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Cited by 20Hepatitis C virus researchImmunotherapy and Immune ResponsesRNA Interference and Gene Delivery

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Simultaneous use of natural adjuvants and cell penetrating peptides improves HCV NS3 antigen-specific immune responses

Alizadeh, Sina, Irani, Shiva, Bolhassani, Azam, Sadat, Seyed Mehdi·2019·Immunology Letters
DOI 10.1016/j.imlet.2019.06.011
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Abstract

To improve an effective hepatitis C virus (HCV) therapeutic vaccine, induction of a strong and long term HCV antigen-specific immune response is an important parameter. HCV non-structural protein 3 (NS3) has antigenic properties and plays a major role in viral clearance. In this study, DNA constructs encoding HCV NS3 and heat shock protein 27 (Hsp27)-NS3 genes, and the recombinant (r) NS3 and rHsp27-NS3 proteins complexed with HR9 and Cady-2 cell penetrating peptides (CPPs) were utilized to evaluate antibody, cytokine and Granzyme B secretion in mice. Herein, the formation of NS3 and Hsp27-NS3 DNA/ HR9 CPP complexes were revealed by gel retardation assay and protection against DNase and protease. Cady-2 peptide was used to form the nanoparticles with rNS3 and rHsp27-NS3 proteins. The size and charge of the nanoparticles were confirmed by SEM and Zetasizer instruments. Next, in vitro transfection of the nanoparticles was assessed by flow cytometry and western blotting. Finally, humoral and cellular immune responses were evaluated using different modalities in mice. Our data showed that HR9 and Cady-2 could form stable nanoparticles with DNA and proteins, respectively and enhance their delivery into HEK-293 T cells in a non-covalent approach. Furthermore, the heterologous Hsp27-NS3 DNA + HR9 prime/rHsp27-NS3+Cady-2 protein boost elicited a higher Th1 cellular immune response with a predominant IgG2a, IgG2b, IFN-γ profile and strong Granzyme B secretion than those induced by other groups. Briefly, the combination of a natural adjuvant (Hsp27) and CPPs (HR9 and Cady-2) could significantly stimulate effective immune responses as a promising approach for development of HCV therapeutic vaccines.

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Metadata

Authors
Alizadeh, S., Irani, S., Bolhassani, A., & Sadat, S. M.
Affiliations
  • Islamic Azad University, Tehran (IR)
  • Pasteur Institute of Iran (IR)
Corresponding author
Bolhassani, Azam
ORCID
Venue
Immunology Letters
Publisher
Elsevier BV
Published
2019-08
Volume
212
Pages
70-80
ISSN
0165-2478 (ISSN-L)
DOI
10.1016/j.imlet.2019.06.011
OpenAlex
W2953629858
Cited by
20
References
56
Citations by year
2024: 3 · 2023: 1 · 2022: 4 · 2021: 4 · 2020: 6 · 2019: 2
FWCI
2.55
Type
journal article
Language
en
Open access
closed
Licence
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations
  • Immunology Letters (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Health Sciences › Medicine › Hepatology › Hepatitis C virus research
  • Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Interference and Gene Delivery
Keywords
hepatitis C virus, HCV NS3, therapeutic vaccines, HSP27, cell-penetrating peptides, DNA nanoparticles, natural adjuvants, antigen-specific immune response, Th1 response, interferon-gamma, granzyme B, humoral immunity, heterologous prime-boost
MeSH terms
Immunogenicity, Vaccine, Viral Proteases, Adjuvants, Immunologic, Animals, Disease Models, Animal, Female, Hepatitis C, Humans, Recombinant Fusion Proteins, Serine Endopeptidases, Viral Hepatitis Vaccines, Hepacivirus, Viral Nonstructural Proteins, Vaccines, DNA, Nucleoside-Triphosphatase, Mice, DEAD-box RNA Helicases, HSP27 Heat-Shock Proteins, HEK293 Cells, Cell-Penetrating Peptides

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CoChat. (2026). Citation check: Simultaneous use of natural adjuvants and cell penetrating peptides improves HCV NS3 antigen-specific immune responses. https://app.cochat.ai/papers/10.1016/j.imlet.2019.06.011
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Alizadeh, S., Irani, S., Bolhassani, A., & Sadat, S. M. (2019). Simultaneous use of natural adjuvants and cell penetrating peptides improves HCV NS3 antigen-specific immune responses. Immunology Letters. https://doi.org/10.1016/j.imlet.2019.06.011