denatured toxin, mice vaccinated with the nanoparticle-detained toxin showed superior protective immunity against toxin-mediated adverse effects. We find that the non-disruptive detoxification approach benefited the immunogenicity and efficacy of toxoid vaccines. We anticipate that this study will open new possibilities in the preparation of antitoxin vaccines against the many virulence factors that threaten public health.

Hu, Che-Ming J.; Fang, Ronnie H.; Luk, Brian T.; Zhang, Liangfang

2013-12-01

267

Safety and immunogenicity of a fully liquid vaccine containing five-component pertussis-diphtheria-tetanus-inactivated poliomyelitis-Haemophilus influenzae type b conjugate vaccines administered at two, four, six and 18 months of age  

PubMed Central

OBJECTIVE The safety, immunogenicity and lot consistency of a fully liquid, five-component acellular pertussis combination vaccine, comprised of diphteria, tetanus and acellular pertussis, inactivated polio vaccine, Haemophilus influenzae type b (DTaP-IPV-Hib [Pediacel, sanofi pasteur, Canada]) were assessed and compared with that of Hib vaccine reconstituted with the five-component acellular pertussis combination vaccine (DTaP-IPV//Hib, Pentacel [sanofi pasteur, Canada]). METHODS Infants were recruited at vaccine study centres in Montreal, Quebec; Simon Fraser Health Region, British Columbia, and southern Alberta after the protocol had been approved by the relevant institutional ethics committees. Written informed consent was obtained from the parents or guardians of all subjects. At two months of age, the infants were randomly assigned to receive one of three consecutive production lots of DTaP-IPV-Hib by intramuscular injection. Reactions to vaccinations were assessed by parental observation and through telephone interviews conducted by study nurses. Blood samples were obtained at two, six, seven, 18 and 19 months of age for measurement of antibodies to vaccine antigens. RESULTS: Most injection site and systemic reactions were mild or moderate, and of brief duration. All infants were protected against tetanus, diphtheria and all three polio serotypes after both primary and booster vaccinations. Antibody responses to pertussis antigens were similar to those observed in Swedish infants, in whom the five-component vaccine was shown to be 85% effective. Proportions of infants with antipolyribosylribitol phosphate antibody of 0.15 ?g/mL or greater and 1.0 ?g/mL or greater, were 97.9% and 88.9%, respectively, following primary immunization, and 100% and 99% following booster vaccination. Safety and immunogenicity results with both reconstituted and fully liquid combination vaccines were comparable. CONCLUSIONS The fully liquid combination vaccine was comparable in terms of safety and immunogenicity with the reconstituted combination vaccine. PMID:18923741

Gold, Ronald; Barreto, Luis; Ferro, Santiago; Thippawong, John; Guasparini, Roland; Meekison, William; Russell, Margaret; Mills, Elaine; Harrison, Dana; Lavigne, Pierre

2007-01-01

268

Haemophilus influenzae type b (Hib) vaccine  

MedlinePLUS

Immunization - Hib; Vaccine - Haemophilus influenzae type b conjugate ... for Disease Control and Prevention. Advisory Committee on Immunization Practices (ACIP) Recommended Immunization Schedules for Persons Aged ...

269

Facial recognition of heroin vaccine opiates: type 1 cross-reactivities of antibodies induced by hydrolytically stable haptenic surrogates of heroin, 6-acetylmorphine, and morphine.  

PubMed

Novel synthetic compounds similar to heroin and its major active metabolites, 6-acetylmorphine and morphine, were examined as potential surrogate haptens for the ability to interface with the immune system for a heroin vaccine. Recent studies have suggested that heroin-like haptens must degrade hydrolytically to induce independent immune responses both to heroin and to the metabolites, resulting in antisera containing mixtures of antibodies (type 2 cross-reactivity). To test this concept, two unique hydrolytically stable haptens were created based on presumed structural facial similarities to heroin or to its active metabolites. After conjugation of a heroin-like hapten (DiAmHap) to tetanus toxoid and mixing with liposomes containing monophosphoryl lipid A, high titers of antibodies after two injections in mice had complementary binding sites that exhibited strong type 1 ("true") specific cross-reactivity with heroin and with both of its physiologically active metabolites. Mice immunized with each surrogate hapten exhibited reduced antinociceptive effects caused by injection of heroin. This approach obviates the need to create hydrolytically unstable synthetic heroin-like compounds to induce independent immune responses to heroin and its active metabolites for vaccine development. Facial recognition of hydrolytically stable surrogate haptens by antibodies together with type 1 cross-reactivities with heroin and its metabolites can help to guide synthetic chemical strategies for efficient development of a heroin vaccine. PMID:24486371

Matyas, Gary R; Rice, Kenner C; Cheng, Kejun; Li, Fuying; Antoline, Joshua F G; Iyer, Malliga R; Jacobson, Arthur E; Mayorov, Alexander V; Beck, Zoltan; Torres, Oscar B; Alving, Carl R

2014-03-14

270

Facial recognition of heroin vaccine opiates: Type 1 cross-reactivities of antibodies induced by hydrolytically stable haptenic surrogates of heroin, 6-acetylmorphine, and morphine  

PubMed Central

Novel synthetic compounds similar to heroin and its major active metabolites, 6-acetylmorphine and morphine, were examined as potential surrogate haptens for the ability to interface with the immune system for a heroin vaccine. Recent studies have suggested that heroin-like haptens must degrade hydrolytically to induce independent immune responses both to heroin and to the metabolites, resulting in antisera containing mixtures of antibodies (type 2 cross-reactivity). To test this concept, two unique hydrolytically stable haptens were created based on presumed structural facial similarities to heroin or to its active metabolites. After conjugation of a heroin-like hapten (DiAmHap) to tetanus toxoid and mixing with liposomes containing monophosphoryl lipid A, high titers of antibodies after two injections in mice had complementary binding sites that exhibited strong type 1 (“true”) specific cross-reactivity with heroin and with both of its physiologically active metabolites. Mice immunized with each surrogate hapten exhibited reduced antinociceptive effects caused by injection of heroin. This approach obviates the need to create hydrolytically unstable synthetic heroin-like compounds to induce independent immune responses to heroin and its active metabolites for vaccine development. Facial recognition of hydrolytically stable surrogate haptens by antibodies together with type 1 cross-reactivities with heroin and its metabolites can help to guide synthetic chemical strategies for efficient development of a heroin vaccine. PMID:24486371

Matyas, Gary R.; Rice, Kenner C.; Cheng, Kejun; Li, Fuying; Antoline, Joshua F. G.; Iyer, Malliga R.; Jacobson, Arthur E.; Mayorov, Alexander V.; Beck, Zoltan; Torres, Oscar; Alving, Carl R.

2014-01-01

271

21 CFR 522.1083 - Gonadotropin releasing factor analog-diphtheria toxoid conjugate.  

Code of Federal Regulations, 2012 CFR

...approved for use in female pigs and barrows. Do not use in intact male pigs intended for breeding because of the disruption of reproductive function. Federal law restricts this drug to use by or on the order of a licensed veterinarian. Pigs should be...

2012-04-01

272

21 CFR 522.1083 - Gonadotropin releasing factor analog-diphtheria toxoid conjugate.  

...Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED...2) Indications for use. For the temporary immunological castration (suppression of testicular function) and reduction of...

2014-04-01

273

21 CFR 522.1083 - Gonadotropin releasing factor analog-diphtheria toxoid conjugate.  

Code of Federal Regulations, 2013 CFR

...Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED...2) Indications for use. For the temporary immunological castration (suppression of testicular function) and reduction of...

2013-04-01

274

S 2 | N A T U R E | V O L 5 0 7 | 6 M A R C H 2 0 1 4 THE AGE OF VACCINES  

E-print Network

; an estimated 103 million cases of childhood diseases since 1924. KEY 1948 Diptheria, Tetanus and Pertussis (DTP Numberofcases ­­­ YEA 920 940930 950 955 960945935925 10 100 1,000 10,000 100,000 1,000,000 Diptheria, Tetanus. In the mid-1940s, the diphtheria toxoid vaccine was combined with vaccines against tetanus and pertussis

Cai, Long

275

Complete List of Vaccines Licensed for Immunization and Distributed in the U.S.  

MedlinePLUS

... Co, Inc Pneumococcal 7-valent Conjugate Vaccine (Diphtheria CRM 197 Protein) Prevnar Wyeth Pharmaceuticals Inc Pneumococcal 13-valent Conjugate Vaccine (Diphtheria CRM 197 Protein) Prevnar 13 Wyeth Pharmaceuticals Inc Poliovirus ...

276

A long acting biodegradable controlled delivery of chitosan microspheres loaded with tetanus toxoide as model antigen.  

PubMed

The chitosan microspheres formulated by emulsion cross-linking method were found to be smooth and spherical without aggregation. The particle size range was between 1 and 90?m. The particle sizes were found to be influenced by the concentration of the chitosan gel. Tetanus toxoide (TT) vaccine was loaded by passive adsorption from an aqueous solution into the preformed chitosan microspheres cross-linked with glutaraldehyde. The loaded TT on to microspheres was estimated by ELISA method. The loading capacity was found to be 40% with microspheres prepared with 1% chitosan gel, 43% for 2% and 46% for the mixed batch of microspheres prepared from 1% and 2% chitosan gel. The loading efficiency was found to decrease with increase in the concentration of chitosan gel. The in vitro release of the antigenic TT into the phosphate buffer at 37°C from different batch of microspheres was studied and release had a remarkable dependence on the size of micropsheres. The percentage release of TT from chitosan microspheres prepared from 1% chitosan gel was 2.7% in 120days and that from 2% chitosan gel was only 2%. The mixed batch of microspheres could release 2.3% in 120days. The antigen integrity was investigated by SDS-PAGE with brilliant blue staining. The SDS-PAGE analysis confirmed that the antigen integrity was not affected by passive adsorption of protein antigen to preformed chitosan microspheres. The study revealed that the cross-linked chitosan microspheres would be an interesting system for long-term delivery of macromolecules drugs. PMID:24051124

Varma, Sujith; Sadasivan, C

2014-03-01

277

Development of a recombinant toxin fragment vaccine for Clostridium difficile infection.  

PubMed

Clostridium difficile infection (CDI) is the major cause of antibiotic-associated diarrhea and pseudomembranous colitis, a disease associated with significant morbidity and mortality. The disease is mostly of nosocomial origin, with elderly patients undergoing anti-microbial therapy being particularly at risk. C. difficile produces two large toxins: Toxin A (TcdA) and Toxin B (TcdB). The two toxins act synergistically to damage and impair the colonic epithelium, and are primarily responsible for the pathogenesis associated with CDI. The feasibility of toxin-based vaccination against C. difficile is being vigorously investigated. A vaccine based on formaldehyde-inactivated Toxin A and Toxin B (toxoids) was reported to be safe and immunogenic in healthy volunteers and is now undergoing evaluation in clinical efficacy trials. In order to eliminate cytotoxic effects, a chemical inactivation step must be included in the manufacturing process of this toxin-based vaccine. In addition, the large-scale production of highly toxic antigens could be a challenging and costly process. Vaccines based on non-toxic fragments of genetically engineered versions of the toxins alleviate most of these limitations. We have evaluated a vaccine assembled from two recombinant fragments of TcdB and explored their potential as components of a novel experimental vaccine against CDI. Golden Syrian hamsters vaccinated with recombinant fragments of TcdB combined with full length TcdA (Toxoid A) developed high titer IgG responses and potent neutralizing antibody titers. We also show here that the recombinant vaccine protected animals against lethal challenge with C. difficile spores, with efficacy equivalent to the toxoid vaccine. The development of a two-segment recombinant vaccine could provide several advantages over toxoid TcdA/TcdB such as improvements in manufacturability. PMID:24662701

Karczewski, Jerzy; Zorman, Julie; Wang, Su; Miezeiewski, Matthew; Xie, Jinfu; Soring, Keri; Petrescu, Ioan; Rogers, Irene; Thiriot, David S; Cook, James C; Chamberlin, Mihaela; Xoconostle, Rachel F; Nahas, Debbie D; Joyce, Joseph G; Bodmer, Jean-Luc; Heinrichs, Jon H; Secore, Susan

2014-05-19

278

Enhancement of Clearance of Bacteria from Murine Lungs by Immunization with Detoxified Lipooligosaccharide from Moraxella catarrhalis Conjugated to Proteins  

Microsoft Academic Search

Moraxella catarrhalis strain 25238 detoxified lipooligosaccharide (dLOS)-protein conjugates induced a sig- nificant rise of bactericidal anti-LOS antibodies in animals. This study reports the effect of active or passive immunization with the conjugates or their antiserum on pulmonary clearance of M. catarrhalis in an aerosol challenge mouse model. Mice were injected subcutaneously with dLOS-tetanus toxoid (dLOS-TT), dLOS- high-molecular-weight proteins (dLOS-HMP) from

WEI-GANG HU; JING CHEN; JAMES F. BATTEY; XIN-XING GU

2000-01-01

279

Verb Conjugations  

NSDL National Science Digital Library

Here each student will be able to practice and enhance their understanding of Spanish Verb Conjugations. Follow the four steps below as you progress through examples, phrases, training, and a review. View the Conjugation Examples and familiarize yourself with the Preterite conjugations. Take a look at the Phrases associated with the Preterite Verbs. Here you will learn how to use Preterite Verbs in sentences. The following link will allow you to practice your conjugations in ...

