scholarly journals Immunogenicity of Simulated PCECV Postexposure Booster Doses 1, 3, and 5 Years after 2-Dose and 3-Dose Primary Rabies Vaccination in Schoolchildren

2011 ◽  
Vol 2011 ◽  
pp. 1-6 ◽  
Author(s):  
Thavatchai Kamoltham ◽  
Wiravan Thinyounyong ◽  
Pakamatz Khawplod ◽  
Phran Phraisuwan ◽  
Phana Phongchamnaphai ◽  
...  
Keyword(s):  
Booster Dose ◽  
Neutralizing Antibody ◽  
Fold Increase ◽  
Primary Vaccination ◽  
Embryo Cell ◽  
Open Label ◽  
Serious Adverse Events ◽  
Anamnestic Response ◽  
Chick Embryo Cell ◽  
Open Label Phase

Objectives. To assess the immunogenicity of intradermal (ID) booster doses of Purified Chick Embryo Cell rabies vaccine (PCECV, Rabipur) administered to Thai schoolchildren one, three and five years after a primary ID pre-exposure (PrEP) vaccination series.Methods. In this follow-up study of a randomized, open-label, phase II clinical trial, two simulated post-exposure booster doses of PCECV were administered on days 0 and 3 intradermally to 703 healthy schoolchildren, one, three or five years after primary vaccination with either two or three ID doses of 0.1 mL PCECV. Blood was drawn immediately before and 7, 14 and 365 days after the first booster dose to determine rabies virus neutralizing antibody (RVNA) concentrations.Results. An anamnestic response of approximately 30-fold increase in RVNA concentrations was demonstrated within 14 days after booster. All children (100%) developed adequate RVNA concentrations above 0.5 IU/mL. No vaccine related serious adverse events were seen in any of the vaccinees.Conclusion. ID rabies PrEP with PCECV is safe and immunogenic in schoolchildren and the anamnestic response to a two booster dose vaccination series was found to be adequate one, three, and five years after a two- or three-dose primary PrEP vaccination series.

Open label phase II studies of modified vaccinia ankara expressing the tumor antigen 5T4 given in conjunction with IFL and FOLFOX chemotherapy regimens: Final analysis of safety and immunogenicity of MVA 5T4 given before, during and after chemotherapy

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 2527-2527
Author(s):  
R. Harrop ◽  
R. Hawkins ◽  
A. Anthoney ◽  
N. Steven ◽  
N. Habib ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Immune Responses ◽  
Phase Ii ◽  
Clinical Benefit ◽  
Open Label ◽  
Serious Adverse Events ◽  
Phase Ii Studies ◽  
Open Label Phase ◽  
Clinical Responses ◽  
Folfox Chemotherapy

2527 Background: 5T4 is a tumour associated antigen that is widely expressed on the surface of most human adenocarcinomas, including colorectal, but rarely in normal cells. Modified Vaccinia Ankara (MVA) has been employed as a vaccine vector to deliver 5T4. Previously, MVA-5T4 has been evaluated in a phase I/II clinical trial in stage IV colorectal cancer patients. MVA-5T4 was shown to be safe and well tolerated and induced 5T4 specific immune responses in most patients. Furthermore, 5T4 specific antibody titres correlated with clinical benefit. Methods: Two open label phase II clinical trials were initiated in which patients with advanced colorectal cancer received MVA-5T4 in conjunction with either 5-FU/leukovorin and irinotecan (TV2-IFL; n=19 patients) or 5-FU/leukovorin and oxaliplatin (TV2-FOLFOX; n=17 patients). MVA-5T4 was administered up to 6 times, 2 prior to, 2 during and 2 post-chemotherapy. The primary objectives were to assess the safety and immunogenicity of MVA-5T4 given in combination with chemotherapy. Results: Recruitment to both trials is complete and MVA-5T4 was well tolerated in all ITT patients, with no serious adverse events being associated with MVA-5T4. 5T4-specific cellular and humoral immune responses were monitored before, during and after chemotherapy in all 23 per protocol patients (n=12 for TV2-IFL and n=11 for TV2-FOLFOX). Following vaccination, all 23 patients mounted 5T4 cellular and/or humoral responses. Immune responses were detectable during chemotherapy in the majority of patients. IFNγ ELISPOT responses to 5T4 peptides revealed precursor frequencies as high as 1 in 1000 PBMCs. Assessment of clinical responses in all PP patients demonstrated an overall response rate of 65% across both trials. Conclusions: MVA-5T4 is safe and well tolerated when administered in conjunction with IFL and FOLFOX chemotherapy regimens. Furthermore, 5T4 specific immune responses are induced in all per protocol patients and can be boosted or maintained during chemotherapy. Encouraging clinical responses have been observed and 5T4 immune responses shown to correlate with clinical benefit. [Table: see text]

