scholarly journals Three Doses of an Experimental Detoxified L3-Derived Lipooligosaccharide Meningococcal Vaccine Offer Good Safety but Low Immunogenicity in Healthy Young Adults

2010 ◽  
Vol 17 (9) ◽  
pp. 1460-1466 ◽  
Author(s):  
Pablo Bonvehí ◽  
Dominique Boutriau ◽  
Javier Casellas ◽  
Vincent Weynants ◽  
Christiane Feron ◽  
...  
Keyword(s):  
Young Adults ◽  
Adverse Events ◽  
Membrane Vesicle ◽  
Geometric Mean ◽  
Fold Increase ◽  
Wild Type ◽  
Serious Adverse Events ◽  
Level 3 ◽  
To Receive ◽  
Type Strains

ABSTRACT This open, randomized phase I study evaluated the safety and reactogenicity of an experimental meningococcal serogroup B (MenB) vaccine obtained from outer membrane vesicle detoxified L3-derived lipooligosaccharide. Healthy young adults (n = 150) were randomized to receive either experimental vaccine (provided in five formulations, n = 25 in each group) or VA-Mengoc-BC (control, n = 25) administered on a 0- to 6-week/6-month schedule. Serum bactericidal assays performed against three MenB wild-type strains assessed the immune response, defined as a 4-fold increase from pre- to postvaccination. No serious adverse events related to vaccination were reported. Pain at the injection site, fatigue, and headache were the most commonly reported adverse events. Solicited adverse events graded level 3 (i.e., preventing daily activity) were pain (up to 17% of the test subjects versus 32% of the controls), fatigue (up to 12% of the test subjects versus 8% of the controls), and headache (up to 4% of any group). Swelling graded level 3 (greater than 50 mm) occurred in up to 4% of the test subjects versus 8% of the controls. The immune responses ranged from 5% to 36% across experimental vaccines for the L3 H44-76 strain (versus 27% for the control), from 0% to 11% for the L3 NZ98/124 strain (versus 23% for the control), and from 0% to 13% for the L2 760676 strain (versus 59% for the control). All geometric mean titers were below those measured with the control vaccine. The five experimental formulations were safe and well tolerated but tended to be less immunogenic than the control vaccine.

scholarly journals Immunogenicity and Safety after Booster Vaccination of Diphtheria, Tetanus, and Acellular Pertussis in Young Adults: an Open Randomized Controlled Trial in Japan

2013 ◽  
Vol 20 (12) ◽  
pp. 1799-1804 ◽  
Author(s):  
Megumi Hara ◽  
Kenji Okada ◽  
Yuko Yamaguchi ◽  
Shingo Uno ◽  
Yasuko Otsuka ◽  
...  
Keyword(s):  
Young Adults ◽  
Adverse Events ◽  
Pertussis Vaccine ◽  
Controlled Trial ◽  
Geometric Mean ◽  
Booster Vaccination ◽  
Acellular Pertussis Vaccine ◽  
Serious Adverse Events ◽  
Booster Immunization ◽  
Registration Number

ABSTRACTThe recent increase of pertussis in young adults in Japan is hypothesized to be due in part to waning protection from the acellular pertussis vaccine. While a booster immunization may prevent an epidemic of pertussis among these young adults, little is known about the safety and immunogenicity of such a booster with the diphtheria, tetanus, and acellular pertussis vaccine (DTaP), which is currently available in Japan. One hundred and eleven medical students with a mean age of 19.4 years were randomly divided into 2 groups of 55 and 56 subjects and received, respectively, 0.2 or 0.5 ml of DTaP. Immunogenicity was assessed by performing the immunoassay using serum, and the geometric mean concentration (GMC), GMC ratio (GMCR), seropositive rate, and booster response rate were calculated. Adverse reactions and adverse events were monitored for 7 days after vaccination. After booster vaccination in the two groups, significant increases were found in the antibodies against pertussis toxin, filamentous hemagglutinin, diphtheria toxoid, and tetanus toxoid, and the booster response rates for all subjects reached 100%. The GMCs and GMCRs against all antigens were significantly higher in the 0.5-ml group than in the 0.2-ml group. No serious adverse events were observed. Frequencies of local reactions were similar in the 2 groups, although the frequency of severe local swelling was significantly higher in the 0.5-ml group. These data support the acceptability of booster immunization using both 0.2 and 0.5 ml of DTaP for young adults for controlling pertussis. (This study was registered at UMIN-CTR under registration number UMIN000010672.)