Smith, Sr.

2007-10-17

280

EFFICACY OF A TYPE C BOTULISM VACCINE IN GREEN-WINGED TEAL  

Microsoft Academic Search

We tested the efficacy of a single dose of Botumink toxoid for protecting wild green- winged teal (Anas crecca) during botulism epizootics caused by Clostridium botulinum type C. We challenged control and immunized ducks with four different doses of type C botulinum toxin to determine the LD50 for this species and to evaluate vaccine protection. Fewer immunized ducks were affected

Tonie E. Rocke; Michael D. Samuel; Pamela K. Swift; Gregory S. Yarris

2000-01-01

281

Randomized, Open-Label Study of the Impact of Age on Booster Responses to the 10-Valent Pneumococcal Nontypeable Haemophilus influenzae Protein D Conjugate Vaccine in Children in India  

PubMed Central

In this phase III, open-label, multicenter, and descriptive study in India, children primed with 3 doses (at ages 6, 10, and 14 weeks) of the 10-valent pneumococcal nontypeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV) were randomized (1:1) to receive a booster dose at 9 to 12 (early booster) or 15 to 18 months old (late booster) in order to evaluate impact of age at booster. We also evaluated a 2-dose catch-up vaccination plus an experimental booster dose in unprimed children age 12 to 18 months. The early booster, late booster, and catch-up vaccinations were administered to 74, 95, and 87 children, respectively; 66, 71, and 81 children, respectively, were included in the immunogenicity according-to-protocol cohort. One month postbooster, for each PHiD-CV serotype, ?95.2% (early booster) and ?93.8% (late booster) of the children had antibody concentrations of ?0.2 ?g/ml; ?96.7% and ?93.0%, respectively, had opsonophagocytic activity (OPA) titers of ?8. The postbooster antibody geometric mean concentrations (GMCs) were in similar ranges for early and late boosters; the OPA titers appeared to be lower for most PHiD-CV serotypes (except 6B and 19F) after the early booster. After dose 2 and postbooster, for each PHiD-CV serotype, ?88.6% and ?96.3%, respectively, of the catch-up immunogenicity according-to-protocol cohort had antibody concentrations of ?0.2 ?g/ml; ?71.4% and ?90.6%, respectively, had OPA titers of ?8. At least 1 serious adverse event was reported by 2 children in the early booster (skin infection and gastroenteritis) and 1 child in the catch-up group (febrile convulsion and urinary tract infection); all were resolved, and none were considered by the investigators to be vaccine related. PHiD-CV induced robust immune responses regardless of age at booster. Booster vaccination following 2 catch-up doses induced robust immune responses indicative of effective priming and immunological memory. (These studies have been registered at www.clinicaltrials.gov under registration no. NCT01030822 and NCT00814710; a protocol summary is available at www.gsk-clinicalstudyregister.com [study ID 112909]). PMID:25008901

Chatterjee, Sukanta; Chhatwal, Jugesh; Simon, Anna; Ravula, Sudheer; Francois, Nancy; Mehta, Shailesh; Strezova, Ana; Borys, Dorota

2014-01-01

282

Cattle Vaccines  

E-print Network

Vaccines deliver antigens that stimulate the body's production of antibodies in response to disease. Cattle can be vaccinated with noninfectious or infectious vaccines. The types of vaccine products, proper handling of vaccines, and vaccination...

Faries Jr., Floron C.

2005-11-11

283

Clostridium difficile Vaccine and Serum Immunoglobulin G Antibody Response to Toxin A  

Microsoft Academic Search

There is a strong association between serum antibody responses to toxin A and protection against Clostrid- ium difficile diarrhea. A parenteral C. difficile toxoid vaccine induced very-high-level responses to anti-toxin A immunoglobulin G (IgG) in the sera of healthy volunteers. After vaccination, the concentrations of anti-toxin A IgG in the sera of all 30 recipients exceeded the concentrations that were

Samer Aboudola; Karen L. Kotloff; Lorraine Kyne; Michel Warny; Eoin C. Kelly; Stavros Sougioultzis; Paul J. Giannasca; Thomas P. Monath; Ciaran P. Kelly

2003-01-01

284

Maternal immunization with vaccines containing recombinant NetB toxin partially protects progeny chickens from necrotic enteritis  

PubMed Central

Avian necrotic enteritis is a major economic and welfare issue throughout the global poultry industry and is caused by isolates of Clostridium perfringens that produce NetB toxin. Previously we have shown that birds directly vaccinated with inactivated C. perfringens type A culture supernatant (toxoid) combined with recombinant NetB (rNetB) protein were significantly protected from homologous and heterologous challenge. In the present study the protective effect of maternal immunization was examined. Broiler breeder hens were injected subcutaneously with genetically toxoided rNetB(S254L) alone, C. perfringens type A toxoid and toxoid combined with rNetB(S254L). Vaccination resulted in a strong serum immunoglobulin Y response to NetB in hens immunized with rNetB(S254L) formulations. Anti-NetB antibodies were transferred to the eggs and on into the hatched progeny. Subclinical necrotic enteritis was induced experimentally in the progeny and the occurrence of specific necrotic enteritis lesions evaluated. Birds derived from hens immunized with rNetB(S254L) combined with toxoid and challenged with a homologous strain (EHE-NE18) at either 14 or 21 days post-hatch had significantly lower levels of disease compared to birds from adjuvant only vaccinated hens. In addition, birds from hens immunized with rNetB(S254L) alone were significantly protected when challenged at 14 days post-hatch. These results demonstrate that maternal immunization with a NetB-enhanced toxoid vaccine is a promising method for the control of necrotic enteritis in young broiler chickens. PMID:24219318

2013-01-01

285

Persistence of immune responses after a single dose of Novartis meningococcal serogroup A, C, W-135 and Y CRM-197 conjugate vaccine (Menveo®) or Menactra® among healthy adolescents  

PubMed Central

The persistence of human bactericidal activity (hSBA) responses in adolescents was assessed 22 months after vaccination with one dose of Menveo® (MenACWY-CRM; Novartis) or Menactra® (MCV4) (sanofi pasteur). The proportion of subjects with hSBA titers ?8 was significantly higher among recipients of MenACWY-CRM than MCV4 for serogroups A, W-135 and Y. PMID:21339701

Baxter, Roger; Anemona, Alessandra; Ciavarro, Giuseppe L; Dull, Peter M

2010-01-01

286

Persistence of immune responses after a single dose of Novartis meningococcal serogroup A, C, W-135 and Y CRM-197 conjugate vaccine (Menveo®) or Menactra® among healthy adolescents.  

PubMed

The persistence of human bactericidal activity (hSBA) responses in adolescents was assessed 22 months after vaccination with one dose of Menveo® (MenACWY-CRM; Novartis) or Menactra® (MCV4) (sanofi pasteur). The proportion of subjects with hSBA titers ?8 was significantly higher among recipients of MenACWY-CRM than MCV4 for serogroups A, W-135 and Y. PMID:21339701

Gill, Christopher J; Baxter, Roger; Anemona, Alessandra; Ciavarro, Giuseppe; Dull, Peter

2010-11-01

287

The efficacy and safety of a nicotine conjugate vaccine (NicVAX®) or placebo co-administered with varenicline (Champix®) for smoking cessation: study protocol of a phase IIb, double blind, randomized, placebo controlled trial  

PubMed Central

Background A potential new treatment in smoking cessation and relapse prevention is nicotine vaccination which is based on active immunization against the nicotine molecule. This immunization will elicit the immune system to produce nicotine-specific antibodies that sequester nicotine in the blood stream, after inhaling tobacco products. The resulting antibody-antigen is too large to cross the blood–brain barrier and is therefore postulated to attenuate the rewarding effect of nicotine by preventing the latter from reaching its receptors in the brain and causing the release of dopamine. The aim of this paper is to describe the design of a phase IIb, multi-center, double blind, randomized, placebo controlled trial to assess the efficacy of the nicotine vaccine NicVAX® co-administered with varenicline (Champix®) and intensive counseling as an aid in smoking cessation and relapse prevention. Methods/design Two centers will include a total of 600 smokers who are motivated to quit smoking. At week ?2 these smokers will be randomized, in a 1:1 ratio, to either 6 injections of NicVAX® or placebo, both co-administered with 12-weeks of varenicline treatment, starting at week 0. The target quit day will be set after 7?days of varenicline treatment at week 1. Smokers will be followed up for 54?weeks. The primary outcome is defined as biochemically validated prolonged smoking abstinence from week 9 to 52. Secondary outcomes include safety, immunogenicity, smoking abstinence from week 37 to 52, abstinence from week 9 to 24, abstinence in the subset of subjects with the highest antibody response, and lapse/relapse rate. Discussion This is the first study to assess the efficacy of a nicotine conjugate vaccine in combination with an evidence-based smoking cessation pharmacotherapy (varenicline) to quit smoking. Although NicVAX® is primarily designed as an aid to smoking cessation, our study is designed to explore its potential to maintain abstinence and prevent relapse. The results of this trial will give a unique insight in the potential of nicotine vaccination for relapse prevention. Trial registration ClinicalTrials.gov: (NCT00995033) PMID:23216646

2012-01-01

288

Determinants of Release Rate of Tetanus Vaccine from Polyester Microspheres  

Microsoft Academic Search

Controlled-release formulations based on poly(lactic) (PLA) and poly(lactic\\/glycolic) acid (PLGA) microspheres containing tetanus vaccine were designed. The polymers forming the microspheres were L-PLA of different molecular weights and DL-PLGA, 50:50. These microspheres were prepared by two solvent elimination procedures, both using a double emulsion, and were characterized for size, morphology, and toxoid release kinetics. The influence of formulation variables such

Maria J. Alonso; Smadar Cohen; Tae G. Park; Rajesh K. Gupta; George R. Siber; Robert Langer

1993-01-01

289

A randomized double-blind trial comparing a two-component acellular to a whole-cell pertussis vaccine in Senegal  

Microsoft Academic Search

A randomized, double-blind trial comparing a diphtheria-tetanus-acellular pertussis vaccine (DTaP) (pertussis toxoid and filamentous hemagglutinin) with a whole-cell vaccine (DTwP) was conducted. A case-contact study was nested in the trial to estimate absolute efficacy. From 1990 through 1994, 4181 children were randomized to receive one of the vaccines at 2, 4, and 6 months. Severe adverse events were monitored weekly

François Simondon; Marie-Pierre Preziosi; Ablaye Yam; Coumba Toure Kane; Laurence Chabirand; Isabelle Iteman; Gary Sanden; Souleymane Mboup; Agnes Hoffenbach; Kim Knudsen; Nicole Guiso; Steven Wassilak; Michel Cadoz

1997-01-01

290

Reduction of Antibody Response to an 11Valent Pneumococcal Vaccine Coadministered with a Vaccine Containing Acellular Pertussis Components  

Microsoft Academic Search

In pneumococcal conjugate vaccines (PCVs), polysaccharide antigens are often conjugated to protein car- riers related to other common vaccines. It is therefore important to test PCV interaction with other pediatric vaccines when administered simultaneously. We assessed the immune response to an 11-valent PCV conjugated to diphtheria and tetanus carriers (PncD\\/T11), administered concomitantly, but in separate sites, with a com- bined

Ron Dagan; David Goldblatt; James R. Maleckar; M. Yaich; Juhani Eskola

2004-01-01

291

Serotype distribution and antimicrobial susceptibilities of nasopharyngeal isolates of Streptococcus pneumoniae from healthy children in the 13-valent pneumococcal conjugate vaccine era.  

