scholarly journals Safety and efficacy of RNA vaccines: State of the art

2021 ◽  
Vol 23 (5) ◽  
pp. 1017-1030
Author(s):  
A. V. Blagov ◽  
A. A. Bukaeva ◽  
V. V. Makarov ◽  
Z. V. Bochkaeva
Keyword(s):  
Clinical Trials ◽  
Ebola Virus ◽  
Viral Infections ◽  
Phase Iii ◽  
Protective Properties ◽  
Market Launch ◽  
The World ◽  
Mass Immunization ◽  
First Results ◽  
The Moment

This review describes principles of action and the method of delivery of mRNA molecules into cells, as well as some of developed RNA vaccines and the results obtained in their study, though they have not been authorized for use yet. In addition, the review discusses efficacy and safety proved for RNA vaccines registered for COVID-19 prevention at the time of writing. The development, clinical trials and market launch of RNA vaccines for mass immunization in a few months can be considered one of the major breakthroughs in pharmacology over the past year. Despite of all seemingly indisputable advantages, none of RNA vaccines had reached Phase III of clinical trials since the moment of its discovery in 1993 until last year. The first experience of the successful use of mRNA vaccines was back in the 90s of the last century, when vaccination of mice with liposomes encoding an antigen-encoding mRNA was found to initiate specific immune response in mice. However, in these years, the method did not find application, due to the toxicity of lipids used. Subsequently, a large number of attempts have been made to develop vaccines against other viral infections, including Zika virus, Dengue virus, Ebola virus, cytomegalovirus, influenza virus and others. Despite the importance for preventing the spread of these diseases, the development of a vaccine preparation is a rather lengthy process, and final success is not guaranteed. However, the COVID-19 pandemic has become speeded the development of mRNA vaccines up.At the time of writing the review, two mRNA-based vaccines have been registered only in the world, both, BNT162b2 and mRNA-1273, were against COVID-19. Their effectiveness and safety are still actively studied. Moreover, it took less than a year for new strains of SARS-CoV-2 to appear, and the efficiency of vaccines against them was found to be lower than against the reference pathogen variant. Considering that the three new strains of SARS-CoV-2, “British”, “African” and “Brazilian”, are rapidly spreading in the world, the first results of efficiency evaluation of vaccines against them have already been published. One may expect that, considering mutations in these strains, the BNT162b2 and mRNA-1273 vaccines will remain effective against the “British” strain, but their protective properties are greatly weakened against the “African” variant.

scholarly journals COVID-19: Role of Nutrition and Supplementation

Nutrients ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 976
Author(s):  
Fiorenzo Moscatelli ◽  
Francesco Sessa ◽  
Anna Valenzano ◽  
Rita Polito ◽  
Vincenzo Monda ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Randomized Clinical Trials ◽  
Viral Infections ◽  
Overweight And Obesity ◽  
Shortness Of Breath ◽  
Nutritional Interventions ◽  
The World ◽  
Diet Regimen ◽  
Specific Diet

At the end of 2019, a new coronavirus (COVID-19) appeared on the world scene, which mainly affects the respiratory system, causing pneumonia and multi-organ failure, and, although it starts with common symptoms such as shortness of breath and fever, in about 2–3% of cases it leads to death. Unfortunately, to date, no specific treatments have been found for the cure of this virus and, therefore, it is advisable to implement all possible strategies in order to prevent infection. In this context, it is important to better define the role of all behaviors, in particular nutrition, in order to establish whether these can both prevent infection and improve the outcome of the disease in patients with COVID-19. In the literature, it is widely shown that states of malnutrition, overweight, and obesity negatively affect the immune system, leading to viral infections, and several studies have shown that nutritional interventions can act as immunostimulators, helping to prevent viral infections. Even if several measures, such as the assumption of a specific diet regimen, the use of dietary supplements, and other similar interventions, are promising for the prevention, management, and recovery of COVID-19 patients, it is important to highlight that strong data from randomized clinical trials are needed to support any such assumption. Considering this particular scenario, we present a literature review addressing several important aspects related to diet and SARS-CoV-2 infection, in order to highlight the importance of diet and supplementation in prevention and management of, as well as recovery from COVID-19.