scholarly journals A randomized study to evaluate safety and immunogenicity of the BNT162b2 COVID-19 vaccine in healthy Japanese adults

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Miwa Haranaka ◽  
James Baber ◽  
Yoichiro Ogama ◽  
Masako Yamaji ◽  
Masakazu Aizawa ◽  
...  
Keyword(s):  
Adverse Events ◽  
Phase 1 ◽  
Geometric Mean ◽  
Randomized Study ◽  
Age Groups ◽  
Serious Adverse Events ◽  
Robust Immune Response ◽  
Japanese Adults ◽  
To Receive ◽  
Ongoing Phase

AbstractWe report interim safety and immunogenicity findings from an ongoing phase 1/2 study of BNT162b2 in healthy Japanese adults. Participants were randomized 3:1 to receive 2 intramuscular injections of 30 μg BNT162b2 or placebo 21 days apart. Overall, 160 individuals were randomized: 119 received BNT162b2, and 41 received placebo. Participants were stratified by age: 20–64 years (n = 130) and 65–85 years (n = 30). More than 97% of BNT162b2 recipients received 2 doses. Local reactions and systemic events were generally transient and mild to moderate. Severe adverse events were uncommon; there were no serious adverse events. One month after dose 2, SARS-CoV-2 50% serum neutralizing geometric mean titers were 571 and 366, and geometric mean fold rises were 55.8 and 36.6, in the younger and older age groups, respectively. In summary, BNT162b2 has an acceptable safety profile and produces a robust immune response, regardless of age, in Japanese adults. (ClinicalTrials.gov, NCT04588480).

Adverse events and blinding in two randomized trials of hyperbaric oxygen for persistent post-concussive symptoms

2019 ◽  
pp. 331-340
Author(s):  
Susan Churchill ◽  
◽  
Kayla Deru ◽  
Lindell K. Weaver ◽  
Steffanie H. Wilson ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Adverse Events ◽  
Hyperbaric Oxygen ◽  
Gas Flow ◽  
Randomized Trials ◽  
Symptom Improvement ◽  
Sham Control ◽  
Serious Adverse Events ◽  
Double Blind ◽  
To Receive

Safety monitoring and successful blinding are important features of randomized, blinded clinical trials. We report chamber- and protocol-related adverse events (AEs) for participants enrolled in two randomized, double-blind clinical trials of hyperbaric oxygen (HBO2) for persistent post-concussive symptoms clinicaltrials.gov identifiers NCT01306968, HOPPS, and NCT01611194, BIMA), as well as the success of maintaining the blind with a low-pressure sham control arm. In both studies, participants were randomized to receive HBO2 (1.5 atmospheres absolute, >99% oxygen) or sham chamber sessions (1.2 atmospheres absolute, room air). In 143 participants undergoing 4,245 chamber sessions, chamber-related adverse events were rare (1.1% in the HOPPS study, 2.2% in the BIMA study). Minor, non-limiting barotrauma was the most frequently reported. Rarely, some participants experienced headache with chamber sessions. No serious adverse events were associated with chamber sessions. An allocation questionnaire completed after intervention revealed that the sham control arm adequately protected the blind in both trials. Participants based allocation assumptions on symptom improvement or lack of symptom improvement and could not discern intervention arm by pressure, smell, taste, or gas flow.

scholarly journals Mycobacterium tuberculosis Dihydrofolate Reductase Is Not a Target Relevant to the Antitubercular Activity of Isoniazid

2010 ◽  
Vol 54 (9) ◽  
pp. 3776-3782 ◽  
Author(s):  
Feng Wang ◽  
Paras Jain ◽  
Gulcin Gulten ◽  
Zhen Liu ◽  
Yicheng Feng ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Dihydrofolate Reductase ◽  
Fold Increase ◽  
Antitubercular Activity ◽  
Experimental Sample ◽  
Wild Type ◽  
Negative Results ◽  
Sequencing Studies ◽  
Type Strains

