scholarly journals Evaluation of Drug Toxicity for DNA Vaccine Candidates Against Infectious Diseases: Hepatitis C as Experimental Model

10.5772/32320 ◽  
2012 ◽  
Author(s):  
Dania Bacard ◽  
Karelia Cosme ◽  
Jos Surez ◽  
Yalena Amador-Caizares ◽  
Santiago Dueas-Carrer
2021 ◽  
Vol 8 ◽  
Author(s):  
Silvia Stefania Longoni ◽  
Natalia Tiberti ◽  
Zeno Bisoffi ◽  
Chiara Piubelli

Following the SARS-CoV-2 pandemic, several clinical trials have been approved for the investigation of the possible use of mAbs, supporting the potential of this technology as a therapeutic approach for infectious diseases. The first monoclonal antibody (mAb), Muromonab CD3, was introduced for the prevention of kidney transplant rejection more than 30 years ago; since then more than 100 mAbs have been approved for therapeutic purposes. Nonetheless, only four mAbs are currently employed for infectious diseases: Palivizumab, for the prevention of respiratory syncytial virus (RSV) infections, Raxibacumab and Obiltoxaximab, for the prophylaxis and treatment against anthrax toxin and Bezlotoxumab, for the prevention of Clostridium difficile recurrence. Protozoan infections are often neglected diseases for which effective and safe chemotherapies are generally missing. In this context, drug resistance and drug toxicity are two crucial problems. The recent advances in bioinformatics, parasite genomics, and biochemistry methodologies are contributing to better understand parasite biology, which is essential to guide the development of new therapies. In this review, we present the efforts that are being made in the evaluation of mAbs for the prevention or treatment of leishmaniasis, Chagas disease, malaria, and toxoplasmosis. Particular emphasis will be placed on the potential strengths and weaknesses of biological treatments in the control of these protozoan diseases that are still affecting hundreds of thousands of people worldwide.


Health ◽  
2010 ◽  
Vol 02 (11) ◽  
pp. 1298-1307
Author(s):  
Sérgio O. de Paula ◽  
Rafael F. O. França ◽  
Danielle M. Lima ◽  
Nina R. Dutra ◽  
Marília B. de Paula ◽  
...  

2015 ◽  
Vol 7 (3) ◽  
pp. 231-242 ◽  
Author(s):  
Samantha J. Griffiths ◽  
Cory M. Dunnigan ◽  
Clark D. Russell ◽  
J�rgen G. Haas

2006 ◽  
Vol 44 (1) ◽  
pp. 9 ◽  
Author(s):  
Marleny González ◽  
Liz Alvarez-Lajonchere ◽  
Julio César Alvarez-Obregón ◽  
Ivis Guerra ◽  
Ariel Viña ◽  
...  

2006 ◽  
Vol 177 (10) ◽  
pp. 7462-7471 ◽  
Author(s):  
Stefania Capone ◽  
Immacolata Zampaglione ◽  
Alessandra Vitelli ◽  
Monica Pezzanera ◽  
Lisa Kierstead ◽  
...  

2018 ◽  
Vol 92 (8) ◽  
pp. e02133-17 ◽  
Author(s):  
Danushka K. Wijesundara ◽  
Jason Gummow ◽  
Yanrui Li ◽  
Wenbo Yu ◽  
Benjamin J. Quah ◽  
...  

