Immunogenicity of a xenogeneic multi-epitope HER2+ breast cancer DNA vaccine targeting the dendritic cell restricted antigen-uptake receptor DEC205
•Developed a novel highly immunogenic multi-epitope HER2 DNA vaccine.•Designed a novel multi-epitope HER2 protein containing 7T and B-cell epitopes.•Used an antibody fragment (ScFvDEC) to target multi-epitope HER2 to dendritic cells.•Elicited strong antibody response and protective IFN-γ response in...
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| Veröffentlicht in: | Vaccine 2022-04, Vol.40 (16), p.2409-2419 |
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| creator | Gül, Aytül Döşkaya, Mert Can, Hüseyin Karakavuk, Muhammet Anıl-İnevi, Müge Sağlam-Metiner, Pelin Atalay-Şahar, Esra Değirmenci-Döşkaya, Aysu Zekioğlu, Osman Gürüz, Adnan Yüksel Gülce-Iz, Sultan Yeniay, Levent |
| description | •Developed a novel highly immunogenic multi-epitope HER2 DNA vaccine.•Designed a novel multi-epitope HER2 protein containing 7T and B-cell epitopes.•Used an antibody fragment (ScFvDEC) to target multi-epitope HER2 to dendritic cells.•Elicited strong antibody response and protective IFN-γ response in murine model.
Breast cancer was ranked first in global cancer incidence in 2020, and HER2 overexpression in breast cancer accounts for 20–30% of breast cancer patients. Current therapeutic strategies increase the survival rate, but resistance to them occurs frequently, and there is an urgent need to develop novel treatments such as DNA vaccines which can induce a specific and long-lasting immune response against HER2 antigens. To enhance the immunogenicity of DNA vaccines, dendritic cells (DCs) can be targeted using multi-epitope proteins that provide accurate immune focusing. For this purpose, we generated a DNA vaccine encoding a fusion protein composed of 1) in silico discovered antigenic epitopes of human and rat HER2 proteins (MeHer2) and 2) a single-chain antibody fragment (ScFv) specific for the DC-restricted antigen-uptake receptor DEC205 (ScFvDEC). The xenogeneic multi-epitope DNA vaccine (pMeHer2) encodes three only T-cell epitopes, two only B-cell epitopes, and two T and B cell epitopes, and pScFvDEC-MeHer2 vaccine additionally encodes ScFvDEC introduced at the N terminus of the MeHer2. Then, mouse groups were immunized with pScFvDEC-MeHer2, pMeHer2, pScFvDEC, pEmpty, and PBS to determine the elicited immune response. pScFvDEC-MeHer2 vaccinated mice showed a strong IgG response (P |
| doi_str_mv | 10.1016/j.vaccine.2022.03.014 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_2641503602</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><els_id>S0264410X22002791</els_id><sourcerecordid>2645863916</sourcerecordid><originalsourceid>FETCH-LOGICAL-c393t-dd93e640244d3668fd8f5ea66290587d744a028d702ecd2edd313f7355a3363b3</originalsourceid><addsrcrecordid>eNqFkV9rFDEUxYNY7Lb6EZSAL0KZMcmdZGaepKyrLZQKouBbyCZ31qw7f0wyxX6OfmGz7upDX3wKJL977sk5hLzkrOSMq7fb8s5Y6wcsBROiZFAyXj0hC97UUAjJm6dkwYSqioqzb6fkLMYtY0wCb5-RU5DAZCOqBXm47vt5GDc4eOvTPR07augv_HOD3tJ-3iVf4OTTOCG9Wn0WF3Qd0MRErRksBvr-9pIerdBkwgaTHzY0fUfqcHDBp6xicbejAWMK3iZ01AzJ5wXFPCXzA_OLxSmNWWu1FEw-Jyed2UV8cTzPydcPqy_Lq-Lm08fr5eVNYaGFVDjXAqqKiapyoFTTuaaTaJQSbf5c7eqqMkw0rmYCrRPoHHDoapDSAChYwzl5c9Cdwvhzzu507-PeqhlwnKPO6XHJQDGR0deP0O04hyG721OyUdBylSl5oGwYYwzY6Sn43oR7zZnet6a3-hiV3remGejcWp57dVSf1z26f1N_a8rAuwOAOY47j0FH6zHH73zOLmk3-v-s-A0d76sh</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2645863916</pqid></control><display><type>article</type><title>Immunogenicity