A Novel Molecular Design for a Hybrid Phage-DNA Construct Against DKK1
Nucleic acid immunization has recently exhibited a great promise for immunotherapy of various diseases. However, it is now clear that powerful strategies are imminently needed to improve their efficiency. In this regard, whole bacteriophage particles have been described as efficient DNA vaccine delivery vehicles, capable of circumventing the limitations of naked DNA immunization. Moreover, phage particles could be engineered to display specific peptides on their surfaces. Given these inherent characteristics of phages, we have designed a novel hybrid phage-DNA immunization vector using both M13 and pAAV plasmid elements. Following the construction and in vitro confirmation of the designed vectors, they were used for comparative mice immunization, carrying the same DNA sequence. The results indicated the efficacy of the designed hybrid phage particles, to elicit higher humoral immunity, in comparison to conventional DNA-immunization vectors (pCI). In light of these findings, it could be concluded that using adeno-associated virus (AAV) expression cassette along with displaying TAT peptide on the surface of the phage particle could be deemed as an appealing strategy to enhance the DNA-immunization and vaccination efficacy.
KeywordsDNA vaccination Phage-DNA vaccination Peptide display DKK1 TAT peptide
The authors wish to thank Tarbiat Modares University for supporting the conduct of this research.
Compliance with Ethical Standards
Conflict of interest
The authors declare that they have no conflict of interest.
Informed consent was obtained from all individual participants included in the study.
Research Involving Human Participants and/or Animals
All applicable international, national, and/or institutional guidelines for the care and use of animals were followed.
- 8.Mard-Soltani, M., Rasaee, M. J., Khalili, S., Sheikhi, A., Hedayati, M., Ghaderi-Zefrehi, H., & Alasvand, M. (2018). The effect of differentially designed fusion proteins to elicit efficient anti-human thyroid stimulating hormone immune responses. Iranian Journal of Allergy, Asthma and Immunology, 17(2), 158–170.Google Scholar
- 9.Jahangiri, A., Amani, J., & Halabian, R. (2017). In silico analyses of Staphylococcal enterotoxin B as a DNA vaccine for cancer therapy. International Journal of Peptide Research and Therapeutics, 24, 1–12.Google Scholar
- 27.Hashemi, H., Bamdad, T., Jamali, A., Pouyanfard, S., & Mohammadi, M. G. (2010). Evaluation of humoral and cellular immune responses against HSV-1 using genetic immunization by filamentous phage particles: A comparative approach to conventional DNA vaccine. Journal of Virological Methods, 163(2), 440–444.CrossRefGoogle Scholar
- 28.Hajitou, A., Trepel, M., Lilley, C. E., Soghomonyan, S., Alauddin, M. M., Marini, F. C. 3rd, Restel, B. H., Ozawa, M. G., Moya, C. A., Rangel, R., Sun, Y., Zaoui, K., Schmidt, M., von Kalle, C., Weitzman, M. D., Gelovani, J. G., Pasqualini, R., & Arap, W. (2006). A hybrid vector for ligand-directed tumor targeting and molecular imaging. Cell, 125(2), 385–398.CrossRefGoogle Scholar
- 34.Ferrari, A., Pellegrini, V., Arcangeli, C., Fittipaldi, A., Giacca, M., & Beltram, F. (2003). Caveolae-mediated internalization of extracellular HIV-1 tat fusion proteins visualized in real time. Molecular Therapy: The Journal of the American Society of Gene Therapy, 8(2), 284–294.CrossRefGoogle Scholar
- 35.Eguchi, A., Akuta, T., Okuyama, H., Senda, T., Yokoi, H., Inokuchi, H., Fujita, S., Hayakawa, T., Takeda, K., Hasegawa, M., & Nakanishi, M. (2001). Protein transduction domain of HIV-1 Tat protein promotes efficient delivery of DNA into mammalian cells. The Journal of Biological Chemistry, 276(28), 26204–26210.CrossRefGoogle Scholar
- 36.Mukai, Y., Sugita, T., Yamato, T., Yamanada, N., Shibata, H., Imai, S., Abe, Y., Nagano, K., Nomura, T., Tsutsumi, Y., Kamada, H., Nakagawa, S., & Tsunoda, S. (2006). Creation of novel protein transduction domain (PTD) mutants by a phage display-based high-throughput screening system. Biological & Pharmaceutical Bulletin, 29(8), 1570–1574.CrossRefGoogle Scholar
- 40.Ling, Y., Liu, W., Clark, J. R., March, J. B., Yang, J., & He, C. (2011). Protection of mice against Chlamydophila abortus infection with a bacteriophage-mediated DNA vaccine expressing the major outer membrane protein. Veterinary Immunology and Immunopathology, 144(3–4), 389–395.CrossRefGoogle Scholar
- 41.Zhang, X., Liu, S., Li, S., Du, Y., Dou, Y., Li, Z., Yuan, H., & Zhao, W. (2015). Designation of a novel DKK1 multiepitope DNA vaccine and inhibition of bone loss in collagen-induced arthritic mice. BioMed Research International. https://doi.org/10.1155/2015/765490.CrossRefPubMedPubMedCentralGoogle Scholar