Immunogenicity of, and Immunologic Memory to, a Reduced Primary Schedule of Meningococcal C-Tetanus Toxoid Conjugate Vaccine in Infants in the United Kingdom

ABSTRACT It has been previously shown that one of the three meningococcal C conjugate (MCC) vaccines introduced in the United Kingdom proved highly immunogenic after the first dose of a three-dose schedule, with evidence of immune memory after dose 3. Thus, in infants a one- or two-dose schedule of this MCC vaccine, conjugated to tetanus toxoid (TT), may suffice. Healthy infants (n = 586) were randomized to receive either one (group 1), two (group 2), or three (group 3) doses of MCC-TT vaccine with a 10-μg polysaccharide booster given at 13 to 14 months of age. Serum bactericidal antibody (SBA) levels were measured by utilizing rabbit complement (rSBA), meningococcal C-specific immunoglobulin G (IgG), and avidity indices (AIs). For groups 1, 2, and 3, the percentages of infants with an rSBA level of ≥8 against strain C11 were 98.4, 100, and 99.4%, respectively. Infants in group 1 with prevaccination rSBA titers of ≥8 had post-primary MCC rSBA geometric mean titers (GMTs) significantly lower than those infants with prevaccination rSBA titers of <8. One dose of MCC-TT vaccine given to infants at 2 months of age yielded significantly lower SBA GMTs and geometric mean AIs (GMAIs) than two or three doses but elicited a significantly greater response after boosting, as reflected by rSBA levels and GMAI. This study provides the first evidence that the number of doses of MCC-TT used in infant immunization schedules could be decreased.

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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

Clinical and Vaccine Immunology ◽

10.1128/cvi.00420-08 ◽

2008 ◽

Vol 16 (2) ◽

pp. 194-199 ◽

Cited By ~ 52

Author(s):

Jo Southern ◽

Ray Borrow ◽

Nick Andrews ◽

Rhonwen Morris ◽

Pauline Waight ◽

...

Keyword(s):

Single Dose ◽

Conjugate Vaccine ◽

Geometric Mean ◽

Tetanus Antitoxin ◽

The United Kingdom ◽

Healthy Infants ◽

Meningococcal Group ◽

Bactericidal Antibody ◽

Polyribosylribitol Phosphate ◽

To Receive

ABSTRACT 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.

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Seroprevalence of Serum Bactericidal Antibodies against Group W135 and Y Meningococci in England in 2009

Clinical and Vaccine Immunology ◽

10.1128/cvi.05515-11 ◽

2011 ◽

Vol 19 (2) ◽

pp. 219-222 ◽

Cited By ~ 18

Author(s):

Caroline L. Trotter ◽

Helen Findlow ◽

Ray Borrow

Keyword(s):

United Kingdom ◽

Geometric Mean ◽

Risk Groups ◽

Natural Immunity ◽

Serum Samples ◽

The United Kingdom ◽

Bactericidal Antibody ◽

Serological Surveillance ◽

Group B ◽

Reference Strains

ABSTRACTSerological surveillance has been used in the United Kingdom to inform vaccine policy for several infections, including those with group C meningococci. Meningococcal conjugate vaccines, containing capsular groups A, W135, and Y in addition to C, are now available, but their use in the United Kingdom is restricted to at-risk groups and travelers to areas of endemicity. The aim of this study was to establish a baseline for natural immunity for groups W135 and Y. Serum samples collected in 2009 from individuals of all ages were obtained from the Health Protection Agency Seroepidemiology Unit, which collects residual sera from participating laboratories across the country. Serum bactericidal antibody (SBA) activity against two reference strains, representing groups Y (strain M03 241125) and W135 (strain M01 240070), was determined with 1,191 sera using a standardized complement-mediated SBA assay, with complement derived from baby rabbits (rSBA). The age-specific geometric mean titers (GMTs) and percentages of individuals with rSBA titers of ≥8 were calculated, together with 95% confidence intervals (CI). Overall, 18.4% and 19.6% had rSBA titers of ≥8 for groups W135 and Y, respectively. Antibody prevalence varied by age. In general, rSBA titers were low for younger children, with serum samples from 7% and 13% of children under 5 years achieving titers of ≥8 against groups W135 and Y, respectively. GMTs peaked for 20- to 24-year-olds for group W135 (GMT, 7.1; 95% CI, 4.7, 10.9) and for 30- to 44-year-olds for group Y (GMT, 8.6; 95% CI, 5.9, 12.7). Unlike seroprevalence against group B meningococci, there was not an obvious peak in SBA titers in samples from teenagers. Natural immunity against group W135 and Y meningococci in England appears to be low.

