Vaccine development against SARS-CoV-2: from virology to vaccine clinical trials

Coronaviruses ◽  
2020 ◽  
Vol 01 ◽  
Author(s):  
Kimia Kardani ◽  
Azam Bolhassani
Keyword(s):  
Clinical Trial ◽  
Clinical Trials ◽  
Phase Ii ◽  
Immune Evasion ◽  
Vaccine Development ◽  
Vaccine Candidate ◽  
Adenovirus Vector ◽  
Vaccine Candidates ◽  
Novel Coronavirus ◽  
The Way

Abstract:: An urgent vaccine development is required against the recent pandemic of a novel coronavirus. Currently, there is no approved vaccine against COVID-19. Vaccination is proved to be the most beneficial way to protect human from infections. Up to now, several vaccine candidates have been conducted to different phases of clinical trials, and more vaccine candidates are on the way to enter the trials. Different vaccine types have developed including inactivated virus vaccines, subunit-based vaccines, adenovirus-vector vaccines, DNA-based vaccines, DC-based vaccines, and mRNA-based vaccines. The mRNA- 1273 was the first vaccine candidate that started evaluating in clinical trial. Also, AZD1222 is the first vaccine candidate that started phase II/III of clinical trials. Both of these vaccine candidates were considered as the promising vaccine candidates against SARS-CoV-2. This review aims to overview and share various strategies to develop efficient therapeutic and preventive vaccines based on the origin, biology, structure, and immune-evasion of SARS-CoV-2.

scholarly journals Viral vector-based vaccines against SARS-CoV-2

2021 ◽  
pp. 295-308
Author(s):  
Kenneth Lundstrom
Keyword(s):  
Clinical Trials ◽  
Vaccine Efficacy ◽  
Measles Virus ◽  
Viral Vectors ◽  
Vaccine Development ◽  
Viral Vector ◽  
Adenovirus Vector ◽  
Influenza Viruses ◽  
Vaccine Candidates ◽  
Lentivirus Vectors

Viral vectors have been frequently applied for vaccine development. It has also been the case for vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) to tackle the coronavirus disease 2019 (COVID-19) pandemic. A multitude of different viral vectors have been mainly targeting the SARS-CoV-2 spike (S) protein as antigen. Intramuscular injection has been most commonly used, but also intranasal administration has been tested. Adenovirus vector-based vaccines are the most advanced with several vaccines receiving Emergency Use Authorization (EUA). The simian ChAdOx1 nCoV-19 vaccine applied as a prime-boost regimen has provided 62.1–90% vaccine efficacy in clinical trials. The Ad26.COV2.S vaccine requires only one immunization to provide protection against SARS-CoV-2. The rAd26-S/rAd5-S vaccine utilizes the Ad26 serotype for the prime immunization followed by a boost with the Ad5 serotype resulting in 91.2% vaccine efficacy. All adenovirus-based vaccines are used for mass vaccinations. Moreover, vaccine candidates based on vaccinia virus and lentivirus vectors have been subjected to clinical evaluation. Among self-replicating RNA viruses, vaccine vectors based on measles virus, rhabdoviruses, and alphaviruses have been engineered and tested in clinical trials. In addition to the intramuscular route of administration vaccine candidates based on influenza viruses and adenoviruses have been subjected to intranasal delivery showing antibody responses and protection against SARS-CoV-2 challenges in animal models. The detection of novel more transmissible and pathogenic SARS-CoV-2 variants added concerns about the vaccine efficacy and needs to be monitored. Moreover, the cause of recently documented rare cases of vaccine-induced immune thrombotic thrombocytopenia (VITT) must be investigated.

scholarly journals Progress and challenges in TB vaccine development

F1000Research ◽  
2018 ◽  
Vol 7 ◽  
pp. 199 ◽  
Author(s):  
Gerald Voss ◽  
Danilo Casimiro ◽  
Olivier Neyrolles ◽  
Ann Williams ◽  
Stefan H.E. Kaufmann ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Vaccine Development ◽  
Scientific Progress ◽  
Human Infection ◽  
Experimental Medicine ◽  
Vaccine Platform ◽  
Vaccine Candidates ◽  
Clinical Endpoints ◽  
Immune Correlates ◽  
Efficacy Trials

