Toxicology and biodistribution study of CIGB-230, a DNA vaccine against hepatitis C virus

2009 ◽  
Vol 28 (8) ◽  
pp. 479-491 ◽  
Author(s):  
Dania Bacardí ◽  
Yalena Amador-Cañizares ◽  
Karelia Cosme ◽  
Dioslaida Urquiza ◽  
José Suárez ◽  
...  

CIGB-230, a mixture of a DNA plasmid expressing hepatitis C virus (HCV) structural antigens and a HCV recombinant capsid protein, has demonstrated to elicit strong immune responses in animals. The present study evaluated the plasmid biodistribution after the administration of CIGB-230 in mice, as well as toxicity of this vaccine candidate in rats. In the biodistribution study, mice received single or repeated intramuscular injections of CIGB-230, 50 μg of plasmid DNA mixed with 5 μg of Co.120 protein. Plasmid presence was assessed in ovaries, kidney, liver, pancreas, mesenteric ganglion, blood, and muscle of the injection site by a qualitative polymerase chain reaction. The toxicology evaluation included treatment groups receiving doses 5, 15, or 50 times higher, according to the body weight, than the expected therapeutic clinical dose. During the first hour after repeated inoculation, a promiscuous distribution was observed. However, 3 months later, plasmid could not be detected in any tissue. There was an absence of detectable adverse effects on key toxicology parameters and no damage evidenced in inspected organs and tissues. These results indicate that CIGB-230 is nontoxic at local and systemic levels and no concerns about persistence are observed, which support clinical testing of this vaccine candidate against HCV.

Author(s):  
Oksana Aleksandrovna Rybachok

Despite the height of the coronavirus infection, the Nobel Prize in Medicine was awarded in Stockholm in October 2020. This event was held online for the first time and was not accompanied by the traditional honoring of the laureates. In his will, Alfred Nobel entrusted the selection of the winner in this nomination to the Karolinska Medical and Surgical University of Stockholm, and the first award in this nomination took place in 1901. Since then, this event has been held 110 times, and 216 scientists have become laureates of the prize in the field of physiology and medicine, since the nominees are often not just one, but a group of researchers. This happened in 2020 - for research in the field of studying the hepatitis C virus, three scientists received the most prestigious award: the British Michael Houghton and the Americans Harvey Alter and Charles Rice. Due to the results of the research, which these three people conducted separately from each other, for the first time it became possible to completely eliminate the virus from the body.


2006 ◽  
Vol 87 (1) ◽  
pp. 61-72 ◽  
Author(s):  
Wen Li ◽  
Jie Li ◽  
D. Lorne J. Tyrrell ◽  
Babita Agrawal

The majority of hepatitis C virus (HCV)-infected individuals become chronically infected, which can result in liver cirrhosis and hepatocellular carcinoma. Patients with chronic HCV are unable to prime and maintain vigorous T-cell responses, which are required to rid the body of the viral infection. Dendritic cells (DCs) are the professional antigen-presenting cells that probably play a dominant role in priming and maintaining vigorous T-cell responses in HCV infection. Furthermore, inefficient DC function may play an important role in HCV chronicity. In order to determine the effect of HCV NS3 and core proteins on phenotype and function of human DCs, recombinant adenoviral vectors containing NS3 or core genes were used to infect human DCs. HCV NS3- or core-protein expression in DCs was confirmed by Western blotting and immunofluorescence staining. The DCs expressing HCV NS3 or core proteins expressed several inflammatory cytokine mRNAs, had a normal phenotype and effectively stimulated allogeneic T cells, as well as T cells specific for another foreign antigen (tetanus toxoid). These findings are important for rational design of cellular-vaccine approaches for the immunotherapy of chronic HCV.


2019 ◽  
Vol 26 (05) ◽  
Author(s):  
Muhammad Usman Sheikh ◽  
Malahat Alina Usman ◽  
Saira Shabbir

Introduction: Being an infectious disease primarily acting on the liver, Hepatitis C is caused due the presence of Hepatitis C virus. In Pakistan, out of every 10 individuals, this virus infects one. According to the World Health Organization, Hepatitis C virus, worldwide, chronically infects 150 million individuals. Hepatitis C is commonly called as “Black Jaundice” in Pakistan. Although there are various risk factors involved with infection caused by Hepatitis C virus, but the most common factors are blood transfusion from unscreened donors, injections, drug abuse and unprotected sexual activity. There are contradictory reports, which depicts that the body fluids other than blood, like saliva and seminal fluid, might be potential sources of this infection. The current study aims to detect the presence of Hepatitis C virus Ribonucleic Acid in the saliva of confirmed infected male patients. At present there are a lot of genotypes of Hepatitis C virus have been reported worldwide but in our country genotype 3 and 2 are more common than the rest. That is why the objective of this study was not only to detect this virus in the saliva of known infected patients but also to determine their genotypes in positive secretions as well. Study Design: Descriptive cross sectional study. Setting: A clinic located in Lahore and The PCR LAB, Jail Road, Lahore, Pakistan. Period: 13 Months. Material and Methods: A sample size of 100 hepatitis C positive patients (statistically calculated), in which the anti-viral therapy was not started, were selected with regard to inclusion and exclusion criteria by non-probability, convenient sampling. Saliva (2 ml) was taken in a sterile container, to detect the occurrence of Hepatitis C virus by Reverse Transcriptase- Polymerase Chain Reaction and subsequent genotyping by multiplex Polymerase Chain Reaction. Results: Out of 100 patients only 7% patients had virus in their saliva. Out of 100, the total saliva positive samples were 7 in number. The subsequent genotyping of the positive samples showed that out of 7 positive cases, 4 cases were of Genotype 2a, 2 cases were of genotype 3a, and only 1 case was of genotype 4. Conclusion: There was very less percentage of Hepatitis C virus Ribonucleic Acid found in the salivary secretions obtained from the patients. Moreover the patients who had positive secretions were mostly of genotype 2a whereas genotype 3a is known to be most significantly present among the population of Pakistan. This study may lead to better planning and management in the transmission of the disease, control and its spread.


2020 ◽  
Vol 9 (2) ◽  
pp. 63-67
Author(s):  
Mohit Gururani

Hepatocellular carcinoma is the world’s sixth leading cause of death due to its quick progression. It has a poor prognosis and a low survival rate. Though there are several factors leading to malignancy, some of them are not yet fully understood. For example HCV. Hepatitis C virus is known to cause hepatocellular carcinoma and clearing the viral load of HCV from the body using DAAs has helped in improved prognosis and prevention of HCC but there is no concrete evidence to prove the direct carcinogenic effects of HCV in causing HCC. The argument is that HCV does not directly causes HCC but its chronic effects in the liver eventually lead up to HCC.


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