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Safety and Immunogenicity of PRP-T Combined with DTP: Excretion of Capsular Polysaccharide and Antibody Response in the Immediate Post-Vaccination Period

PEDIATRICS ◽

10.1542/peds.95.4.522 ◽

1995 ◽

Vol 95 (4) ◽

pp. 522-527

Author(s):

Melanie A. Miller ◽

Carlton K. Meschievitz ◽

Gerard A. Ballanco ◽

Robert S. Daum

Keyword(s):

Tetanus Toxoid ◽

Capsular Polysaccharide ◽

Oral Polio Vaccine ◽

Haemophilus Influenzae Type ◽

Type B ◽

Polio Vaccine ◽

Group 3 ◽

Group 2 ◽

Change In Mean ◽

Group 1

Objective. To evaluate whether combining Haemophilus influenzae type b capsular polysaccharide covalently linked to tetanus toxoid (PRP-T) and diphtheria-tetanus-pertussis (DTP) in one syringe produced a vaccine that was safe and immunogenic. Design. Randomized clinical trial. Setting. Suburban New Orleans pediatric population. Participants. Convenience sample of 150 healthy infants. Methods. Enrollees were randomized to receive DTP and PRP-T in one injection (Group 1), DTP and PRP-T separately (Group 2), or DTP and H influenzae type b capsular saccharide coupled to a nontoxic variant of diphtheria toxin, CRM197, (HbOC) separately (Group 3) at 2, 4, and 6 months of age. All infants received oral polio vaccine at 2 and 4 months of age. Parents were instructed to record side effects on a standardized form after each vaccine administration. Blood was drawn before each immunization and at 7 months of age; an additional blood and a urine specimen was obtained 2 to 3 days after one of the vaccination visits. Serum was assayed for H influenzae anticapsular antibody (anti-PRP), anti-pertussis toxoid, anti-fimbrial hemagglutinins, anti-diphtheria and anti-tetanus toxoid antibodies, and antibody to polio viruses. Urine was assayed for H influenzae type b capsular polysaccharide. Results. The rate of occurrence of fever did not differ significantly between groups. Local swelling and erythema occurred more often at the administration site in Group 1 infants than at the DTP administration sites of infants in Groups 2 and 3 after the first and second vaccinations. The mean concentration of all antibodies we assayed did not differ significantly when Group 1 and 2 infants were compared. HbOC recipients (Group 3) had lower mean anti-H influenzae anticapsular antibody and higher mean anti-diphtheria and anti-tetanus antibody concentrations after two and three doses compared with Group 1 and Group 2 infants. No group had a significant change in mean anti-PRP antibody concentration 2 to 3 days after vaccination with any dose. After vaccination, antigenuria occurred less frequently in Group 1 infants (54%, 78%, and 72% in Groups 1, 2, and 3, respectively, P < .01). Conclusions. Combining PRP-T and DTP produced a combination vaccine associated with a slight increase in the rate of erythema and swelling but with similar immunogenicity of the vaccine components and oral polio vaccine.