scholarly journals In vitro assessment and phase I randomized clinical trial of anfibatide a snake venom derived anti-thrombotic agent targeting human platelet GPIbα

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Benjamin Xiaoyi Li ◽  
Xiangrong Dai ◽  
Xiaohong Ruby Xu ◽  
Reheman Adili ◽  
Miguel Antonio Dias Neves ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Platelet Aggregation ◽  
Phase I ◽  
Human Platelet ◽  
Open Label ◽  
Serious Adverse Events ◽  
Open Label Phase ◽  
Deinagkistrodon Acutus

AbstractThe interaction of platelet GPIbα with von Willebrand factor (VWF) is essential to initiate platelet adhesion and thrombosis, particularly under high shear stress conditions. However, no drug targeting GPIbα has been developed for clinical practice. Here we characterized anfibatide, a GPIbα antagonist purified from snake (Deinagkistrodon acutus) venom, and evaluated its interaction with GPIbα by surface plasmon resonance and in silico modeling. We demonstrated that anfibatide interferds with both VWF and thrombin binding, inhibited ristocetin/botrocetin- and low-dose thrombin-induced human platelet aggregation, and decreased thrombus volume and stability in blood flowing over collagen. In a single-center, randomized, and open-label phase I clinical trial, anfibatide was administered intravenously to 94 healthy volunteers either as a single dose bolus, or a bolus followed by a constant rate infusion of anfibatide for 24 h. Anfibatide inhibited VWF-mediated platelet aggregation without significantly altering bleeding time or coagulation. The inhibitory effects disappeared within 8 h after drug withdrawal. No thrombocytopenia or anti-anfibatide antibodies were detected, and no serious adverse events or allergic reactions were observed during the studies. Therefore, anfibatide was well-tolerated among healthy subjects. Interestingly, anfibatide exhibited pharmacologic effects in vivo at concentrations thousand-fold lower than in vitro, a phenomenon which deserves further investigation.Trial registration: Clinicaltrials.gov NCT01588132.

scholarly journals Safety and immunogenicity of a recombinant DNA COVID-19 vaccine containing the coding regions of the spike and nucleocapsid proteins: Preliminary results from an open-label, phase 1 trial in healthy adults aged 19-55 years

2021 ◽  
Author(s):  
Jin Young Ahn ◽  
Jeongsoo Lee ◽  
You Suk Suh ◽  
Young Goo Song ◽  
Yoon-Jeong Choi ◽  
...  
Keyword(s):  
T Cell ◽  
Plasmid Dna ◽  
Phase 1 ◽  
T Cell Responses ◽  
Neutralizing Antibody ◽  
Dna Encoding ◽  
Open Label ◽  
Cell Responses ◽  
Open Label Phase ◽  
Trial Participants