PubMed

Few epidemiological data are available since the introduction of 13-valent pneumococcal vaccine (PCV13) in 2010. We conducted a cross-sectional study to estimate the prevalence of Streptococcus pneumoniae (SP) nasopharyngeal carriage in healthy Italian infants and young children and to evaluate the impact of PCV13 on pneumococcal colonization. In the trimester September-December 2011 nasopharyngeal swabs were collected from healthy children aged 3-59 months presenting for routine well careat 16 primary care pediatricians in Milan. SP carriage isolates were serotyped and tested for antimicrobial resistance using EUCAST breakpoints. Among 1250 enrolled children, 618 had received at least 1 dose of PCV13, 292 at least 1 dose of PCV7, 94 a combination of the two vaccines and 246 were not vaccinated. The prevalence of SP carriage was 27% (95% confidence interval [CI] 25-30). At multivariable analysis, age?25 months (prevalence ratio [PR]=0.74) and use of antibiotics in the previous 3 months (PR=0.67) were associated with lower SP carriage prevalence. Having siblings (PR=1.79 for 1 sibling and PR=2.23 for ?2 siblings), day-care attendance (PR=2.27) and respiratory tract infections in the previous 3 months (PR=1.39) were associated with higher SP carriage prevalence. The immunization status for SP was not associated with SP carriage at univariable or at multivariable analysis. The most common carriage isolates were 6C, 19A and 23A. The prevalence of the six additional PCV13 serotypes carriage in children appropriately vaccinated with PCV13 was lower than in children appropriately vaccinated with PCV7 (0 vs. 0.060); the greater reduction in prevalence of carriage was observed for serotype 19A (0 vs. 0.041). Serotype 6C was the most common drug-resistant serotype (17.2%). Further epidemiological studies are needed to assess changes in circulating SP serotypes following the large-scale introduction of PCV13. PMID:24342249

Zuccotti, Gianvincenzo; Mameli, Chiara; Daprai, Laura; Garlaschi, Maria Laura; Dilillo, Dario; Bedogni, Giorgio; Faccini, Marino; Gramegna, Maria; Torresani, Erminio; Ballerini, Emanuela; Benincaso, Annarita; Bonvissuto, Milena; Bricalli, Dorella; Brioschi, Manuela; Calloni, Cinzia Simona; Camiletti, Marina Irene; Colella, Giacomo; De Angelis, Laura; Decarlis, Silvia; Di Nello, Francesca; Dozzi, Massimiliano; Galli, Erica; Gandini, Vera; Giuliani, Maria Grazia; Laviola, Franca; Loda, Barbara; Macedoni, Maddalena; Mazzucchi, Elisabetta; Metta, Maria Gabriella; Moscatiello, Anna; Nannini, Pilar; Petruzzi, Mariangela; Picicco, Damiano; Picciotti, Michela; Pisanelli, Stefania; Porta, Norberto; Ramponi, Giulia; Redaelli, Francesca; Rubini, Riccardo; Sala, Natascia; Saitta, Vincenzo; Scelza, Giuseppina; Tiso, Rosa Maria; Tomasetto, Mariangela; Torcoletti, Matteo; Travaini, Marta; Valentini, Maurizio; Vessia, Chiara

2014-01-23

292

Antibody responses of Macaca fascicularis against a new inactivated polio vaccine derived from Sabin strains (sIPV) in DTaP-sIPV vaccine.  

PubMed

Antibody responses of Macaca fascicularis against a new tetravalent vaccine composed of diphtheria toxoid, tetanus toxoid, acellular pertussis antigens, and inactivated poliovirus derived from Sabin strains (sIPV) was investigated to predict an optimal dose of sIPV in a new tetravalent vaccine (DTaP-sIPV) prior to conducting a dose-defined clinical study. Monkeys were inoculated with DTaP-sIPVs containing three different antigen units of sIPVs: Vaccine A (types 1:2:3 = 3:100:100 DU), Vaccine B (types 1:2:3 = 1.5:50:50 DU), and Vaccine C (types 1:2:3 = 0.75:25:25 DU). There was no difference in the average titers of neutralizing antibody against the attenuated or virulent polioviruses between Vaccines A and B. The average neutralizing antibody titers of Vaccine C tended to be lower than those of Vaccines A and B. The sIPV antigens did not affect the anti-diphtheria or anti-tetanus antibody titers of DTaP-sIPV. Furthermore, the average neutralizing antibody titers of Vaccine A against the attenuated and virulent polioviruses were comparable between M. fascicularis and humans. These results suggest that M. fascicularis may be a useful animal model for predicting the antibody responses to sIPVs in humans, and that it may be likely to reduce the amount of sIPVs contained in DTaP-sIPVs, even for humans. PMID:23375165

Sato, Y; Shiosaki, K; Goto, Y; Sonoda, K; Kino, Y

2013-05-01

293

Post Hoc Analysis of a Randomized Double-Blind Trial of the Correlation of Functional and Binding Antibody Responses Elicited by 13-Valent and 7-Valent Pneumococcal Conjugate Vaccines and Association with Nasopharyngeal Colonization  

PubMed Central

In a randomized double-blind trial in healthy Israeli infants in Israel who received the 13-valent or 7-valent pneumococcal conjugate vaccine (PCV13 or PCV7, respectively) at 2, 4, 6, and 12 months, PCV13 significantly reduced nasopharyngeal (NP) colonization of serotypes 1, 6A, 7F, 19A, cross-reacting 6C, and the common PCV7 serotype 19F, from ages 7 to 24 months. No differences were observed between the vaccine groups for serotype 3 or for the remaining common PCV7 serotypes. For serotype 5, too few events were observed to draw an inference. Generally consistent with these findings, PCV13 elicited significantly higher enzyme-linked immunosorbent assay (ELISA) IgG-binding antibody responses than did PCV7 for the additional PCV13 serotypes 1, 3, 5, 6A, 7F, 19A, and for the common serotype 19F, with similar or lower responses for the remaining common serotypes. To further assess immunogenicity and colonization, we conducted a post hoc analysis of PCV13 functional antibody responses measured by opsonophagocytic activity (OPA) assays in a randomly selected subset of subjects. The pattern of functional antibody OPA responses elicited by PCV13 relative to PCV7 was similar to that of the ELISA anticapsular IgG-binding antibody responses described above. In addition, the OPA responses generally correlated positively with IgG responses for all 13 serotypes among the PCV13 recipients and for all 7 common serotypes and the additional serotype 6A but not for 19A or the other serotypes unique to PCV13 among the PCV7 recipients. This post hoc analysis supports an association between serum OPA functional and IgG-binding antibody levels, allowing for a transfer of inferred associations between IgG responses and NP colonization to OPA responses. PMID:24990907

Juergens, Christine; Patterson, Scott; Trammel, James; Greenberg, David; Givon-Lavi, Noga; Cooper, David; Gurtman, Alejandra; Gruber, William C.; Scott, Daniel A.

2014-01-01

294

[Development of monoclonal latex diagnostic kit for diphtheria toxin and toxoid detection].  

PubMed

Latex diagnostic kit with high specificity and sensitivity of diphtheria toxin and toxoid detection has been developed on the basis of protective monoclonal antibodies to diphtheria toxin and polyacrolein microspheres. Diagnostic kit was stable during 1 year of shelf-life (time of the study). PMID:17886375

Gavrilova, N F; Sviridov, V V; Iakovleva, I V; Raspopova, E N; Gneralova, A N; Lukin, Iu V

2007-01-01

295

Amino acid analysis of peptide loading ratios in conjugate vaccines: a comparison of direct electrochemical detection and 6-aminoquinolyl-N-hydroxysuccinimidyl carbamate pre-column derivatization methods.  

PubMed

Amino acid analysis using direct electrochemical detection was compared with precolumn fluorescent derivatization using 6-aminoquinolyl- N-hydroxysuccinimidyl carbamate (AQC) for evaluation of the degree of covalent coupling of peptides to a carrier-protein complex derived from the bacteria Neisseria meningitidis. AQC derivatization was found to give superior sensitivity compared to electrochemical detection, with less interference from sample components such as carbohydrates or buffer salts. Hydrolysis time and temperature were optimized for maximal recoveries of the marker amino acid 6-aminohexanoic acid (epsilon-Ahx) and the unique amino acids S-dicarboxyethyl cysteine (SDCEC) and S-carboxymethyl homocysteine (SCHMC), which are generated upon the hydrolysis of the covalent linkage between the peptide and the carrier protein. Quantitation of these amino acids enabled the determination of the ratio of peptide to protein in the conjugate samples. PMID:18072716

Nahas, Deborah D; Palladino, Jennifer S; Joyce, Joseph G; Hepler, Robert W

2008-01-01

296

Reactogenicity and immunogenicity of reduced antigen content diphtheria–tetanus–acellular pertussis vaccines as a booster in 4–7-year-old children primed with diphtheria–tetanus–whole cell pertussis vaccine before 2 years of age  

Microsoft Academic Search

Background. The recent introduction of acellular pertussis vaccines (Pa) offers the possibility of booster doses in older children and adults. This can be conveniently accomplished by combining acellular pertussis antigens with diphtheria and tetanus toxoids. However the optimal dosage for the booster injection has not yet been determined.Objective. To compare the reactogenicity and immunogenicity of diphtheria–tetanus–acellular pertussis vaccines (DTPa) with

Ron Dagan; Karim Igbaria; Lolita Piglansky; Francis Van Brusteghem; Vincent Melot; Achim Kaufhold

1999-01-01

297

Streptococcus pneumoniae serotype distribution in children in the Russian Federation before the introduction of pneumococcal conjugate vaccines into the National Immunization Program.  

PubMed

WHO recommends the inclusion of PCVs in childhood vaccination programs world-wide. Many countries including the Russian Federation are currently planning the inclusion of PCVs in their National Immunization Programs and, therefore, data on the pneumococcal serotype distribution is important to estimate the potential disease impact. Here we review eight recent epidemiological studies on the pneumococcal serotype distribution from Russia. Across all studies, serotypes 6B, 14, 19F and 23F were the most prevalent. Interestingly, serotype 3 was relatively common. Serotype 19A was prevalent among AOM, CAP and nasopharyngeal isolates and among antibiotic resistant isolates in all age groups. The differences in serotype coverage between PCV10 and PCV13 were up to 26%. Based on the current data on serotype distribution, a wide use of PCVs in Russia may lead to a significant reduction of the pneumococcal disease burden. PMID:24350587

Tatochenko, Vladimir; Sidorenko, Sergey; Namazova-Baranova, Leila; Mayanskiy, Nikolay; Kulichenko, Tatiana; Baranov, Alexander; Lobzin, Yury; Kharit, Susanna; Kozlov, Roman; Andreeva, Irina; Muravjev, Alexander; Chagaryan, Aida; Koroleva, Irina; Beloshitskiy, Grigoriy; Mironov, Konstantin; Degtyareva, Elena; Reinert, Ralf René

2014-02-01

298

Generation of a Tumor Vaccine Candidate Based on Conjugation of a MUC1 Peptide to Polyionic Papillomavirus Virus-Like Particles (VLPs)  

PubMed Central

Virus-like particles (VLPs) are promising vaccine technology due to their safety and ability to elicit strong immune responses. Chimeric VLPs can extend this technology to low immunogenicity foreign antigens. However, insertion of foreign epitopes into the sequence of self-assembling proteins can have unpredictable effects on the assembly process. We aimed to generate chimeric bovine papillomavirus (BPV) VLPs displaying a repetitive array of polyanionic docking sites on their surface. These VLPs can serve as platform for covalent coupling of polycationic fusion proteins. We generated baculoviruses expressing chimeric BPV L1 protein with insertion of a polyglutamic-cysteine residue in the BC, DE, HI loops and the H4 helix. Expression in insect cells yielded assembled VLPs only from insertion in HI loop. Insertion in DE loop and H4 helix resulted in partially formed VLPs and capsomeres, respectively. The polyanionic sites on the surface of VLPs and capsomeres were decorated with a polycationic MUC1 peptide containing a polyarginine-cysteine residue fused to twenty amino acids of the MUC1 tandem repeat through electrostatic interactions and redox-induced disulfide bond formation. MUC1- fully assembled VLPs induced robust activation of bone marrow-derived dendritic cells, which could then present MUC1 antigen to MUC1-specific T cell hybridomas and primary naïve MUC1-specific T cells obtained from a MUC1-specific TCR transgenic mice. Immunization of human MUC1 transgenic mice, where MUC1 is a self-antigen, with the VLP vaccine induced MUC1-specific CTL, delayed the growth of MUC1 transplanted tumors and elicited complete tumor rejection in some animals. PMID:20652244

Pejawar-Gaddy, Sharmila; Rajawat, Yogendra; Hilioti, Zoe; Xue, Jia; Gaddy, Daniel F.; Finn, Olivera J.; Viscidi, Raphael P.; Bossis, Ioannis

2011-01-01

299

Influenza vaccine  

MedlinePLUS

Vaccine - influenza; Immunization - influenza; Flu shot; Flu vaccine ... with Vaccines: Recommendations of the Advisory Committee on Immunization Practices (ACIP) United States, 2013-2014. Available at: ...

300

Vaccine process technology.  

