A novel recombinant protein vaccine containing the different E7 proteins of the HPV16, 18, 6, 11 E7 linked to the HIV-1 Tat (47-57) improve cytotoxic immune responses.


Journal

Biotechnology letters
ISSN: 1573-6776
Titre abrégé: Biotechnol Lett
Pays: Netherlands
ID NLM: 8008051

Informations de publication

Date de publication:
Sep 2021
Historique:
received: 09 01 2021
accepted: 13 07 2021
pubmed: 28 7 2021
medline: 11 1 2022
entrez: 27 7 2021
Statut: ppublish

Résumé

Human papillomavirus infection (HPV) is the most common viral infection which is causes of cervical, penal, vulvar, anal and, oropharyngeal cancer. E7 protein of HPV is a suitable target for induction of T cell responses and controlling HPV-related cancer. The aim of the current study was to designed and evaluated a novel fusion protein containing the different E7 proteins of the HPV 16, 18, 6 and 11, linked to the cell-penetrating peptide HIV-1 Tat 49-57, in order to improve cytotoxic immune responses in in-vitro and in-vivo. In this study whole sequence of HPV16,18,6,11 E7-Tat (47-57) and HPV16,18,6,11 E7 cloned into the vector and expressed in E. coli (BL21). The purified protein was confirmed by SDS page and western blotting and then injected into the C57BL/6 mice. The efficiency of the fusion protein vaccine was assessed by antibody response assay, cytokine assay (IL-4 and IFN-γ), CD + 8 cytotoxicity assay and tumor challenge experiment. Result showed that fusion proteins containing Adjuvant (IFA,CFA) could express higher titer of antibody. Also, we showed that vaccination with E7-Tat and, E7-Tat-ADJ induced high frequencies of E7-specific CD8 + T cells and CD107a expression as well as IFN-γ level and enhanced long-term survival in the therapeutic animal models. Our finding suggested that this novel fusion protein vaccine was able to induce therapeutic efficacy and immunogenicity by improving CD8 + T cell in TC-1 tumor bearing mice; so this vaccine may be appreciated for research against HPV and tumor immunotherapies.

Identifiants

pubmed: 34313864
doi: 10.1007/s10529-021-03166-2
pii: 10.1007/s10529-021-03166-2
doi:

Substances chimiques

Cancer Vaccines 0
Papillomavirus E7 Proteins 0
Papillomavirus Vaccines 0
Peptide Fragments 0
Recombinant Fusion Proteins 0
Vaccines, Synthetic 0
tat Gene Products, Human Immunodeficiency Virus 0
tat peptide (47-57), Human immunodeficiency virus 1 0

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

1933-1944

Subventions

Organisme : haghshenas
ID : 3049

Informations de copyright

© 2021. The Author(s), under exclusive licence to Springer Nature B.V.

