scholarly journals Engineering a Novel Bivalent Oral Vaccine against Enteric Fever

2021 ◽  
Vol 22 (6) ◽  
pp. 3287
Author(s):  
Annelise Soulier ◽  
Claudia Prevosto ◽  
Mary Chol ◽  
Livija Deban ◽  
Rocky M. Cranenburgh
Keyword(s):  
Clinical Trial ◽  
Clinical Trials ◽  
Phase I ◽  
Growth Kinetics ◽  
Enteric Fever ◽  
Vaccine Candidate ◽  
Oral Vaccine ◽  
Gene Encoding ◽  
Genetic Changes ◽  
Flic Gene

Enteric fever is a major global healthcare issue caused largely by Salmonella enterica serovars Typhi and Paratyphi A. The objective of this study was to develop a novel, bivalent oral vaccine capable of protecting against both serovars. Our approach centred on genetically engineering the attenuated S. Typhi ZH9 strain, which has an excellent safety record in clinical trials, to introduce two S. Paratyphi A immunogenic elements: flagellin H:a and lipopolysaccharide (LPS) O:2. We first replaced the native S. Typhi fliC gene encoding flagellin with the highly homologous fliC gene from S. Paratyphi A using Xer-cise technology. Next, we replaced the S. Typhi rfbE gene encoding tyvelose epimerase with a spacer sequence to enable the sustained expression of O:2 LPS and prevent its conversion to O:9 through tyvelose epimerase activity. The resulting new strain, ZH9PA, incorporated these two genetic changes and exhibited comparable growth kinetics to the parental ZH9 strain. A formulation containing both ZH9 and ZH9PA strains together constitutes a new bivalent vaccine candidate that targets both S. Typhi and S. Paratyphi A antigens to address a major global healthcare gap for enteric fever prophylaxis. This vaccine is now being tested in a Phase I clinical trial (NCT04349553).

scholarly journals Immunogenicity and Safety of Inactivated Sabin-Strain Polio Vaccine “PoliovacSin”: Clinical Trials Phase I and II

Vaccines ◽  
2021 ◽  
Vol 9 (6) ◽  
pp. 565
Author(s):  
Anastasia Piniaeva ◽  
Georgy Ignatyev ◽  
Liubov Kozlovskaya ◽  
Yury Ivin ◽  
Anastasia Kovpak ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Clinical Trials ◽  
Phase I ◽  
Safety Profile ◽  
Neutralizing Antibody ◽  
Polio Eradication ◽  
Controlled Clinical Trial ◽  
Double Blind ◽  
Good Tolerability ◽  
Poliomyelitis Vaccine

Global polio eradication requires both safe and effective vaccines, and safe production processes. Sabin oral poliomyelitis vaccine (OPV) strains can evolve to virulent viruses and result in poliomyelitis outbreaks, and conventional inactivated poliomyelitis vaccine (Salk-IPV) production includes accumulation of large stocks of neurovirulent wild polioviruses. Therefore, IPV based on attenuated OPV strains seems a viable option. To increase the global supply of affordable inactivated vaccine in the still not-polio free world we developed an IPV made from the Sabin strains–PoliovacSin. Clinical trials included participants 18–60 years of age. A phase I single-center, randomized, double-blind placebo-controlled clinical trial included 60 participants, who received one dose of PoliovacSin or Placebo. A phase II multicenter, randomized, double-blind, comparative clinical trial included 200 participants, who received one dose of PoliovacSin or Imovax Polio. All vaccinations were well tolerated, and PoliovacSin had a comparable safety profile to the Placebo or the reference Imovax Polio preparations. A significant increase in neutralizing antibody levels to polioviruses types 1–3 (Sabin and wild) was observed in PoliovacSin and Imovax Polio vaccinated groups. Therefore, clinical trials confirmed good tolerability, low reactogenicity, and high safety profile of the PoliovacSin and its pronounced immunogenic properties. The preparation was approved for clinical trials involving infants.

