Evaluations of Immunogenicity and Efficacy of A Novel HPV16 E6 and E7 Multi-epitope DNA Vaccine

Xiangjie CUI; Yufen TAO; Lanfang ZHU; Yufeng YAO; Li SHI

doi:10.12259/j.issn.2095-610X.S20240503

Volume 45 Issue 5

May 2024

Turn off MathJax

Article Contents

Abstract

References

Relative Articles

Article Navigation > Journal of Kunming Medical University > 2024 > 45(5): 16-22

Yijun AN, Lidan YU, Meisu ZHAO, Dongmei MA, Chunhua YANG, Yao KONG. The Application of Prognostic Model of Lysosomal Related Genes in Bladder Cancer[J]. Journal of Kunming Medical University, 2024, 45(5): 66-72. doi: 10.12259/j.issn.2095-610X.S20240510

Citation:

Xiangjie CUI, Yufen TAO, Lanfang ZHU, Yufeng YAO, Li SHI. Evaluations of Immunogenicity and Efficacy of A Novel HPV16 E6 and E7 Multi-epitope DNA Vaccine[J]. Journal of Kunming Medical University, 2024, 45(5): 16-22. doi: 10.12259/j.issn.2095-610X.S20240503

Citation:

PDF( 2114 KB)

Evaluations of Immunogenicity and Efficacy of A Novel HPV16 E6 and E7 Multi-epitope DNA Vaccine

doi: 10.12259/j.issn.2095-610X.S20240503

Institute of Medical Biology，Chinese Academy of Medical Sciences & Peking Union Medical College，Kunming Yunnan 650118，China

Received Date: 2024-01-16
Available Online: 2024-04-30
Publish Date: 2024-05-31

Abstract

Abstract

Objective To construct and evaluate the specific CTL cell response induced by HPV16 E6 and E7 multi epitope DNA vaccines and their intervention effects on tumor growth so as to reveal their potential as candidate HPV therapeutic vaccines. Methods The CTL epitopes of human HLA-A^*02:01, HLA-A^*11:01, HLA-A^*24:02 restriction and C57BL/6 mouse H-2b restriction were predicted by the MHC-I processing and MHC-I binding methods in the IEDB website, and then screened for co-presentation of both based on scoring as well as ELISPOT experiment. The predicted CTL epitopes obtained were constructed into a multi-epitope DNA vaccine （pVAX1-10P）, and the immunological interventions were performed in the mice transplanted with TC-1 tumour cells from prophylactic and therapeutic strategies respectively, and the ability of pVAX1-10P to induce specific CTL responses was assessed by flow cytometry. Results Prediction and screening yielded 10 CTL antigenic epitopes co-presented by human and murine MHC molecules. ELISPOT results showed that each peptide in the experimental group induced the specific immune responses in mouse lymphocytes. The constructed multi-epitope DNA vaccine, pVAX1-10P, induced the specific cellular immunity and significantly inhibited the tumour growth in both prophylactic and therapeutic experiments. Conclusion The constructed HPV16 E6 and E7 multi-epitope DNA vaccine, pVAX1-10P can induce specific CTL response and inhibit the tumour growth, which is expected as a promising candidate of HPV therapeutic DNA vaccine.
- Cervical cancer,
- Human papillomavirus 16,
- E6 protein,
- E7 protein,
- Multi-epitope DNA vaccine

FullText(HTML)

References(32)

