Design and evaluation of a multi-epitope DNA vaccine against HPV16

Cervical cancer, among the deadliest cancers affecting women globally, primarily arises from persistent infection with high-risk human papillomavirus (HPV). To effectively combat persistent infection and prevent the progression of precancerous lesions into malignancy, a therapeutic HPV vaccine is un...

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Main Authors: Lanfang Zhu, Xiangjie Cui, Zhiling Yan, Yufen Tao, Lei Shi, Xinwen Zhang, Yufeng Yao, Li Shi
Format: Article
Language:English
Published: Taylor & Francis Group 2024-12-01
Series:Human Vaccines & Immunotherapeutics
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Online Access:https://www.tandfonline.com/doi/10.1080/21645515.2024.2352908
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author Lanfang Zhu
Xiangjie Cui
Zhiling Yan
Yufen Tao
Lei Shi
Xinwen Zhang
Yufeng Yao
Li Shi
author_facet Lanfang Zhu
Xiangjie Cui
Zhiling Yan
Yufen Tao
Lei Shi
Xinwen Zhang
Yufeng Yao
Li Shi
author_sort Lanfang Zhu
collection DOAJ
description Cervical cancer, among the deadliest cancers affecting women globally, primarily arises from persistent infection with high-risk human papillomavirus (HPV). To effectively combat persistent infection and prevent the progression of precancerous lesions into malignancy, a therapeutic HPV vaccine is under development. This study utilized an immunoinformatics approach to predict epitopes of cytotoxic T lymphocytes (CTLs) and helper T lymphocytes (HTLs) using the E6 and E7 oncoproteins of the HPV16 strain as target antigens. Subsequently, through meticulous selection of T-cell epitopes and other necessary elements, a multi-epitope vaccine was constructed, exhibiting good immunogenic, physicochemical, and structural characteristics. Furthermore, in silico simulations showed that the vaccine not only interacted well with toll-like receptors (TLR2/TLR3/TLR4), but also induced a strong innate and adaptive immune response characterized by elevated Th1-type cytokines, such as interferon-gamma (IFN-γ) and interleukin-2 (IL2). Additionally, our study investigated the effects of different immunization intervals on immune responses, aiming to optimize a time-efficient immunization program. In animal model experiments, the vaccine exhibited robust immunogenic, therapeutic, and prophylactic effects. Administered thrice, it consistently induced the expansion of specific CD4 and CD8 T cells, resulting in substantial cytokines release and increased proliferation of memory T cell subsets in splenic cells. Overall, our findings support the potential of this multi-epitope vaccine in combating HPV16 infection and signify its candidacy for future HPV vaccine development.
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spelling doaj-art-c5fcac59691546ddb006a8f86a2ad1b82025-08-20T02:16:40ZengTaylor & Francis GroupHuman Vaccines & Immunotherapeutics2164-55152164-554X2024-12-0120110.1080/21645515.2024.2352908Design and evaluation of a multi-epitope DNA vaccine against HPV16Lanfang Zhu0Xiangjie Cui1Zhiling Yan2Yufen Tao3Lei Shi4Xinwen Zhang5Yufeng Yao6Li Shi7Department of Immunogenetics, Institute of Medical Biology, Chinese Academy of Medical Sciences & Peking Union Medical College, Kunming, ChinaDepartment of Immunogenetics, Institute of Medical Biology, Chinese Academy of Medical Sciences & Peking Union Medical College, Kunming, ChinaDepartment of Gynaecologic Oncology, The No. 3 Affiliated Hospital of Kunming Medical University, Kunming, ChinaDepartment of Immunogenetics, Institute of Medical Biology, Chinese Academy of Medical Sciences & Peking Union Medical College, Kunming, ChinaDepartment of Immunogenetics, Institute of Medical Biology, Chinese Academy of Medical Sciences & Peking Union Medical College, Kunming, ChinaDepartment of Immunogenetics, Institute of Medical Biology, Chinese Academy of Medical Sciences & Peking Union Medical College, Kunming, ChinaYunnan Key Laboratory of Vaccine Research & Development on Severe Infectious Disease, Institute of Medical Biology, Chinese Academy of Medical Sciences & Peking Union Medical College, Kunming, ChinaDepartment of Immunogenetics, Institute of Medical Biology, Chinese Academy of Medical Sciences & Peking Union Medical College, Kunming, ChinaCervical cancer, among the deadliest cancers affecting women globally, primarily arises from persistent infection with high-risk human papillomavirus (HPV). To effectively combat persistent infection and prevent the progression of precancerous lesions into malignancy, a therapeutic HPV vaccine is under development. This study utilized an immunoinformatics approach to predict epitopes of cytotoxic T lymphocytes (CTLs) and helper T lymphocytes (HTLs) using the E6 and E7 oncoproteins of the HPV16 strain as target antigens. Subsequently, through meticulous selection of T-cell epitopes and other necessary elements, a multi-epitope vaccine was constructed, exhibiting good immunogenic, physicochemical, and structural characteristics. Furthermore, in silico simulations showed that the vaccine not only interacted well with toll-like receptors (TLR2/TLR3/TLR4), but also induced a strong innate and adaptive immune response characterized by elevated Th1-type cytokines, such as interferon-gamma (IFN-γ) and interleukin-2 (IL2). Additionally, our study investigated the effects of different immunization intervals on immune responses, aiming to optimize a time-efficient immunization program. In animal model experiments, the vaccine exhibited robust immunogenic, therapeutic, and prophylactic effects. Administered thrice, it consistently induced the expansion of specific CD4 and CD8 T cells, resulting in substantial cytokines release and increased proliferation of memory T cell subsets in splenic cells. Overall, our findings support the potential of this multi-epitope vaccine in combating HPV16 infection and signify its candidacy for future HPV vaccine development.https://www.tandfonline.com/doi/10.1080/21645515.2024.2352908HPVmulti-epitope vaccinecancer vaccineimmunoinformaticsimmune simulation
spellingShingle Lanfang Zhu
Xiangjie Cui
Zhiling Yan
Yufen Tao
Lei Shi
Xinwen Zhang
Yufeng Yao
Li Shi
Design and evaluation of a multi-epitope DNA vaccine against HPV16
Human Vaccines & Immunotherapeutics
HPV
multi-epitope vaccine
cancer vaccine
immunoinformatics
immune simulation
title Design and evaluation of a multi-epitope DNA vaccine against HPV16
title_full Design and evaluation of a multi-epitope DNA vaccine against HPV16
title_fullStr Design and evaluation of a multi-epitope DNA vaccine against HPV16
title_full_unstemmed Design and evaluation of a multi-epitope DNA vaccine against HPV16
title_short Design and evaluation of a multi-epitope DNA vaccine against HPV16
title_sort design and evaluation of a multi epitope dna vaccine against hpv16
topic HPV
multi-epitope vaccine
cancer vaccine
immunoinformatics
immune simulation
url https://www.tandfonline.com/doi/10.1080/21645515.2024.2352908
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