Enhanced Immune Response Following DNA Immunization Through In Vivo Electroporation

2016 ◽  
Vol 35 (5) ◽  
pp. 239-244
Author(s):  
David J. Hawksworth ◽  
Robert Ziemann ◽  
Sharmila Manoj
Keyword(s):  
Immune Response ◽  
Dna Immunization ◽  
In Vivo Electroporation

In vivo electroporation enhances the potency of poly-lactide co-glycolide (PLG) plasmid DNA immunization

Vaccine ◽  
2010 ◽  
Vol 28 (50) ◽  
pp. 7852-7864 ◽  
Author(s):  
Christine M. Barbon ◽  
Lisa Baker ◽  
Christa Lajoie ◽  
Urban Ramstedt ◽  
Mary Lynne Hedley ◽  
...  
Keyword(s):  
Plasmid Dna ◽  
Dna Immunization ◽  
In Vivo Electroporation

scholarly journals DNA Immunization Using in vivo Electroporation for Generating Monoclonal Antibodies Against Mouse IL-9R

BIO-PROTOCOL ◽  
2019 ◽  
Vol 9 (4) ◽  
Author(s):  
Shogo Takatsuka ◽  
Hiroyuki Yamada ◽  
Kei Haniuda ◽  
Marina Ichihashi ◽  
Joe Chiba ◽  
...  
Keyword(s):  
Monoclonal Antibodies ◽  
Dna Immunization ◽  
In Vivo Electroporation

scholarly journals Reciprocal Inhibition of Immunogenic Performance in Mice of Two Potent DNA Immunogens Targeting HCV-Related Liver Cancer

2021 ◽  
Vol 9 (5) ◽  
pp. 1073
Author(s):  
Juris Jansons ◽  
Dace Skrastina ◽  
Alisa Kurlanda ◽  
Stefan Petkov ◽  
Darya Avdoshina ◽  
...  
Keyword(s):  
Immune Response ◽  
Liver Cancer ◽  
Reverse Transcriptase ◽  
Core Protein ◽  
Protein Translation ◽  
Reciprocal Inhibition ◽  
Full Length ◽  
Dna Immunization ◽  
Malignant Cells

Chronic HCV infection and associated liver cancer impose a heavy burden on the healthcare system. Direct acting antivirals eliminate HCV, unless it is drug resistant, and partially reverse liver disease, but they cannot cure HCV-related cancer. A possible remedy could be a multi-component immunotherapeutic vaccine targeting both HCV-infected and malignant cells, but also those not infected with HCV. To meet this need we developed a two-component DNA vaccine based on the highly conserved core protein of HCV to target HCV-infected cells, and a renowned tumor-associated antigen telomerase reverse transcriptase (TERT) based on the rat TERT, to target malignant cells. Their synthetic genes were expression-optimized, and HCV core was truncated after aa 152 (Core152opt) to delete the domain interfering with immunogenicity. Core152opt and TERT DNA were highly immunogenic in BALB/c mice, inducing IFN-γ/IL-2/TNF-α response of CD4+ and CD8+ T cells. Additionally, DNA-immunization with TERT enhanced cellular immune response against luciferase encoded by a co-delivered plasmid (Luc DNA). However, DNA-immunization with Core152opt and TERT mix resulted in abrogation of immune response against both components. A loss of bioluminescence signal after co-delivery of TERT and Luc DNA into mice indicated that TERT affects the in vivo expression of luciferase directed by the immediate early cytomegalovirus and interferon-β promoters. Panel of mutant TERT variants was created and tested for their expression effects. TERT with deleted N-terminal nucleoli localization signal and mutations abrogating telomerase activity still suppressed the IFN-β driven Luc expression, while the inactivated reverse transcriptase domain of TERT and its analogue, enzymatically active HIV-1 reverse transcriptase, exerted only weak suppressive effects, implying that suppression relied on the presence of the full-length/nearly full-length TERT, but not its enzymatic activity. The effect(s) could be due to interference of the ectopically expressed xenogeneic rat TERT with biogenesis of mRNA, ribosomes and protein translation in murine cells, affecting the expression of immunogens. HCV core can aggravate this effect, leading to early apoptosis of co-expressing cells, preventing the induction of immune response.

Generation of monoclonal antibodies against Blo t 3 using DNA immunization with in vivo electroporation

2003 ◽  
Vol 33 (5) ◽  
pp. 663-668 ◽  
Author(s):  
L. Yang ◽  
N. Cheong ◽  
D. Y. Wang ◽  
B. W. Lee ◽  
I. C. Kuo ◽  
...  
Keyword(s):  
Monoclonal Antibodies ◽  
Dna Immunization ◽  
In Vivo Electroporation

Intramuscular DNA immunization with in vivo electroporation induces antigen-specific cellular and humoral immune responses in both systemic and gut-mucosal compartments

Vaccine ◽  
2012 ◽  
Vol 30 (50) ◽  
pp. 7278-7285 ◽  
Author(s):  
Masaki Shoji ◽  
Kazufumi Katayama ◽  
Masashi Tachibana ◽  
Kyoko Tomita ◽  
Fuminori Sakurai ◽  
...  
Keyword(s):  
Immune Responses ◽  
Dna Immunization ◽  
In Vivo Electroporation ◽  
Humoral Immune ◽  
Humoral Immune Responses

scholarly journals Effect of Plasmid DNA Vaccine Design and In Vivo Electroporation on the Resulting Vaccine-Specific Immune Responses in Rhesus Macaques