Références

Akhondnezhad M, Haghshenas MR, Ghasemi M, Mousavi T (2018) The prevalence and genotyping of human papillomavirus in patients with oral tumors in health centers and clinics of Mazandaran in Iran. VirusDisease 29(3):297–302
doi: 10.1007/s13337-018-0472-2
Alipour S, Mahdavi A, Abdoli A (2017) The effects of CpG-ODNs and Chitosan adjuvants on the elicitation of immune responses induced by the HIV-1-Tat-based candidate vaccines in mice. Pathogens Dis 75(2):013
Barra F, Leone Roberti Maggiore U, Bogani G, Ditto A, Signorelli M, Martinelli F, Chiappa V, Lorusso D, Raspagliesi F, Ferrero S (2019) New prophylactics human papilloma virus (HPV) vaccines against cervical cancer. J Obstet Gynaecol 39(1):1–10
doi: 10.1080/01443615.2018.1493441
Bates JT, Uematsu S, Akira S, Mizel SB (2009) Direct stimulation of tlr5+/+ CD11c+ cells is necessary for the adjuvant activity of flagellin. J Immunol 182(12):7539–7547
doi: 10.4049/jimmunol.0804225
Blum JS, Wearsch PA, Cresswell P (2013) Pathways of antigen processing. Annu Rev Immunol 31:443–473
doi: 10.1146/annurev-immunol-032712-095910
Cafaro A, Tripiciano A, Picconi O, Sgadari C, Moretti S, Buttò S, Monini P, Ensoli B (2019) Anti-tat immunity in HIV-1 infection: effects of naturally occurring and vaccine-induced antibodies against tat on the course of the disease. Vaccines 7(3):99
doi: 10.3390/vaccines7030099
Du R-H, Liang L-R, Yang C-Q, Wang W, Cao T-Z, Li M, Guo G-Y, Du J, Zheng C-L, Zhu Q (2020) Predictors of mortality for patients with COVID-19 pneumonia caused by SARS-CoV-2: a prospective cohort study. Eur Respir J 55(5):2000524
doi: 10.1183/13993003.00524-2020
Eagar TN, Miller SD (2019) Helper T-cell subsets and control of the inflammatory response. Clinical Immunology, 5th edn. Elsevier, Amsterdam, pp 235–245
Fanales-Belasio E, Moretti S, Nappi F, Barillari G, Micheletti F, Cafaro A, Ensoli B (2002) Native HIV-1 Tat protein targets monocyte-derived dendritic cells and enhances their maturation, function, and antigen-specific T cell responses. J Immunol 168(1):197–206
doi: 10.4049/jimmunol.168.1.197
Gulati T, Huang C, Caramia F, Raghu D, Paul PJ, Goode RJ, Keam SP, Williams SG, Haupt S, Kleifeld O (2018) Proteotranscriptomic measurements of E6-Associated Protein (E6AP) targets in DU145 prostate cancer cells. Mol Cell Proteomics 17(6):1170–1183
doi: 10.1074/mcp.RA117.000504
Haghshenas MR, Mousavi T, Moosazadeh M, Afshari M (2016) Human papillomavirus and breast cancer in Iran: a meta-analysis. Iran J Basic Med Sci 19(3):231
pubmed: 27114791 pmcid: 4834111
Haghshenas MR, Mousavi T, Kheradmand M, Afshari M, Moosazadeh M (2017) Efficacy of human papillomavirus l1 protein vaccines (cervarix and gardasil) in reducing the risk of cervical intraepithelial neoplasia: a meta-analysis. Int J Prev Med 8:442
Jeannin P, Renno T, Goetsch L, Miconnet I, Aubry J-P, Delneste Y, Herbault N, Baussant T, Magistrelli G, Soulas C (2000) OmpA targets dendritic cells, induces their maturation and delivers antigen into the MHC class I presentation pathway. Nat Immunol 1(6):502
doi: 10.1038/82751
Kim TG, Kim CH, Won EH, Bae SM, Ahn WS, Park JB, Sin JI (2004) CpG-ODN-stimulated dendritic cells act as a potent adjuvant for E7 protein delivery to induce antigen-specific antitumour immunity in a HPV 16 E7-associated animal tumour model. Immunology 112(1):117–125
doi: 10.1111/j.1365-2567.2004.01851.x
Kim C-H, Hong M-J, Park S-D, Kim C-K, Park M-Y, Sohn H-J, Cho H-I, Kim T-G, Hong Y-K (2006) Enhancement of anti-tumor immunity specific to murine glioma by vaccination with tumor cell lysate-pulsed dendritic cells engineered to produce interleukin-12. Cancer Immunol Immunother 55(11):1309–1319
doi: 10.1007/s00262-006-0134-x
Laus R, Graddis TJ, Hakim I, Vidovic D (2000) Enhanced major histocompatibility complex class I-dependent presentation of antigens modified with cationic and fusogenic peptides. Nat Biotechnol 18(12):1269
doi: 10.1038/82377
Levy O, Goriely S, Kollmann TR (2013) Immune response to vaccine adjuvants during the first year of life. Vaccine 31(21):2500–2505
doi: 10.1016/j.vaccine.2012.10.016
Li J, Chen S, Ge J, Lu F, Ren S, Zhao Z, Pu X, Chen X, Sun J, Gu Y (2017) A novel therapeutic vaccine composed of a rearranged human papillomavirus type 16 E6/E7 fusion protein and Fms-like tyrosine kinase-3 ligand induces CD8+ T cell responses and antitumor effect. Vaccine 35(47):6459–6467
doi: 10.1016/j.vaccine.2017.09.003
Mellman I, Steinman RM (2001) Dendritic cells: specialized and regulated antigen processing machines. Cell 106(3):255–258
doi: 10.1016/S0092-8674(01)00449-4
Monroy-García A, Gómez-Lim MA, Weiss-Steider B, Hernández-Montes J, Huerta-Yepez S, Rangel-Santiago JF, Santiago-Osorio E, García MDLM (2014) Immunization with an HPV-16 L1-based chimeric virus-like particle containing HPV-16 E6 and E7 epitopes elicits long-lasting prophylactic and therapeutic efficacy in an HPV-16 tumor mice model. Arch Virol 159(2):291–305
doi: 10.1007/s00705-013-1819-z
Mousavi T, Saravi SS, Valadan R, Haghshenas MR, Rafiei A, Jafarpour H, and Shamshirian A (2019) Different types of adjuvants in prophylactic and therapeutic human papillomavirus vaccines in laboratory animals: a systematic review. Arch Virol 1–22
Mousavi T, Rafiei A, reza Haghshenas M, Sadeghian-Kiadehi SF, Valadan R (2020) Molecular prevalence and phylogenetic analysis of human papillomavirus in normal cervical samples from northern Iran. Gene Rep 21:100958
doi: 10.1016/j.genrep.2020.100958
Münger K, Androphy EJ, McBride AA (2018) Regulation of the papillomavirus E6 and E7 oncoproteins by the viral E1 and E2 proteins. Viral regulatory structures and their degeneracy. CRC Press, Boca Raton, pp 35–52
Shahbazi S, Bolhassani A (2018) Comparison of six cell penetrating peptides with different properties for in vitro and in vivo delivery of HPV16 E7 antigen in therapeutic vaccines. Int Immunopharmacol 62:170–180
doi: 10.1016/j.intimp.2018.07.006
Singh-Jasuja H, Toes RE, Spee P, Münz C, Hilf N, Schoenberger SP, Ricciardi-Castagnoli P, Neefjes J, Rammensee H-G, Arnold-Schild D (2000) Cross-presentation of glycoprotein 96–associated antigens on major histocompatibility complex class I molecules requires receptor-mediated endocytosis. J Exp Med 191(11):1965–1974
doi: 10.1084/jem.191.11.1965
Su X, Xu W, Guan R, Wang Y, Wu J, Zhai L, Chen G, Hu S (2016) Adjuvant effect of docetaxel on HPV16 L2E6E7 fusion protein vaccine in a mouse model. Int Immunopharmacol 38:16–25
doi: 10.1016/j.intimp.2016.05.005
Tanaka Y, Dowdy SF, Linehan DC, Eberlein TJ, Goedegebuure PS (2003) Induction of antigen-specific CTL by recombinant HIV trans-activating fusion protein-pulsed human monocyte-derived dendritic cells. J Immunol 170(3):1291–1298
doi: 10.4049/jimmunol.170.3.1291
Tang J, Yin R, Tian Y, Huang Z, Shi J, Fu X, Wang L, Wu Y, Hao F, Ni B (2012) A novel self-assembled nanoparticle vaccine with HIV-1 Tat49-57/HPV16 E749–57 fusion peptide and GM-CSF DNA elicits potent and prolonged CD8+ T cell-dependent anti-tumor immunity in mice. Vaccine 30(6):1071–1082
doi: 10.1016/j.vaccine.2011.12.029
Wu X, Ma X, Li Y, Xu Y, Zheng N, Xu S, Nawaz W, Wu Z (2019) Induction of neutralizing antibodies by human papillomavirus vaccine generated in mammalian cells. Antibody Ther 2(2):45–53
doi: 10.1093/abt/tbz004
Xu W-X, Wang J, Tang H-P, He Y-P, Zhu Q-X, Gupta SK, Gu S-H, Huang Q, Ji C-N, Liu L-F (2016) Epitomics: IgG-epitome decoding of E6, E7 and L1 proteins from oncogenic human papillomavirus type 58. Sci Rep 6:34686
doi: 10.1038/srep34686
Zhao B, Wang Y, Zhang Y, Li Y, Zhang X, Xu Y, Chen L, Li C, Ju Y, Meng S (2013) TAT-mediated gp96 transduction to APCs enhances gp96-induced antiviral and antitumor T cell responses. Vaccine 31(3):545–552
doi: 10.1016/j.vaccine.2012.11.011
Zou L, Peng Q, Wang P, Zhou B (2017) Progress in research and application of HIV-1 TAT-derived cell-penetrating peptide. J Membr Biol 250(2):115–122
doi: 10.1007/s00232-016-9940-z