ABSTRACT Mycobacterium tuberculosis enoyl-acyl-ACP reductase (InhA) has been demonstrated to be the primary target of isoniazid (INH). Recently, it was postulated that M. tuberculosis dihydrofolate reductase (DHFR) is also a target of INH, based on the findings that a 4R-INH-NADP adduct synthesized from INH by a nonenzymatic approach showed strong inhibition of DHFR in vitro, and overexpression of M. tuberculosis dfrA in M. smegmatis conferred a 2-fold increase of resistance to INH. In the present study, a plasmid expressing M. tuberculosis dfrA was transformed into M. smegmatis and M. tuberculosis strains, respectively. The transformant strains were tested for their resistance to INH. Compared to the wild-type strains, overexpression of dfrA in M. smegmatis and M. tuberculosis did not confer any resistance to INH based on the MIC values. Similar negative results were obtained with 14 other overexpressed proteins that have been proposed to bind some form of INH-NAD(P) adduct. An Escherichia coli cell-based system was designed that allowed coexpression of both M. tuberculosis katG and dfrA genes in the presence of INH. The DHFR protein isolated from the experimental sample was not found bound with any INH-NADP adduct by enzyme inhibition assay and mass spectroscopic analysis. We also used whole-genome sequencing to determine whether polymorphisms in dfrA could be detected in six INH-resistant clinical isolates known to lack mutations in inhA and katG, but no such mutations were found. The dfrA overexpression experiments, together with the biochemical and sequencing studies, conclusively demonstrate that DHFR is not a target relevant to the antitubercular activity of INH.

scholarly journals Safety and Immunogenicity of SARS-CoV-2 S-2P Protein Vaccine MVC-COV1901 in People Living with HIV

2021 ◽  
Author(s):  
Shu-Hsing Cheng ◽  
Chia En Lien ◽  
Szu-Min Hsieh ◽  
Chien-Yu Cheng ◽  
Wang-Da Liu ◽  
...  
Keyword(s):  
Geometric Mean ◽  
People Living With Hiv ◽  
Protein Vaccine ◽  
Wild Type ◽  
Control Groups ◽  
Hiv Viral Load ◽  
Serious Adverse Events ◽  
Living With Hiv ◽  
And Control ◽  
Hiv Negative

Objectives To provide data on the immune response to COVID-19 vaccines in people living with HIV (PWH), MVC-COV1901, a recombinant protein vaccine containing S-2P protein adjuvanted with CpG 1018 and aluminium hydroxide, was assessed. Methods A total of 57 PWH of ≥ 20 years of age who are on stable antiretroviral therapy and with CD4+ T cell ≥ 350 cells/mm3 and HIV viral load < 103 copies/ml were compared with 882 HIV-negative participants. Participants received 2 doses of MVC-COV1901 28 days apart. Safety and the immunogenicity were evaluated. Results No vaccine-related serious adverse events (SAEs) were recorded. Seroconversion rates (SCRs) of 100% and 99.8% were achieved in people living with HIV (PWH) and comparators, respectively, 28 days after second dose. The geometric mean titers (GMTs) (95% confidence interval [CI]) against wild type SARS-CoV-2 virus were 136.62 IU/mL (WHO Standardized International Unit) (95% CI 114.3-163.3) and 440.41 IU/mL (95% CI 421.3-460.4), for PWH and control groups, respectively, after adjusting for sex, age, BMI category, and comorbidity, and the adjusted GMT ratio of comparator/PWH was 3.22 (95% CI 2.6-4.1). A higher CD4/CD8 ratio was associated with a higher GMT (R=0.27, p=0.039). Conclusions MVC-COV1901 has shown robust safety but weaker immunogenicity responses in PWH. As a result, a third dose or booster doses of MVC-COV1901 may be appropriate for PWH.

scholarly journals Immunogenicity and safety of a tetravalent dengue vaccine in dengue-naïve adolescents in Mexico City

2021 ◽  
Vol 45 ◽  
pp. 1
Author(s):  
Shibadas Biswal ◽  
Jorge Fernando Mendez Galvan ◽  
Mercedes Macias Parra ◽  
Juan-Francisco Galan-Herrera ◽  
Monica Belisa Carrascal Rodriguez ◽  
...  
Keyword(s):  
Adverse Events ◽  
Injection Site ◽  
Mexico City ◽  
Neutralizing Antibodies ◽  
Geometric Mean ◽  
Dengue Vaccine ◽  
Microneutralization Assay ◽  
To Receive

