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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

Authors Li M, Jiang Y, Xu C, Zhang Z, Sun X

Received 8 February 2013

Accepted for publication 13 March 2013

Published 9 May 2013 Volume 2013:8(1) Pages 1843—1854

DOI https://doi.org/10.2147/IJN.S43827

Checked for plagiarism Yes

Review by Single-blind

Peer reviewer comments 3

Man Li,1 Yuhong Jiang,1 Chaoqun Xu,2 Zhirong Zhang,1 Xun Sun1

1Key Laboratory of Drug Targeting, Ministry of Education, West China School of Pharmacy, Sichuan University, Chengdu, People’s Republic of China; 2Sichuan Academy of Chinese Medicine Sciences, Chengdu, Sichuan, People’s Republic of China

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.

Keywords: human immunodeficiency virus, heterologous vaccination, mannosylated polyethyleneimine, DNA delivery, immune response

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