scholarly journals Two Live Attenuated Vaccines against Recent Low–and Highly Pathogenic H7N9 Influenza Viruses Are Safe and Immunogenic in Ferrets

Vaccines ◽  
2018 ◽  
Vol 6 (4) ◽  
pp. 74 ◽  
Author(s):  
Larisa Rudenko ◽  
Irina Kiseleva ◽  
Elena Krutikova ◽  
Ekaterina Stepanova ◽  
Irina Isakova-Sivak ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Phase I ◽  
Reverse Genetics ◽  
Vaccine Candidate ◽  
Clinical Signs ◽  
Influenza Viruses ◽  
Phase I Clinical Trial ◽  
World Health ◽  
Histological Data ◽  
Health Organization

Influenza H7N9 virus is a potentially pandemic subtype to which most people are immunologically naïve. To be better prepared for the potential occurrence of an H7N9 pandemic, in 2017 the World Health Organization recommended developing candidate vaccine viruses from two new H7N9 viruses, A/Guangdong/17SF003/2016 (A/GD) and A/Hong Kong/125/2017 (A/HK). This report describes the development of live attenuated influenza vaccine (LAIV) candidates against A/GD and A/HK viruses and study of their safety and immunogenicity in the ferret model in order to choose the most promising one for a phase I clinical trial. The A/HK-based vaccine candidate (A/17/HK) was developed by classical reassortment in eggs. The A/GD-based vaccine candidate (A/17/GD) was generated by reverse genetics. Ferrets were vaccinated with two doses of LAIV or phosphate-buffered saline. Both H7N9 LAIVs tested were safe for ferrets, as shown by absence of clinical signs, and by virological and histological data; they were immunogenic after a single vaccination. These results provide a compelling argument for further testing of these vaccines in volunteers. Since the A/HK virus represents the cluster that has caused the majority of human cases, and because the A/HK-based LAIV candidate was developed by classical reassortment, this is the preferred candidate for a phase I clinical trial.

scholarly journals Phase I Clinical Trial of a Recombinant Blood Stage Vaccine Candidate for Plasmodium falciparum Malaria Based on MSP1 and EBA175

PLoS ONE ◽  
2015 ◽  
Vol 10 (4) ◽  
pp. e0117820 ◽  
Author(s):  
Chetan E. Chitnis ◽  
Paushali Mukherjee ◽  
Shantanu Mehta ◽  
Syed Shams Yazdani ◽  
Shikha Dhawan ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Plasmodium Falciparum ◽  
Phase I ◽  
Falciparum Malaria ◽  
Vaccine Candidate ◽  
Plasmodium Falciparum Malaria ◽  
Blood Stage ◽  
Phase I Clinical Trial

A Study on the Characteristics of Healthy Volunteers who Participate in Phase I Clinical Trials in Korea

2021 ◽  
pp. 155626462110342
Author(s):  
Ji-Hye Seo ◽  
Ock-Joo Kim ◽  
Sang-Ho Yoo ◽  
Eun Kyung Choi ◽  
Ji-Eun Park
Keyword(s):  
Clinical Trial ◽  
Clinical Trials ◽  
Phase I ◽  
Healthy Volunteers ◽  
Health Science ◽  
Trial Participation ◽  
Phase I Clinical Trials ◽  
Financial Reward ◽  
Therapeutic Purpose ◽  
The Republic

