scholarly journals Approaches to quality control, preclinical and clinical studies of live recombinant viral vector vaccines

2021 ◽  
Vol 21 (4) ◽  
pp. 212-224
Author(s):  
L. M. Khantimirova ◽  
D. V. Gorenkov ◽  
S. G. Guseva ◽  
V. A. Merkulov ◽  
A. A. Soldatov
Keyword(s):  
Quality Control ◽  
Clinical Studies ◽  
Vaccine Development ◽  
Viral Vector ◽  
Virus Genome ◽  
Heterologous Antigen ◽  
Risk Benefit Assessment ◽  
Regulatory Guidelines ◽  
Preclinical And Clinical Studies ◽  
Japanese Guidelines

At present, there are not much data on the clinical use of live recombinant viral vector vaccines. Characteristics of new vaccines should be factored into requirements/recommendations for quality control, preclinical and clinical studies of vaccines in order to enable further risk/benefit assessment. The aim of this study was to analyse current approaches to quality control, preclinical and clinical studies of live recombinant viral vector vaccines. The paper provides an overview of the licensed live viral vector vaccines and those at various stages of clinical trials. The authors analysed Russian, European, American, and Japanese guidelines related to quality issues, preclinical and clinical studies of live viral vector vaccines. The analysis demonstrated that the regulatory requirements for live recombinant viral vector vaccines include assessment of a detailed rationale for vaccine development, including information on the choice of the vector, the origin of the heterologous antigen gene(s), elements related to the transgene(s) expression, as well as assessment of the genetic and phenotypic stability of the recombinant virus, the risk of reversion to virulence or recombination with wild type strains, the potential for virus genome integration into the host cell chromosome, the pre-existing immunity to the vector, the intensity of the immune response elicited by the vector, and the reusability of the vector. The choice and number of applicable toxicological and pharmacological models will depend on these aspects. The results of the analysis of approaches to quality control, preclinical and clinical studies of live recombinant viral vector vaccines may be used in the development of Russian regulatory guidelines harmonised with the international norms and regulations.

scholarly journals Russian and International Regulatory Recommendations for the Development and Marketing Authorisation of COVID-19 Vaccines in the Context of the Pandemic

2020 ◽  
Vol 20 (4) ◽  
pp. 228-244
Author(s):  
A. A. Soldatov ◽  
Zh. I. Avdeeva ◽  
V. P. Bondarev ◽  
V. A. Merkulov ◽  
V. D. Mosyagin ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Clinical Studies ◽  
Marketing Authorisation ◽  
Fast Track ◽  
Vaccine Development ◽  
The United States ◽  
The European Union ◽  
Regulatory Requirements ◽  
Good Tolerability ◽  
Preclinical And Clinical Studies

The progress of the COVID-19 pandemic initiated research to develop vaccines against this novel coronavirus infection. The WHO and national regulatory authorities in many countries have elaborated guidelines to speed up the development and authorisation of COVID-19 vaccines.The aim of the study was to analyse international and Russian regulatory recommendations for the development and fast-track approval of COVID-19 vaccines in the context of the pandemic, as well as to summarise the preliminary published results of the first stages of preclinical and clinical studies. The paper analyses approaches to fast-track approval of medicines in the face of the pandemic in Russia, the European Union, and the United States. It summarises regulatory requirements for the quality of COVID-19 vaccines, as well as for preclinical, and clinical studies. It describes the first results of COVID-19 vaccine development. The analysed regulatory documents allow for accelerated authorisation due to reduction of time spent on evaluation of vaccine quality, safety, and efficacy. Another option is the so-called conditional marketing authorisation when a vaccine is registered based on incomplete preclinical and clinical data provided that all the studies will be completed after the vaccine authorisation. The paper summarises the results of clinical trials of COVID-19 vaccines. The few published preliminary results of the first phases of COVID-19 vaccine clinical trials demonstrate the vaccines’ good tolerability, safety, and immunogenicity. Evaluation of adenovirusbased vaccines showed that almost half of the volunteers had had high antibody titers to adenovirus before the study, which resulted in milder adverse reactions and low immunogenicity. In addition, the immune response was weaker in the older group of subjects (45–60 years) as compared to the subjects younger than 45 years. The results of the analysis of regulatory requirements for the development and marketing authorisation of COVID-19 vaccines in the context of the pandemic, as well as of national and international regulatory approaches to vaccine development and authorisation can be used as a basis for the development of Russian requirements for COVID-19 vaccines in the context of the pandemic.