PubMed

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 perspective, Quality by Design (QbD) and Process Analytical Technology (PAT) are important initiatives that can be applied effectively to many types of vaccine processes. Universal demand for vaccines requires that a manufacturer plan to supply tens and sometimes hundreds of millions of doses per year at low cost. To enable broader use, there is intense interest in improving temperature stability to allow for excursions from a rigid cold chain supply, especially at the point of vaccination. Finally, there is progress in novel routes of delivery to move away from the traditional intramuscular injection by syringe approach. PMID:22407777

Josefsberg, Jessica O; Buckland, Barry

2012-06-01

301

Impact of Pneumococcal Conjugate Vaccines on the Incidence of Pneumonia in Hospitalized Children after Five Years of Its Introduction in Uruguay  

PubMed Central

Background Data on the burden of pneumococcal disease and the most frequent serotypes demonstrated that invasive disease and pneumonia were important manifestations affecting children under 5 years of age. Therefore, pneumococcal diseases prevention became a public health priority. Uruguay was the first Latin American country to incorporate PCV7 into its National Immunization Program. The aim of this study is to compare the incidence rates for hospitalized pneumonia in children from the pre PCV introduction period and the following five years of PCVs application in Uruguay. Methods and Findings Population-based surveillance of pneumonia hospitalization rates, in children, less than 14 years of age, had been performed prior pneumococcal vaccination, and continued following PCV7 introduction and PCV13 replacement, using the same methodology. Hospitalized children with pneumonia were enrolled from January 1, 2009 through December 31st, 2012. The study was carried out in an area with a population of 238,002 inhabitants of whom 18, 055 were under five years of age. Patients with acute lower respiratory infections for whom a chest radiograph was performed on admission were eligible. Digitalized radiographs were interpreted by a reference radiologist, using WHO criteria. Pneumonia was confirmed in 2,697 patients, 1,267 with consolidated and 1,430 with non consolidated pneumonia of which incidence decrease, between 2009 and 2012, was 27.3% and 46.4% respectively. 2001–2004 and 2009–2012 comparison showed a significant difference of 20.4% for consolidated pneumonia hospitalizations. A significant incidence decline was recorded among children 6 to 35 months of age. Conclusions An overall significant reduction in pneumonia hospitalizations was observed following the introduction of PCV7 and furthermore following the change to PCV13. PMID:24905093

Hortal, Maria; Estevan, Miguel; Meny, Miguel; Iraola, Ines; Laurani, Hilda

2014-01-01

302

Evaluation of TLR Agonists as Potential Mucosal Adjuvants for HIV gp140 and Tetanus Toxoid in Mice  

PubMed Central

In the present study we investigate the impact of a range of TLR ligands and chitosan as potential adjuvants for different routes of mucosal immunisation (sublingual (SL), intranasal (IN), intravaginal (IVag) and a parenteral route (subcutaneous (SC)) in the murine model. We assess their ability to enhance antibody responses to HIV-1 CN54gp140 (gp140) and Tetanus toxoid (TT) in systemic and vaginal compartments. A number of trends were observed by route of administration. For non-adjuvanted antigen, SC>SL>IN immunisation with respect to systemic IgG responses, where endpoint titres were greater for TT than for gp140. In general, co-administration with adjuvants increased specific IgG responses where IN?=?SC>SL, while in the vaginal compartment IN>SL>SC for specific IgA. In contrast, for systemic and mucosal IgA responses to antigen alone SL>IN?=?SC. A number of adjuvants increased specific systemic IgA responses where in general IN>SL>SC immunisation, while for mucosal responses IN?=?SL>SC. In contrast, direct intravaginal immunisation failed to induce any detectable systemic or mucosal responses to gp140 even in the presence of adjuvant. However, significant systemic IgG responses to TT were induced by intravaginal immunisation with or without adjuvant, and detectable mucosal responses IgG and IgA were observed when TT was administered with FSL-1 or Poly I?C. Interestingly some TLRs displayed differential activity dependent upon the route of administration. MPLA (TLR4) suppressed systemic responses to SL immunisation while enhancing responses to IN or SC immunisation. CpG B enhanced SL and IN responses, while having little or no impact on SC immunisation. These data demonstrate important route, antigen and adjuvant effects that need to be considered in the design of mucosal vaccine strategies. PMID:23272062

Buffa, Viviana; Klein, Katja; Fischetti, Lucia; Shattock, Robin J.

2012-01-01

303

Comparative Estimation of Coverage between National Immunization Program Vaccines and Non-NIP Vaccines in Korea  

PubMed Central

This study aimed to describe the differences in vaccination coverage between National Immunization Program (NIP) vaccines and non-NIP vaccines in Korea and to identify factors affecting the difference. Nationwide face-to-face interview-based questionnaire survey among randomly selected 4,374 participants aged 7-83 months was conducted. Vaccination coverage analyzed according to the birth cohorts, geographic areas, and socio-demographic characteristics. We found that NIP vaccines recorded higher primary vaccination coverage compared to non-NIP vaccines (95.9%-100% vs 30.7%-85.4%). The highest rate was Haemophilus influenzae type b (Hib) vaccine (85.4%), which was introduced in 1996, and the lowest rate was rotavirus vaccine (30.7%), which was introduced recently. On multivariate analysis, having a sibling were significantly associated with lower uptake of Hib vaccine, pneumococcal conjugate vaccine (PCV), and rotavirus vaccine; while, older mother's age and attendance to daycare center were significantly associated with lower uptake of PCV and rotavirus vaccine (P < 0.001). We found differences in the vaccine coverage rate between NIP vaccines and non-NIP vaccines; and the data suggests potential disparity in accessing non-NIP vaccines in Korea. Expansion of NIP to include non-NIP vaccines can provide better protection against the diseases through increased coverage. PMID:24015031

Choe, Young June; Yang, Jae Jeong; Park, Sue K.; Lee, Hoan Jong

2013-01-01

304

A Nonadjuvanted Transcutaneous Tetanus Patch Is Effective in Boosting Anti-Tetanus Toxoid Immune Responses  

PubMed Central

Dry tetanus toxoid (TTx) patches were formulated without any adjuvant, with excipients to impart antigen stabilization and to enhance skin delivery. The booster effects of the TTx patches were assessed using a guinea pig model. The study revealed significant rises in TTx IgG titers induced by the TTx patches after a low-dose subcutaneous (s.c.) prime with TTx adsorbed to aluminum hydroxide. The TTx patch can therefore be considered an effective alternative to a subcutaneous booster. PMID:24334688

Seid, Robert C.; Reinisch, Christoph; Schlegl, Robert; Moehlen, Michael; Meinke, Andreas

2014-01-01

305

Microbiological characterization of Streptococcus pneumoniae and non-typeable Haemophilus influenzae isolates as primary causes of acute otitis media in Bulgarian children before the introduction of conjugate vaccines  

PubMed Central

Background Pneumococcal and Haemophilus influenzae type b (Hib) vaccines were introduced in our national immunisation program in April 2010. The aims of this retrospective, laboratory-based study were to determine the serotypes and antibiotic resistance of Streptococcus pneumoniae and H. influenzae isolates from middle ear fluid (MEF) collected before the introduction of immunization. Methods S. pneumoniae (n?=?128) and H. influenzae (n?=?40) strains isolated from MEF of children with AOM between 1994 and 2011 were studied. MICs were determined by a microdilution assay. Serotyping of S. pneumoniae was done by Quellung method and PCR capsular typing was used for H. influenzae. Macrolide resistance genes were detected by PCR for erythromycin resistant S. pneumoniae (ERSP). DNA sequencing of ftsI gene was performed for ampicillin nonsusceptible H. influenzae. Results The most common serotypes found among children with pneumococcal AOM were 19 F (20.3%), 6B (15.6%), and 19A (10.9%). The potential coverage rates by the PCV7, PCV10 and PCV13 of children aged?

2013-01-01

306

Epidemiology and population structure of serotypes 1, 5 and 7f carried by children in Portugal from 1996-2010 before introduction of the 10-valent and 13-valent pneumococcal conjugate vaccines.  

PubMed

Among the over 90 serotypes of Streptococcus pneumoniae described, serotypes 1, 5, and 7F account for a significant proportion of invasive disease worldwide and are now covered by the most recent 10- and 13-valent pneumococcal conjugate vaccines (PCVs). The epidemiology of these serotypes in carriage remains poorly studied because they are rarely detected. We aimed to gain insights into the epidemiology and population structure of serotypes 1, 5 and 7F carried by children in Portugal before PCV10 and PCV13 became widely used. Isolates obtained in cross-sectional studies carried out over a 15-year period (1996-2010) were retrospectively pooled and characterized. Of 5,123 pneumococci obtained, 70 were associated with serotypes 1 (n?=?21), 5 (n?=?7), and 7F (n?=?42). The highest prevalence detected was 3.3% for serotype 1 in 2006, 1% for serotype 5 in 2009, and 3.3% for serotype 7F in 2006; Serotype 1 was associated with PMEN international clones Sweden(1)-28(ST306) and Sweden(1)-40(ST304); serotype 5 was associated with Colombia(5)-19(ST289); and serotype 7F was associated with Netherlands(7F)-39(ST191). All these isolates were fully susceptible. Most carriers of serotypes 1 (86%), 5 (86%), and 7F (91%) were older than two years but a significant association with older age was only observed for serotype 7F (p?=?0.006). Evidence for cross-transmission was obtained. In conclusion, we were able to detect and characterize the rarely carried serotypes 1, 5, and 7F among healthy children in Portugal. These data will constitute an important baseline for upcoming surveillance studies aimed to establish the impact of novel PCVs targeting these serotypes in carriage. PMID:24058686

Almeida, Sónia T; de Lencastre, Hermínia; Sá-Leão, Raquel

2013-01-01

307

Toxoids of Pseudomonas aeruginosa exotoxin-A: photoaffinity inactivation of purified toxin and purified toxin derivatives.  

PubMed Central

For the preparation of greatly detoxified but highly immunogenic toxoids, two enzymatically active, low-toxicity derivatives of Pseudomonas aeruginosa exotoxin-A were further inactivated by photoaffinity labeling. These derivatives were formed during toxin purification, when a relatively crude toxin preparation was concentrated by ammonium sulfate precipitation and subsequently dialyzed. These derivatives, designated peak-1 protein (PK-1) and peak-2 protein (PK-2) were antigenically indistinguishable from native toxin, but had isoelectric points (5.00 and 4.90, respectively) that were different from that of the native toxin (4.95). Although the enzymatic activities and molecular weights of PK-1 and PK-2 were similar to those of native toxin, their toxicities were greatly reduced (ca. 500-fold). Photoaffinity labeling of fully active toxin-A, purified by a process which limits the formation of these derivatives, decreased its enzymatic activity (ca. 30-fold) and toxicity (ca. 100-fold). Likewise, photoaffinity labeling of purified PK-1 and PK-2 decreased their enzymatic activities and toxicities (ca. 30-fold and 100-fold, respectively) and, thus, yielded toxoids that were ca. 50,000-fold less toxic than unpurified native toxin. These toxoids were irreversibly detoxified and highly immunogenic during 9 months of storage at 4 degrees C. Images PMID:6321348

Callahan, L T; Martinez, D; Marburg, S; Tolman, R L; Galloway, D R

1984-01-01

308

Efficacy of a type C botulism vaccine in green-winged teal.  

PubMed

We tested the efficacy of a single dose of Botumink toxoid for protecting wild green-winged teal (Anas crecca) during botulism epizootics caused by Clostridium botulinum type C. We challenged control and immunized ducks with four different doses of type C botulinum toxin to determine the LD50 for this species and to evaluate vaccine protection. Fewer immunized ducks were affected with botulism than control ducks, indicating that a single dose of Botumink toxoid could increase the survival of ducks during epizootics. However, the frequency of immunized ducks with signs of botulism increased with the challenge dose of botulinum toxin. Even at doses of botulinum toxin approximately 2 to 4 green-winged teal LD50, about 50% of the immunized ducks were affected. We believe an improved vaccine or a better delivery system is required to justify immunization of wild birds for experimental survival studies. PMID:10941734

Rocke, T E; Samuel, M D; Swift, P K; Yarris, G S

2000-07-01

309

Efficacy of a type C botulism vaccine in green-winged teal  

USGS Publications Warehouse

We tested the efficacy of a single dose of Botumink toxoid for protecting wild green-winged teal (Anas crecca) during botulism epizootics caused by Clostridium botulinum type C. We challenged control and immunized ducks with four different doses of type C botulinum toxin to determine the LD50 for this species and to evaluate vaccine protection. Fewer immunized ducks were affected with botulism than control ducks, indicating that a single dose of Botumink toxoid could increase the survival of ducks during epizootics. However, the frequency of immunized ducks with signs of botulism increased with the challenge dose of botulinum toxin. Even at doses of botulinum toxin approximately 2 to 4 green-winged teal LD50, about 50% of the immunized ducks were affected. We believe an improved vaccine or a better delivery system is required to justify immunization of wild birds for experimental survival studies.