The phase I trial is the first step in administering a drug to humans, but it has no therapeutic purpose. Under the absence of therapeutic purpose, healthy volunteers demonstrated different motivations, unlike the actual patients participating in trials. There were many reported motivations, such as financial motivation, contributing to the health science, accessing ancillary health care benefits, scientific interest or interest in the goals of the study, meeting people, and general curiosity. The aim of this study was to identify the motivation and characteristics of healthy volunteers participating in phase I trials in the Republic of Korea. We gave surveys to 121 healthy volunteers to study their demographic characteristics and the reasons of participation. We identified whether the decision to participate in the research was influenced by demographic factors and whether the perception and attitudes toward the research were influenced by the characteristics of the healthy volunteers. After completion of the first survey, 12 healthy volunteers who had participated in a phase I clinical trial were selected to answer the second interview. According to our survey, most healthy volunteers were unmarried men and economically dependent. Most of them participated in the study because of financial reward. The most important factor to measure financial reward was the research period. Also, 43% of the volunteers were university students, 42% answered “university graduation” and 55% were residing in family-owned houses. Many healthy volunteers were found to be living in family homes and to have a student status or lack of economic independence. Results of the survey showed that 64% of respondents indicated having more than one clinical trial participation. In-depth interviews showed that healthy volunteers had diverse motivation to participate in research and that healthy volunteer perceive the clinical trial positively. The main motivation for healthy volunteers’ participation in research was “financial reward.” Healthy volunteers also considered research schedules, processes, and safety, and had a positive perception of clinical trials, but they thought that the public has a negative perception.

scholarly journals Provider Recommendations for Phase I Clinical Trials Within a Shared Decision-Making Model in Phase I Cancer Clinical Trial Discussions

2020 ◽  
Vol 16 (9) ◽  
pp. e859-e867
Author(s):  
Rachel S. Hianik ◽  
Gavin P. Campbell ◽  
Eli Abernethy ◽  
Colleen Lewis ◽  
Christina S. Wu ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Decision Making ◽  
Clinical Trials ◽  
Phase I ◽  
Shared Decision Making ◽  
Phase I Trial ◽  
Performance Status ◽  
Shared Decision ◽  
Phase I Clinical Trials ◽  
Decision Making Model

PURPOSE: Debate continues over whether explicit recommendations for a clinical trial should be included as an element of shared decision making within oncology. We aimed to determine if and how providers make explicit recommendations in the setting of phase I cancer clinical trials. METHODS: Twenty-three patient/provider conversations about phase I trials were analyzed to determine how recommendations are made and how the conversations align with a shared decision-making framework. In addition, 19 providers (9 of whose patient encounters were observed) were interviewed about the factors they consider when deciding whether to recommend a phase I trial. RESULTS: We found that providers are comprehensive in the factors they consider when recommending clinical trials. The two most frequently stated factors were performance status (89%) and patient preferences (84%). Providers made explicit recommendations in 19 conversations (83%), with 12 of those being for a phase I trial (12 [63%] of 19). They made these recommendations in a manner consistent with a shared decision-making model; 18 (95%) of the 19 conversations during which a recommendation was made included all steps, or all but 1 step, of shared decision making, as did 11 of the 12 conversations during which a phase I trial was recommended. In 7 (58%) of these later conversations, providers also emphasized the importance of the patient’s opinion. CONCLUSION: We suggest that providers not hesitate to make explicit recommendations for phase I clinical trials, because they are able to do so in a manner consistent with shared decision making. With further research, these results can be applied to other clinical trial settings.

scholarly journals Correction: Phase I Clinical Trial of a Recombinant Blood Stage Vaccine Candidate for Plasmodium falciparum Malaria Based on MSP1 and EBA175

PLoS ONE ◽  
2015 ◽  
Vol 10 (9) ◽  
pp. e0137816 ◽  
Author(s):  
Chetan E. Chitnis ◽  
Paushali Mukherjee ◽  
Shantanu Mehta ◽  
Syed Shams Yazdani ◽  
Shikha Dhawan ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Plasmodium Falciparum ◽  
Phase I ◽  
Falciparum Malaria ◽  
Vaccine Candidate ◽  
Plasmodium Falciparum Malaria ◽  
Blood Stage ◽  
Phase I Clinical Trial ◽  
Correction Phase

scholarly journals Phase I/II Clinical Trial of the Anti-Podoplanin Monoclonal Antibody Therapy in Dogs with Malignant Melanoma

