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

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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:

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

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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

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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

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