2007 ◽  
Vol 81 (10) ◽  
pp. 5257-5269 ◽  
Author(s):  
Amara Luckay ◽  
Maninder K. Sidhu ◽  
Rune Kjeken ◽  
Shakuntala Megati ◽  
Siew-Yen Chong ◽  
...  
Keyword(s):  
Immune Response ◽  
Immune Responses ◽  
Plasmid Dna ◽  
Vaccine Design ◽  
Fold Increase ◽  
Specific Cell ◽  
In Vivo Electroporation ◽  
High Molecular Weight Dna ◽  
Hiv 1

ABSTRACT Since human immunodeficiency virus (HIV)-specific cell-mediated immune (CMI) responses are critical in the early control and resolution of HIV infection and correlate with postchallenge outcomes in rhesus macaque challenge experiments, we sought to identify a plasmid DNA (pDNA) vaccine design capable of eliciting robust and balanced CMI responses to multiple HIV type 1 (HIV-1)-derived antigens for further development. Previously, a number of two-, three-, and four-vector pDNA vaccine designs were identified as capable of eliciting HIV-1 antigen-specific CMI responses in mice (M. A. Egan et al., Vaccine 24:4510-4523, 2006). We then sought to further characterize the relative immunogenicities of these two-, three-, and four-vector pDNA vaccine designs in nonhuman primates and to determine the extent to which in vivo electroporation (EP) could improve the resulting immune responses. The results indicated that a two-vector pDNA vaccine design elicited the most robust and balanced CMI response. In addition, vaccination in combination with in vivo EP led to a more rapid onset and enhanced vaccine-specific immune responses. In macaques immunized in combination with in vivo EP, we observed a 10- to 40-fold increase in HIV-specific enzyme-linked immunospot assay responses compared to those for macaques receiving a 5-fold higher dose of vaccine without in vivo EP. This increase in CMI responses translates to an apparent 50- to 200-fold increase in pDNA vaccine potency. Importantly, in vivo EP enhanced the immune response against the less immunogenic antigens, resulting in a more balanced immune response. In addition, in vivo EP resulted in an approximate 2.5-log10 increase in antibody responses. The results further indicated that in vivo EP was associated with a significant reduction in pDNA persistence and did not result in an increase in pDNA associated with high-molecular-weight DNA relative to macaques receiving the pDNA without EP. Collectively, these results have important implications for the design and development of an efficacious vaccine for the prevention of HIV-1 infection.

scholarly journals Reciprocal Inhibition of Immunogenic Performance in Mice of Two Potent DNA Immunogens Targeting HCV Related Liver Cancer

2021 ◽  
Author(s):  
Juris Jansons ◽  
Dace Skrastina ◽  
Alisa Kurlanda ◽  
Stefan Petkov ◽  
Darya Avdoshina ◽  
...  
Keyword(s):  
Immune Response ◽  
Liver Cancer ◽  
Reverse Transcriptase ◽  
Core Protein ◽  
Protein Translation ◽  
Reciprocal Inhibition ◽  
Full Length ◽  
Dna Immunization ◽  
Malignant Cells

Chronic HCV infection and associated liver cancer impose a heavy burden on the healthcare system. Direct acting antivirals eliminate HCV, unless it is drug resistant, and partially reverse liver disease, but they cannot cure HCV-related cancer. Possible remedy could be a multi-component immunotherapeutic vaccine targeting both HCV-infected and malignant cells, also those not infected with HCV. To meet this need we developed a two-component DNA vaccine based on the highly conserved core protein of HCV to target HCV-infected cells, and a renowned tumor associated antigen telomerase reverse transcriptase (TERT) based on the rat TERT, to target malignant cells. Their synthetic genes were expression-optimized, and HCV core was truncated after aa 152 (Core152opt) to delete the domain interfering with immunogenicity. Core152opt and TERT DNA were highly immunogenic in BALB/c mice, inducing IFN-γ/IL-2/TNF-α response of CD4+ and CD8+ T cells. Also, DNA-immunization with TERT enhanced cellular immune response against luciferase encoded by a co-delivered plasmid (Luc DNA). However, DNA-immunization with Core152opt and TERT mix resulted in abrogation of immune response against both components. A loss of bioluminescent signal after co-delivery of TERT and Luc DNA into mice indicated that TERT affects the in vivo expression of luciferase directed by the immediate early cytomegalovirus and interferon-β promoters. Panel of mutant TERT variants was created and tested for their expression effects. TERT with deleted N-terminal nucleoli localization signal and mutations abrogating telomerase activity still suppressed the IFN-β driven Luc expression, while the inactivated reverse transcriptase domain of TERT and its analogue, enzymatically active HIV-1 reverse transcriptase, exerted only weak suppressive effects, implying that suppression relied on the presence of the full-length/nearly full-length TERT, but not its enzymatic activity. The effect(s) could be due to interference of the ectopically expressed xenogeneic rat TERT with biogenesis of mRNA, ribosomes and protein translation in murine cells, affecting the expression of immunogens. HCV core can aggravate this effect, leading to early apoptosis of co-expressing cells, preventing the induction of immune response.

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