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

2011 ◽  
Vol 18 (5) ◽  
pp. 878-884 ◽  
Author(s):  
Timo Vesikari ◽  
Aino Karvonen ◽  
Ray Borrow ◽  
Nick Kitchin ◽  
Martine Baudin ◽  
...  
Keyword(s):  
Conjugate Vaccine ◽  
Geometric Mean ◽  
Fold Increase ◽  
Concomitant Administration ◽  
Rotavirus Vaccine ◽  
Open Label ◽  
Seroprotection Rate ◽  
Content Type ◽  
Healthy Infants ◽  
Sequential Administration

ABSTRACTRotaTeq (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, andHaemophilus influenzaetype 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.

Persistence of pneumococcal antibodies after primary immunisation with a polysaccharide–protein conjugate vaccine

2019 ◽  
Vol 104 (7) ◽  
pp. 680-684
Author(s):  
Petra Zimmermann ◽  
Kirsten P Perrett ◽  
Guy Berbers ◽  
Nigel Curtis
Keyword(s):  
Conjugate Vaccine ◽  
Pneumococcal Disease ◽  
Geometric Mean ◽  
Antibody Concentration ◽  
Protective Effects ◽  
Seroprotection Rate ◽  
Correlate Of Protection ◽  
Antibody Persistence ◽  
Protein Conjugate ◽  
Healthy Infants

IntroductionDespite immunisation, antibiotics and intensive care management, infection with Streptococcus pneumoniae remains a major cause of morbidity and mortality in children. The WHO currently recommends vaccinating infants with either a 3+0 schedule (6 weeks, 3–4 and 4–6 months of age) or 2+1 schedule (2 doses before 6 months of age, plus a booster dose at 9–15 months of age). This study investigated pneumococcal antibody responses, including persistence of antibodies, after immunisation of healthy infants with a 3+0 schedule.MethodsWe measured pneumococcal antibody concentrations to all 13 antigens included in the 13-valent pneumococcal conjugate vaccine (PCV13) after immunisation with a 3+0 schedule in 91 infants at 7 months and in 311 infants at 13 months of age. The geometric mean concentrations (GMCs) and the proportion of infants with an antibody concentration above the standard threshold correlate of protection (seroprotection rate) were calculated at both time points.ResultsAt 7 months of age, GMCs varied between 0.52 µg/mLand 11.52 µg/mL, and seroprotection rates varied between 69% and 100%. At 13 months of age, GMCs had decreased to between 0.22 µg/mLand 3.09 µg/mL, with the lowest responses against serotype 4, followed by 19A, 3, 6B and 23F. Seroprotection rates at 13 months of age were below 90% for most serotypes, with the lowest rates for serotype 4 (23%) followed by 19A (50%), 23F (61%) and 6B (64%).ConclusionOur study shows that at 13 months of age, many infants vaccinated with a 3+0 schedule have pneumococcal antibody concentrations below the standard threshold correlate of protection. To optimise protection against pneumococcal disease through early childhood and to improve antibody persistence and indirect protective effects, immunisation schedules with booster doses might be necessary.

scholarly journals Pharmacokinetic Interactions between Primaquine and Chloroquine

2014 ◽  
Vol 58 (6) ◽  
pp. 3354-3359 ◽  
Author(s):  
Sasithon Pukrittayakamee ◽  
Joel Tarning ◽  
Podjanee Jittamala ◽  
Prakaykaew Charunwatthana ◽  
Saranath Lawpoolsri ◽  
...  
Keyword(s):  
Oral Dose ◽  
Hospital Admissions ◽  
Geometric Mean ◽  
Pharmacokinetic Interaction ◽  
Plasmodium Ovale ◽  
Open Label ◽  
Content Type ◽  
Reference Number ◽  
Electrocardiographic Changes ◽  
To Receive

ABSTRACTChloroquine combined with primaquine has been the standard radical curative regimen forPlasmodium vivaxandPlasmodium ovalemalaria for over half a century. In an open-label crossover pharmacokinetic study, 16 healthy volunteers (4 males and 12 females) aged 20 to 47 years were randomized into two groups of three sequential hospital admissions to receive a single oral dose of 30 mg (base) primaquine, 600 mg (base) chloroquine, and the two drugs together. The coadministration of the two drugs did not affect chloroquine or desethylchloroquine pharmacokinetics but increased plasma primaquine concentrations significantly (P≤ 0.005); the geometric mean (90% confidence interval [CI]) increases were 63% (47 to 81%) in maximum concentration and 24% (13 to 35%) in total exposure. There were also corresponding increases in plasma carboxyprimaquine concentrations (P≤ 0.020). There were no significant electrocardiographic changes following primaquine administration, but there was slight corrected QT (QTc) (Fridericia) interval lengthening following chloroquine administration (median [range] = 6.32 [−1.45 to 12.3] ms;P< 0.001), which was not affected by the addition of primaquine (5.58 [1.74 to 11.4] ms;P= 0.642). This pharmacokinetic interaction may explain previous observations of synergy in preventingP. vivaxrelapse. This trial was registered at ClinicalTrials.gov under reference number NCT01218932.