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Randomized, Controlled Trial of a 13-Valent Pneumococcal Conjugate Vaccine Administered Concomitantly with an Influenza Vaccine in Healthy Adults

Clinical and Vaccine Immunology ◽

10.1128/cvi.00176-12 ◽

2012 ◽

Vol 19 (8) ◽

pp. 1296-1303 ◽

Cited By ~ 39

Author(s):

Robert W. Frenck ◽

Alejandra Gurtman ◽

John Rubino ◽

William Smith ◽

Martin van Cleeff ◽

...

Keyword(s):

Influenza Vaccine ◽

Conjugate Vaccine ◽

Pneumococcal Conjugate Vaccine ◽

Controlled Trial ◽

Geometric Mean ◽

Enzyme Linked Immunosorbent Assay ◽

Serious Adverse Events ◽

Double Blind ◽

Group 2 ◽

Group 1

ABSTRACTA randomized, double-blind, phase 3 trial evaluated the immunogenicity, safety, and tolerability of a 13-valent pneumococcal conjugate vaccine (PCV13) coadministered with trivalent inactivated influenza vaccine (TIV) in pneumococcal vaccine-naive adults. Participants ages 50 to 59 years (n= 1,116) received TIV with PCV13 (group 1) or placebo (group 2) (1:1 randomization); 1 month later, group 1 received placebo and group 2 received PCV13. A hemagglutination inhibition (HAI) assay for TIV and a standardized enzyme-linked immunosorbent assay for pneumococcal serotype-specific immunoglobulin G (IgG) were performed and opsonophagocytic activity (OPA) titers (assessedpost hoc) were measured at baseline and 1 and 2 months postvaccination. The rises in HAI assay geometric mean titer (GMT) and percentage of participants in groups 1 and 2 with ≥4-fold increases in HAI responses (A/H1N1, 84.0% and 81.2%, respectively; A/H3N2, 71.1% and 69.5%, respectively; and B, 60.6% and 60.3%, respectively) were similar. In group 1, all serotypes met the predefined IgG geometric mean concentration (GMC) ratio noninferiority criterion relative to group 2, but GMCs were lower in group 1 than group 2. When comparing group 1 with group 2, 5 serotypes did not meet the OPA GMT ratio noninferiority criterion, and OPA GMTs were significantly lower for 10 serotypes. PCV13 injection site reactions were similar and mostly mild in both groups. Systemic events were more frequent in group 1 (86.2%) than group 2 (76.7%;P< 0.001); no vaccine-related serious adverse events occurred. Coadministration of PCV13 and TIV was well tolerated but associated with lower PCV13 antibody responses and is of unknown clinical significance. Given the positive immunologic attributes of PCV13, concomitant administration with TIV should be dictated by clinical circumstances.

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Serological Basis for Use of Meningococcal Serogroup C Conjugate Vaccines in the United Kingdom: Reevaluation of Correlates of Protection

Infection and Immunity ◽

10.1128/iai.69.3.1568-1573.2001 ◽

2001 ◽

Vol 69 (3) ◽

pp. 1568-1573 ◽

Cited By ~ 234

Author(s):

Ray Borrow ◽

Nick Andrews ◽

David Goldblatt ◽

Elizabeth Miller

Keyword(s):