Rocke, T.E.; Samuel, M.D.; Swift, P.K.; Yarris, G.S.

2000-01-01

310

Acellular pertussis vaccines: the rationale for an efficacy trial in Germany.  

PubMed

After concern about the safety of diphtheria-tetanus toxoid-whole cell pertussis vaccines (DTPw), the recommendation to vaccinate children with DTPw was withdrawn in 1974 in the former West Germany. This led pertussis cases to increase to an estimated 100,000 annually. Despite renewal of the vaccination recommendation in 1991, vaccine use remained low. The German health care structure assures regular contact between most children and pediatricians. This enabled the conduct of a large efficacy trial with a diphtheria-tetanus toxoid-acellular pertussis (DTPa) vaccine. Because a placebo-controlled trial was not ethically possible, a prospective household contact study with a blinded clinical follow-up was done. Possible study participants were screened by their pediatrician, who also initiated diagnostic procedures. Clinical follow-up was done by another locally based but independent and blinded physician. Vaccine efficacy was calculated to be 89% (95% confidence interval, 76.6%-94.6%). None of the identified confounding factors biased results in favor of the DTPa vaccine. PMID:8896531

Schmitt, H J; Schuind, A; Knuf, M; Zepp, F; Beutel, K; Wirsing von König, C H; Neiss, A; Bock, H L; Bogaerts, H; Clemens, R

1996-11-01

311

Glycoprotein Vaccines DOI: 10.1002/anie.201006327  

E-print Network

Glycoprotein Vaccines DOI: 10.1002/anie.201006327 A Coordinated Synthesis and Conjugation Strategy for the Preparation of Homogeneous Glycoconjugate Vaccine Candidates** Elizabeth J. Grayson, Gonçalo J. L. Bernardes are the center of many therapeutic strat- egies[1­3] and carbohydrate-based vaccines in particular hold great

Davis, Ben G.

312

Tiff over anti-tetanus vaccine now erupted into battle. International / Philippines.  

PubMed

Anti-abortionists in the Philippines have generated widespread fears in the country that tetanus toxoid used in the anti-tetanus vaccine campaign contains trace amounts of human chorionic gonadotropin (HCG) to induce abortion. The World Health Organization (WHO) notes that this widespread, unfounded fear has already resulted in a 45% drop in tetanus toxoid coverage during national immunization days in 1995 compared to 1994. Since up to 5 million women were not immunized in 1995, 300-400 more babies will contract tetanus and die in the year to come. Pro-life Philippines is ostensibly the creator and supporter of these newly-generated fears about tetanus toxoid. The mass hysteria is, however, most likely part of a church-led campaign against the government's population policies and the popularity of former Health Secretary Juan Flavier. Millions of Filipino women have for years received anti-tetanus vaccines to prevent tetanus in both mothers and their newborn children. Tetanus remains a problem for newborns in the Philippines where local midwives often use unsanitary knives to sever the umbilical cord at birth. Since the immunization drive was stepped up in 1990, the number of babies affected by tetanus has fallen from more than 25 per day in the mid-1980s to four currently. The vaccine currently supplied by UNICEF has been used for more than 50 years in many countries and is one of the basics in immunization. The Department of Health notes no unusual increase in abortions since 1990, the year the anti-tetanus drive was accelerated. Prior to 1990, anti-tetanus vaccination had been going on in the Philippines since 1983. Even WHO assurances that tetanus toxoid contains no abortifacients have failed to allay public fear. It is unfortunate that the people and groups behind this misinformation campaign have done so much damage to a decidedly beneficial and needed health program. PMID:12289950

1995-07-24

313

Randomized, controlled trial of the long term safety, immunogenicity and efficacy of RTS,S/AS02D malaria vaccine in infants living in a malaria-endemic region  

PubMed Central

Background The RTS,S/AS malaria candidate vaccine is being developed with the intent to be delivered, if approved, through the Expanded Programme on Immunization (EPI) of the World Health Organization. Safety, immunogenicity and efficacy of the RTS,S/AS02D vaccine candidate when integrated into a standard EPI schedule for infants have been reported over a nine-month surveillance period. This paper describes results following 20?months of follow up. Methods This Phase IIb, single-centre, randomized controlled trial enrolled 340 infants in Tanzania to receive three doses of RTS,S/AS02D or hepatitis B vaccine at 8, 12, and 16?weeks of age. All infants also received DTPw/Hib (diphtheria and tetanus toxoids, whole-cell pertussis vaccine, conjugated Haemophilus influenzae type b vaccine) at the same timepoints. The study was double-blinded to month 9 and single-blinded from months 9 to 20. Results From month 0 to 20, at least one SAE was reported in 57/170 infants who received RTS,S/AS02D (33.5%; 95% confidence interval [CI]: 26.5, 41.2) and 62/170 infants who received hepatitis B vaccine (36.5%; 95% CI: 29.2, 44.2). The SAE profile was similar in both vaccine groups; none were considered to be related to vaccination. At month 20, 18?months after completion of vaccination, 71.8% of recipients of RTS,S/AS02D and 3.8% of recipients of hepatitis B vaccine had seropositive titres for anti-CS antibodies; seroprotective levels of anti-HBs antibodies remained in 100% of recipients of RTS,S/AS02D and 97.7% recipients of hepatitis B vaccine. Anti-HBs antibody GMTs were higher in the RTS,S/AS02D group at all post-vaccination time points compared to control. According to protocol population, vaccine efficacy against multiple episodes of malaria disease was 50.7% (95% CI: -6.5 to 77.1, p?=?0.072) and 26.7% (95% CI: -33.1 to 59.6, p?=?0.307) over 12 and 18?months post vaccination, respectively. In the Intention to Treat population, over the 20-month follow up, vaccine efficacy against multiple episodes of malaria disease was 14.4% (95% CI: -41.9 to 48.4, p?=?0.545). Conclusions The acceptable safety profile and good tolerability of RTS,S/AS02D in combination with EPI vaccines previously reported from month 0 to 9 was confirmed over a 20?month surveillance period in this infant population. Antibodies against both CS and HBsAg in the RTS,S/AS02D group remained significantly higher compared to control for the study duration. Over 18?months follow up, RTS,S/AS02D prevented approximately a quarter of malaria cases in the study population. Clinical trials Gov identifier: NCT00289185 PMID:23297680

2013-01-01

314

Vaccination coverage among children in kindergarten - United States, 2013-14 school year.  

PubMed

State and local vaccination requirements for school entry are implemented to maintain high vaccination coverage and protect schoolchildren from vaccine-preventable diseases. Each year, to assess state and national vaccination coverage and exemption levels among kindergartners, CDC analyzes school vaccination data collected by federally funded state, local, and territorial immunization programs. This report describes vaccination coverage in 49 states and the District of Columbia (DC) and vaccination exemption rates in 46 states and DC for children enrolled in kindergarten during the 2013-14 school year. Median vaccination coverage was 94.7% for 2 doses of measles, mumps, and rubella (MMR) vaccine; 95.0% for varying local requirements for diphtheria, tetanus toxoid, and acellular pertussis (DTaP) vaccine; and 93.3% for 2 doses of varicella vaccine among those states with a 2-dose requirement. The median total exemption rate was 1.8%. High exemption levels and suboptimal vaccination coverage leave children vulnerable to vaccine-preventable diseases. Although vaccination coverage among kindergartners for the majority of reporting states was at or near the 95% national Healthy People 2020 targets for 4 doses of DTaP, 2 doses of MMR, and 2 doses of varicella vaccine, low vaccination coverage and high exemption levels can cluster within communities. Immunization programs might have access to school vaccination coverage and exemption rates at a local level for counties, school districts, or schools that can identify areas where children are more vulnerable to vaccine-preventable diseases. Health promotion efforts in these local areas can be used to help parents understand the risks for vaccine-preventable diseases and the protection that vaccinations provide to their children. PMID:25321068

Seither, Ranee; Masalovich, Svetlana; Knighton, Cynthia L; Mellerson, Jenelle; Singleton, James A; Greby, Stacie M

2014-10-17

315

A potential krimpsiekte vaccine.  

PubMed

Krimpsiekte, a chronic form of cardiac glycoside poisoning, is an important plant-induced intoxication of small stock in South Africa. It is caused by cumulative, neurotoxic bufadienolides, such as cotyledoside. A cotyledoside-bovine serum albumin conjugate was synthesized to immunize animals. The efficacy of the cotyledoside-conjugate in inducing an immunological response was ascertained in rabbits (n = 4) and sheep (n = 4) by determining cotyledoside antibody titres with an ELISA using cotyledoside-hen ovalbumin as antigen. The formation of anticotyledoside antibodies was induced in both rabbits and sheep following immunization with the cotyledoside-protein conjugate. Protection provided by the vaccine was demonstrated by challenging sheep (n = 4) with repeated, daily doses of cotyledoside (0.015 mg/kg) administered intravenously, commencing 45 days after the initial vaccination. One control animal died on Day 3 of the challenge period and the other was severely affected after administration of the third cotyledoside dose. The immunized ewes (n = 2) remained clinically unaffected and the challenge was suspended following six daily injections. Vaccination as a means of preventing krimpsiekte seems to be quite feasible and deserves further investigation. PMID:18453240

Botha, C J; Crafford, J E; Butler, V P; Stojanovic, M N; Labuschagne, L

2007-12-01

316

Diversity of the Antibody Response to Tetanus Toxoid: Comparison of Hybridoma Library to Phage Display Library  

PubMed Central

Monoclonal antibodies are important tools in research and since the 1990s have been an important therapeutic class targeting a wide variety of diseases. Earlier methods of mAb production relied exclusively on the lengthy process of making hybridomas. The advent of phage display technology introduced an alternative approach for mAb production. A potential concern with this approach is its complete dependence on an in vitro selection process, which may result in selection of VH-VL pairs normally eliminated during the in vivo selection process. The diversity of VH-VL pairs selected from phage display libraries relative to an endogenous response is unknown. To address these questions, we constructed a panel of hybridomas and a phage display library using the spleen of a single tetanus toxoid-immunized mouse and compared the diversity of the immune response generated using each technique. Surprisingly, the tetanus toxoid-specific antibodies produced by the hybridoma library exhibited a higher degree of VH-VL genetic diversity than their phage display-derived counterparts. Furthermore, the overlap among the V-genes from each library was very limited. Consistent with the notion that accumulation of many small DNA changes lead to increased antigen specificity and affinity, the phage clones displayed substantial micro-heterogeneity. Contrary to previous reports, we found that antigen specificity against tetanus toxoid is encoded by both V? and VH genes. Finally, the phage-derived tetanus-specific clones had a lower binding affinity than the hybridomas, a phenomenon thought to be the result of random pairing of the V-genes. PMID:25268771

Sorouri, Mahsa; Fitzsimmons, Sean P.; Aydanian, Antonina G.; Bennett, Sonita; Shapiro, Marjorie A.

2014-01-01

317

Booster Vaccination: The Role of Reduced Antigen Content Vaccines as a Preschool Booster  

PubMed Central

The need for boosters for tetanus, diphtheria, pertussis, and polio, starting from preschool age, is related to the waning immune protection conferred by vaccination, the elimination/reduction of natural boosters due to large-scale immunization programs, and the possibility of reintroduction of wild agents from endemic areas. Taking into account the relevance of safety/tolerability in the compliance with vaccination among the population, it have been assessed whether today enough scientific evidences are available to support the use of dTap-IPV booster in preschool age. The review of the literature was conducted using the PubMed search engine. A total of 41 works has been selected; besides, the documentation produced by the World Health Organization, the European Centre for Disease Control, and the Italian Ministry of Health has been consulted. Many recent papers confirm the opportunity to use a low antigenic dose vaccine starting from 4 to 6 years of age. There is also evidence that 10 years after immunization the rate of seroprotected subjects against diphtheria does not differ significantly between those vaccinated with paediatric dose (DTaP) or reduced dose (dTaP or dTap) product. The dTpa vaccine is highly immunogenic for diphtheria toxoids regardless of prior vaccination history (2 + 1 and 3 + 1 schedules). PMID:24678509

Conversano, Michele; Zivelonghi, Giambattista; Zoppi, Giorgio

2014-01-01

318

Booster vaccination: the role of reduced antigen content vaccines as a preschool booster.  