References

[1]	Alay I,Kaya C,Karaca I,et al. The effect of being diagnosed with human papillomavirus infection on women's sexual lives[J]. J Med Virol,2020,92(8):1290-1297. doi: 10.1002/jmv.25623
[2]	Yu L L, Majerciak V, Zheng Z M. HPV16 and HPV18 genome structure, expression, and post-transcriptional regulation[J]. Int J Mol Sci,2022,23(9):4943.
[3]	Williamson A L. Recent developments in human papillomavirus (HPV) vaccinology[J]. Viruses,2023,15(7):1440. doi: 10.3390/v15071440
[4]	Chen W,Sun H,Molijn A,et al. The variable characteristics of human papillomavirus in squamous cell carcinoma and adenocarcinoma of cervix in China[J]. J Low Genit Tract Dis,2018,22(4):355-361. doi: 10.1097/LGT.0000000000000408
[5]	Lei J,Ploner A,Elfstrom K M,et al. HPV vaccination and the risk of invasive cervical cancer[J]. N Engl J Med,2020,383(14):1340-1348. doi: 10.1056/NEJMoa1917338
[6]	Messa L, Loregian A. HPV-induced cancers: Preclinical therapeutic advancements[J]. Expert Opin Investig Drugs,2022,31(1):79-93.
[7]	Yan F, Cowell L, Tomkies A, et al. Therapeutic vaccination for HPV-mediated cancers[J]. Current Otorhinolaryngology Reports,2023,11(1):44-61.
[8]	Ortiz-Pedraza Y,Munoz-Bello J O,Ramos-Chavez L A,et al. HPV16 E6 and E7 oncoproteins stimulate the glutamine pathway maintaining cell proliferation in a SNAT1-dependent fashion[J]. Viruses,2023,15(2):324. doi: 10.3390/v15020324
[9]	Welters M J,Kenter G G,Piersma S J,et al. Induction of tumor-specific CD4+ and CD8+ T-cell immunity in cervical cancer patients by a human papillomavirus type 16 E6 and E7 long peptides vaccine[J]. Clin Cancer Res,2008,14(1):178-187. doi: 10.1158/1078-0432.CCR-07-1880
[10]	Yan F,Cowell L G,Tomkies A,et al. Therapeutic vaccination for HPV-mediated cancers[J]. Curr Otorhinolaryngol Rep,2023,11(1):44-61. doi: 10.1007/s40136-023-00443-8
[11]	Song X,Xu L,Yan R,et al. Construction of eimeria tenella multi-epitope DNA vaccines and their protective efficacies against experimental infection[J]. Vet Immunol Immunopathol,2015,166(3-4):79-87. doi: 10.1016/j.vetimm.2015.05.005
[12]	Radwan J, Babik W, Kaufman J, et al. Advances in the evolutionary understanding of MHC polymorphism[J]. Trends Genet,2020,36(4):298-311.
[13]	Chandran S S, Klebanoff C A. T cell receptor-based cancer immunotherapy: Emerging efficacy and pathways of resistance[J]. Immunol Rev,2019,290(1):127-147.
[14]	Kelley J, Walter L, Trowsdale J. Comparative genomics of major histocompatibility complexes[J]. Immunogenetics,2005,56(10):683-695.
[15]	Cho. H I, Celis E. Design of immunogenic and effective multi-epitope DNA vaccines for melanoma[J]. Cancer Immunol Immunother,2012,61(3):343-351. doi: 10.1007/s00262-011-1110-7
[16]	Rashidi S, Faraji S N, Mamaghani AJ, et al. Bioinformatics analysis for the purpose of designing a novel multi-epitope DNA vaccine against Leishmania major[J]. Sci Rep,2022,12(1):18119.
[17]	Robinson J,Barker D J,Georgiou X,et al. IPD-IMGT/HLA database[J]. Nucleic Acids Res,2020,48(D1):D948-D955.