scholarly journals Open-Label Crossover Study of Primaquine and Dihydroartemisinin-Piperaquine Pharmacokinetics in Healthy Adult Thai Subjects

2014 ◽  
Vol 58 (12) ◽  
pp. 7340-7346 ◽  
Author(s):  
Borimas Hanboonkunupakarn ◽  
Elizabeth A. Ashley ◽  
Podjanee Jittamala ◽  
Joel Tarning ◽  
Sasithon Pukrittayakamee ◽  
...  
Keyword(s):  
Crossover Study ◽  
Hospital Admissions ◽  
Geometric Mean ◽  
Radical Cure ◽  
Open Label ◽  
Time Curve ◽  
Content Type ◽  
Concentration Time ◽  
Pharmacokinetic Assessment ◽  
Adult Volunteers

ABSTRACTDihydroartemisinin-piperaquine is an artemisinin-based combination treatment (ACT) recommended by the WHO for uncomplicatedPlasmodium falciparummalaria, and it is being used increasingly for resistant vivax malaria where combination with primaquine is required for radical cure. The WHO recently reinforced its recommendations to add a single dose of primaquine to ACTs to reduceP. falciparumtransmission in low-transmission settings. The pharmacokinetics of primaquine and dihydroartemisinin-piperaquine were evaluated in 16 healthy Thai adult volunteers in a randomized crossover study. Volunteers were randomized to two groups of three sequential hospital admissions to receive 30 mg (base) primaquine, 3 tablets of dihydroartemisinin-piperaquine (120/960 mg), and the drugs together at the same doses. Blood sampling was performed over 3 days following primaquine and 36 days following dihydroartemisinin-piperaquine dosing. Pharmacokinetic assessment was done with a noncompartmental approach. The drugs were well tolerated. There were no statistically significant differences in dihydroartemisinin and piperaquine pharmacokinetics with or without primaquine. Dihydroartemisinin-piperaquine coadministration significantly increased plasma primaquine levels; geometric mean ratios (90% confidence interval [CI]) of primaquine combined versus primaquine alone for maximum concentration (Cmax), area under the concentration-time curve from 0 h to the end of the study (AUC0–last), and area under the concentration-time curve from 0 h to infinity (AUC0–∞) were 148% (117 to 187%), 129% (103 to 163%), and 128% (102 to 161%), respectively. This interaction is similar to that described recently with chloroquine and may result in an enhanced radical curative effect. (This study has been registered at ClinicalTrials.gov under registration no. NCT01525511.)

scholarly journals 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

2013 ◽  
Vol 20 (10) ◽  
pp. 1647-1653 ◽  
Author(s):  
Timo Vesikari ◽  
Sven Arne Silfverdal ◽  
Florence Boisnard ◽  
Stéphane Thomas ◽  
Grace Mwawasi ◽  
...  
Keyword(s):  
Haemophilus Influenzae ◽  
Tetanus Toxoid ◽  
Geometric Mean ◽  
Vaccination Schedule ◽  
Haemophilus Influenzae Type ◽  
Type B ◽  
Seroprotection Rate ◽  
Post Dose ◽  
Content Type ◽  
Robust Immune Response

ABSTRACTThis study compared the levels of immunogenicity and safety of diphtheria–tetanus toxoid–five-component acellular pertussis (DTaP5), inactivated poliovirus (IPV), andHaemophilus influenzaetype 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.)

scholarly journals Randomized, Placebo-Controlled, Double-Blind Phase 2 Trial Comparing the Reactogenicity and Immunogenicity of a Single Standard Dose to Those of a High Dose of CVD 103-HgR Live Attenuated Oral Cholera Vaccine, with Shanchol Inactivated Oral Vaccine as an Open-Label Immunologic Comparator