United Kingdom ◽

Geometric Mean ◽

Avidity Index ◽

Conjugate Vaccines ◽

Correlates Of Protection ◽

The United Kingdom ◽

Serum Bactericidal Assay ◽

Natural Protection ◽

Rabbit Complement ◽

Avidity Maturation

ABSTRACT The antibody data supporting the use of meningococcal serogroup C conjugate (MCC) vaccines in the United Kingdom were generated by serum bactericidal assay (SBA) using rabbit complement (rSBA). This may give higher titers than those obtained with human complement (hSBA), for which the “gold standard” correlate of protection for meningococcal C disease is a titer of ≥4. Comparison of rSBA and hSBA titers in sera from unvaccinated adults with an rSBA titer of ≥8 showed that for 93% (27 of 29) the titer was ≥4 by hSBA, confirming natural protection. Furthermore, sera from MCC vaccinees showed that an rSBA titer of <8 or ≥128 discriminated susceptibility and protection well (85% with rSBA titers of <8 had hSBA titers of <4, and 99% with rSBA titers of ≥128 had hSBA titers of ≥4). However, discrimination was poor in the rSBA titer range 8 to 64, with only 60% having hSBA titers of ≥4. In such cases we propose that protection can be assumed if there is a fourfold rise in titer between pre- and postvaccination sera or if there is a characteristic booster response to a polysaccharide challenge dose with, if available, evidence of antibody avidity maturation or an hSBA titer of result ≥4. Applying these criteria to toddlers, 10 to 40% of whom had titers in the range 8 to 64 after a single dose of MCC vaccine, showed that 94% had a fourfold rise in titer, including 98% of those in the titer range 8 to 64. In addition, of those with titers of <128 post-MCC vaccination, 90% had titers of ≥128 after a 10-μg polysaccharide booster dose, compared with only 7% of unprimed age-matched toddlers given a full 50-μg dose. Furthermore, the increase in geometric mean avidity index pre- and postbooster was independent of post-primary MCC titer. These results indicated that the majority of toddlers with an rSBA titer between 8 and 64, and some of those with an hSBA result of <4, have mounted a protective immune response with the induction of immunological memory.

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Pharmacokinetics and Tolerability of Oseltamivir Combined with Probenecid

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.00047-08 ◽

2008 ◽

Vol 52 (9) ◽

pp. 3013-3021 ◽

Cited By ~ 39

Author(s):

Mark Holodniy ◽

Scott R. Penzak ◽

Timothy M. Straight ◽

Richard T. Davey ◽

Kelvin K. Lee ◽

...

Keyword(s):

Geometric Mean ◽

Pharmacokinetic Analysis ◽

Pharmacokinetic Data ◽

Oseltamivir Carboxylate ◽

Versus Group ◽

Group 3 ◽

The Mean ◽

Group 2 ◽

Mean Concentration ◽

Group 1

ABSTRACT Oseltamivir is an inhibitor of influenza virus neuraminidase, which is approved for use for the treatment and prophylaxis of influenza A and B virus infections. In the event of an influenza pandemic, oseltamivir supplies may be limited; thus, alternative dosing strategies for oseltamivir prophylaxis should be explored. Healthy volunteers were randomized to a three-arm, open-label study and given 75 mg oral oseltamivir every 24 h (group 1), 75 mg oseltamivir every 48 h (q48h) combined with 500 mg probenecid four times a day (group 2), or 75 mg oseltamivir q48h combined with 500 mg probenecid twice a day (group 3) for 15 days. Pharmacokinetic data, obtained by noncompartmental methods, and safety data are reported. Forty-eight subjects completed the pharmacokinetic analysis. The study drugs were generally well tolerated, except for one case of reversible grade 4 thrombocytopenia in a subject in group 2. The calculated 90% confidence intervals (CIs) for the geometric mean ratios between groups 2 and 3 and group 1 were outside the bioequivalence criteria boundary (0.80 to 1.25) at 0.63 to 0.89 for group 2 versus group 1 and 0.57 to 0.90 for group 3 versus group 1. The steady-state apparent oral clearance of oseltamivir carboxylate was significantly less in groups 2 (7.4 liters/h; 90% CI, 6.08 to 8.71) and 3 (7.19 liters/h; 90% CI, 6.41 to 7.98) than in group 1 (9.75 liters/h; 90% CI, 6.91 to 12.60) (P < 0.05 for both comparisons by analysis of variance). The (arithmetic) mean concentration at 48 h for group 2 was not significantly different from the mean concentration at 24 h for group 1 (42 ± 76 and 81 ± 54 ng/ml, respectively; P = 0.194), but the mean concentration at 48 h for group 3 was significantly less than the mean concentration at 24 h for group 1 (23 ± 26 and 81 ± 54 ng/ml, respectively; P = 0.012). Alternate-day dosing of oseltamivir plus dosing with probenecid four times daily achieved trough oseltamivir carboxylate concentrations adequate for neuraminidase inhibition in vitro, and this combination should be studied further.