scholarly journals Self-Replicating RNA Viruses for RNA Therapeutics

Molecules ◽  
2018 ◽  
Vol 23 (12) ◽  
pp. 3310 ◽  
Author(s):  
Kenneth Lundstrom
Keyword(s):  
Clinical Trials ◽  
Phase I ◽  
Tumor Cells ◽  
Neutralizing Antibodies ◽  
Ebola Virus ◽  
Vaccine Development ◽  
Rna Viruses ◽  
Antibody Responses ◽  
Phase Iii ◽  
Phase I Clinical Trials

Self-replicating single-stranded RNA viruses such as alphaviruses, flaviviruses, measles viruses, and rhabdoviruses provide efficient delivery and high-level expression of therapeutic genes due to their high capacity of RNA replication. This has contributed to novel approaches for therapeutic applications including vaccine development and gene therapy-based immunotherapy. Numerous studies in animal tumor models have demonstrated that self-replicating RNA viral vectors can generate antibody responses against infectious agents and tumor cells. Moreover, protection against challenges with pathogenic Ebola virus was obtained in primates immunized with alphaviruses and flaviviruses. Similarly, vaccinated animals have been demonstrated to withstand challenges with lethal doses of tumor cells. Furthermore, clinical trials have been conducted for several indications with self-amplifying RNA viruses. In this context, alphaviruses have been subjected to phase I clinical trials for a cytomegalovirus vaccine generating neutralizing antibodies in healthy volunteers, and for antigen delivery to dendritic cells providing clinically relevant antibody responses in cancer patients, respectively. Likewise, rhabdovirus particles have been subjected to phase I/II clinical trials showing good safety and immunogenicity against Ebola virus. Rhabdoviruses have generated promising results in phase III trials against Ebola virus. The purpose of this review is to summarize the achievements of using self-replicating RNA viruses for RNA therapy based on preclinical animal studies and clinical trials in humans.

Current advances in novel SARS-CoV-2 disease (COVID-19) treatment and intervention strategies

Coronaviruses ◽  
2020 ◽  
Vol 01 ◽  
Author(s):  
Mohammad Khalid Parvez ◽  
Kartika Padhan
Keyword(s):  
Clinical Trials ◽  
Ebola Virus ◽  
Management Strategies ◽  
Intervention Strategies ◽  
Phase Iii ◽  
World Health ◽  
Plasma Therapy ◽  
Health Crisis ◽  
Vaccine Candidates ◽  
Poor Countries

Background: Down the seven months of the novel SARS-CoV-2 disease (COVID-19) outbreak in China and its global spread, there is a remarkable understanding of its epidemiology, pathobiology and clinical management strategies. While countering a heavy toll on health and economy, world’s regional authorities are enforcing safety guidelines and providing patient care. Currently, there is no globally approved treatment or intervention for COVID-19. Methods: A structured online literature search for peer-reviewed articles was conducted on the PubMed, Europe PMC, Google, WHO, CDC, FDA and ClinicalTrials portals, using phrases such as COVID-19 treatment and intervention, COVID-19 drugs and COVID-19 vaccines. Results: Analysis of the retrieved data showed that as a part of ‘Solidarity Clinical Trials’, hundreds of treatment and intervention strategies, including antiviral drugs, cytokine antagonists, convalescent plasma therapy and vaccine candidates have been registered, worldwide. Of these, while remdesivir the anti-Ebola virus drug has been granted approval as ‘emergency use’ drug in USA, favipiravir, the anti-flu drug has been recently approved in Russia. Tocilizumab and sarilumab, the cytokine (IL-6) antagonists have entered Phase-II/III clinical trials in hospitalized COVID-19 patients. Among the leading vaccine candidates, an mRNA-1273 vaccine along with Pfizer mRNA candidate and Oxford ChAdOx1vaccine have entered Phase-III trial. Conclusion: The world health authorities have strongly and quickly responded to COVID-19 pandemic. Nonetheless, it is imperative for world bodies to unite in combating this health crisis by developing costeffective drugs and vaccines, and making them accessible to resource-poor countries.