The Bacille Calmette Guerin (BCG) vaccine can provide decades of protection against tuberculosis (TB) disease, and although imperfect, BCG is proof that vaccine mediated protection against TB is a possibility. A new TB vaccine is, therefore, an inevitability; the question is how long will it take us to get there? We have made substantial progress in the development of vaccine platforms, in the identification of antigens and of immune correlates of risk of TB disease. We have also standardized animal models to enable head-to-head comparison and selection of candidate TB vaccines for further development.  To extend our understanding of the safety and immunogenicity of TB vaccines we have performed experimental medicine studies to explore route of administration and have begun to develop controlled human infection models. Driven by a desire to reduce the length and cost of human efficacy trials we have applied novel approaches to later stage clinical development, exploring alternative clinical endpoints to prevention of disease outcomes. Here, global leaders in TB vaccine development discuss the progress made and the challenges that remain. What emerges is that, despite scientific progress, few vaccine candidates have entered clinical trials in the last 5 years and few vaccines in clinical trials have progressed to efficacy trials. Crucially, we have undervalued the knowledge gained from our “failed” trials and fostered a culture of risk aversion that has limited new funding for clinical TB vaccine development. The unintended consequence of this abundance of caution is lack of diversity of new TB vaccine candidates and stagnation of the clinical pipeline. We have a variety of new vaccine platform technologies, mycobacterial antigens and animal and human models.  However, we will not encourage progression of vaccine candidates into clinical trials unless we evaluate and embrace risk in pursuit of vaccine development.

scholarly journals Safety and Effectiveness of Favipiravir for Novel Coronavirus (COVID-19): A Rapid Review of Available Evidence

2021 ◽  
Author(s):  
Mohammadreza Mobinizadeh ◽  
Morteza Arab-Zozani
Keyword(s):  
Clinical Trial ◽  
Clinical Trials ◽  
Therapeutic Potential ◽  
Data Extraction ◽  
Rapid Review ◽  
Eligibility Criteria ◽  
Clinical Trial Registration ◽  
Registration System ◽  
Novel Coronavirus ◽  
First Time

Context: Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) appeared for the first time in December 2019 in Wuhan, China. Due to the lack of unified and integrated evidence for Favipiravir, this study was conducted to rapidly review the existing evidence to help evidence-based decision-making on the therapeutic potential of this drug in the treatment of COVID-19 patients. Evidence Acquisition: This study is a rapid Health Technology Assessment (HTA). By searching pertinent databases, the research team collected relevant articles and tried to create a policy guide through a thematic approach. This rapid review was done in four steps: (1) Searching for evidence through databases; (2) screening the evidence considering eligibility criteria; (3) data extraction; and (4) analyzing the data through thematic analysis. Results: After applying the inclusion criteria, four studies were finally found, including three review studies and a clinical trial that was temporarily removed by its publisher from the journal’s website. After searching the sources mentioned in the articles, two ongoing clinical trials were found in China. Also, by searching the clinical trial website, www.clinicaltrials.gov, five clinical trials were found in the search. The result of the search in the clinical trial registration system in Iran showed a study that is in the process of patient recruitment. A limited number of other articles were found, mostly in the form of reflections from physicians or researchers and letters to editors who have predicted the drug’s performance on SARS-CoV-2, which needs further clinical study to be approved. Conclusions: With the available evidence, it is not possible to make a definite conclusion about the safety and efficacy of Favipiravir in the treatment of patients with COVID-19.

Evaluating the Financial Impact of Clinical Trials in Oncology: Results From a Pilot Study From the Association of American Cancer Institutes/Northwestern University Clinical Trials Costs and Charges Project

2000 ◽  
Vol 18 (15) ◽  
pp. 2805-2810 ◽  
Author(s):  
Charles L. Bennett ◽  
Tammy J. Stinson ◽  
Victor Vogel ◽  
Lyn Robertson ◽  
Donald Leedy ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Clinical Trials ◽  
Pilot Study ◽  
Medical Care ◽  
Phase Ii ◽  
Third Party ◽  
Disease Stage ◽  
Cancer Center ◽  
Policy Debate ◽  
Economic Analyses