of a xenogeneic multi-epitope HER2+ breast cancer DNA vaccine targeting the dendritic cell restricted antigen-uptake receptor DEC205</title><source>MEDLINE</source><source>Elsevier ScienceDirect Journals</source><creator>Gül, Aytül ; Döşkaya, Mert ; Can, Hüseyin ; Karakavuk, Muhammet ; Anıl-İnevi, Müge ; Sağlam-Metiner, Pelin ; Atalay-Şahar, Esra ; Değirmenci-Döşkaya, Aysu ; Zekioğlu, Osman ; Gürüz, Adnan Yüksel ; Gülce-Iz, Sultan ; Yeniay, Levent</creator><creatorcontrib>Gül, Aytül ; Döşkaya, Mert ; Can, Hüseyin ; Karakavuk, Muhammet ; Anıl-İnevi, Müge ; Sağlam-Metiner, Pelin ; Atalay-Şahar, Esra ; Değirmenci-Döşkaya, Aysu ; Zekioğlu, Osman ; Gürüz, Adnan Yüksel ; Gülce-Iz, Sultan ; Yeniay, Levent</creatorcontrib><description>•Developed a novel highly immunogenic multi-epitope HER2 DNA vaccine.•Designed a novel multi-epitope HER2 protein containing 7T and B-cell epitopes.•Used an antibody fragment (ScFvDEC) to target multi-epitope HER2 to dendritic cells.•Elicited strong antibody response and protective IFN-γ response in murine model.
Breast cancer was ranked first in global cancer incidence in 2020, and HER2 overexpression in breast cancer accounts for 20–30% of breast cancer patients. Current therapeutic strategies increase the survival rate, but resistance to them occurs frequently, and there is an urgent need to develop novel treatments such as DNA vaccines which can induce a specific and long-lasting immune response against HER2 antigens. To enhance the immunogenicity of DNA vaccines, dendritic cells (DCs) can be targeted using multi-epitope proteins that provide accurate immune focusing. For this purpose, we generated a DNA vaccine encoding a fusion protein composed of 1) in silico discovered antigenic epitopes of human and rat HER2 proteins (MeHer2) and 2) a single-chain antibody fragment (ScFv) specific for the DC-restricted antigen-uptake receptor DEC205 (ScFvDEC). The xenogeneic multi-epitope DNA vaccine (pMeHer2) encodes three only T-cell epitopes, two only B-cell epitopes, and two T and B cell epitopes, and pScFvDEC-MeHer2 vaccine additionally encodes ScFvDEC introduced at the N terminus of the MeHer2. Then, mouse groups were immunized with pScFvDEC-MeHer2, pMeHer2, pScFvDEC, pEmpty, and PBS to determine the elicited immune response. pScFvDEC-MeHer2 vaccinated mice showed a strong IgG response (P < 0.0001) and pScFvDEC-MeHer2 induced a significant IgG2a increase (P < 0.01). The percentages of both IFN-γ secreting CD4 and CD8 T cells were higher in mice immunized with pScFvDEC-MeHer2 compared with the pMeHer2. pScFvDEC-MeHer2 and pMeHer2 secreted significantly higher levels of extracellular IFN-γ compared with to control groups (P < 0.0001). In addition, the IFN-γ level of the pScFvDEC-MeHer2 vaccine group was approximately two times higher than the pMeHer2 group (P < 0.0001). Overall, this study identified the pScFvDECMeHer2 construct as a potential DNA vaccine candidate, supporting further studies to be conducted on HER2+ animal models.