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Enhanced immune response against HIV-1 induced by a heterologous DNA prime-adenovirus boost vaccination using mannosylated polyethyleneimine as DNA vaccine adjuvant

BACKGROUND: The heterologous deoxyribonucleic acid (DNA) prime-adenovirus (AdV) boost vaccination approach has been widely applied as a promising strategy against human immunodeficiency virus (HIV)-1. However, the problem of inefficient delivery and lack of specificity of DNA vaccine remains a major...

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Autores principales: Li, Man, Jiang, Yuhong, Xu, Chaoqun, Zhang, Zhirong, Sun, Xun
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Dove Medical Press 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3656813/
https://www.ncbi.nlm.nih.gov/pubmed/23690682
http://dx.doi.org/10.2147/IJN.S43827
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author Li, Man
Jiang, Yuhong
Xu, Chaoqun
Zhang, Zhirong
Sun, Xun
author_facet Li, Man
Jiang, Yuhong
Xu, Chaoqun
Zhang, Zhirong
Sun, Xun
author_sort Li, Man
collection PubMed
description BACKGROUND: The heterologous deoxyribonucleic acid (DNA) prime-adenovirus (AdV) boost vaccination approach has been widely applied as a promising strategy against human immunodeficiency virus (HIV)-1. However, the problem of inefficient delivery and lack of specificity of DNA vaccine remains a major issue. In this paper, to improve the transfection of DNA vaccine and realize dendritic cell targeting, we used mannosylated polyethyleneimine (man-PEI) as a DNA vector carrier. METHOD: The DNA plasmid encoding antigen HIV gag fragment was constructed by polymerase chain reaction. Then the DNA plasmid was complexed with man-PEI. The in vitro transfection efficiency of man-PEI/DNA was analyzed on DC 2.4 cells. Mice were primed with 25 μg pVAX1-HIV gag plasmid complexed with man-PEI, 100 μg naked pVAX1-HIV gag plasmid, or empty pVAX1 vector and boosted by AdV encoding the same antigen. The antibody titer, CD4(+) and CD8(+) T-cell response, as well as interferon-γ and interleukin-4 levels in serum and in splenocytes culture were analyzed using flow cytometry or enzyme-linked immunosorbent assay to evaluate the immune response. To test a long-term effect of the vaccination regimen, CD8(+) memory T-cell was also detected by flow cytometry. RESULTS: The pVAX1-HIV gag was constructed successfully. The in vitro transfection efficiency in dendritic cells was significantly higher than naked DNA plasmid. Compared with 100 μg naked DNA/AdV group, the immunoglobulin G2a antibody titer, T-cell response percentage, and cytokine production level induced by man-PEI/DNA/AdV group were significantly higher at a lower DNA dose. Also, the man-PEI/DNA could stimulate a memory CD8(+) T-cell response. CONCLUSION: Owing to the adjuvant effect of man-PEI, the man-PEI/pVAX1-HIV gag priming plus AdV boosting strategy proved to be a potent vaccine candidate against HIV, which could induce a stronger immune response with a lower DNA dose.
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spelling pubmed-36568132013-05-20 Enhanced immune response against HIV-1 induced by a heterologous DNA prime-adenovirus boost vaccination using mannosylated polyethyleneimine as DNA vaccine adjuvant Li, Man Jiang, Yuhong Xu, Chaoqun Zhang, Zhirong Sun, Xun Int J Nanomedicine Original Research BACKGROUND: The heterologous deoxyribonucleic acid (DNA) prime-adenovirus (AdV) boost vaccination approach has been widely applied as a promising strategy against human immunodeficiency virus (HIV)-1. However, the problem of inefficient delivery and lack of specificity of DNA vaccine remains a major issue. In this paper, to improve the transfection of DNA vaccine and realize dendritic cell targeting, we used mannosylated polyethyleneimine (man-PEI) as a DNA vector carrier. METHOD: The DNA plasmid encoding antigen HIV gag fragment was constructed by polymerase chain reaction. Then the DNA plasmid was complexed with man-PEI. The in vitro transfection efficiency of man-PEI/DNA was analyzed on DC 2.4 cells. Mice were primed with 25 μg pVAX1-HIV gag plasmid complexed with man-PEI, 100 μg naked pVAX1-HIV gag plasmid, or empty pVAX1 vector and boosted by AdV encoding the same antigen. The antibody titer, CD4(+) and CD8(+) T-cell response, as well as interferon-γ and interleukin-4 levels in serum and in splenocytes culture were analyzed using flow cytometry or enzyme-linked immunosorbent assay to evaluate the immune response. To test a long-term effect of the vaccination regimen, CD8(+) memory T-cell was also detected by flow cytometry. RESULTS: The pVAX1-HIV gag was constructed successfully. The in vitro transfection efficiency in dendritic cells was significantly higher than naked DNA plasmid. Compared with 100 μg naked DNA/AdV group, the immunoglobulin G2a antibody titer, T-cell response percentage, and cytokine production level induced by man-PEI/DNA/AdV group were significantly higher at a lower DNA dose. Also, the man-PEI/DNA could stimulate a memory CD8(+) T-cell response. CONCLUSION: Owing to the adjuvant effect of man-PEI, the man-PEI/pVAX1-HIV gag priming plus AdV boosting strategy proved to be a potent vaccine candidate against HIV, which could induce a stronger immune response with a lower DNA dose. Dove Medical Press 2013 2013-05-09 /pmc/articles/PMC3656813/ /pubmed/23690682 http://dx.doi.org/10.2147/IJN.S43827 Text en © 2013 Li et al, publisher and licensee Dove Medical Press Ltd. This is an Open Access article which permits unrestricted noncommercial use, provided the original work is properly cited.
spellingShingle Original Research
Li, Man
Jiang, Yuhong
Xu, Chaoqun
Zhang, Zhirong
Sun, Xun
Enhanced immune response against HIV-1 induced by a heterologous DNA prime-adenovirus boost vaccination using mannosylated polyethyleneimine as DNA vaccine adjuvant
title Enhanced immune response against HIV-1 induced by a heterologous DNA prime-adenovirus boost vaccination using mannosylated polyethyleneimine as DNA vaccine adjuvant
title_full Enhanced immune response against HIV-1 induced by a heterologous DNA prime-adenovirus boost vaccination using mannosylated polyethyleneimine as DNA vaccine adjuvant
title_fullStr Enhanced immune response against HIV-1 induced by a heterologous DNA prime-adenovirus boost vaccination using mannosylated polyethyleneimine as DNA vaccine adjuvant
title_full_unstemmed Enhanced immune response against HIV-1 induced by a heterologous DNA prime-adenovirus boost vaccination using mannosylated polyethyleneimine as DNA vaccine adjuvant
title_short Enhanced immune response against HIV-1 induced by a heterologous DNA prime-adenovirus boost vaccination using mannosylated polyethyleneimine as DNA vaccine adjuvant
title_sort enhanced immune response against hiv-1 induced by a heterologous dna prime-adenovirus boost vaccination using mannosylated polyethyleneimine as dna vaccine adjuvant
topic Original Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3656813/
https://www.ncbi.nlm.nih.gov/pubmed/23690682
http://dx.doi.org/10.2147/IJN.S43827
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