Objective. To describe the immunogenicity and safety of a tetravalent dengue vaccine (TAK-003) in healthy adolescents living in Mexico City, an area considered non-endemic for dengue (NCT03341637). Methods. Participants aged 12–17 years were randomized 3:1 to receive two doses (Month 0 and Month 3) of TAK-003 or placebo. Immunogenicity was assessed by microneutralization assay of dengue neutralizing antibodies at baseline, Months 4 and 9. Solicited and unsolicited adverse events (AEs) were recorded after each vaccination. Serious (SAEs) and medically-attended AEs (MAAEs) were recorded throughout the study. Results. 400 adolescents were enrolled, 391 (97.8%) completed the study. Thirty-six (9%) were baseline seropositive to ≥1 serotypes (reciprocal titer ≥10). Geometric mean titers (GMTs) in baseline seronegative TAK-003 recipients were 328, 1743, 120, and 143 at Month 4, and 135, 741, 46, and 38 at Month 9 against DENV-1, -2, -3, and -4, respectively. Placebo GMTs remained <10. Tetravalent seropositivity rates in vaccine recipients were 99.6% and 85.8% at Months 4 and 9, respectively. One MAAE in each group was considered treatment-related (TAK-003: injection-site erythema, and placebo: pharyngitis). Conclusion. TAK-003 was immunogenic against all four serotypes and was well tolerated in dengue-naïve adolescents living in Mexico City.

Phase 1 Safety and Immunogenicity Study of a Respiratory Syncytial Virus Vaccine With an Adenovirus 26 Vector Encoding Prefusion F (Ad26.RSV.preF) in Adults Aged ≥60 Years

2020 ◽  
Vol 222 (6) ◽  
pp. 979-988 ◽  
Author(s):  
Kristi Williams ◽  
Arangassery Rosemary Bastian ◽  
Robert Allen Feldman ◽  
Edmund Omoruyi ◽  
Els de Paepe ◽  
...  
Keyword(s):  
Older Adults ◽  
Respiratory Syncytial Virus ◽  
Adverse Events ◽  
Immune Responses ◽  
Phase 1 ◽  
Geometric Mean ◽  
High Dose ◽  
Serious Adverse Events ◽  
Syncytial Virus ◽  
Vector Particles

Abstract Background Despite the high disease burden of respiratory syncytial virus (RSV) in older adults, there is no approved vaccine. We evaluated the experimental RSV vaccine, Ad26.RSV.preF, a replication-incompetent adenovirus 26 vector encoding the F protein stabilized in prefusion conformation. Methods This phase 1 clinical trial was performed in healthy adults aged ≥60 years. Seventy-two participants received 1 or 2 intramuscular injections of low-dose (LD; 5 × 1010 vector particles) or high-dose (HD; 1 × 1011 vector particles) Ad26.RSV.preF vaccine or placebo, with approximately 12 months between doses and 2-year follow-up for safety and immunogenicity outcomes. Results Solicited adverse events were reported by 44% of vaccine recipients and were transient and mild or moderate in intensity. No serious adverse events were related to vaccination. After the first vaccination, geometric mean titers for RSV-A2 neutralization increased from baseline (432 for LD and 512 for HD vaccine) to day 29 (1031 for LD and 1617 for HD). Pre-F–specific antibody geometric mean titers and median frequencies of F-specific interferon γ–secreting T cells also increased substantially from baseline. These immune responses were still maintained above baseline levels 2 years after immunization and could be boosted with a second immunization at 1 year. Conclusions Ad26.RSV.preF (LD and HD) had an acceptable safety profile and elicited sustained humoral and cellular immune responses after a single immunization in older adults.

Dasatinib Compared with Imatinib In Newly Diagnosed Chronic Myelogenous Leukemia In Chronic Phase (CML-CP):Results of Japanese Subset Analysis In DASISION Trial.

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 4484-4484
Author(s):  
Michinori Ogura ◽  
Hirohisa Nakamae ◽  
Shin Fujisawa ◽  
Kenichi Ishizawa ◽  
Masafumi Taniwaki ◽  
...  
Keyword(s):  
Adverse Events ◽  
Kinase Inhibitor ◽  
Chronic Phase ◽  
Japanese Patients ◽  
Myelogenous Leukemia ◽  
Molecular Response ◽  
Newly Diagnosed ◽  
Serious Adverse Events ◽  
Subset Analysis ◽  
To Receive

