Background: Various promising procedures have been used to improve the potency of DNA vaccines for the treatment of human papillomavirus type 16 (HPV16) infections. Interleukin-12 (IL12) is a powerful adjuvant that can contribute to T cell-mediated protection against many pathogens, specifically viruses. Considering the important role of T cell-mediated immunity in tumor clearance, the induction of these responses can help control the progression of tumors in animal models. We have demonstrated that the co-administration of codon-optimized E7 (uE7) gene of HPV16 with interleukin-12 is effective in the development of antitumor responses.
Objectives: The present study examined the co-administration of codon-optimized HPV16 E7 gene with murine interleukin-12 gene (mIL-12) as a vaccine adjuvant in tumor mice model.
Materials And Methods: C57BL/6 mice were studied for tumor progression after injection of recombinant DNA vaccines. Lactate dehydrogenase (LDH) and IFN-γ were measured to evaluate the activity of cytotoxic T lymphocytes (CTLs). Measurements of tumor volume and MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] assay were used for assessment of therapeutic antitumor effects of the vaccines.
Results: Results showed that DNA vaccines, specifically codon-optimized E7/murine interleukin-12 (mIL-12), elicited significant differences in levels of IFN-γ and cytotoxic T lymphocyte (CTLs) responses compared to control groups. Furthermore, higher antitumor response and lower tumor size in the vaccine group was significantly evident compared to control group.
Conclusion: The co-administration of codon-optimized HPV16 E7 gene with IL12 significantly enhances the DNA vaccine potency against HPV16-associated cervical cancer.
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http://dx.doi.org/10.1016/j.micpath.2019.04.028 | DOI Listing |
Mol Ther Methods Clin Dev
December 2024
International Centre for Genetic Engineering and Biotechnology (ICGEB), Padriciano 99, 34149 Trieste, Italy.
Crigler-Najjar syndrome is an ultra-rare monogenic recessive liver disease caused by gene mutations. Complete UGT1A1 deficiency results in severe unconjugated hyperbilirubinemia in newborns that, if not treated, may lead to brain damage and death. Treatment is based on intensive phototherapy, but its efficacy decreases with age, rendering liver transplantation the only curative option.
View Article and Find Full Text PDFMicrob Pathog
July 2019
Infectious Disease Research Center, Golestan University of Medical Sciences, Gorgan, Iran; Department of Microbiology, Faculty of Medicine, Golestan University of Medical Sciences, Gorgan, Iran. Electronic address:
Background: Various promising procedures have been used to improve the potency of DNA vaccines for the treatment of human papillomavirus type 16 (HPV16) infections. Interleukin-12 (IL12) is a powerful adjuvant that can contribute to T cell-mediated protection against many pathogens, specifically viruses. Considering the important role of T cell-mediated immunity in tumor clearance, the induction of these responses can help control the progression of tumors in animal models.
View Article and Find Full Text PDFPLoS One
May 2016
Service Immunology, Scientific Institute for Public Health (WIV-ISP Site Ukkel), Brussels, Belgium.
The only tuberculosis vaccine currently available, bacille Calmette-Guérin (BCG) is a poor inducer of CD8(+) T cells, which are particularly important for the control of latent tuberculosis and protection against reactivation. As the induction of strong CD8(+) T cell responses is a hallmark of DNA vaccines, a combination of BCG with plasmid DNA encoding a prototype TB antigen (Ag85A) was tested. As an alternative animal model, pigs were primed with BCG mixed with empty vector or codon-optimized pAg85A by the intradermal route and boosted with plasmid delivered by intramuscular electroporation.
View Article and Find Full Text PDFCell Biosci
June 2015
Departments of Pathology, School of Medicine, Johns Hopkins University, CRBII Room 307, 1550 Orleans Street, Baltimore, MD 21231 USA ; Oncology, Johns Hopkins Medical Institutions, Baltimore, MD USA.
Background: DNA vaccines have emerged as attractive candidates for the control of human papillomavirus (HPV)-associated malignancies. However, DNA vaccines suffer from limited immunogenicity and thus strategies to enhance DNA vaccine potency are needed. We have previously demonstrated that for DNA vaccines encoding HPV-16 E7 antigen (CRT/E7) linkage with calreticulin (CRT) linked enhances both the E7-specific CD8(+) T cell immune responses and antitumor effects against E7-expressing tumors.
View Article and Find Full Text PDFJ Immunol Methods
August 2012
FU-Berlin, Fachbereich Biologie, Chemie, Pharmazie, Berlin, Germany.
DNA immunization is a convenient and effective way of inducing a specific antibody response. In mammals, co-administration of vectors encoding immunostimulatory cytokines can enhance the humoral response resulting in elevated antibody titers. We therefore set out to investigate the effect using avian interleukin 1β (IL-1β) and avian interleukin 6 (IL-6) as genetic adjuvants when immunizing laying hens.
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