scholarly journals Viral Vector-Based Melanoma Gene Therapy

Biomedicines ◽  
2020 ◽  
Vol 8 (3) ◽  
pp. 60 ◽  
Author(s):  
Altijana Hromic-Jahjefendic ◽  
Kenneth Lundstrom
Keyword(s):  
Gene Therapy ◽  
Malignant Melanoma ◽  
Clinical Studies ◽  
Measles Virus ◽  
Viral Vectors ◽  
Viral Vector ◽  
Oncolytic Viruses ◽  
Full Potential ◽  
Herpes Simplex Viruses ◽  
Preclinical And Clinical Studies

Gene therapy applications of oncolytic viruses represent an attractive alternative for cancer treatment. A broad range of oncolytic viruses, including adenoviruses, adeno-associated viruses, alphaviruses, herpes simplex viruses, retroviruses, lentiviruses, rhabdoviruses, reoviruses, measles virus, Newcastle disease virus, picornaviruses and poxviruses, have been used in diverse preclinical and clinical studies for the treatment of various diseases, including colon, head-and-neck, prostate and breast cancer as well as squamous cell carcinoma and glioma. The majority of studies have focused on immunotherapy and several drugs based on viral vectors have been approved. However, gene therapy for malignant melanoma based on viral vectors has not been utilized to its full potential yet. This review represents a summary of the achievements of preclinical and clinical studies using viral vectors, with the focus on malignant melanoma.

scholarly journals Probiotic triangle of success; strain production, clinical studies and product development

2020 ◽  
Vol 367 (19) ◽  
Author(s):  
Sofia D Forssten ◽  
Arja Laitila ◽  
Johanna Maukonen ◽  
Arthur C Ouwehand
Keyword(s):  
Clinical Studies ◽  
Culture Media ◽  
Health Benefit ◽  
High Yield ◽  
Customer Requirements ◽  
Regulatory Guidelines ◽  
Challenges And Opportunities ◽  
The Right ◽  
Preclinical And Clinical Studies ◽  
Processing Aids

ABSTRACT The successful development of probiotic foods and dietary supplements rests on three pillars; each with their specific challenges and opportunities. First, strain production; this depends on selecting the right strain with promising technological properties and safety profile. Further the manufacturing of the strain in a stable format at sufficiently high yield, following regulatory and customer requirements on culture media ingredients and other processing aids. The second pillar are the preclinical and clinical studies to document that the strain is a probiotic and exerts a health benefit on the host, the consumer. Especially when aiming for a regulator approved health claim, clinical studies need to be thoroughly performed; following appropriate ethical, scientific and regulatory guidelines. Finally, the probiotic will need to be incorporated in a product that can be brought to the consumer; a dietary supplement or a functional food. Because of the live nature of probiotics, specific challenges may need to be dealt with. Although experience from other strains is helpful in the process, the development is strain specific. Commercialisation and marketing of probiotics are strictly but differently regulated in most jurisdictions; defining what can and cannot be claimed.

scholarly journals Principles and Challenges in anti-COVID-19 Vaccine Development

2021 ◽  
pp. 1-11
Author(s):  
Zuzana Strizova ◽  
Jitka Smetanova ◽  
Jirina Bartunkova ◽  
Tomas Milota
Keyword(s):  
Clinical Trials ◽  
Immune Responses ◽  
Vaccine Development ◽  
Viral Vector ◽  
Health It ◽  
Therapeutic Approaches ◽  
Clinical Phase ◽  
Adaptive Immune ◽  
Limited Efficacy ◽  
Safe Vaccine

The number of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-infected patients keeps rising in most of the European countries despite the pandemic precaution measures. The current antiviral and anti-inflammatory therapeutic approaches are only supportive, have limited efficacy, and the prevention in reducing the transmission of SARS-CoV-2 virus is the best hope for public health. It is presumed that an effective vaccination against SARS-CoV-2 infection could mobilize the innate and adaptive immune responses and provide a protection against severe forms of coronavirus disease 2019 (COVID-19) disease. As the race for the effective and safe vaccine has begun, different strategies were introduced. To date, viral vector-based vaccines, genetic vaccines, attenuated vaccines, and protein-based vaccines are the major vaccine types tested in the clinical trials. Over 80 clinical trials have been initiated; however, only 18 vaccines have reached the clinical phase II/III or III, and 4 vaccine candidates are under consideration or have been approved for the use so far. In addition, the protective effect of the off-target vaccines, such as <i>Bacillus</i> Calmette-Guérin and measles vaccine, is being explored in randomized prospective clinical trials with SARS-CoV-2-infected patients. In this review, we discuss the most promising anti-COVID-19 vaccine clinical trials and different vaccination strategies in order to provide more clarity into the ongoing clinical trials.