PubMed

The need for boosters for tetanus, diphtheria, pertussis, and polio, starting from preschool age, is related to the waning immune protection conferred by vaccination, the elimination/reduction of natural boosters due to large-scale immunization programs, and the possibility of reintroduction of wild agents from endemic areas. Taking into account the relevance of safety/tolerability in the compliance with vaccination among the population, it have been assessed whether today enough scientific evidences are available to support the use of dTap-IPV booster in preschool age. The review of the literature was conducted using the PubMed search engine. A total of 41 works has been selected; besides, the documentation produced by the World Health Organization, the European Centre for Disease Control, and the Italian Ministry of Health has been consulted. Many recent papers confirm the opportunity to use a low antigenic dose vaccine starting from 4 to 6 years of age. There is also evidence that 10 years after immunization the rate of seroprotected subjects against diphtheria does not differ significantly between those vaccinated with paediatric dose (DTaP) or reduced dose (dTaP or dTap) product. The dTpa vaccine is highly immunogenic for diphtheria toxoids regardless of prior vaccination history (2 + 1 and 3 + 1 schedules). PMID:24678509

Gabutti, Giovanni; Trucchi, Cecilia; Conversano, Michele; Zivelonghi, Giambattista; Zoppi, Giorgio

2014-01-01

319

Vaccines for cocaine abuse.  

PubMed

Treatments for cocaine abuse have been disappointingly ineffective, especially in comparison with those for some other abused substances. A new approach, using vaccination to elicit specific antibodies to block the access of cocaine to the brain, has shown considerable promise in animal models, and more recently in human trials. The mechanism of action for the antibody effect on cocaine is very likely to be the straightforward and intuitive result of the binding of the drug in circulation by antibodies, thereby reducing its entry into the central nervous system and thus its pharmacological effects. The effectiveness of such antibodies on drug pharmacodynamics is a function of both the quantitative and the qualitative properties of the antibodies, and this combination will determine the success of the clinical applications of anti-cocaine vaccines in helping addicts discontinue cocaine abuse. This review will discuss these issues and present the current developmental status of cocaine conjugate vaccines. PMID:19276665

Orson, Frank M; Kinsey, Berma M; Singh, Rana A K; Wu, Yan; Kosten, Thomas R

2009-04-01

320

Vaccines for Cocaine Abuse  

PubMed Central

Treatments for cocaine abuse have been disappointingly ineffective, especially in comparison with those for some other abused substances. A new approach, using vaccination to elicit specific antibodies to block the access of cocaine to the brain, has shown considerable promise in animal models, and more recently in human trials. The mechanism of action for the antibody effect on cocaine is very likely to be the straightforward and intuitive result of the binding of the drug in circulation by antibodies, thereby reducing its entry into the central nervous system and thus its pharmacological effects. The effectiveness of such antibodies on drug pharmacodynamics is a function of both the quantitative and the qualitative properties of the antibodies, and this combination will determine the success of the clinical applications of anti-cocaine vaccines in helping addicts discontinue cocaine abuse. This review will discuss these issues and present the current developmental status of cocaine conjugate vaccines. PMID:19276665

Orson, Frank M.; Kinsey, Berma M.; Singh, Rana A. K.; Wu, Yan; Kosten, Thomas R.

2010-01-01

321

[Economical effect of vaccine].  

PubMed

In Japan, some vaccines are provided partially or only at citizens' own expense, while France and Germany publicly cover immunization on the basis of findings in economical effect on VPD (vaccine preventable disease). Such study recently conducted in Japan by the government was reported. According to cost comparative analysis, pneumococcal conjugate vaccine (PCV) for both children and adults, mumps, and varicella were found to have certain economical effect, while cervical cancer, hepatitis B, and Hib virus were not. Cost effectiveness analysis found PCV for adults, pertussis, mumps, and cervical cancer to have favorable effect, while not for Hib and PCV for children. These results offer some perspective, but cautious interpretation may be necessary since premises differ among analyses. PMID:21922773

Kawabuchi, Koichi

2011-09-01

322

Transcutaneous Immunization Studies in Mice Using Diphtheria Toxoid-Loaded Vesicle Formulations and a Microneedle Array  

Microsoft Academic Search

Purpose  To determine the immunogenicity of diphtheria toxoid (DT) formulated in two types of vesicles following transcutaneous immunization\\u000a (TCI) of mice onto microneedle array-treated skin.\\u000a \\u000a \\u000a \\u000a \\u000a Methods  DT-containing cationic liposomes or anionic surfactant-based vesicles were prepared by extrusion and sonication. The physicochemical\\u000a properties were characterized in terms of size, ?-potential, vesicle elasticity and antigen association. TCI was performed\\u000a by applying formulations onto intact

Zhi Ding; Suzanne M. Bal; Stefan Romeijn; Gideon F. A. Kersten; Wim Jiskoot; Joke A. Bouwstra

2011-01-01

323

Leptospirosis vaccines  

PubMed Central

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

Wang, Zhijun; Jin, Li; Wegrzyn, Alicja

2007-01-01

324

Vaccine Shortages  

MedlinePLUS

... produce the vaccine fast enough to meet the demand. The company decides to stop making the vaccine ... will last and what to do until new supplies arrive. Typically, the vaccine supply is not completely ...

325

HPV vaccine  

MedlinePLUS

Vaccine - HPV; Immunization - HPV; Gardasil; Cervarix; HPV2; HPV4; Vaccine to prevent cervical cancer ... of Obstetricians and Gynecologists. Committee Opinion No. 588: Human Papillomavirus Vaccination. Obstet Gynecol . 2014;123:712-8. American ...

326

A vaccine conjugate of 'ISCAR' immunocarrier and peptide epitopes of the E7 cervical cancer-associated protein of human papillomavirus type 16 elicits specific Th1- and Th2-type responses in immunized mice in the absence of oil-based adjuvants.  

PubMed Central

TraT protein, known as ISCAR (= Immunostimulatory Carrier), is one of a family of integral membrane proteins (Imps) of Escherichia coli representing powerful carrier molecules which when injected into experimental animals generate substantial antibody and T proliferative responses to molecules conjugated to it. We extend these findings to show that ISCAR functions to stimulate Th1- and Th2-type responses, including specific cytotoxic T cells and tumour protection. We report here that by conjugating to ISCAR a 19mer peptide containing linear B epitopes, a T helper (Th) epitope, and a H-2b-restricted T cytotoxic (CTL) epitope of E7 protein of human papillomavirus type 16 (HPV16), and immunizing C57B1/6 (H-2b) mice, we elicited (i) specific IgG2a and IgG1 antibodies; (ii) IL-2 and IL-4 production by specifically recalled lymph node cells in vitro; (iii) cytotoxic T lymphocytes which specifically killed both E7 peptide-pulsed, and whole E7 gene-transfected tumour target cells; and (iv) in vivo protection against an E7 gene-transfected tumour cell inoculum. These findings have implications for the design of vaccines to stimulate immune responses to endogenously processed target antigens (e.g. tumour-associated antigens) without the unwanted side effects of oil-based adjuvants. In addition they support the case for a E7-targeted therapeutic vaccine for HPV-associated human cervical cancer. PMID:7544248

Tindle, R W; Croft, S; Herd, K; Malcolm, K; Geczy, A F; Stewart, T; Fernando, G J

1995-01-01

327

Footrot vaccines and vaccination.  

PubMed

Research on footrot in small ruminants, which is caused by Dichelobacter nodosus, has led to development of vaccines and their application for control, treatment and eradication of the disease in sheep. Footrot vaccines have evolved over decades to contain monovalent whole cell, multivalent recombinant fimbrial, and finally mono or bivalent recombinant fimbrial antigens. Initially whole cell vaccines made against the few known serogroups of D. nodosus were found to be inefficient in control of the disease in the field, which was attributed to the presence of other unidentified serogroups and also the use of inefficient adjuvants. Fimbriae or pili, which are the basis for antigenic variation, were found to be the major protective and also curative antigens but they are not cross protective between the different serogroups. Multivalent vaccines incorporating all the known serogroups have been proven to be of limited efficacy due to the phenomenon of antigenic competition. Recent studies in Nepal, Bhutan and Australia have shown that outbreak-specific vaccination which involves targeting identified serogroups with mono- or bivalent recombinant fimbrial vaccines, can be very effective in sheep and goats. Where multiple serogroups are present in a flock, antigenic competition can be overcome by sequentially targeting the serogroups with different bivalent vaccines every 3 months. A common antigen which would confer immunity to all serogroups would be the ideal immunogen but the initial studies were not successful in this area. Until universal antigen/s are available, flock specific mono or bivalent fimbrial vaccines are likely to be the most effective tool for control and eradication of footrot in sheep and goats. Future research in footrot vaccines should be focused on improving the duration of prophylaxis by incorporating new and emerging immunomodulators or adjuvants with modified delivery vehicles, discovering a common antigen and understanding the mechanisms of acquired immunity. PMID:24736003

Dhungyel, Om; Hunter, James; Whittington, Richard

2014-05-30

328

Enhanced mucosal immune responses against tetanus toxoid using novel delivery system comprised of chitosan-functionalized gold nanoparticles and botanical adjuvant: characterization, immunogenicity, and stability assessment.  

PubMed

Approaches based on combined use of delivery systems and adjuvants are being favored to maximize efficient mucosal delivery of antigens. Here, we describe a novel delivery system comprised of chitosan-functionalized gold nanoparticles (CsAuNPs) and saponin-containing botanical adjuvant; Asparagus racemosus extract (ARE) for oral delivery of tetanus toxoid (TT). A significant increase in TT-specific IgG (34.53-fold) and IgA (43.75-fold) was observed when TT-CsAuNPs were formulated with ARE (TT-ARE-CsAuNPs). The local IgA immune responses for TT also showed a significant increase (106.5-fold in intestine washes and 99.74-fold in feces) with ARE-based formulations as compared with plain TT group. No effect of ARE was observed on size, charge, and loading properties of CsAuNPs. Additionally, no effect of ARE and CsAuNPs was observed on antigenicity and secondary structure of TT as determined by fluorescence, circular dichroism, and Fourier transform infrared spectroscopy. The stability studies demonstrated excellent stability profile of formulation at recommended storage conditions. The study establishes the possible role of immunomodulatory adjuvants in particulate delivery systems for mucosal delivery of vaccines. © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 103:3448-3456, 2014. PMID:25219511

Barhate, Ganesh; Gautam, Manish; Gairola, Sunil; Jadhav, Suresh; Pokharkar, Varsha

2014-11-01

329

Chickenpox vaccine  

MedlinePLUS

Immunization - chickenpox; Vaccine - VAR;Immunization - VAR; Varicella zoster vaccine ... for Disease Control and Prevention. Advisory Committee on Immunization Practices (ACIP) Recommended Immunization Schedules for Persons Aged ...

330

Neonatal BCG vaccination is associated with enhanced T-helper 1 immune responses to heterologous infant vaccines  

PubMed Central

Neonatal Bacille Calmette Guérin (BCG) vaccination has been reported to have beneficial effects beyond preventing infantile tuberculous meningitis and miliary disease. We hypothesized that BCG vaccine given at birth would enhance T-helper 1 (Th1) immune responses to the first vaccines given later in infancy. We conducted a nested case-control study of neonatal BCG vaccination and its heterologous Th1 immune effects in 2–3 months old infants. BCG vaccination at birth was associated with an increased frequency of interferon-? (IFN-?) producing spot-forming cells (SFC) to tetanus toxoid 2–3 months later. The frequency of IFN-? producing SFC to polioviruses 1–3 also trended higher among infants who received BCG vaccination at birth. The frequency of IFN-?+/tumor necrosis factor-? (TNF-?)+CD45RO+CD4+ T-cells upon stimulation with phorbol myristate acetate (PMA)/Ionomycin was higher in 2–3 months old infants who received BCG vaccination at birth compared to those who did not. The circulating frequency of forkhead box P3 (FoxP3)+ CD45RO+ regulatory CD4+ T-cells also trended lower in these infants. Neonatal BCG vaccination is associated with heterologous Th1 immune effects 2–3 months later. PMID:24611083

Libraty, Daniel H.; Zhang, Lei; Woda, Marcia; Acosta, Luz P.; Obcena, AnaMae; Brion, Job D.; Capeding, Rosario Z.

2014-01-01

331

VACCINE INFORMATION STATEMENT Hepatitis B Vaccine  

E-print Network

VACCINE INFORMATION STATEMENT Hepatitis B Vaccine What You Need to Know ManyVaccine; - beingstuckwithausedneedle. 2 Hepatitis B vaccine: Why get vaccinated? Hepatitis hepatitis B vaccine and when? Children and Adolescents · Babiesnormallyget3dosesofhepatitisBvaccine: 1st

Tennessee, University of

332

Identification of human antibody fragment clones specific for tetanus toxoid in a bacteriophage. lambda. immunoexpression library  

SciTech Connect

The authors have applied a molecular biology approach to the identification of human monoclonal antibodies. Human peripheral blood lymphocyte mRNA was converted to cDNA and a select subset was amplified by the polymerase chain reaction. These products, containing coding sequences for numerous immunoglobulin heavy- and {kappa} light-chain variable and constant region domains, were inserted into modified bacteriophase {lambda} expression vectors and introduced into Escherichia coli by infection to yield a combinatorial immunoexpression library. Clones with binding activity to tetanus toxoid were identified by filter hybridization with radiolabeled antigen and appeared at a frequency of 0.2{percent} in the library. These human antigen binding fragments, consisting of a heavy-chain fragment covalently linked to a light chain, displayed high affinity of binding to tetanus toxoid with equilibrium constants in the nanomolar range but did not cross-react with other proteins tested. They estimate that this human immunoexpression library contains 20,000 clones with high affinity and specificity to our chosen antigen.