PURPOSE: Medical care for clinical trials is often not reimbursed by insurers, primarily because of concern that medical care as part of clinical trials is expensive and not part of standard medical practice. In June 2000, President Clinton ordered Medicare to reimburse for medical care expenses incurred as part of cancer clinical trials, although many private insurers are concerned about the expense of this effort. To inform this policy debate, the costs and charges of care for patients on clinical trials are being evaluated. In this Association of American Cancer Institutes (AACI) Clinical Trials Costs and Charges pilot study, we describe the results and operational considerations of one of the first completed multisite economic analyses of clinical trials. METHODS: Our pilot effort included assessment of total direct medical charges for 6 months of care for 35 case patients who received care on phase II clinical trials and for 35 matched controls (based on age, sex, disease, stage, and treatment period) at five AACI member cancer centers. Charge data were obtained for hospital and ancillary services from automated claims files at individual study institutions. The analyses were based on the perspective of a third-party payer. RESULTS: The mean age of the phase II clinical trial patients was 58.3 years versus 57.3 years for control patients. The study population included persons with cancer of the breast (n = 24), lung (n = 18), colon (n = 16), prostate (n = 4), and lymphoma (n = 8). The ratio of male-to-female patients was 3:4, with greater than 75% of patients having stage III to IV disease. Total mean charges for treatment from the time of study enrollment through 6 months were similar: $57,542 for clinical trial patients and $63,721 for control patients (1998 US$; P = .4) CONCLUSION: Multisite economic analyses of oncology clinical trials are in progress. Strategies that are not likely to overburden data managers and clinicians are possible to devise. However, these studies require careful planning and coordination among cancer center directors, finance department personnel, economists, and health services researchers.

scholarly journals Characterization of the Immune Response of MERS-CoV Vaccine Candidates Derived from Two Different Vectors in Mice

Viruses ◽  
2020 ◽  
Vol 12 (1) ◽  
pp. 125 ◽  
Author(s):  
Entao Li ◽  
Feihu Yan ◽  
Pei Huang ◽  
Hang Chi ◽  
Shengnan Xu ◽  
...  
Keyword(s):  
Immune Responses ◽  
Antibody Response ◽  
Rabies Virus ◽  
Vaccine Development ◽  
Vaccine Candidate ◽  
Viral Vector ◽  
Vaccine Vector ◽  
Vaccine Candidates ◽  
Cellular Immune Responses ◽  
Cellular Immune

Middle East respiratory syndrome (MERS) is an acute, high-mortality-rate, severe infectious disease caused by an emerging MERS coronavirus (MERS-CoV) that causes severe respiratory diseases. The continuous spread and great pandemic potential of MERS-CoV make it necessarily important to develop effective vaccines. We previously demonstrated that the application of Gram-positive enhancer matrix (GEM) particles as a bacterial vector displaying the MERS-CoV receptor-binding domain (RBD) is a very promising MERS vaccine candidate that is capable of producing potential neutralization antibodies. We have also used the rabies virus (RV) as a viral vector to design a recombinant vaccine by expressing the MERS-CoV S1 (spike) protein on the surface of the RV. In this study, we compared the immunological efficacy of the vaccine candidates in BALB/c mice in terms of the levels of humoral and cellular immune responses. The results show that the rabies virus vector-based vaccine can induce remarkably earlier antibody response and higher levels of cellular immunity than the GEM particles vector. However, the GEM particles vector-based vaccine candidate can induce remarkably higher antibody response, even at a very low dose of 1 µg. These results indicate that vaccines constructed using different vaccine vector platforms for the same pathogen have different rates and trends in humoral and cellular immune responses in the same animal model. This discovery not only provides more alternative vaccine development platforms for MERS-CoV vaccine development, but also provides a theoretical basis for our future selection of vaccine vector platforms for other specific pathogens.

scholarly journals Phase II Multicenter Randomized Controlled Clinical Trial on the Efficacy of Intra-articular Injection of Autologous Bone Marrow Mesenchymal Stem Cells with Platelet Rich Plasma for the Treatment of Knee Osteoarthritis

2020 ◽  
Author(s):  
José María Lamo-Espinosa ◽  
Juan F. Blanco ◽  
Mikel Sánchez ◽  
Victoria Moreno ◽  
Froilán Granero-Moltó ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Bone Marrow ◽  
Clinical Trials ◽  
Knee Osteoarthritis ◽  
Phase Ii ◽  
Stromal Cells ◽  
Platelet Rich Plasma ◽  
X Ray ◽  
The Mean