Unescheduled visits in cancer patients treated in a clinical trials unit (CTU).

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e17580-e17580
Author(s):  
Lydia Gaba ◽  
Iván Victoria ◽  
Óscar Reig ◽  
Sandra Lopez ◽  
Pedro Gascon ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Metastatic Cancer ◽  
Epidemiological Data ◽  
Phase Iii ◽  
Phase Iii Clinical Trials ◽  
Skin Symptoms ◽  
Clinical Trials Unit ◽  
The Moment ◽  
Relationship Of ◽  
Chemotherapy Agents

e17580 Background: A number of unscheduled visits may occur in addition to the predefined protocol-specific visit calendars in a CTU. The aim of this prospective study was to characterize and assesss the frequency, causes and the probable relationship of the emergencies with the investigational products (IPs). Methods: A consecutive sample of patients treated in a CTU who presented an urgent medical consultation from July 2012 to January 2013 was registered. Epidemiological data, characteristics of emergency visits and relationship with IPs were revised. Results: 141 patients were registered; 75 men (53.2%) and 66 women (46.8%) with a median age of 61.4 years. Most of them had metastatic cancer and 63 patients (44.7%) had been included in phase III clinical trials. Tumors which produced a higher number of events were melanoma (n=53, 37.6%), colorectal (n=24, 17%) and breast cancer (n=21, 14.9%). Those treatments associated with more unscheduled consultations were chemotherapy agents, Braf inhibitors and antiEGFR antibodies. Of those, 45.4% were in-person consultations, whereas the 54.6% were performed by phone. The main causes were pain (18.4%), diarrhea (12.1%), fever (12.1%) and skin symptoms (10.6%). 48.9% were related to an adverse event of the IPs. 78.7% of the consultations were oriented and specifically treated at the moment of the appointment, whereas the 21.3% had to be referred to another service. 36.2% of the unscheduled visits were directly related with the IPs. Of those, 30% were 3-4 graded. Conclusions: Patients treated on a clinical trial generated an elevated number of unescheduled visits and a significant percentage of them are related to the IPs. Most of them should be managed by staff with the appropriate knowledge and training.

scholarly journals Ongoing Clinical and Immunization Trials for Novel Zoonotic Covid -19 Pandemic

2021 ◽  
pp. 85-93
Author(s):  
Ramya Kumari B. S.
Keyword(s):  
Clinical Trials ◽  
Mortality Rate ◽  
Infectious Diseases ◽  
Phase I ◽  
Viral Infection ◽  
Host Cell ◽  
Phase Iii ◽  
Specific Level ◽  
Contagious Diseases ◽  
The World

Some of the contagious diseases have created history and also remains with us today. So it becomes utmost important to understand such infectious diseases and exploring their remedies. One such disease which has created havoc across the globe is COVID-19, caused by an agent SARS CoV-2 virus. The current threat of coronavirus is the human health and economy, which can be overcome by the development of a target vaccine at a specific level by blocking the entry of virus inside the host cell. This step not only will reduce the morbidity and mortality rate associated with this viral infection but will also improve upon the prevailing economy crisis. Hence, this review chapter aims at the ongoing clinical and immunization trials for novel zoonotic COVID-19 pandemic. Currently the clinical trials are happening throughout the world and all the trials are to be registered in publicly available domain which is recommended by ICMJE. Different phase of trials in various parts of the globe, includes Phase-I to Phase-III and insights of vaccine developers involved in the development of COVID vaccines are the focused areas in this review chapter.

scholarly journals Anti-HCV antiviral therapies as an alternative for the treatment of Covid-19

2020 ◽  
Vol 9 (10) ◽  
pp. e9489109406
Author(s):  
Giuliene Rocha de Medeiros ◽  
Isabela Cristina Cordeiro Farias ◽  
João Victor Cordeiro Farias ◽  
Penelopy Rodrigues de Macedo
Keyword(s):  
Clinical Trials ◽  
Hepatitis C ◽  
Clinical Results ◽  
Antiviral Therapies ◽  
The World ◽  
Qualitative Nature ◽  
Catalytic Mechanisms ◽  
Type Studies ◽  
The Moment ◽  
Potential Inhibitors