2017 ◽  
Vol 24 (12) ◽  
Author(s):  
Samba O. Sow ◽  
Milagritos D. Tapia ◽  
Wilbur H. Chen ◽  
Fadima C. Haidara ◽  
Karen L. Kotloff ◽  
...  
Keyword(s):  
Developing Countries ◽  
Standard Dose ◽  
Oral Vaccine ◽  
Geometric Mean ◽  
High Dose ◽  
Cholera Vaccine ◽  
Open Label ◽  
Double Blind ◽  
Content Type ◽  
Single Standard

ABSTRACTReactive immunization with a single-dose cholera vaccine that could rapidly (within days) protect immunologically naive individuals during virgin soil epidemics, when cholera reaches immunologically naive populations that have not experienced cholera for decades, would facilitate cholera control. One dose of attenuatedVibrio choleraeO1 classical Inaba vaccine CVD 103-HgR (Vaxchora) containing ≥2 × 108CFU induces vibriocidal antibody seroconversion (a correlate of protection) in >90% of U.S. adults. A previous CVD 103-HgR commercial formulation required ≥2 × 109CFU to elicit high levels of seroconversion in populations in developing countries. We compared the vibriocidal responses of Malians (individuals 18 to 45 years old) randomized to ingest a single ≥2 × 108-CFU standard dose (n= 50) or a ≥2 × 109-CFU high dose (n= 50) of PaxVax CVD 103-HgR with buffer or two doses (n= 50) of Shanchol inactivated cholera vaccine (the immunologic comparator). To maintain blinding, participants were dosed twice 2 weeks apart; CVD 103-HgR recipients ingested placebo 2 weeks before or after ingesting vaccine. Seroconversion (a ≥4-fold vibriocidal titer rise) between the baseline and 14 days after CVD 103-HgR ingestion and following the first and second doses of Shanchol were the main outcomes measured. By day 14 postvaccination, the rates of seroconversion after ingestion of a single standard dose and a high dose of CVD 103-HgR were 71.7% (33/46 participants) and 83.3% (40/48 participants), respectively. The rate of seroconversion following the first dose of Shanchol, 56.0% (28/50 participants), was significantly lower than that following the high dose of CVD 103-HgR (P= 0.003). The vibriocidal geometric mean titer (GMT) of the high dose of CVD 103-HgR exceeded the GMT of the standard dose at day 14 (214 versus 95,P= 0.045) and was ∼2-fold higher than the GMT on day 7 and day 14 following the first Shanchol dose (P> 0.05). High-dose CVD 103-HgR is recommended for accelerated evaluation in developing countries to assess its efficacy and practicality in field situations. (This study has been registered at ClinicalTrials.gov under registration no. NCT02145377.)

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

2014 ◽  
Vol 22 (2) ◽  
pp. 185-192 ◽  
Author(s):  
Juan Carlos Tinoco ◽  
Christine Juergens ◽  
Guillermo M. Ruiz Palacios ◽  
Jorge Vazquez-Narvaez ◽  
Hermann Leo Enkerlin-Pauwells ◽  
...  
Keyword(s):  
Immune Responses ◽  
Conjugate Vaccine ◽  
Pneumococcal Conjugate Vaccine ◽  
Geometric Mean ◽  
The United States ◽  
Age Group ◽  
Open Label ◽  
Serious Adverse Events ◽  
Vaccine Type ◽  
Study Population

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

scholarly journals Enterobactin-Specific Antibodies Induced by a Novel Enterobactin Conjugate Vaccine

2019 ◽  
Vol 85 (10) ◽  
Author(s):  
Huiwen Wang ◽  
Ximin Zeng ◽  
Yiming Mo ◽  
Bin He ◽  
Hening Lin ◽  
...  
Keyword(s):  
Conjugate Vaccine ◽  
Iron Acquisition ◽  
Fold Increase ◽  
Immune Intervention ◽  
Gram Negative ◽  
Content Type ◽  
Specific Antibodies ◽  
Specific Igg ◽  
Dependent Growth ◽  
High Level