Abstract Background: Mesenchymal stromal cells are a safe and promising option to treat knee osteoarthritis as previously demonstrated in different clinical trials. However, their efficacy, optimal dose and addition of adjuvants must be determined. Here, we evaluated the clinical effects of a dose of 100x106 bone marrow mesenchymal stromal cells (BM-MSCs) in combination with Platelet Rich Plasma (PRGF®) as adjuvant in a randomized clinical trial.Methods: A phase II, multicenter, randomized clinical trial with active control was conducted. Sixty patients diagnosed with knee OA were randomly assigned to 3 weekly doses of PRGF® or intraarticular administration of 100x106 cultured autologous BM-MSCs plus PRGF®. Patients were followed up for 12 months, and pain and function were assessed using VAS and WOMAC and by measuring the knee range of motion range. X-ray and magnetic resonance imaging analyses were performed to analyze joint damage.Results: No adverse effects were reported after BM-MSC administration or during follow-up. According to VAS, the mean value (SD) for PRGF® and BM-MSC with PRGF® went from 5 (1.8) to 4.5 (2.2) (p=0.389) and from 5.3 (1.9) to 3.5 (2.5) (p=0.01), respectively at 12 months.. In WOMAC, the mean (SD) baseline and 12-month overall WOMAC scores in patients treated with PRGF® was 31.9 (16.2) and 22.3 (15.8) respectively (p=0.002) while that for patients treated with BM-MSC plus PRGF® was 33.4 (18.7) and 23.0 (16.6) (p=0.053). Although statistical significances between groups have been not detected, only patients being treated with BM-MSC plus PRGF® could be considered as a OA treatment responders following OARSI criteria. X-ray and MRI (WORMS protocol) revealed no changes in knee joint space width or joint damage.Conclusions: Treatment with BM-MSC associated with PRGF® was shown to be a viable therapeutic option for osteoarthritis of the knee, with clinical improvement at the end of follow-up. Further phase III clinical trials would be necessary to confirm the efficacy. Clinical Trials.gov identifier NCT02365142. Nº EudraCT: 2011-006036-23

scholarly journals What are the most promising treatments and vaccine candidates for COVID-19? A global survey of experts involved in virus research (Preprint)

2020 ◽  
Author(s):  
Bernardo Pereira Cabral ◽  
Luiza Braga ◽  
Fabio Mota
Keyword(s):  
Clinical Trial ◽  
Clinical Trials ◽  
Clinical Trial Data ◽  
Scientific Publications ◽  
Vaccine Candidates ◽  
Short Period ◽  
The World ◽  
Virus Research ◽  
Short Time ◽  
Effective Drugs

BACKGROUND The Coronavirus Disease 2019 (COVID-19) pandemic presents a great public health challenge around the world, especially given the urgency to identify effective drugs and develop a vaccine in a short period of time. Globally, there are several drug and vaccine candidates currently in clinical trials, yet it is not yet clear which will prove successful. OBJECTIVE This study addresses this gap by mapping the treatments and vaccine candidates currently in clinical trials and assessing the opinions on these candidates of virus-related researchers from all over the world. METHODS Clinical trial data were obtained from ClinicalTrials.gov and the survey’s respondents were authors of recent scientific publications related to viruses, SARS virus, coronavirus, and COVID-19 indexed in the Web of Science Core Collection. RESULTS The results show that remdesivir, immunoglobulin from cured patients and plasma are considered the most promising treatments, and ChAdOx1 and mRNA-1273 the most promising vaccine candidates. They also indicate that a vaccine could be available within eighteen months. CONCLUSIONS Changes in the clinical trial process are currently being implemented worldwide in an attempt to accelerate the discovery of an entirely new vaccine to prevent COVID-19 8. These changes may be why the respondents felt it would take such a short time to develop a vaccine. Despite the relatively high percentage of unknown answers, which may be linked to the short-term perspective of this survey and the current uncertainties surrounding the subject at hand, the results of this survey suggest that the efforts made so far to accelerate the discovery of a new vaccine are in line with its purpose. If these expectations are confirmed, perhaps the discovery that will bring an end to the COVID-19 pandemic is not so very far away

scholarly journals Global distribution of single amino acid polymorphisms in Plasmodium vivax Duffy-binding-like domain and implications for vaccine development efforts

Open Biology ◽  
2020 ◽  
Vol 10 (9) ◽  
pp. 200180
Author(s):  
Payal Mittal ◽  
Siddhartha Mishra ◽  
Sonalika Kar ◽  
Veena Pande ◽  
Abhinav Sinha ◽  
...  
Keyword(s):  
Plasmodium Vivax ◽  
Binding Sites ◽  
Vaccine Development ◽  
Vaccine Candidate ◽  
Neutralizing Antibody ◽  
Single Amino Acid ◽  
Vaccine Candidates ◽  
Malaria Burden ◽  
Single Amino Acid Polymorphisms ◽  
Polymorphic Residue