The current pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread alarmingly around the world at a significantly faster speed than previous coronaviral outbreaks. Due to the lack of a vaccine at the moment, an early antiviral intervention can prevent the spread of the disease worldwide and improve the clinical results of infected patients. The SARS-CoV-2 virus and the Hepatitis C virus (HCV) have a similar structure, replication, and catalytic mechanisms, therefore, several studies have considered the potential for antiviral activity of anti-HCV drugs such as remdesivir, simeprevir, sofosbuvir, and daclatasvir against SARS-CoV-2. Therefore, the present study aims to evaluate and discuss the antivirals already available against HCV, which have also been shown to be potential inhibitors of SARS-CoV-2 replication. The study was based on a literature review, of a qualitative nature and an exploratory type. Studies with anti-HCV drugs are promising and are already considered to start clinical trials in patients infected with the new coronavirus, having been observed as inhibitors of SARS-CoV-2 viral replication. Thus, the present study brings a pharmaco-clinical review on antivirals remdesivir, simeprevir, sofosbuvir, and daclatasvir, considering the main studies carried out to date in the treatment for Covid-19.

COVID-19, Gender, and Intersectional Discrimination: Can the Promise of International Human Rights Meet the Moment?

2020 ◽  
Vol 114 ◽  
pp. 377-381
Author(s):  
Amanda M. Klasing
Keyword(s):  
Human Rights ◽  
Ebola Virus ◽  
Disease Outbreaks ◽  
Northeast Brazil ◽  
International Human Rights ◽  
Gender Inequity ◽  
The World ◽  
Women And Girls ◽  
International Human ◽  
The Moment

Human rights documentation around the world has shown that crises disproportionately or distinctly impacts women and girls, whether conflict or natural disaster-related. This is true for disease outbreaks as well. Human Rights Watch has raised the concerns about the gendered impacts of the Ebola virus outbreaks in West Africa, or the human rights dimensions of the Zika virus impacts in northeast Brazil. The COVID-19 pandemic and response are no different. We are already seeing the disproportionate and gendered ways government responses to the pandemic are generating harm to women and girls and reinforcing longstanding gender inequity.

scholarly journals Anticancer bispecific antibody R&D advances: a study focusing on research trend worldwide and in China

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Zhonghan Zhang ◽  
Fan Luo ◽  
Jiaxin Cao ◽  
Feiteng Lu ◽  
Yang Zhang ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Clinical Research ◽  
Phase I ◽  
Bispecific Antibody ◽  
Gastroesophageal Junction ◽  
Nasopharyngeal Cancer ◽  
Phase Iii ◽  
Research Trend ◽  
Distribution Analysis ◽  
The World

Abstract Background The bispecific antibody (bsAbs) research around the world has undergone great changes. We analyzed the global trend of bsAbs research and compared the differences in clinical research of bsAbs between China and worldwide. Methods BsAbs research clinical trials information was retrieved through the online open-resource clinical trial registration platform. Research information including organizations, identity numbers, locations, phases, participating centers, conditions, status, enrollment, targets, spectrums of mechanism of action (MOA), and start date was collected. Clinical trials were divided into two categories based on the attributes of pharmaceutical companies (international or China-initiated or involved). Results From 1997 to 2020, 272 clinical trials regarding bsAbs research were retrieved. Twenty-nine percent of the studies were contributed by companies from Chinese institutions, which followed the USA and ranked second. The clinical trials of bsAbs are mainly concentrated on phase I (n = 161), phase I/II (n = 54), and phase II (n = 51), and the number of phase III trials is still rare (n = 4). Tumor species distribution analysis shows that there are significantly higher focuses on gastric cancer (n = 18), esophageal/gastroesophageal junction cancer (n = 16), bladder cancer (n = 10), biliary malignant tumor (n = 8), nasopharyngeal cancer (n = 6), and thymic cancer (n = 2) in China. BsAbs target and spectrums of MOA analysis showed that international companies mainly focus on bsAbs with CD3-based (n = 63) target with MOA of T-cell redirection, while researches in China pay more attention to PD-1 (n = 9)/PD-L1 (n = 7) axises with MOA of double immune checkpoint blocking. Conclusion Global bsAbs research increased rapidly during the 1997 to 2020 period. The developed countries in America and Europe are leading the trend of bsAbs research. Anticancer bsAbs clinical research in China is booming and chasing after the world trend.