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To study the effectiveness of cord blood Albumin as a predictor of neonatal jaundice

International Journal of Contemporary Pediatrics ◽

10.18203/2349-3291.ijcp20170724 ◽

2017 ◽

Vol 4 (2) ◽

pp. 645

Author(s):

Nithu A. George ◽

Shyam Sudhir M. K.

Keyword(s):

Cord Blood ◽

Neonatal Jaundice ◽

Mode Of Delivery ◽

The Body ◽

Neonatal Hyperbilirubinemia ◽

Healthy Infants ◽

Group 3 ◽

Blood Albumin ◽

Group 2 ◽

Group 1

Background: Neonatal hyperbilirubinemia is one of the commonest problems in newborn. It can be due to different etiologies. Most often it is physiological jaundice. The main reasons for physiological jaundice is that in an infant the liver is not mature enough to handle the freely circulating bilirubin due to higher volume of short life erythrocytes in the circulation and low level of albumin. Early detection of neonatal jaundice is essential to prevent developing kernicterus as well as discharge the babies early. Albumin is synthesized by liver and helps in the transport of unconjugated bilirubin by binding to bilirubin it and thus making it nontoxic to the body. Low levels of albumin make bilirubin free and toxic to the body. Hence, this study was done to evaluate effectiveness of cord blood albumin as a predictor of neonatal Hyperbilirubinemia.Methods: 50 term healthy newborns were included in the study with the term babies of both genders from any mode of delivery, birth weight >2.5 kg, APGAR score more than 7 at 1st and 5th minutes of life and without Rh incapability. Cord blood albumin levels were measured. Blood test for bilirubin was done when required and baby was managed accordingly.Results: Out of the total 50 neonates enrolled, 7 belonged to group 1 (albumin <2.8 g/dl), 34 to group 2 (2.8-3.3 g/dl), and 9 to group 3 (>3.3 g/dl). Out of the total 7 neonates in group 1, 6 (85.71%) was icteric at 24-48 hours and 1 (14.29%) was icteric at >72 hours. All the 7 neonates developed Hyperbilirubinemia requiring phototherapy. 3 (42.86%) out the 7-neonate required phototherapy for more than 24 hours. Out of the total 34 neonates in group 2, 20 (58.82%) was icteric at >72 hours, 12 (35.29%) at 48-72 hours and 2 (5.88%) at 24-48 hours. Only 12 (35.29%) neonates had Hyperbilirubinemia requiring phototherapy. Out of the total 9 neonates in group 3, 1 was icteric at 48 - 72 hours and 8 was icteric at >72 hours. But only 2 had Hyperbilirubinemia requiring phototherapy.Conclusions: Cord blood albumin is an effective way to predict neonatal Hyperbilirubinemia in term healthy infants.

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The Disposition of Cefazolin and Tobramycin following Intraperitoneal Administration in Patients on Continuous Ambulatory Peritoneal Dialysis

Peritoneal Dialysis International ◽

10.1177/089686088300300207 ◽

1983 ◽

Vol 3 (2) ◽

pp. 73-76 ◽

Cited By ~ 13

Author(s):

Thomas W. Paton ◽

Arifie Manuel ◽

Lawrence B. Cohen ◽

Scott E. Walker

Keyword(s):