[18]	Gonzalez-Galarza F F,Mccabe A,Santos E,et al. Allele frequency net database (AFND) 2020 update: Gold-standard data classification,open access genotype data and new query tools[J]. Nucleic Acids Res,2020,48(D1):D783-D788.
[19]	He Y,Li J,Mao W,et al. HLA common and well-documented alleles in China[J]. HLA,2018,92(4):199-205. doi: 10.1111/tan.13358
[20]	Enokida. T, Moreira A, Bhardwaj N. Vaccines for immunoprevention of cancer[J]. J Clin Invest,2021,131(9):e146956.
[21]	Namvar A,Panahi H A,Agi E,et al. Development of HPV(16,18,31,45) E5 and E7 peptides-based vaccines predicted by immunoinformatics tools[J]. Biotechnol Lett,2020,42(3):403-418. doi: 10.1007/s10529-020-02792-6
[22]	Goradel N H,Negahdari B,Mohajel N,et al. Heterologous administration of HPV16 E7 epitope-loaded nanocomplexes inhibits tumor growth in mouse model [J]. Int Immunopharmacol,2021,101(Pt B): 108298.
[23]	Zhang Y,Ren F,Ni B,et al. Tumor targeting nanoparticle E7(49-57)-HSP110-RGD elicits potent anti-tumor immune response in a CD8-dependent manner in cervical cancer-bearing mouse model[J]. Hum Vaccin Immunother,2021,17(10):3529-3538. doi: 10.1080/21645515.2021.1933875
[24]	Ghanaat M,Kaboosi H,Negahdari B,et al. Heterologous prime-boost vaccination using adenovirus and albumin nanoparticles as carriers for human papillomavirus 16 E7 epitope[J]. Curr Pharm Biotechnol,2023,24(9):1195-1203. doi: 10.2174/1389201023666220922122531
[25]	Tseng S H,Cheng M A,Farmer E,et al. Albumin and interferon-beta fusion protein serves as an effective vaccine adjuvant to enhance antigen-specific CD8+ T cell-mediated antitumor immunity[J]. J Immunother Cancer,2022,10(4):e004342. doi: 10.1136/jitc-2021-004342
[26]	Slingluff C L,Jr. The present and future of peptide vaccines for cancer: Single or multiple,long or short,alone or in combination?[J]. Cancer J,2011,17(5):343-350. doi: 10.1097/PPO.0b013e318233e5b2
[27]	Liu W,Tang H,Li L,et al. Peptide-based therapeutic cancer vaccine: Current trends in clinical application[J]. Cell Prolif,2021,54(5):e13025. doi: 10.1111/cpr.13025
[28]	Pardoll D M. Spinning molecular immunology into successful immunotherapy[J]. Nat Rev Immunol,2002,2(4):227-238. doi: 10.1038/nri774
[29]	Nezafat N,Sadraeian M,Rahbar M R,et al. Production of a novel multi-epitope peptide vaccine for cancer immunotherapy in TC-1 tumor-bearing mice[J]. Biologicals,2015,43(1):11-17. doi: 10.1016/j.biologicals.2014.11.001
[30]	Wang Q,Li Q F,Zang J,et al. A novel multi-epitope vaccine of HPV16 E5E6E7 oncoprotein delivered by HBc VLPs induced efficient prophylactic and therapeutic antitumor immunity in tumor mice model[J]. Vaccine,2022,40(52):7693-7702. doi: 10.1016/j.vaccine.2022.10.069
[31]	Gul A, Doskaya M, Can H, et al. Immunogenicity of a xenogeneic multi-epitope HER2(+) breast cancer DNA vaccine targeting the dendritic cell restricted antigen-uptake receptor DEC205[J]. Vaccine,2022,40(16):2409-2419.
[32]	De Oliveira L M,Morale M G,Chaves A A,et al. Design,immune responses and anti-tumor potential of an HPV16 E6E7 multi-epitope vaccine[J]. PLoS One,2015,10(9):e0138686. doi: 10.1371/journal.pone.0138686