Auteurs

Tahoora Mousavi (T)

Molecular and Cell Biology Research Center (MCBRC), Faculty of Medicine, Mazandaran University of Medical Sciences, Sari, Iran.
Molecular and Cell Biology Research Center (MCBRC), Hemoglobinopathy Institute, Mazandaran University of Medical Sciences, Sari, Iran.

Reza Valadan (R)

Molecular and Cell Biology Research Center (MCBRC), Faculty of Medicine, Mazandaran University of Medical Sciences, Sari, Iran.
Immunology Department, Faculty of Medicine, Mazandaran University of Medical Sciences, Sari, Iran.

Alireza Rafiei (A)

Molecular and Cell Biology Research Center (MCBRC), Faculty of Medicine, Mazandaran University of Medical Sciences, Sari, Iran.
Immunology Department, Faculty of Medicine, Mazandaran University of Medical Sciences, Sari, Iran.

Ali Abbasi (A)

Department of Community Medicine, Sari Branch, Islamic Azad University, Sari, Iran.

Mohammad Reza Haghshenas (MR)

Department of Microbiology, Molecular and Cell Biology Research Center, Faculty of Medicine, Mazandaran University of Medical Sciences, Sari, Iran. Haghshenas2001@yahoo.com.

Articles similaires

[Redispensing of expensive oral anticancer medicines: a practical application].

Lisanne N van Merendonk, Kübra Akgöl, Bastiaan Nuijen
1.00
Humans Antineoplastic Agents Administration, Oral Drug Costs Counterfeit Drugs

Smoking Cessation and Incident Cardiovascular Disease.

Jun Hwan Cho, Seung Yong Shin, Hoseob Kim et al.
1.00
Humans Male Smoking Cessation Cardiovascular Diseases Female
Humans United States Aged Cross-Sectional Studies Medicare Part C
1.00
Humans Yoga Low Back Pain Female Male

Classifications MeSH