ABSTRACTA universal hepatitis C virus (HCV) vaccine should elicit multiantigenic, multigenotypic responses, which are more likely to protect against challenge with the range of genotypes and subtypes circulating in the community. A vaccine cocktail and vaccines encoding consensus HCV sequences are attractive approaches to achieve this goal. Consequently, in a series of mouse vaccination studies, we compared the immunogenicity of a DNA vaccine encoding a consensus HCV nonstructural 5B (NS5B) protein to that of a cocktail of DNA plasmids encoding the genotype 1b (Gt1b) and Gt3a NS5B proteins. To complement this study, we assessed responses to a multiantigenic cocktail regimen by comparing a DNA vaccine cocktail encoding Gt1b and Gt3a NS3, NS4, and NS5B proteins to a single-genotype NS3/4/5B DNA vaccine. To thoroughly evaluatein vivocytotoxic T lymphocyte (CTL) and T helper (Th) cell responses against Gt1b and Gt3a HCV peptide-pulsed target cells, we exploited a novel fluorescent-target array (FTA). FTA and enzyme-linked immunosorbent spot (ELISpot) analyses collectively indicated that the cocktail regimens elicited higher responses to Gt1b and Gt3a NS5B proteins than those with the consensus vaccine, while the multiantigenic DNA cocktail significantly increased the responses to NS3 and NS5B compared to those elicited by the single-genotype vaccines. Thus, a DNA cocktail vaccination regimen is more effective than a consensus vaccine or a monovalent vaccine at increasing the breadth of multigenotypic T cell responses, which has implications for the development of vaccines for communities where multiple HCV genotypes circulate.IMPORTANCEDespite the development of highly effective direct-acting antivirals (DAA), infections with hepatitis C virus (HCV) continue, particularly in countries where the supply of DAA is limited. Furthermore, patients who eliminate the virus as a result of DAA therapy can still be reinfected. Thus, a vaccine for HCV is urgently required, but the heterogeneity of HCV strains makes the development of a universal vaccine difficult. To address this, we developed a novel cytolytic DNA vaccine which elicits robust cell-mediated immunity (CMI) to the nonstructural (NS) proteins in vaccinated animals. We compared the immune responses against genotypes 1 and 3 that were elicited by a consensus DNA vaccine or a DNA vaccine cocktail and showed that the cocktail induced higher levels of CMI to the NS proteins of both genotypes. This study suggests that a universal HCV vaccine can most readily be achieved by use of a DNA vaccine cocktail.


2019 ◽  
Vol 10 ◽  
Author(s):  
Makutiro Ghislain Masavuli ◽  
Danushka K. Wijesundara ◽  
Alexander Underwood ◽  
Dale Christiansen ◽  
Linda Earnest-Silveira ◽  
...  

2014 ◽  
Vol 1 (suppl_1) ◽  
pp. S209-S209
Author(s):  
Cody Chastain ◽  
Susan E. Beekmann ◽  
Erika Wallender ◽  
Todd Hulgan ◽  
Jack Stapleton ◽  
...  

Vaccines ◽  
2019 ◽  
Vol 7 (2) ◽  
pp. 37 ◽  
Author(s):  
Liu

This review provides a comparison of the theoretical issues and experimental findings for plasmid DNA and mRNA vaccine technologies. While both have been under development since the 1990s, in recent years, significant excitement has turned to mRNA despite the licensure of several veterinary DNA vaccines. Both have required efforts to increase their potency either via manipulating the plasmid DNA and the mRNA directly or through the addition of adjuvants or immunomodulators as well as delivery systems and formulations. The greater inherent inflammatory nature of the mRNA vaccines is discussed for both its potential immunological utility for vaccines and for the potential toxicity. The status of the clinical trials of mRNA vaccines is described along with a comparison to DNA vaccines, specifically the immunogenicity of both licensed veterinary DNA vaccines and select DNA vaccine candidates in human clinical trials.


2020 ◽  
Vol 185 ◽  
pp. 03042
Author(s):  
Yu Fang

The Coronavirus Disease-2019 (COVID-19) pandemic has led to a critical economic crash around the globe, affecting billions of people worldwide. Without a cure, the number of cases continues to increase exponentially. Countries, including the United States, Brazil, and India, currently lead in the number of cases with numbers soaring in the millions. Immunization is crucial to preventing the spread of infectious diseases and can help a large number of individuals quickly while keeping current cases under control. Following the publication of the genome sequence of SARS-CoV-2, vaccine development has been accelerated at an unprecedented rate. 115 vaccine candidates are currently under study with the hope of finding an ideal solution and mitigating the Coronavirus incidence rate. With some vaccine candidates having more potential than others, this review focuses on the characterization of different vaccine options. The analysis of probable vaccines, including mRNA vaccines and adenovirus vaccines, is conducted, and the scientific reasoning behind the vaccines is also discussed. In this review, the latest strategy vaccine is introduced and the effective vaccines are analysed.


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