</description><identifier>ISSN: 0264-410X</identifier><identifier>EISSN: 1873-2518</identifier><identifier>DOI: 10.1016/j.vaccine.2022.03.014</identifier><identifier>PMID: 35305824</identifier><language>eng</language><publisher>Netherlands: Elsevier Ltd</publisher><subject>Animal models ; Animals ; Antibodies ; Antigen presentation ; Antigens ; Breast cancer ; Breast Neoplasms - prevention & control ; Cancer therapies ; Cancer vaccines ; CD4 antigen ; CD8 antigen ; Chemotherapy ; Clinical trials ; Cloning ; DC-targeting vaccine ; Dendritic Cells ; Deoxyribonucleic acid ; DNA ; DNA vaccine ; DNA vaccines ; Epidermal growth factor ; Epitopes ; Epitopes, T-Lymphocyte - genetics ; ErbB-2 protein ; Female ; Fusion protein ; HER2 ; Humans ; Immune response ; Immune system ; Immunization ; Immunogenicity ; Immunoglobulin G ; Kinases ; Lymphocytes ; Lymphocytes B ; Lymphocytes T ; Medical prognosis ; Mice ; Multi-epitope ; Peptides ; Plasmids ; Proteins ; Proteomics ; Radiation therapy ; Rats ; Receptor, ErbB-2 - genetics ; Receptors ; Servers ; Survival ; Vaccines ; Vaccines, DNA ; Xenogeneic ; γ-Interferon</subject><ispartof>Vaccine, 2022-04, Vol.40 (16), p.2409-2419</ispartof><rights>2022 Elsevier Ltd</rights><rights>Copyright © 2022 Elsevier Ltd. All rights reserved.</rights><rights>2022. Elsevier Ltd</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c393t-dd93e640244d3668fd8f5ea66290587d744a028d702ecd2edd313f7355a3363b3</citedby><cites>FETCH-LOGICAL-c393t-dd93e640244d3668fd8f5ea66290587d744a028d702ecd2edd313f7355a3363b3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S0264410X22002791$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,776,780,3537,27901,27902,65534</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/35305824$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Gül, Aytül</creatorcontrib><creatorcontrib>Döşkaya, Mert</creatorcontrib><creatorcontrib>Can, Hüseyin</creatorcontrib><creatorcontrib>Karakavuk, Muhammet</creatorcontrib><creatorcontrib>Anıl-İnevi, Müge</creatorcontrib><creatorcontrib>Sağlam-Metiner, Pelin</creatorcontrib><creatorcontrib>Atalay-Şahar, Esra</creatorcontrib><creatorcontrib>Değirmenci-Döşkaya, Aysu</creatorcontrib><creatorcontrib>Zekioğlu, Osman</creatorcontrib><creatorcontrib>Gürüz, Adnan Yüksel</creatorcontrib><creatorcontrib>Gülce-Iz, Sultan</creatorcontrib><creatorcontrib>Yeniay, Levent</creatorcontrib><title>Immunogenicity of a xenogeneic multi-epitope HER2+ breast cancer DNA vaccine targeting the dendritic cell restricted antigen-uptake receptor DEC205</title><title>Vaccine</title><addtitle>Vaccine</addtitle><description>•Developed a novel highly immunogenic multi-epitope HER2 DNA vaccine.•Designed a novel multi-epitope HER2 protein containing 7T and B-cell epitopes.•Used an antibody fragment (ScFvDEC) to target multi-epitope HER2 to dendritic cells.•Elicited strong antibody response and protective IFN-γ response in murine model.