Background : We investigated the safety and immunogenicity of two recombinant COVID-19 DNA vaccine candidates in first-in-human trials. GX-19 contains plasmid DNA encoding SARS-CoV-2 spike protein, and GX-19N contains plasmid DNA encoding SARS-CoV-2 receptor binding domain (RBD) foldon and nucleocapsid protein (NP) as well as plasmid DNA encoding SARS-CoV-2 spike protein. Methods : Two open-label phase 1 trials of GX-19 and GX-19N safety and immunogenicity were performed in healthy adults aged 19-55 years. GX-19 trial participants received two vaccine injections (1.5 mg or 3.0 mg, 1:1 ratio) four weeks apart. GX-19N trial participants received two 3.0 mg vaccine injections four weeks apart. Findings : Between June 17 and July 30 and December 28 and 31, 2020, 40 and 21 participants were enrolled in the GX-19 and GX-19N trials, respectively. Thirty-two participants (52.5%) reported 80 treatment-emergent adverse events (AE) after vaccination. All solicited AEs were mild except one case of moderate fatigue reported in the 1.5 mg GX-19 group. Binding antibody responses increased after vaccination in all groups. The geometric mean titers (GMTs) of spike-binding antibodies on day 57 were 85.74, 144.20, and 201.59 in the 1.5 mg, 3.0 mg GX-19 groups and the 3.0 mg GX-19N group, respectively. In GX-19N group, neutralizing antibody response (50% neutralizing titer using FRNT) significantly increased after vaccination, but GMT of neutralizing antibody on day 57 (37.26) was lower than those from human convalescent serum (288.78). GX-19N induced stronger T cell responses than GX-19. The magnitude of GX-19N-induced T cell responses was comparable to those observed in the convalescent PBMCs. GX-19N induced both SARS-CoV-2 spike- and NP-specific T cell responses, and the amino acid sequences of 15-mer peptides containing NP-specific T cell epitopes identified in GX-19N-vaccinated participants were identical with those of diverse SARS-CoV-2 variants Interpretation : GX-19N is safe, tolerated and induces humoral and broad SARS-CoV-2-specific T cell response which may enable cross-reactivity to emerging SARS-CoV-2 variants. Funding : This research was supported by Korea Drug Development Fund funded by Ministry of Science and ICT, Ministry of Trade, Industry, and Energy, and Ministry of Health and Welfare (HQ20C0016, Republic of Korea).

scholarly journals 636. Immunogenicity, Safety and Tolerability of a Booster Dose of Clostridium difficile Vaccine and 4 Year Antibody Persistence

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S378-S378
Author(s):  
Shon A Remich ◽  
Nicholas Kitchin ◽  
Michael W Pride ◽  
Annaliesa S Anderson ◽  
Ping Li ◽  
...  
Keyword(s):  
Safety Profile ◽  
Booster Dose ◽  
Geometric Mean ◽  
Primary Vaccination ◽  
The United States ◽  
Post Dose ◽  
Serious Adverse Events ◽  
Antibody Persistence ◽  
Dose Levels ◽  
To Receive

Abstract Background Clostroidides difficile (C difficile) is a common cause of antibiotic-associated diarrhea. To date, there is no vaccine to prevent C. difficile infection (CDI). This extension of a phase 2 study explores the immunogenicity, safety, and tolerability of a 4th dose, and antibody persistence of a three-dose regimen of a toxoid-based C difficile vaccine in 300 healthy adults 65 to 85 years of age in the United States. Methods The first stage of this study was conducted from 16 July 2015 to 7 March 2017, in which subjects were enrolled and randomized to receive one of two antigen dose levels (100µg or 200µg total toxoid A and B) or placebo, administered in one of two three-dose regimens: Days 1, 8 & 30 or Months 0, 1 & 6. Immunogenicity testing was conducted on samples obtained at each of nine study visits through 12 months post dose 3. In this extension stage, subjects who had received vaccine in the first stage were re-randomized at 12 months post dose 3 to receive either a booster dose or placebo in a 1:1 ratio. Subjects were followed for immunogenicity three (3) years post booster (four years post dose #3) Results Peak antibody response to vaccination was observed between day 8 and 30 following booster administration. Both regimens demonstrated robust anamnestic responses with peak levels above the three-dose peak (stage 1). Toxin A geometric mean concentrations (GMCs) remained above pre-booster GMCs, 3 years post booster for both dose levels and regimens. Antibody persistence for both groups demonstrated stable antibody levels four years after the primary vaccination series among subjects who did not receive a booster dose. No Grade 4 reactogenicity was reported during the study. Pain was the most common local reaction. Adverse event rates per subject were similar between both regimens and placebo. There were no Serious Adverse Events (SAEs) considered related to the investigational product at any dose or regimen. The safety profile was consistent with what was seen in the first stage of the study. Conclusion A booster dose of Clostroidides difficile vaccine candidate is highly immunogenic, well tolerated and demonstrates an acceptable safety profile in both dose groups for the Day and the Month regimens. Antibody persistence remains stable from 12 months to 4-year post dose 3. Disclosures Nicholas Kitchin, MD, Pfizer, Inc (Employee) Michael W. Pride, PhD, Pfizer (Employee, Shareholder) Annaliesa S. Anderson, PhD, Pfizer (Employee, Shareholder) Chris Webber, MD, Pfizer Inc (Employee, Shareholder)