scholarly journals Are We Paving the Way to Dig Out of the “Pandemic Hole”? A Narrative Review on SARS-CoV-2 Vaccination: From Animal Models to Human Immunization

2021 ◽  
Vol 9 (3) ◽  
pp. 53
Author(s):  
Giuseppe Tardiolo ◽  
Pina Brianti ◽  
Daniela Sapienza ◽  
Pia dell’Utri ◽  
Viviane Di Dio ◽  
...  
Keyword(s):  
Animal Models ◽  
Viral Vector ◽  
Herd Immunity ◽  
Population Level ◽  
Narrative Review ◽  
Therapeutic Interventions ◽  
Preclinical Research ◽  
Inactivated Vaccines ◽  
Preclinical And Clinical Studies ◽  
Social Upheaval

The Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is a new pathogen agent causing the coronavirus infectious disease (COVID-19). This novel virus originated the most challenging pandemic in this century, causing economic and social upheaval internationally. The extreme infectiousness and high mortality rates incentivized the development of vaccines to control this pandemic to prevent further morbidity and mortality. This international scenario led academic scientists, industries, and governments to work and collaborate strongly to make a portfolio of vaccines available at an unprecedented pace. Indeed, the robust collaboration between public systems and private companies led to resolutive actions for accelerating therapeutic interventions and vaccines mechanism. These strategies contributed to rapidly identifying safe and effective vaccines as quickly and efficiently as possible. Preclinical research employed animal models to develop vaccines that induce protective and long-lived immune responses. A spectrum of vaccines is worldwide under investigation in various preclinical and clinical studies to develop both individual protection and safe development of population-level herd immunity. Companies employed and developed different technological approaches for vaccines production, including inactivated vaccines, live-attenuated, non-replicating viral vector vaccines, as well as acid nucleic-based vaccines. In this view, the present narrative review provides an overview of current vaccination strategies, taking into account both preclinical studies and clinical trials in humans. Furthermore, to better understand immunization, animal models on SARS-CoV-2 pathogenesis are also briefly discussed.

scholarly journals Toxic Animal-Based Medicinal Materials Can Be Effective in Treating Endometriosis: A Scoping Review

Toxins ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 145
Author(s):  
Su-In Hwang ◽  
Young-Jin Yoon ◽  
Soo-Hyun Sung ◽  
Ki-Tae Ha ◽  
Jang-Kyung Park
Keyword(s):  
Side Effects ◽  
Clinical Studies ◽  
Malignant Tumors ◽  
Experimental Studies ◽  
Herbal Medicines ◽  
Treatment Method ◽  
Reproductive Age ◽  
Dependent Growth ◽  
Gynecological Disorder ◽  
Preclinical And Clinical Studies

Animal toxins and venoms have recently been developed as cancer treatments possessing tumor cell growth-inhibitory, antiangiogenesis, and proapoptotic effects. Endometriosis is a common benign gynecological disorder in reproductive-age women, and no definite treatment for this disorder is without severe side effects. As endometriosis and malignant tumors share similar characteristics (progressive, invasive, estrogen-dependent growth, and recurrence), animal toxins and venoms are thought to be effective against endometriosis. The objective of this study was to outline studies using toxic animal-based medicinal materials (TMM) as endometriosis treatment and to explore its clinical applicability. Preclinical and clinical studies using TMM were searched for in four databases from inception to October 2020. A total of 20 studies of TMM on endometriosis were included. In eight clinical studies, herbal medicines containing TMM were effective in relieving symptoms of endometriosis, with no side effects. In twelve experimental studies, the main therapeutic mechanisms of TMM against endometriosis were proapoptotic, antiangiogenesis, estrogen level-reducing, and possible anti-inflammatory effects. TMM are thus considered promising sources for the development of an effective treatment method for endometriosis. Further studies are needed to clarify the therapeutic mechanism of TMM against endometriosis and to provide sufficient grounds for clinical application.

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