Breast cancer was ranked first in global cancer incidence in 2020, and HER2 overexpression in breast cancer accounts for 20–30% of breast cancer patients. Current therapeutic strategies increase the survival rate, but resistance to them occurs frequently, and there is an urgent need to develop novel treatments such as DNA vaccines which can induce a specific and long-lasting immune response against HER2 antigens. To enhance the immunogenicity of DNA vaccines, dendritic cells (DCs) can be targeted using multi-epitope proteins that provide accurate immune focusing. For this purpose, we generated a DNA vaccine encoding a fusion protein composed of 1) in silico discovered antigenic epitopes of human and rat HER2 proteins (MeHer2) and 2) a single-chain antibody fragment (ScFv) specific for the DC-restricted antigen-uptake receptor DEC205 (ScFvDEC). The xenogeneic multi-epitope DNA vaccine (pMeHer2) encodes three only T-cell epitopes, two only B-cell epitopes, and two T and B cell epitopes, and pScFvDEC-MeHer2 vaccine additionally encodes ScFvDEC introduced at the N terminus of the MeHer2. Then, mouse groups were immunized with pScFvDEC-MeHer2, pMeHer2, pScFvDEC, pEmpty, and PBS to determine the elicited immune response. pScFvDEC-MeHer2 vaccinated mice showed a strong IgG response (P < 0.0001) and pScFvDEC-MeHer2 induced a significant IgG2a increase (P < 0.01). The percentages of both IFN-γ secreting CD4 and CD8 T cells were higher in mice immunized with pScFvDEC-MeHer2 compared with the pMeHer2. pScFvDEC-MeHer2 and pMeHer2 secreted significantly higher levels of extracellular IFN-γ compared with to control groups (P < 0.0001). In addition, the IFN-γ level of the pScFvDEC-MeHer2 vaccine group was approximately two times higher than the pMeHer2 group (P < 0.0001). Overall, this study identified the pScFvDECMeHer2 construct as a potential DNA vaccine candidate, supporting further studies to be conducted on HER2+ animal models.</description><subject>Animal models</subject><subject>Animals</subject><subject>Antibodies</subject><subject>Antigen presentation</subject><subject>Antigens</subject><subject>Breast cancer</subject><subject>Breast Neoplasms - prevention & control</subject><subject>Cancer therapies</subject><subject>Cancer vaccines</subject><subject>CD4 antigen</subject><subject>CD8 antigen</subject><subject>Chemotherapy</subject><subject>Clinical trials</subject><subject>Cloning</subject><subject>DC-targeting vaccine</subject><subject>Dendritic Cells</subject><subject>Deoxyribonucleic acid</subject><subject>DNA</subject><subject>DNA vaccine</subject><subject>DNA vaccines</subject><subject>Epidermal growth factor</subject><subject>Epitopes</subject><subject>Epitopes, T-Lymphocyte - genetics</subject><subject>ErbB-2 protein</subject><subject>Female</subject><subject>Fusion protein</subject><subject>HER2</subject><subject>Humans</subject><subject>Immune response</subject><subject>Immune system</subject><subject>Immunization</subject><subject>Immunogenicity</subject><subject>Immunoglobulin G</subject><subject>Kinases</subject><subject>Lymphocytes</subject><subject>Lymphocytes B</subject><subject>Lymphocytes T</subject><subject>Medical prognosis</subject><subject>Mice</subject><subject>Multi-epitope</subject><subject>Peptides</subject><subject>Plasmids</subject><subject>Proteins</subject><subject>Proteomics</subject><subject>Radiation therapy</subject><subject>Rats</subject><subject>Receptor, ErbB-2 - genetics</subject><subject>Receptors</subject><subject>Servers</subject><subject>Survival</subject><subject>Vaccines</subject><subject>Vaccines, DNA</subject><subject>Xenogeneic</subject><subject>γ-Interferon</subject><issn>0264-410X</issn><issn>1873-2518</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2022</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>8G5</sourceid><sourceid>BENPR</sourceid><sourceid>GUQSH</sourceid><sourceid>M2O</sourceid><recordid>eNqFkV9rFDEUxYNY7Lb6EZSAL0KZMcmdZGaepKyrLZQKouBbyCZ31qw7f0wyxX6OfmGz7upDX3wKJL977sk5hLzkrOSMq7fb8s5Y6wcsBROiZFAyXj0hC97UUAjJm6dkwYSqioqzb6fkLMYtY0wCb5-RU5DAZCOqBXm47vt5GDc4eOvTPR07augv_HOD3tJ-3iVf4OTTOCG9Wn0WF3Qd0MRErRksBvr-9pIerdBkwgaTHzY0fUfqcHDBp6xicbejAWMK3iZ01AzJ5wXFPCXzA_OLxSmNWWu1FEw-Jyed2UV8cTzPydcPqy_Lq-Lm08fr5eVNYaGFVDjXAqqKiapyoFTTuaaTaJQSbf5c7eqqMkw0rmYCrRPoHHDoapDSAChYwzl5c9Cdwvhzzu507-PeqhlwnKPO6XHJQDGR0deP0O04hyG721OyUdBylSl5oGwYYwzY6Sn43oR7zZnet6a3-hiV3remGejcWp57dVSf1z26f1N_a8rAuwOAOY47j0FH6zHH73zOLmk3-v-s-A0d76sh</recordid><startdate>20220406</startdate><enddate>20220406</enddate><creator>Gül, Aytül</creator><creator>Döşkaya, Mert</creator><creator>Can, Hüseyin</creator><creator>Karakavuk, Muhammet</creator><creator>Anıl-İnevi, Müge</creator><creator>Sağlam-Metiner, Pelin</creator><creator>Atalay-Şahar, Esra</creator><creator>Değirmenci-Döşkaya, Aysu</creator><creator>Zekioğlu, Osman</creator><creator>Gürüz, Adnan Yüksel</creator><creator>Gülce-Iz, Sultan</creator><creator>Yeniay, Levent</creator><general>Elsevier Ltd</general><general>Elsevier Limited</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7QL</scope><scope>7RV</scope><scope>7T2</scope><scope>7T5</scope><scope>7U9</scope><scope>7X7</scope><scope>7XB</scope><scope>88C</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>8G5</scope><scope>ABUWG</scope><scope>AEUYN</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>GUQSH</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9-</scope><scope>K9.</scope><scope>KB0</scope><scope>LK8</scope><scope>M0R</scope><scope>M0S</scope><scope>M0T</scope><scope>M1P</scope><scope>M2O</scope><scope>M7N</scope><scope>M7P</scope><scope>MBDVC</scope><scope>NAPCQ</scope><scope>PHGZM</scope><scope>PHGZT</scope><scope>PJZUB</scope><scope>PKEHL</scope><scope>PPXIY</scope><scope>PQEST</scope><scope>PQGLB</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>Q9U</scope><scope>7X8</scope></search><sort><creationdate>20220406</creationdate><title>Immunogenicity of a xenogeneic multi-epitope HER2+ breast cancer DNA vaccine targeting the dendritic cell restricted antigen-uptake receptor DEC205</title><author>Gül, Aytül ; Döşkaya, Mert ; Can, Hüseyin ; Karakavuk, Muhammet ; Anıl-İnevi, Müge ; Sağlam-Metiner, Pelin ; Atalay-Şahar, Esra ; Değirmenci-Döşkaya, Aysu ; Zekioğlu, Osman ; Gürüz, Adnan Yüksel ; Gülce-Iz, Sultan ; Yeniay, Levent</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c393t-dd93e640244d3668fd8f5ea66290587d744a028d702ecd2edd313f7355a3363b3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2022</creationdate><topic>Animal models</topic><topic>Animals</topic><topic>Antibodies</topic><topic>Antigen presentation</topic><topic>Antigens</topic><topic>Breast cancer</topic><topic>Breast Neoplasms - prevention & control</topic><topic>Cancer therapies</topic><topic>Cancer vaccines</topic><topic>CD4 antigen</topic><topic>CD8 antigen</topic><topic>Chemotherapy</topic><topic>Clinical trials</topic><topic>Cloning</topic><topic>DC-targeting vaccine</topic><topic>Dendritic Cells</topic><topic>Deoxyribonucleic acid</topic><topic>DNA</topic><topic>DNA vaccine</topic><topic>DNA vaccines</topic><topic>Epidermal growth factor</topic><topic>Epitopes</topic><topic>Epitopes, T-Lymphocyte - genetics</topic><topic>ErbB-2 protein</topic><topic>Female</topic><topic>Fusion protein</topic><topic>HER2</topic><topic>Humans</topic><topic>Immune response</topic><topic>Immune system</topic><topic>Immunization</topic><topic>Immunogenicity</topic><topic>Immunoglobulin G</topic><topic>Kinases</topic><topic>Lymphocytes</topic><topic>Lymphocytes B</topic><topic>Lymphocytes T</topic><topic>Medical prognosis</topic><topic>Mice</topic><topic>Multi-epitope</topic><topic>Peptides</topic><topic>Plasmids</topic><topic>Proteins</topic><topic>Proteomics</topic><topic>Radiation