scholarly journals Safety and Efficacy of Daratumumab in Patients with Proliferative GN with Monoclonal Immunoglobulin Deposits

2021 ◽  
pp. ASN.2020101541
Author(s):  
Ladan Zand ◽  
S. Vincent Rajkumar ◽  
Nelson Leung ◽  
Sanjeev Sethi ◽  
Mireille El Ters ◽  
...  
Keyword(s):  
Partial Remission ◽  
Monoclonal Gammopathy ◽  
Complete Response ◽  
Clinical Trial Registry ◽  
Open Label ◽  
Serious Adverse Events ◽  
Safety And Efficacy ◽  
Phase 2 Trial ◽  
Open Label Phase ◽  
Registration Number

BackgroundTreatment of proliferative GN with monoclonal Ig deposits (PGNMID) is not established. A monoclonal anti-CD38 antibody (daratumumab) is effective in treating multiple myeloma. Abnormal plasma cell clones may play a role in the pathogenesis of PGNMID.MethodsWe evaluated daratumumab’s safety and efficacy in an open-label, phase 2 trial in 11 adults with PGNMID and one with C3 glomerulopathy (C3G) with monoclonal gammopathy. Patients had an eGFR >20 ml/min per 1.73 m2 and proteinuria >1 g/d. They received daratumumab intravenously (16 mg/kg) once weekly for 8 weeks, and then every other week for eight additional doses. Primary outcome was safety, defined as major infections, grade 3 or 4 anemia, leukopenia, or thrombocytopenia. Secondary outcomes were rate of complete remission (proteinuria <500 mg/d with <15% decline in baseline eGFR) or partial remission (>50% reduction in 24-hour proteinuria with <30% decline in eGFR) and proteinuria at 6 and 12 months.ResultsOne patient with C3G had GN unrelated to the monoclonal gammopathy, and one with PGNMID did not complete the first infusion. Five serious adverse events occurred. During the 12 months of the trial, six of the ten patients with PGNMID who received at least one dose of daratumumab had a partial response, and four had a complete response (an overall response rate of 100%). Three patients experienced relapse, two of whom re-entered partial remission after resuming daratumumab therapy. Proteinuria declined significantly, from a median of 4346 mg/d to 1264 mg/d by 12 months.ConclusionsDaratumumab demonstrated an acceptable safety profile and resulted in significant improvement in proteinuria while stabilizing kidney function in patients with PGNMID, suggesting the drug merits further investigation.Clinical Trial registry name and registration number:Daratumumab in Treatment of PGNMID and C3 GN, NCT03095118

scholarly journals Durability of antibody responses elicited by a single dose of Ad26.COV2.S and substantial increase following late boosting

2021 ◽  
Author(s):  
Jerald Sadoff ◽  
Mathieu Le Gars ◽  
Vicky Cardenas ◽  
Georgi Shukarev ◽  
Nathalie Vaissiere ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Single Dose ◽  
Booster Dose ◽  
Age Groups ◽  
Neutralizing Antibody ◽  
Primary Vaccination ◽  
Antibody Responses ◽  
Binding Antibody ◽  
Antibody Levels ◽  
The Impact