Plasmodium vivax ( Pv ) malaria continues to be geographically widespread with approximately 15 million worldwide cases annually. Along with other proteins, Duffy-binding proteins (DBPs) are used by plasmodium for RBC invasion and the parasite-encoded receptor binding regions lie in their Duffy-binding-like (DBL) domains—thus making it a prime vaccine candidate. This study explores the sequence diversity in Pv DBL globally, with an emphasis on India as it remains a major contributor to the global Pv malaria burden. Based on 1358 Pv DBL protein sequences available in NCBI, we identified 140 polymorphic sites within 315 residues of Pv DBL. Alarmingly, country-wise mapping of SAAPs from field isolates revealed varied and distinct polymorphic profiles for different nations. We report here 31 polymorphic residue positions in the global SAAP profile, most of which map to the Pv DBL subdomain 2 ( α 1– α 6). A distinct clustering of SAAPs distal to the DARC-binding sites is indicative of immune evasive strategies by the parasite. Analyses of Pv DBL-neutralizing antibody complexes revealed that between 24% and 54% of interface residues are polymorphic. This work provides a framework to recce and expand the polymorphic space coverage in Pv DBLs as this has direct implications for vaccine development studies. It also emphasizes the significance of surveying global SAAP distributions before or alongside the identification of vaccine candidates.

scholarly journals Review of Current Vaccine Development Strategies to Prevent Coronavirus Disease 2019 (COVID-19)

2020 ◽  
Vol 48 (7) ◽  
pp. 800-809 ◽  
Author(s):  
Bindu M. Bennet ◽  
Jayanthi Wolf ◽  
Rodrigo Laureano ◽  
Rani S. Sellers
Keyword(s):  
Clinical Trials ◽  
Scientific Community ◽  
Safety Assessment ◽  
Vaccine Development ◽  
Safety Data ◽  
Efficacy And Safety ◽  
Clinical Safety ◽  
Safety And Efficacy ◽  
Vaccine Candidates ◽  
Current Vaccine

The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) outbreak that started in Wuhan, China, in 2019 resulted in a pandemic not seen for a century, and there is an urgent need to develop safe and efficacious vaccines. The scientific community has made tremendous efforts to understand the disease, and unparalleled efforts are ongoing to develop vaccines and treatments. Toxicologists and pathologists are involved in these efforts to test the efficacy and safety of vaccine candidates. Presently, there are several SARS-CoV-2 vaccines in clinical trials, and the pace of vaccine development has been highly accelerated to meet the urgent need. By 2021, efficacy and safety data from clinical trials are expected, and potentially a vaccine will be available for those most at risk. This review focuses on the ongoing SARS-CoV-2 vaccine development efforts with emphasis on the nonclinical safety assessment and discusses emerging preliminary data from nonclinical and clinical studies. It also provides a brief overview on vaccines for other coronaviruses, since experience gained from these can be useful in the development of SARS-CoV-2 vaccines. This review will also explain why, despite this unprecedented pace of vaccine development, rigorous standards are in place to ensure nonclinical and clinical safety and efficacy. [Box: see text]

Current Status on Treatments and Clinical Trials for COVID-19 (Preprint)

2020 ◽  
Author(s):  
Guosheng Yin ◽  
Chenyang Zhang ◽  
Huaqing Jin
Keyword(s):  
Clinical Trials ◽  
Phase Ii ◽  
Developmental Process ◽  
Current Situation ◽  
Current Status ◽  
The Novel ◽  
Fast Speed ◽  
Death Toll ◽  
Number Of Patients ◽  
Novel Coronavirus

UNSTRUCTURED With the worldwide rapidly growing number of patients infected with the novel coronavirus (COVID-19), the death toll has also been climbing up at a fast speed. There is an urgent need to search for cures for COVID-19 patients. A large number of clinical trials have been launched to test some existing or new antiviral therapeutics and vaccines. In contrast to starting from the scratch, many trials are initiated directly in phase II or III with the hope to expedite the developmental process. We summarize the information on the registered trials for the top ten COVID-19 drugs, and give an overview on the current situation and trend of treatments and clinical trials. In particular, we review those trials that have already been finished and discuss lessons that can be learned from them.

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