therapy</topic><topic>Rats</topic><topic>Receptor, ErbB-2 - genetics</topic><topic>Receptors</topic><topic>Servers</topic><topic>Survival</topic><topic>Vaccines</topic><topic>Vaccines, DNA</topic><topic>Xenogeneic</topic><topic>γ-Interferon</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Gül, Aytül</creatorcontrib><creatorcontrib>Döşkaya, Mert</creatorcontrib><creatorcontrib>Can, Hüseyin</creatorcontrib><creatorcontrib>Karakavuk, Muhammet</creatorcontrib><creatorcontrib>Anıl-İnevi, Müge</creatorcontrib><creatorcontrib>Sağlam-Metiner, Pelin</creatorcontrib><creatorcontrib>Atalay-Şahar, Esra</creatorcontrib><creatorcontrib>Değirmenci-Döşkaya, Aysu</creatorcontrib><creatorcontrib>Zekioğlu, Osman</creatorcontrib><creatorcontrib>Gürüz, Adnan Yüksel</creatorcontrib><creatorcontrib>Gülce-Iz, Sultan</creatorcontrib><creatorcontrib>Yeniay, Levent</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Nursing & Allied Health Database</collection><collection>Health and Safety Science Abstracts (Full archive)</collection><collection>Immunology Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Healthcare Administration Database (Alumni)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Public Health Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>Research Library (Alumni Edition)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest One Sustainability</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection (ProQuest)</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>Research Library Prep</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>Consumer Health Database (Alumni Edition)</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>ProQuest Biological Science Collection</collection><collection>Consumer Health Database</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Healthcare Administration Database</collection><collection>Medical Database</collection><collection>Research Library</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biological Science Database</collection><collection>Research Library (Corporate)</collection><collection>Nursing & Allied Health Premium</collection><collection>ProQuest Central (New)</collection><collection>ProQuest One Academic (New)</collection><collection>ProQuest Health & Medical Research Collection</collection><collection>ProQuest One Academic Middle East (New)</collection><collection>ProQuest One Health & Nursing</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Applied & Life Sciences</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central Basic</collection><collection>MEDLINE - Academic</collection><jtitle>Vaccine</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Gül, Aytül</au><au>Döşkaya, Mert</au><au>Can, Hüseyin</au><au>Karakavuk, Muhammet</au><au>Anıl-İnevi, Müge</au><au>Sağlam-Metiner, Pelin</au><au>Atalay-Şahar, Esra</au><au>Değirmenci-Döşkaya, Aysu</au><au>Zekioğlu, Osman</au><au>Gürüz, Adnan Yüksel</au><au>Gülce-Iz, Sultan</au><au>Yeniay, Levent</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Immunogenicity of a xenogeneic multi-epitope HER2+ breast cancer DNA vaccine targeting the dendritic cell restricted antigen-uptake receptor DEC205</atitle><jtitle>Vaccine</jtitle><addtitle>Vaccine</addtitle><date>2022-04-06</date><risdate>2022</risdate><volume>40</volume><issue>16</issue><spage>2409</spage><epage>2419</epage><pages>2409-2419</pages><issn>0264-410X</issn><eissn>1873-2518</eissn><abstract>•Developed a novel highly immunogenic multi-epitope HER2 DNA vaccine.•Designed a novel multi-epitope HER2 protein containing 7T and B-cell epitopes.•Used an antibody fragment (ScFvDEC) to target multi-epitope HER2 to dendritic cells.•Elicited strong antibody response and protective IFN-γ response in murine model.