Mullinax, R.L.; Gross, E.A.; Amberg, J.R.; Hogrefe, H.H.; Kubitz, M.M.; Greener, A.; Alting-Mees, M.; Ardourel, D.; Short, J.M.; Sorge, J.A. (Stratagene, La Jolla, CA (USA)); Hay, B.N.; Shopes, B. (Stratacyte, La Jolla, CA (USA))

1990-10-01

333

Development of Streptococcus pneumoniae Vaccines Using Live Vectors  

PubMed Central

Streptococcus pneumoniae still causes severe morbidity and mortality worldwide, especially in young children and the elderly. Much effort has been dedicated to developing protein-based universal vaccines to conquer the current shortcomings of capsular vaccines and capsular conjugate vaccines, such as serotype replacement, limited coverage and high costs. A recombinant live vector vaccine delivering protective antigens is a promising way to achieve this goal. In this review, we discuss the researches using live recombinant vaccines, mainly live attenuated Salmonella and lactic acid bacteria, to deliver pneumococcal antigens. We also discuss both the limitations and the future of these vaccines. PMID:25309747

Wang, Shifeng; Curtiss, Roy

2014-01-01

334

Evaluation of synergistic effect of biodegradable polymeric nanoparticles and aluminum based adjuvant for improving vaccine efficacy.  

PubMed

Aluminum based adjuvants have been used widely to induce long lasting protective immunity through vaccination. But reported incidences of toxicity and side effects of aluminum have raised concerns regarding their safety in childhood vaccines. The present study demonstrates the synergistic effect of admixture of polylactic acid-polyethylene glycol (PLA-PEG) based biodegradable nanoparticles (NPs) and aluminum phosphate as a potential adjuvant system using tetanus toxoid (TT) as a model antigen. The immunological activity of the admixture formulation was maintained up to 180 days of storage at 5 °C±3 °C. Percent adsorption/encapsulation of tetanus toxoid increased to nearly 90% in admixture formulation as compared to 55% in conventional vaccine. Admixture preparation (PLA-PEG-Al 0.2 mg-TT and PLA-Al 0.2 mg-TT) showed 80% and 50% survival respectively, even at 180 days as compared to 30% survival observed in the conventional tetanus vaccine. The present study established the feasibility to formulate a dosage form with improved efficacy and reduced aluminum concentration for vaccination. PMID:24939616

Bansal, Vivek; Kumar, Manoj; Dalela, Manu; Brahmne, H G; Singh, Harpal

2014-08-25

335

Medical Management of Acute Radiation Syndromes : Immunoprophylaxis by Antiradiation Vaccine  

NASA Astrophysics Data System (ADS)

Introduction: Traditionally, the treatment of Acute Radiation Syndrome (ARS) includes supportive therapy, cytokine therapy, blood component transfusions and even stem cell transplantation. Recommendations for ARS treatment are based on clinical symptoms, laboratory results, radiation exposure doses and information received from medical examinations. However, the current medical management of ARS does not include immune prophylaxis based on antiradiation vaccines or immune therapy with hyperimmune antiradiation serum. Immuneprophylaxis of ARS could result from stimulating the immune system via immunization with small doses of radiation toxins (Specific Radiation Determinants-SRD) that possess significant immuno-stimulatory properties. Methods: Principles of immuno-toxicology were used to derive this method of immune prophylaxis. An antiradiation vaccine containing a mixture of Hematotoxic, Neurotoxic and Non-bacterial (GI) radiation toxins, underwent modification into a toxoid forms of the original SRD radiation toxins. The vaccine was administered to animals at different times prior to irradiation. The animals were subjected to lethal doses of radiation that induced different forms of ARS at LD 100/30. Survival rates and clinical symptoms were observed in both control and vaccine-treated animals. Results: Vaccination with non-toxic doses of Radiation toxoids induced immunity from the elaborated Specific Radiation Determinant (SRD) toxins. Neutralization of radiation toxins by specific antiradiation antibodies resulted in significantly improved clinical symptoms in the severe forms of ARS and observed survival rates of 60-80% in animals subjected to lethal doses of radiation expected to induce different forms of ARS at LD 100/30. The most effective vaccination schedule for the antiradiation vaccine consisted of repeated injections 24 and 34 days before irradiation. The vaccine remained effective for the next two years, although the specific immune memory probably persists for a much longer time period. Conclusion: The medical management of ARS by the application of an ARS-specific antiradiation vaccine resulted in significant increases of post-radiation survival rates, even in the absence of traditional ARS therapeutic treatments. The decreased mortality and improved clinical symptoms observed in animals treated with the antiradiation vaccine may lessen the burden of medical therapy and pharmaceuticals required for treatment. However, we hypothesize that a combination of the traditional treatment methods and specific immune prophylaxis by an antiradiation vaccine will potentially be even more effective than either alone.

Popov, Dmitri; Maliev, Vecheslav; Jones, Jeffrey; Casey, Rachael; Kedar, Prasad

336

Pneumococcal proteins that may constitute the next generation vaccine for pneumococcal disease  

Microsoft Academic Search

Cross-reactive “common” pneumococcal antigens offer an attractive alternative, or complement, to polysaccharides and polysaccharide-protein conjugate vaccines. These common antigens should be protective against strains of a wider range of capsular types than can be achieved with conjugate vaccines. Common protein antigens would be expected to be highly immunogenic in young children and should be able to be manufactured relatively inexpensively

David E. Briles; Susan K. Hollingshead; Marilyn J. Crain; Bing Ren; Shaper Mirza; James Watt; Jason Johnston

2003-01-01

337

Anthrax capsule vaccine protects against experimental infection.  

PubMed

Efficacy of a poly-gamma-D-glutamic acid anthrax capsule vaccine was assessed in a mouse model of infection. Capsule by itself was protective against lethal challenge with a toxin(-), capsule(+) Bacillus anthracis strain. Conjugation of capsule to bovine serum albumin resulted in enhanced IgG anti-capsule antibodies measured by ELISA, but completely abrogated the protection. The protective unconjugated capsule vaccine elicited significantly higher IgM titers and opsonic activity than did the non-protective capsule conjugate. When tested against a fully virulent toxin(+), capsule(+) B. anthracis strain, neither capsule nor protective antigen alone was protective. However, the combination of the two protected against a lethal challenge. These results suggest that capsule may enhance the protection afforded by protective antigen vaccines against anthrax if opsonizing antibodies are produced. Surprisingly, some protection was also observed when protective antigen was conjugated to itself. PMID:15519706

Chabot, Donald J; Scorpio, Angelo; Tobery, Steven A; Little, Stephen F; Norris, Sarah L; Friedlander, Arthur M

2004-11-15

338

Metal-leachate-induced conjugate protein instability.  

PubMed

During the scale-up of an ultrafiltration/diafiltration (UF/DF) step for a protein-based conjugate vaccine, significant precipitation was observed at room temperature. It was found that a specific type of metal hosebarb fitting used in the UF/DF system, when placed in the conjugate solution, caused the precipitation. Inductively Coupled Plasma Mass Spectrometry analysis showed significant amounts of Ni(II), Zn(II), and Cu(II) present in the conjugate solution. A kinetic study showed that the concentration of these metal ions gradually increased with increasing incubation time with a corresponding decrease in conjugate concentration. Direct spiking of trace amounts of NiCl?, ZnCl?, and CuCl? into the conjugate solution also caused precipitation, and spiking studies showed that the metal ions caused precipitation of the conjugate but not of the carrier protein, antigen, or carrier protein + linker. The precipitation was found to be significantly dependent on buffer species but not solution pH and led to an irreversible loss of tertiary structure even after dissolution in and removal of guanidine hydrochloride. The precipitation is likely the result of formation of transition-metal complexes with histidine residues on the antigen peptide, which may involve both intraconjugate and interconjugate antigens. Such complexation may lead to formation of multimers that may exceed the solubility limit. PMID:22644953

Li, Ning; Osborne, Brandi; Singh, Satish K; Wang, Wei

2012-08-01

339

Gold nanorod vaccine for respiratory syncytial virus  

PubMed Central

Respiratory syncytial virus (RSV) is a major cause of pneumonia and wheezing in infants and the elderly, but to date there is no licensed vaccine. We developed a gold nanorod construct that displayed the major protective antigen of the virus, the fusion protein (F). Nanorods conjugated to RSV F were formulated as a candidate vaccine preparation by covalent attachment of viral protein using a layer-by-layer approach. In vitro studies using ELISA, confocal microscopy and circular dichroism revealed that conformation-dependent epitopes were maintained during conjugation, and transmission electron microscopy studies showed that a dispersed population of particles could be achieved. Human dendritic cells treated with the vaccine-induced immune responses in primary human T cells. These results suggest that this vaccine approach may be a potent method for immunizing against viruses such as RSV with surface glycoproteins that are targets for the human immune response. PMID:23799651

Stone, John W.; Thornburg, Natalie J.; Blum, David L.; Kuhn, Sam J.; Wright, David W.; Crowe, James E.

2013-01-01

340

Gold nanorod vaccine for respiratory syncytial virus  

NASA Astrophysics Data System (ADS)

Respiratory syncytial virus (RSV) is a major cause of pneumonia and wheezing in infants and the elderly, but to date there is no licensed vaccine. We developed a gold nanorod construct that displayed the major protective antigen of the virus, the fusion protein (F). Nanorods conjugated to RSV F were formulated as a candidate vaccine preparation by covalent attachment of viral protein using a layer-by-layer approach. In vitro studies using ELISA, electron microscopy and circular dichroism revealed that conformation-dependent epitopes were maintained during conjugation, and transmission electron microscopy studies showed that a dispersed population of particles could be achieved. Human dendritic cells treated with the vaccine induced immune responses in primary human T cells. These results suggest that this vaccine approach may be a potent method for immunizing against viruses such as RSV with surface glycoproteins that are targets for the human immune response.

Stone, John W.; Thornburg, Natalie J.; Blum, David L.; Kuhn, Sam J.; Wright, David W.; Crowe, James E., Jr.

2013-07-01

341

O:2-CRM(197) conjugates against Salmonella Paratyphi A.  

PubMed

Enteric fevers remain a common and serious disease, affecting mainly children and adolescents in developing countries. Salmonella enterica serovar Typhi was believed to cause most enteric fever episodes, but several recent reports have shown an increasing incidence of S. Paratyphi A, encouraging the development of a bivalent vaccine to protect against both serovars, especially considering that at present there is no vaccine against S. Paratyphi A. The O-specific polysaccharide (O:2) of S. Paratyphi A is a protective antigen and clinical data have previously demonstrated the potential of using O:2 conjugate vaccines. Here we describe a new conjugation chemistry to link O:2 and the carrier protein CRM(197), using the terminus 3-deoxy-D-manno-octulosonic acid (KDO), thus leaving the O:2 chain unmodified. The new conjugates were tested in mice and compared with other O:2-antigen conjugates, synthesized adopting previously described methods that use CRM(197) as carrier protein. The newly developed conjugation chemistry yielded immunogenic conjugates with strong serum bactericidal activity against S. Paratyphi A. PMID:23144798

Micoli, Francesca; Rondini, Simona; Gavini, Massimiliano; Lanzilao, Luisa; Medaglini, Donata; Saul, Allan; Martin, Laura B

2012-01-01

342

Polio Vaccination  

MedlinePLUS

... the benefits of OPV use (i.e. intestinal immunity, secondary spread) outweighed the risk for vaccine-associated ... to its advantages over IPV in providing intestinal immunity and providing secondary spread of the vaccine to ...

343

Meningococcal Vaccines  

MedlinePLUS

... common after MCV4 than after MPSV4.A small percentage of people who receive the vaccine develop a ... Vaccine Information Statement. U.S. Department of Health and Human Services/Centers for Disease Control and Prevention National ...

344

[Cholera update and vaccination problems].  

PubMed

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. PMID:9812307

Fournier, J M; Villeneuve, S

1998-01-01

345

Tetanus vaccine may be laced with anti-fertility drug. International / developing countries.  