Abstract Abstract 4484 Background: Dasatinib is a highly potent BCR-ABL kinase inhibitor. The previous report from the global DASISION trial showed dasatinib 100 mg once daily resulted in significantly higher and faster rates of complete cytogenetic response (CCyR) and major molecular response (MMR) compared with imatinib; both treatment arms were well-tolerated (N Engl J Med. 2010;362:2260-70). The objective of this subset analysis was to assess the efficacy and safety of dasatinib compared with imatinib in the Japanese population. Methods: Forty-nine Japanese patients (total 519 pts) with newly diagnosed CML-CP were randomly assigned to receive dasatinib 100 mg QD or imatinib 400 mg QD. Confirmed CCyR (cCCyR; CCyR on 2 consecutive assessments at least 28 days apart) was the primary efficacy endpoint with MMR as an important secondary endpoint. The safety profiles were also evaluated. Results: Minimum follow-up time and median treatment duration were 12 months and 15 months, respectively. Twenty-six patients with median age 56 (range, 21–70) years were treated with dasatinib and 23 patients with median age 52 (range, 22–77) years were treated with imatinib. Overall 89% of patients receiving dasatinib and 83% of patients receiving imatinib continue to receive treatment. The cCCyR rate by 12 months (primary endpoint), CCyR rate by 12 months and MMR rate at any time in dasatinib arm were higher than those in imatinib for Japanese patients (96% vs 70%, 96% vs 78%, and 73% vs 48%, respectively). Grade 3/4 cytopenias in dasatinib arm and imatinib arm were as follows: anemia (8% vs 4%), neutropenia (27% vs 39%), and thrombocytopenia (8% vs 9%). Non-hematologic and drug-related adverse events occurring in ≥10% of patients are shown as Table. No deaths were reported in either group. Drug-related serious adverse events were rarely reported and all events were not severe (Grade 1–2, including vomiting, hypoxia and cardiomyopathy in dasatinib arm). Conclusion: Dasatinib showed higher rates of cCCyR and MMR compared with imatinib. Both treatments were well tolerated. Given the predictive value of 12 months cCCyR, dasatinib may improve long-term outcomes in Japanese patients with newly diagnosed CML-CP. Disclosures: Ueda: Bristol-Myers K.K.: Employment. Seriu:Bristol-Myers K.K.: Employment. Bradley-Garelik:Bristol-Myers Squibb: Employment. Zhu:Bristol-Myers Squibb: Employment.

scholarly journals Safety and immunogenicity of a seasonal trivalent inactivated split influenza vaccine: a double blind, phase III randomized clinical trial in healthy Serbian adults

2020 ◽  
Vol 8 ◽  
pp. 251513552092533
Author(s):  
Goran Stevanovic ◽  
Aleksandar Obradovic ◽  
Snezana Ristic ◽  
Dragan Petrovic ◽  
Branislava Milenkovic ◽  
...  
Keyword(s):  
Adverse Events ◽  
Influenza Vaccine ◽  
Injection Site ◽  
Controlled Trial ◽  
Geometric Mean ◽  
Phase Iii ◽  
Serious Adverse Events ◽  
Double Blind ◽  
Post Vaccination ◽  
Robust Immune Response

This study was a phase III, multicenter, double-blind, randomized, placebo-controlled trial to evaluate the safety and immunogenicity of a seasonal trivalent split, inactivated influenza vaccine (TIV) in healthy Serbian adults between the ages of 18 and 65 years. This egg-based vaccine was manufactured by the Institute of Virology, Vaccines and Sera, Torlak, Belgrade, Serbia. A total of 480 participants were assigned randomly in a ratio of 2:1 to receive a single intramuscular dose (0.5 ml) of the vaccine (15 µg of hemagglutinin per strain) or placebo (phosphate-buffered saline). Participants were monitored for safety, including solicited and unsolicited adverse events (AEs) and serious adverse events (SAEs). No SAEs related to vaccination were reported. Injection site pain (51.3%), injection site tenderness (40.4%), tiredness (17.0%), and headache (15.1%) were the most commonly reported solicited events in the vaccine group. Incidence of related unsolicited AEs was low (1.3%) among vaccinees. Hemagglutinin inhibition (HAI) titers were measured before and 21 days after vaccination in 151 participants. Overall, HAI seroconversion rates to H1 and H3 were observed in 90.1% and 76.2% of vaccinees, respectively. For B antigen, it was 51.5%, likely due to high pre-vaccination titers. Post-vaccination seroprotection rates were in the range of 78.2–95.0% for the three antigens. Post-vaccination geometric mean titers (GMT) were at least 3.8 times higher than baseline levels for all the three strains among vaccinees. Overall, the study showed that the vaccine was safe and well tolerated, and induced a robust immune response against all three vaccine strains. ClinicalTrials.gov identifier: NCT02935192, October 17, 2016

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