ABSTRACTEnterobactin (Ent)-mediated high-affinity iron acquisition is critical for Gram-negative bacteria to survive in the host. Given the bacteriostatic effect of lipocalin resulting from its potent Ent-binding ability, immune intervention directly targeting Ent is promising for iron-dependent pathogen control. Recently, an Ent conjugate vaccine was reported, but it still has several significant weaknesses. In this study, we sought to develop an innovative Ent conjugate vaccine that can induce a high level of antibodies directed against Ent and to provide solid evidence demonstrating siderophore-binding capacity of Ent-specific antibodies. Using a simple method, we successfully conjugated purified Ent to different carriers, including keyhole limpet hemocyanin (KLH), bovine serum albumin, and CmeC, a vaccine candidate forCampylobactercontrol. Subcutaneous immunization of rabbits with the KLH-Ent conjugate triggered a strong systemic IgG immune response with an up to 16,384-fold increase in IgG titer directed against whole conjugate and an up to 4,096-fold increase in the level of specific anti-Ent IgG. To evaluate the ability of Ent-specific IgG to bind to the Ent derivatives presentin vivo, various Ent derivatives were chemically synthesized and a unique enzyme-linked immunosorbent assay method was developed. The Ent-specific IgG also displayed exceptional reactivity to ferric Ent, a linear trimer of Ent, and different salmochelins. Growth assays further demonstrated that the Ent-specific antibodies significantly inhibited Ent-dependent growth ofCampylobacterspp. andEscherichia coli. Collectively, this study reports an efficient method to prepare a new type of Ent conjugate vaccines for inducing a high level of Ent-specific antibodies, which can bind to various Ent derivatives and display lipocalin-like bacteriostatic features.IMPORTANCEEnt-mediated high-affinity iron acquisition is a universal and critical contributor for Gram-negative pathogens to survive and infect hosts. Published information has supported an innovative immune intervention strategy that directly targets Ent to starve pathogens by limiting the availability of iron to be utilized. Compared to a recently published Ent conjugate, there are three advantages of the vaccine described in this study: ease of preparation, induction of high titer of anti-Ent IgG, and the ability of Ent-specific antibodies to bind various Ent derivatives, including the salmochelins that help enteric pathogens evade sequestration of siderophores by host lipocalins. In addition, the Ent-specific antibodies were demonstrated to function similarly to lipocalin to interfere with the Ent-dependent growth ofCampylobacterandE. coliunder iron-restricted conditions. This study has significant potential for broader applications to prevent and control various Gram-negative infections in humans and animals.

scholarly journals Comparison of Immunogenicity and Safety between a Single Dose and One Booster Trivalent Inactivated Influenza Vaccination in Patients with Chronic Kidney Disease: A 20-Week, Open-Label Trial

Vaccines ◽  
2021 ◽  
Vol 9 (3) ◽  
pp. 192
Author(s):  
Yu-Tzu Chang ◽  
Tsai-Chieh Ling ◽  
Ya-Yun Cheng ◽  
Chien-Yao Sun ◽  
Jia-Ling Wu ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Influenza Vaccination ◽  
Vaccine Efficacy ◽  
Dose Regimen ◽  
Geometric Mean ◽  
Fold Increase ◽  
Open Label ◽  
Baseline Serum ◽  
The One

Background: Non-dialysis-dependent chronic kidney disease (CKD-ND) patients are recommended to receive a one-dose influenza vaccination annually. However, studies investigating vaccine efficacy in the CKD-ND population are still lacking. In this study, we aimed to evaluate vaccine efficacy between the one-dose and two-dose regimen and among patients with different stages of CKD throughout a 20-week follow-up period. Methods: We conducted a single-center, non-randomized, open-label, controlled trial among patients with all stages of CKD-ND. Subjects were classified as unvaccinated, one-dose, and two-dose groups (4 weeks apart) after enrollment. Serial changes in immunological parameters (0, 4, 8, and 20 weeks after enrollment), including seroprotection, geometric mean titer (GMT), GMT fold-increase, seroconversion, and seroresponse, were applied to evaluate vaccine efficacy. Results: There were 43, 84, and 71 patients in the unvaccinated, one-dose, and two-dose vaccination groups, respectively. At 4–8 weeks after vaccination, seroprotection rates in the one- and two-dose group for H1N1, H3N2, and B ranged from 82.6–95.8%, 97.4–100%, and 73.9–100%, respectively. The concomitant seroconversion and GMT fold-increases nearly met the suggested criteria for vaccine efficacy for the elderly population. Although the seroprotection rates for all of the groups were adequate, the seroconversion and GMT fold-increase at 20 weeks after vaccination did not meet the criteria for vaccine efficacy. The two-dose regimen had a higher probability of achieving seroprotection for B strains (Odds ratio: 3.5, 95% confidence interval (1.30–9.40)). No significant differences in vaccine efficacy were found between early (stage 1–3) and late (stage 4–5) stage CKD. Conclusions: The standard one-dose vaccination can elicit sufficient protective antibodies. The two-dose regimen induced a better immune response when the baseline serum antibody titer was low. Monitoring change in antibody titers for a longer duration is warranted to further determine the current vaccine strategy in CKD-ND population.

Sign in / Sign up

Export Citation Format

Share Document