Steady State ◽

Intraperitoneal Administration ◽

Dose Schedule ◽

Loading Dose ◽

Bacterial Peritonitis ◽

Maintenance Schedule ◽

Group I ◽

Steady State Levels ◽

Group 2 ◽

Group 1

Two groups of patients with bacterial peritonitis were studied to examine the pharmacokinetics of intraperitoneal tobramycin and cefazolin. In Group I, four patients received tobramycin (5 mg/l) and cefazolin (75 mg/1) in two litres of dialysate for 12 consecutive exchanges. In Group 2, five patients received a loading dose of tobramycin (50 mg/1) and cefazolin (500 mg/l) intraperitoneally in exchange one. In exchanges three through 12, the maintenance schedule was tobramycin (7.5 mg/1) and cefazolin (250 mg/l). Tobramycin was measured by EMIT and cefazolin (in Group 2 only) by HPLC. Serum and dialysate levels were determined at the end of each of 12 exchanges. In Group 1, steady -state tobramycin levels appeared in 48 hours in both serum and dialysate to levels of 2.1 ± 0.2 μg/ml (x ± SEM) and 2.5 ± 0.3 μg/ml respectively. In Group 2, the loading dose schedule provided levels in serum at the end of the first dwell for tobramycin of 4.3 ± 0.64 μg/ml and for cefazolin 54.8 ± 6.7 μg/ml. Steady state levels for tobramycin and cefazolin were 3.7 ± 0.15 μg/ml and 110.9 ± 8 μg/ml respectively. Concomitant dialysate levels for tobramycin were 3.9 ± 0.17 μg/ml and for cefazolin 80.6 ± 26 μg/ml.

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FOLFIRNOX for advanced pancreatic cancer (aPDAC) according to schedule and dose modifications: Clinical feasibility and impact of supportive care.

Journal of Clinical Oncology ◽

10.1200/jco.2015.33.3_suppl.372 ◽

2015 ◽

Vol 33 (3_suppl) ◽

pp. 372-372

Author(s):

Vanja Vaccaro ◽

Isabella Sperduti ◽

Davide Melisi ◽

Emilio Bria ◽

Enrico Vasile ◽

...

Keyword(s):

Advanced Pancreatic Cancer ◽

Dose Schedule ◽

Outpatient Basis ◽

Biliary Stents ◽

Complete Control ◽

Group 2 ◽

Dose Modifications ◽

The Impact ◽

Dose Reductions ◽

Group 1

372 Background: Although FOLFIRINOX is considered one of the standards for aPDAC, concerns emerged with regard to the safety profile in clinical practice. Thus, we investigated the impact of dose/schedule modifications and additional supportive measures. Methods: The clinical charts of 292 aPDAC patients (pts) receiving classic (group 1) or modified (m)FOLFIRINOX (group 2) were retrieved at 8 Institutions. Results: Table summarizes pts’ characteristics;82/709 and 188/1127 pts/cycles were analyzed for groups 1 and 2, respectively. Overall toxicity was mild; significant differences in G2-4 toxicities between the two groups: asthenia (12.5% vs 6%, p<0.0001), anemia (6.1% vs 3.1%, p=0. 003), diarrhea (6.5% vs 4%, p=0.02), and thrombocytopenia (5.4% vs 0.5%, p<0.0001), favouring group 2, and neutropenia (4.7% vs 12.3%, p<0.0001), favouring group 1. G-CSF was used more frequently in group 1 (80% vs 36%, p<0.0001). Dose delays were comparable between the two groups; dose reductions were more common in group 2 (39% vs 28%, p<0.00001). No differences in the complete control of nausea/vomiting at cycle 1 (no N/V) with or without aprepitant were observed (50% vs 45%, respectively). The presence of a biliary stent did not appear to significantly worsen toxicity. Overall ORR and disease control rate (DCR: PR+SD) were 40% and 62%, respectively, without significant differences between the two groups. Median PFS was 7 mos for both groups. Median OS, however, was significantly longer in group 2 (12 vs 18 mos, respectively; p=0.01). Conclusions: Both schedulesare easily manageable and well tolerated and may be safely administered on an outpatient basis in pts carrying biliary stents as well. The minimal differences in toxicity and efficacy obtained with mFolfirinox require additional investigation. [Table: see text]

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