PubMed

A priest, president of Human Life International (HLI) based in Maryland, has asked Congress to investigate reports of women in some developing countries unknowingly receiving a tetanus vaccine laced with the anti-fertility drug human chorionic gonadotropin (hCG). If it is true, he wants Congress to publicly condemn the mass vaccinations and to cut off funding to UN agencies and other involved organizations. The natural hormone hCG is needed to maintain pregnancy. The hormone would produce antibodies against hCG to prevent pregnancy. In the fall of 1994, the Pro Life Committee of Mexico was suspicious of the protocols for the tetanus toxoid campaign because they excluded all males and children and called for multiple injections of the vaccine in only women of reproductive age. Yet, one injection provides protection for at least 10 years. The Committee had vials of the tetanus vaccine analyzed for hCG. It informed HLI about the tetanus toxoid vaccine. HLI then told its World Council members and HLI affiliates in more than 60 countries. Similar tetanus vaccines laced with hCG have been uncovered in the Philippines and in Nicaragua. In addition to the World Health Organization (WHO), other organizations involved in the development of an anti-fertility vaccine using hCG include the UN Population Fund, the UN Development Programme, the World Bank, the Population Council, the Rockefeller Foundation, the US National Institute of Child Health and Human Development, the All India Institute of Medical Sciences, and Uppsala, Helsinki, and Ohio State universities. The priest objects that, if indeed the purpose of the mass vaccinations is to prevent pregnancies, women are uninformed, unsuspecting, and unconsenting victims. PMID:12346214

346

Adjuvanticity of pGPL-Mc and LRS in the immune responses of monkeys to oral immunization with diphtheria and tetanus toxoids  

Microsoft Academic Search

Experiments were carried out to examine the adjuvanticity of polar glycopeptidolipids of Mycobacterium chelonae (pGPL-Mc) or the London rocket seed (LRS) when combined with diphtheria and tetanus toxoids in an oral immunization of the African green monkey. The results showed that none of the monkeys receiving diphtheria and tetanus toxoids combined with 25 mg\\/kg of pGPL-Mc showed an increase in

Hossein Mirchamsy; Tsehay Neway; Mohammad Hamedi; Charles Pilet

1997-01-01

347

Smallpox Vaccine  

MedlinePLUS

... outbreak of the disease. In most cases, the vaccine causes mild side effects, such as soreness around the vaccination site, fever, ... very small percentage of people will suffer serious side effects and may even die. Thus the vaccine is only necessary when there has been an ...

348

Vaccination Mathematics  

E-print Network

Vaccination Strategies for Epidemic Models Douglas B. Meade Department of Mathematics University://www.math.sc.edu/~meade/ 27 May 1999 #12; May 1999 IMA Mathematical Biology Seminar 0 Vaccination Strategies for Epidemic and natural death -- no death from infection -- no vaccination Ref: Shulgin, Stone, and Agur, Bull Math Bio

Meade, Douglas B.

349

Safety and immunogenicity of fully liquid DTaP?-IPV-Hib pediatric combination vaccine (Pediacel®) compared to DTaP?-HBV-IPV/Hib (Infanrix® Hexa) when coadministered with heptavalent pneumococcal conjugate vaccine (PCV7) as a booster at 11-18 months of age: a phase III, modified double-blind, randomized, controlled, multicenter study.  

PubMed

This study compared the safety and immunogenicity of DTaP?-IPV-Hib vaccine (followed by monovalent hepatitis B vaccine [HBV]) and DTaP?-HBV-IPV/Hib vaccines, both coadministered with PCV7, as a fourth-dose booster in toddlers 11-18 months who had a hexavalent vaccine primary series. The fever rate within 4 days of DTaP?-IPV-Hib was noninferior to DTaP?-HBV-IPV/Hib. DTaP?-IPV-Hib induced a marked immune response and had a similar safety and immunogenicity profile compared with DTaP?-HBV-IPV/Hib. Fully liquid DTaP?-IPV-Hib can be used as a booster after a hexavalent vaccine primary series; where required, a fourth dose of monovalent HBV can be administered after DTaP?-IPV-Hib (NCT ID: NCT00355654). PMID:22691430

Berner, Reinhard; Boisnard, Florence; Thomas, Stéphane; Mwawasi, Grace; Reynolds, Donna

2012-07-27

350

Carbohydrate-based vaccines with a glycolipid adjuvant for breast cancer  

PubMed Central

Globo H (GH) is a hexasaccharide specifically overexpressed on a variety of cancer cells and therefore, a good candidate for cancer vaccine development. To identify the optimal carrier and adjuvant combination, we chemically synthesized and linked GH to a carrier protein, including keyhole limpet hemocyanion, diphtheria toxoid cross-reactive material (CRM) 197 (DT), tetanus toxoid, and BSA, and combined with an adjuvant, and it was administered to mice for the study of immune response. Glycan microarray analysis of the antiserum obtained indicated that the combination of GH-DT adjuvanted with the ?-galactosylceramide C34 has the highest enhancement of anti-GH IgG. Compared with the phase III clinical trial vaccine, GH–keyhole limpet hemocyanion/QS21, the GH-DT/C34 vaccine elicited more IgG antibodies, which are more selective for GH and the GH-related epitopes, stage-specific embryonic antigen 3 (SSEA3) and SSEA4, all of which were specifically overexpressed on breast cancer cells and breast cancer stem cells with SSEA4 at the highest level (>90%). We, therefore, further developed SSEA4-DT/C34 as a vaccine candidate, and after immunization, it was found that the elicited antibodies are also IgG-dominant and very specific for SSEA4. PMID:23355685

Huang, Yen-Lin; Hung, Jung-Tung; Cheung, Sarah K. C.; Lee, Hsin-Yu; Chu, Kuo-Ching; Li, Shiou-Ting; Lin, Yu-Chen; Ren, Chien-Tai; Cheng, Ting-Jen R.; Hsu, Tsui-Ling; Yu, Alice L.; Wu, Chung-Yi; Wong, Chi-Huey

2013-01-01

351

Population genomics of post-vaccine changes in pneumococcal epidemiology  

PubMed Central

Whole genome sequencing of 616 asymptomatically carried pneumococci was used to study the impact of the 7-valent pneumococcal conjugate vaccine. Comparison of closely related isolates revealed the role of transformation in facilitating capsule switching to non-vaccine serotypes and the emergence of drug resistance. However, such recombination was found to occur at significantly different rates across the species, and the evolution of the population was primarily driven by changes in the frequency of distinct genotypes extant pre-vaccine. These alterations resulted in little overall effect on accessory genome composition at the population level, contrasting with the fall in pneumococcal disease rates after the vaccine’s introduction. PMID:23644493

Croucher, Nicholas J.; Finkelstein, Jonathan A.; Pelton, Stephen I.; Mitchell, Patrick K.; Lee, Grace M.; Parkhill, Julian; Bentley, Stephen D.; Hanage, William P.; Lipsitch, Marc

2013-01-01

352

DNA conjugation andDNA conjugation and reversibility onreversibility on  

E-print Network

DNA conjugation andDNA conjugation and reversibility onreversibility on chitosan surfaceschitosan surfaceschitosan surfaceschitosan surfaces Rubloff Research Group Accomplishments #12;DNA conjugation and reversibility onDNA conjugation and reversibility on chitosan surfaceschitosan surfaces Accomplishment Single

Rubloff, Gary W.

353

Mucosal and systemic antibody responses against an acellular pertussis vaccine in mice after intranasal co-administration with recombinant cholera toxin B subunit as an adjuvant  

Microsoft Academic Search

To investigate the possibility of intranasal immunization with an acellular pertussis vaccine, groups of mice were administered intranasally with aluminium-non-adsorbed pertussis toxoid (PTd; 0.5 or 5?g) and formalin-treated filamentous hemagglutinin (fFHA; 5?g) with and without recombinant cholera toxin B subunit (rCTB; 10?g) as a mucosal adjuvant. At a low concentration of PTd, the following things became clear: (1) earlier and

Masanori Isaka; Yoko Yasuda; Tooru Taniguchi; Satoshi Kozuka; Keiko Matano; Jun-ichi Maeyama; Kazunori Morokuma; Kunio Ohkuma; Norihisa Goto; Kunio Tochikubo

2003-01-01

354

VACCINE INFORMATION STATEMENT Hepatitis A Vaccine  

E-print Network

VACCINE INFORMATION STATEMENT Hepatitis A Vaccine What You Need to Know Many Vaccine Information 1,000 cases). Hepatitis A vaccine can prevent hepatitis A. 2 Who should get hepatitis A vaccine and when? WHO? Some people should be routinely vaccinated with hepatitis A vaccine: · All children between

Leistikow, Bruce N.

355

Therapeutic HIV Vaccines What is a vaccine?  

E-print Network

Therapeutic HIV Vaccines What is a vaccine? A vaccine is a medical product designed to stimulate there are currently no vaccines to prevent or treat HIV, researchers are developing and testing potential HIV vaccines. HIV vaccines designed to prevent HIV infection in HIV negative people are called preventive vaccines

Levin, Judith G.

356

VACCINE INFORMATION STATEMENT Influenza Vaccine  

E-print Network

. The viruses in the vaccine have been weakened so they can't make you sick. A different vaccine, the "flu shot disease that year. While flu vaccine cannot prevent all cases of flu, it is our best defense against are not feeling well. They might suggest waiting. But you should come back. #12;· You should get the flu shot

Oklahoma, University of

357

DNA vaccines  

NASA Astrophysics Data System (ADS)

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.

Gregersen, Jens-Peter

2001-12-01

358

Clostridium difficile Recombinant Toxin A Repeating Units as a Carrier Protein for Conjugate Vaccines: Studies of Pneumococcal Type 14, Escherichia coli K1, and Shigella flexneri Type 2a Polysaccharides in Mice  

Microsoft Academic Search

Unlike the native protein, a nontoxic peptide (repeating unit of the native toxin designated rARU) from Clostridium difficile toxin A (CDTA) afforded an antigen that could be bound covalently to the surface polysac- charides of pneumococcus type 14, Shigella flexneri type 2a, and Escherichia coli K1. The yields of these poly- saccharide-protein conjugates were significantly increased by prior treatment of

DANKA PAVLIAKOVA; J. SCOTT MONCRIEF; DAVID M. LYERLY; GERALD SCHIFFMAN; DOLORES A. BRYLA; JOHN B. ROBBINS; RACHEL SCHNEERSON

2000-01-01

359

Vaccination of travelers: how far have we come and where are we going?  

PubMed

Vaccine recommendations are a prominent part of health preparations before international travel. We review progress made in the past decade regarding vaccines used primarily by persons traveling from high-income countries to low- and middle-income countries. The combined hepatitis A-B vaccine, the recently licensed Vero cell-derived Japanese encephalitis vaccine and conjugated quadrivalent meningococcal vaccines are discussed. This article provides updates on yellow fever vaccine-associated visceral and neurologic adverse events, indications for influenza vaccine in travelers, the rapid immunization schedule for tick-borne encephalitis vaccine, schedules for postexposure rabies prophylaxis, and new insights about oral cholera vaccines following the outbreak in Haiti. The future should bring vaccines for serogroup B Neiserria meningitidis, dengue and malaria, as well as an inactivated yellow fever vaccine. PMID:22043959

Chen, Lin H; Hill, David R; Wilder-Smith, Annelies

2011-11-01

360

Panel 6: Vaccines  

PubMed Central

Objective To update progress on the effectiveness of vaccine for prevention of acute otitis media (AOM) and identification of promising candidate antigens against Streptococcus pneumoniae, nontypeable Haemophilus influenzae, and Moraxella catarrhalis. Review Methods Literature searches were performed in OvidSP and PubMed restricted to articles published between June 2007 and September 2011. Search terms included otitis media, vaccines, vaccine antigens, and each of the otitis pathogens and candidate antigens identified in the ninth conference report. Conclusions The current report provides further evidence for the effectiveness of pneumococcal conjugate vaccines (PCVs) in the prevention of otitis media. Observational studies demonstrate a greater decline in AOM episodes than reported in clinical efficacy trials. Unmet challenges include extending protection to additional serotypes and additional pathogens, the need to prevent early episodes, the development of correlates of protection for protein antigens, and the need to define where an otitis media vaccine strategy fits with priorities for child health. Implications for Practice Acute otitis media continues to be a burden on children and families, especially those who suffer from frequent recurrences. The 7-valent PCV (PCV7) has reduced the burden of disease as well as shifted the pneumococcal serotypes and the distribution of otopathogens currently reported in children with AOM. Antibiotic resistance remains an ongoing challenge. Multiple candidate antigens have demonstrated the necessary requirements of conservation, surface exposure, immunogenicity, and protection in animal models. Further research on the role of each antigen in pathogenesis, in the development of correlates of protection in animal models, and in new adjuvants to elicit responses in the youngest infants is likely to be productive and permit more antigens to move into human clinical trials. PMID:23536534

Pelton, Stephen I.; Pettigrew, Melinda M.; Barenkamp, Stephen J.; Godfroid, Fabrice; Grijalva, Carlos G.; Leach, Amanda; Patel, Janak; Murphy, Timothy F.; Selak, Sanja; Bakaletz, Lauren O.

2014-01-01