Glycoprotein GP as a basis for the universal vaccine against Ebola virus disease

2019 ◽  
pp. 78-85
Author(s):  
IV Dolzhikova ◽  
AI Tukhvatulin ◽  
AS Gromova ◽  
DM Grousova ◽  
NM Tukhvatulina ◽  
...  
Keyword(s):  
Ebola Virus ◽  
Viral Infections ◽  
Vaccine Development ◽  
Virus Disease ◽  
Ebola Virus Disease ◽  
Universal Vaccine ◽  
Protective Properties ◽  
Protective Epitope ◽  
Zaire Ebolavirus ◽  
Immunodominant Epitopes

Ebola virus disease (EVD) is one of the deadliest viral infections affecting humans and nonhuman primates. Of 6 known representatives of the Ebolavirus genus responsible for the disease, 3 can infect humans, causing acute highly contagious fever characterized by up to 90% fatality. These include Bundibugyo ebolavirus (BDBV), Zaire ebolavirus (ZEBOV) and Sudan ebolavirus (SUDV). The majority of the reported EVD cases are caused by ZEBOV. Vaccine development against the virus started in 1976, immediately after the causative agent of the infection was identified. So far, 4 vaccines have been approved. All of them are based on the protective epitope of the ZEBOV glycoprotein GP. Because SUDV and BDBV can also cause outbreaks and epidemics, it is vital to design a vaccine capable of conferring protection against all known ebolaviruses posing a threat to the human population. This article presents systematized data on the structure, immunogenicity and protective properties of ebolavirus glycoprotein GP, looks closely at the immunodominant epitopes of ZEBOV, SUDV and BDBV glycoprotein GP required to elicit a protective immune response, and offers a rational perspective on the development of a universal vaccine against EVD that relies on the use of vectors expressing two variants of GP represented by ZEBOV and SUDV.

scholarly journals Vaccine Development against COVID-19: Study from Pre-Clinical Phases to Clinical Trials and Global Use

Vaccines ◽  
2021 ◽  
Vol 9 (8) ◽  
pp. 836
Author(s):  
Sagheer Ahmed ◽  
Saeed Khan ◽  
Imran Imran ◽  
Fadwa Al Mughairbi ◽  
Fahad Sultan Sheikh ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Vaccine Development ◽  
Clinical Investigation ◽  
World Health ◽  
Phase 3 ◽  
Global Demand ◽  
The World ◽  
Advanced Stages ◽  
The Moment ◽  
Health Organization

As per the World Health Organization (WHO), more than 288 vaccines against COVID-19 are being developed, with an estimated 184 being presently investigated in the pre-clinical phases, while 104 of these vaccine candidates are at various stages of clinical trials. Twelve of these are in the advanced stages of clinical investigation, and promising results in the phase 3 trials have already paved the way for their regulatory approval and subsequent dissemination for global use. Preliminary and interim results of some of these candidate vaccines are being analyzed for public dissemination. Some of these vaccines have already been rolled out to immunize not only the highest risk individuals but also the general population in several countries. Once their safety and efficacy are established, the next limiting step would be their mass manufacturing by the pharmaceutical companies to fulfill the global demand. The challenge of manufacturing billions of doses of high-quality vaccines is under-appreciated at the moment. A massive vaccination drive would be needed to protect people of all ages. The timely and coordinated execution of the vaccination effort would require unprecedented coordination at the national and international levels for generating funds to purchase the required doses of vaccines, fair distribution of doses and managing the mechanics of delivering vaccines throughout the world.

Sign in / Sign up

Export Citation Format

Share Document