Cells ◽  
2020 ◽  
Vol 9 (11) ◽  
pp. 2529
Author(s):  
Satoshi Kamoto ◽  
Masahiro Shinada ◽  
Daiki Kato ◽  
Sho Yoshimoto ◽  
Namiko Ikeda ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Clinical Trials ◽  
Malignant Melanoma ◽  
Adverse Effects ◽  
Phase I ◽  
Tumor Cells ◽  
Antibody Therapy ◽  
Human Tumor ◽  
Preclinical Trial ◽  
Canine Tumor

Podoplanin (PDPN), a small transmembrane mucin-like glycoprotein, is ectopically expressed on tumor cells. PDPN is known to be linked with several aspects of tumor malignancies in certain types of human and canine tumors. Therefore, it is considered to be a novel therapeutic target. Monoclonal antibodies targeting PDPN expressed in human tumor cells showed obvious anti-tumor effects in preclinical studies using mouse models. Previously, we generated a cancer-specific mouse–dog chimeric anti-PDPN antibody, P38Bf, which specifically recognizes PDPN expressed in canine tumor cells. In this study, we investigated the safety and anti-tumor effects of P38Bf in preclinical and clinical trials. P38Bf showed dose-dependent antibody-dependent cellular cytotoxicity against canine malignant melanoma cells. In a preclinical trial with one healthy dog, P38Bf administration did not induce adverse effects over approximately 2 months. In phase I/II clinical trials of three dogs with malignant melanoma, one dog vomited, and all dogs had increased serum levels of C-reactive protein, although all adverse effects were grade 1 or 2. Severe adverse effects leading to withdrawal of the clinical trial were not observed. Furthermore, one dog had stable disease with P38Bf injections. This is the first reported clinical trial of anti-PDPN antibody therapy using spontaneously occurring canine tumor models.

scholarly journals Phase I Randomised Clinical Trial of an HIV-1CN54, Clade C, Trimeric Envelope Vaccine Candidate Delivered Vaginally

PLoS ONE ◽  
2011 ◽  
Vol 6 (9) ◽  
pp. e25165 ◽  
Author(s):  
David J. Lewis ◽  
Carol A. Fraser ◽  
Abdel N. Mahmoud ◽  
Rebecca C. Wiggins ◽  
Maria Woodrow ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Phase I ◽  
Vaccine Candidate ◽  
Randomised Clinical Trial ◽  
Clade C ◽  
Trimeric Envelope

scholarly journals Integrated deep learned transcriptomic and structure-based predictor of clinical trials outcomes

2016 ◽  
Author(s):  
Artem V. Artemov ◽  
Evgeny Putin ◽  
Quentin Vanhaelen ◽  
Alexander Aliper ◽  
Ivan V. Ozerov ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Clinical Trials ◽  
Systems Biology ◽  
Phase I ◽  
Biological Data ◽  
Drug Induced ◽  
Multi Stage ◽  
Pathway Activation ◽  
Trial Outcomes ◽  
Analytical Tools

AbstractDespite many recent advances in systems biology and a marked increase in the availability of high-throughput biological data, the productivity of research and development in the pharmaceutical industry is on the decline. This is primarily due to clinical trial failure rates reaching up to 95% in oncology and other disease areas. We have developed a comprehensive analytical and computational pipeline utilizing deep learning techniques and novel systems biology analytical tools to predict the outcomes of phase I/II clinical trials. The pipeline predicts the side effects of a drug using deep neural networks and estimates drug-induced pathway activation. It then uses the predicted side effect probabilities and pathway activation scores as an input to train a classifier which predicts clinical trial outcomes. This classifier was trained on 577 transcriptomic datasets and has achieved a cross-validated accuracy of 0.83. When compared to a direct gene-based classifier, our multi-stage approach dramatically improves the accuracy of the predictions. The classifier was applied to a set of compounds currently present in the pipelines of several major pharmaceutical companies to highlight potential risks in their portfolios and estimate the fraction of clinical trials that were likely to fail in phase I and II.

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