Breast cancer was ranked first in global cancer incidence in 2020, and HER2 overexpression in breast cancer accounts for 20–30% of breast cancer patients. Current therapeutic strategies increase the survival rate, but resistance to them occurs frequently, and there is an urgent need to develop novel treatments such as DNA vaccines which can induce a specific and long-lasting immune response against HER2 antigens. To enhance the immunogenicity of DNA vaccines, dendritic cells (DCs) can be targeted using multi-epitope proteins that provide accurate immune focusing. For this purpose, we generated a DNA vaccine encoding a fusion protein composed of 1) in silico discovered antigenic epitopes of human and rat HER2 proteins (MeHer2) and 2) a single-chain antibody fragment (ScFv) specific for the DC-restricted antigen-uptake receptor DEC205 (ScFvDEC). The xenogeneic multi-epitope DNA vaccine (pMeHer2) encodes three only T-cell epitopes, two only B-cell epitopes, and two T and B cell epitopes, and pScFvDEC-MeHer2 vaccine additionally encodes ScFvDEC introduced at the N terminus of the MeHer2. Then, mouse groups were immunized with pScFvDEC-MeHer2, pMeHer2, pScFvDEC, pEmpty, and PBS to determine the elicited immune response. pScFvDEC-MeHer2 vaccinated mice showed a strong IgG response (P < 0.0001) and pScFvDEC-MeHer2 induced a significant IgG2a increase (P < 0.01). The percentages of both IFN-γ secreting CD4 and CD8 T cells were higher in mice immunized with pScFvDEC-MeHer2 compared with the pMeHer2. pScFvDEC-MeHer2 and pMeHer2 secreted significantly higher levels of extracellular IFN-γ compared with to control groups (P < 0.0001). In addition, the IFN-γ level of the pScFvDEC-MeHer2 vaccine group was approximately two times higher than the pMeHer2 group (P < 0.0001). Overall, this study identified the pScFvDECMeHer2 construct as a potential DNA vaccine candidate, supporting further studies to be conducted on HER2+ animal models.</abstract><cop>Netherlands</cop><pub>Elsevier Ltd</pub><pmid>35305824</pmid><doi>10.1016/j.vaccine.2022.03.014</doi><tpages>11</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0264-410X |
| ispartof | Vaccine, 2022-04, Vol.40 (16), p.2409-2419 |
| issn | 0264-410X 1873-2518 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_2641503602 |
| source | MEDLINE; Elsevier ScienceDirect Journals |
| subjects | Animal models Animals Antibodies Antigen presentation Antigens Breast cancer Breast Neoplasms - prevention & control Cancer therapies Cancer vaccines CD4 antigen CD8 antigen Chemotherapy Clinical trials Cloning DC-targeting vaccine Dendritic Cells Deoxyribonucleic acid DNA DNA vaccine DNA vaccines Epidermal growth factor Epitopes Epitopes, T-Lymphocyte - genetics ErbB-2 protein Female Fusion protein HER2 Humans Immune response Immune system Immunization Immunogenicity Immunoglobulin G Kinases Lymphocytes Lymphocytes B Lymphocytes T Medical prognosis Mice Multi-epitope Peptides Plasmids Proteins Proteomics Radiation therapy Rats Receptor, ErbB-2 - genetics Receptors Servers Survival Vaccines Vaccines, DNA Xenogeneic γ-Interferon |
| title | Immunogenicity of a xenogeneic multi-epitope HER2+ breast cancer DNA vaccine targeting the dendritic cell restricted antigen-uptake receptor DEC205 |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-18T21%3A33%3A12IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Immunogenicity%20of%20a%20xenogeneic%20multi-epitope%20HER2+%20breast%20cancer%20DNA%20vaccine%20targeting%20the%20dendritic%20cell%20restricted%20antigen-uptake%20receptor%20DEC205&rft.jtitle=Vaccine&rft.au=G%C3%BCl,%20Ayt%C3%BCl&rft.date=2022-04-06&rft.volume=40&rft.issue=16&rft.spage=2409&rft.epage=2419&rft.pages=2409-2419&rft.issn=0264-410X&rft.eissn=1873-2518&rft_id=info:doi/10.1016/j.vaccine.2022.03.014&rft_dat=%3Cproquest_cross%3E2645863916%3C/proquest_cross%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2645863916&rft_id=info:pmid/35305824&rft_els_id=S0264410X22002791&rfr_iscdi=true |