AbstractBackgroundWe evaluated the durability of SARS-CoV-2 antibody levels elicited by the single dose Janssen COVID-19 vaccine, Ad26.COV2.S, and the impact on antibody responses of boosting with Ad26.COV2.S after 6 months in clinical trial participants.MethodsSpike-binding antibody and SARS-CoV-2 neutralizing antibody levels elicited by a single-dose Ad26.COV2.S (5×1010 viral particles [vp]) primary regimen and booster doses (5×1010 vp and 1.25×1010 vp) were assessed by ELISA and wild-type VNA in sera from participants in a Phase 1/2a clinical trial (Cohort 1a, 18–55 years old, N=25; Cohort 2a, 18–55 years old boosted at 6 months, N=17; Cohort 3, ≥65 years old, N=22) and a Phase 2 clinical trial (18–55 and ≥65-year old participants boosted at 6 months, total N=73). Neutralizing antibody levels were determined approximately 8 months after the primary vaccination in participants aged 18–55 years and approximately 9 months in participants aged ≥65 years. Binding antibody levels were evaluated 6 months after primary vaccination and 7- and 28-days after booster doses in both age groups.ResultsA single dose of Ad26.COV2.S elicited neutralizing antibodies that remained largely stable for approximately 8–9 months and binding antibodies that remained stable for at least 6 months irrespective of age group. A 5×1010 vp booster dose at 6 months post prime vaccination in 18–55-year-old adults elicited a steep and robust 9-fold increase at Day 7 post boost compared to Day 29 levels following the initial immunization. A lower booster dose of 1.25×1010 vp at 6 months in adults 18–55 and ≥65 years of age also elicited a rapid and high increase of 6–7.7 fold at Day 28 post boost compared to Day 29 levels following the initial immunization, with similar magnitude of post-boost responses in both age groups.ConclusionsA single dose of Ad26.COV2.S, which demonstrated protection in a Phase 3 efficacy trial, elicited durable neutralizing and binding antibodies for at least 8 and 6 months, respectively, in adults >18 years of age at levels similar to Day 29 responses. A 5×1010 vp or 1.25×1010 vp booster dose at 6 months elicited rapid and robust increases in spike binding antibody levels. The anamnestic responses after booster immunization imply robust immune memory elicited by single-dose Ad26.COV2.S.

scholarly journals Clinical evaluation of purified chick embryo cell rabies vaccine administered intradermally in animal exposures

2018 ◽  
Vol 5 (2) ◽  
pp. 585
Author(s):  
Ravish S. Hardanahalli ◽  
Veena V. ◽  
Ramesh Holla ◽  
Rachana R. Annadani ◽  
Sathish Chandra M. R.
Keyword(s):  
Cell Culture ◽  
Chick Embryo ◽  
Adverse Drug Events ◽  
Neutralizing Antibody ◽  
Embryo Cell ◽  
Human Rabies ◽  
Post Exposure Prophylaxis ◽  
Post Exposure ◽  
Chick Embryo Cell ◽  
Exposure Prophylaxis

Background: In India, presently there are two purified chick embryo cell culture vaccines (PCECV) viz., Rabipur (Flury LEP strain) and Vaxirab – N (Pitman Moore strain) which are commonly used both in public as well as private sectors. The present study was conducted to assess the clinical efficacy in terms of safety, immunogenicity and survival status of both the PCECV administered animal exposures taking complete PEP at the anti-rabies clinic.Methods: A longitudinal study was conducted at the anti-rabies clinic, Kempegowda Institute of Medical Sciences (KIMS), Bangalore, India. 86 suspect rabid dog bite cases attending clinic were enrolled and followed up for 1year. All the animal bite cases were given post exposure prophylaxis of full course of PCECV i.e. Rabipur or Vaxirab - N as per schedule intradermally using updated Thai Red Cross regimen. The rabies virus neutralizing antibody (RVNA) concentrations on days 14, 28, 90, and 180 were tested by modified rapid fluores­cent focus inhibition test.Results: Out of 86 study subjects, 43 subjects received Rabipur and another 43 subjects received Vaxirab –N vaccines. The incidence of adverse drug events (ADEs) was found to be 9.3%. All subjects had protective RVNA titers of ³0.5 IU/ml from day 14 till day 180. All the study subjects were healthy and alive after 6 months of completing PEP.Conclusions: The currently available purified chick embryo cell culture rabies vaccines are safe, immunogenic and clinically effective for post exposure prophylaxis in animal bite cases, which will help in eliminating human rabies by 2020. 

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