Relative Articles(20)

Relative Articles

[1]	Liyan MENG, Chaoqun WANG, Xinghui CHEN, Junjing HE, Yaru NIU, Lisha MA. Risk Factors of Persistent HPV Infection in Patients with Early Cervical Cancer after Operation. Journal of Kunming Medical University, 2024, 45(4): 152-156. doi: 10.12259/j.issn.2095-610X.S20240422
[2]	Ni GUO, Cheng ZHANG, Chao HONG, Weipeng LIU, Yufeng YAO, Zhiling YAN. Correlation of KRAS Gene 3′ UTR Polymorphisms with Cervical Cancer and Cervical Intraepithelial Neoplasia in Chinese Han Population in Yunnan Province. Journal of Kunming Medical University, 2024, 45(2): 14-22. doi: 10.12259/j.issn.2095-610X.S20240203
[3]	Chunxia MIAO, Yina WANG, Yunxia ZHANG. Expression of EMC6，C-myc and BCL-2 in Cervical Cancer Tissues and Prognosis Analysis. Journal of Kunming Medical University, 2024, 45(7): 62-68. doi: 10.12259/j.issn.2095-610X.S20240709
[4]	Xiangchuan QIN, Jinqiu LI, Xiaojing HUANG, Kuerban HUTUBIDING·, Hasim AXIANGU·. Effect of HPV E6 on Proliferation，Invasion and Migration of Cervical Cancer Cells Through Rap1 Signaling Pathway. Journal of Kunming Medical University, 2024, 45(9): 9-16. doi: 10.12259/j.issn.2095-610X.S20240902
[5]	Jinbao XIAO, Junda ZHAO, Junqi MA. Metabolomics of Siha Supernatant in Cervical Cancer Cells with Down-regulated HPV16 E6/E7 Expression. Journal of Kunming Medical University, 2024, 45(1): 22-27. doi: 10.12259/j.issn.2095-610X.S20240104
[6]	Qin XIE, Chunyang ZHAO, Baosu ZHANG, Hongbo ZHAO. Potential Mechanism of Thioridazine in Anti-cervical Cancer. Journal of Kunming Medical University, 2022, 43(3): 13-20. doi: 10.12259/j.issn.2095-610X.S20220317
[7]	Honglan CHEN, Yi WU, Tao HU, Yuming WANG. Potential Value of G6PD Activity Detection in the Peripheral Blood for the Diagnosis and Prognosis of Cervical Cancer Patients with High Risk Human Papillomavirus Infection. Journal of Kunming Medical University, 2022, 43(2): 89-95. doi: 10.12259/j.issn.2095-610X.S20220203
[8]	Juan ZHANG, Hong-yun ZHANG. The Value of Endocervical Curettage in Cervical Cancer Screening. Journal of Kunming Medical University, 2021, 42(8): 123-127. doi: 10.12259/j.issn.2095-610X.S20210822
[9]	Ding-ji TAN, Hong-li YIN, Rui ZHU, Xi ZHANG, Xin YU, Yong FEI, Xin LI, Ming DUAN, Liang HE, Hong-ying YANG. Analysis of Vaginal Microecological in Women with Cervical Intraepithelial Neoplasia and Cervical Cancer. Journal of Kunming Medical University, 2021, 42(8): 118-122. doi: 10.12259/j.issn.2095-610X.S20210821
[10]	Qing Qing , Liu Yang , Zhou Hong Lin . . Journal of Kunming Medical University, 2020, 41(06): 162-166.
[11]	Zhou Xu Ru , Wang Xi , Tian Jie , Xie Ling Ling , Xu Hong Yu , Li Xiao Lan . . Journal of Kunming Medical University, 2019, 40(01): 87-91.
[12]	Hu Tao , Liu Guang Cai , Hong Ying , Chen Hong Lan , Chang Ye Fei , Jiang Shui , Tan Ya Xin , Xi Yang Yan Bin , Chen Bo . Effect of G6PD Knockdown on the Expression of miRNAs in Cervical Cancer Cells. Journal of Kunming Medical University, 2019, 40(03): 6-10.
[13]	Hu Tao , Hong Ying , Chen Hong Lan , Chang Ye Fei , Jiang Shui , Xi Yang Yan Bin , Tan Ya Xin , Li Shan , Liu Guang Cai , Wu Xiao Hong . . Journal of Kunming Medical University, 2018, 39(12): 11-15.
[14]	Yang Zheng Hao . . Journal of Kunming Medical University,
[15]	Wei Jie . . Journal of Kunming Medical University,
[16]	Li Zheng . . Journal of Kunming Medical University,
[17]	Zhao Dong Yan . . Journal of Kunming Medical University,
[18]	Yan Zhi Ling . . Journal of Kunming Medical University,
[19]	Liu Hui Jin . . Journal of Kunming Medical University,
[20]	Huang Ya . . Journal of Kunming Medical University,