{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,18]],"date-time":"2026-06-18T02:39:21Z","timestamp":1781750361383,"version":"3.54.5"},"reference-count":27,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2021,4,24]],"date-time":"2021-04-24T00:00:00Z","timestamp":1619222400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["EXC 2180 (390900677)"],"award-info":[{"award-number":["EXC 2180 (390900677)"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Ernst-Jung Stiftung","award":["Ernst Jung-Preis f\u00fcr Medizin 2016"],"award-info":[{"award-number":["Ernst Jung-Preis f\u00fcr Medizin 2016"]}]},{"DOI":"10.13039\/501100002345","name":"University of T\u00fcbingen","doi-asserted-by":"publisher","award":["generic funding"],"award-info":[{"award-number":["generic funding"]}],"id":[{"id":"10.13039\/501100002345","id-type":"DOI","asserted-by":"publisher"}]},{"name":"University Hospital T\u00fcbingen","award":["generic funding"],"award-info":[{"award-number":["generic funding"]}]},{"name":"Medical Faculty at the University of T\u00fcbingen","award":["(\u201cAngewandte Klinische Forschung\u201d (AKF) program"],"award-info":[{"award-number":["(\u201cAngewandte Klinische Forschung\u201d (AKF) program"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Vaccines"],"abstract":"<jats:p>We describe the results of two vaccinations of a self-experimenting healthy volunteer with SARS-CoV-2-derived peptides performed in March and April 2020, respectively. The first set of peptides contained eight peptides predicted to bind to the individual\u2019s HLA molecules. The second set consisted of ten peptides predicted to bind promiscuously to several HLA-DR allotypes. The vaccine formulation contained the new TLR 1\/2 agonist XS15 and was administered as an emulsion in Montanide as a single subcutaneous injection. Peripheral blood mononuclear cells isolated from blood drawn before and after vaccinations were assessed using Interferon-\u03b3 ELISpot assays and intracellular cytokine staining. We detected vaccine-induced CD4 T cell responses against six out of 11 peptides predicted to bind to HLA-DR after 19 days, following vaccination, for one peptide already at day 12. We used these results to support the design of a T-cell-inducing vaccine for application in high-risk patients, with weakened lymphocyte performance. Meanwhile, an according vaccine, incorporating T cell epitopes predominant in convalescents, is undergoing clinical trial testing.<\/jats:p>","DOI":"10.3390\/vaccines9050428","type":"journal-article","created":{"date-parts":[[2021,4,25]],"date-time":"2021-04-25T02:12:57Z","timestamp":1619316777000},"page":"428","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":27,"title":["Designing a SARS-CoV-2 T-Cell-Inducing Vaccine for High-Risk Patient Groups"],"prefix":"10.3390","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1614-2647","authenticated-orcid":false,"given":"Hans-Georg","family":"Rammensee","sequence":"first","affiliation":[{"name":"Department of Immunology, Institute for Cell Biology, University of T\u00fcbingen, Auf der Morgenstelle 15, 72076 T\u00fcbingen, Germany"},{"name":"German Cancer Consortium (DKTK) and German Cancer Research Center (DKFZ), Partner Site T\u00fcbingen, 72076 T\u00fcbingen, Germany"},{"name":"Cluster of Excellence iFIT (EXC2180) \u201cImage-Guided and Functionally Instructed Tumor Therapies\u201d, University of T\u00fcbingen, 72076 T\u00fcbingen, Germany"},{"name":"Cluster of Excellence CMFI (EXC2124) \u201cControlling Microbes to Fight Infections\u201d, University of T\u00fcbingen, 72076 T\u00fcbingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6410-2378","authenticated-orcid":false,"given":"C\u00e9cile","family":"Gouttefangeas","sequence":"additional","affiliation":[{"name":"Department of Immunology, Institute for Cell Biology, University of T\u00fcbingen, Auf der Morgenstelle 15, 72076 T\u00fcbingen, Germany"},{"name":"German Cancer Consortium (DKTK) and German Cancer Research Center (DKFZ), Partner Site T\u00fcbingen, 72076 T\u00fcbingen, Germany"},{"name":"Cluster of Excellence iFIT (EXC2180) \u201cImage-Guided and Functionally Instructed Tumor Therapies\u201d, University of T\u00fcbingen, 72076 T\u00fcbingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sonja","family":"Heidu","sequence":"additional","affiliation":[{"name":"Department of Immunology, Institute for Cell Biology, University of T\u00fcbingen, Auf der Morgenstelle 15, 72076 T\u00fcbingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6111-3901","authenticated-orcid":false,"given":"Reinhild","family":"Klein","sequence":"additional","affiliation":[{"name":"Department of Hematology, Oncology, Clinical Immunology and Rheumatology, University Hospital T\u00fcbingen, Otfried-M\u00fcller-Str. 10, 72076 T\u00fcbingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beate","family":"Preu\u00df","sequence":"additional","affiliation":[{"name":"Department of Hematology, Oncology, Clinical Immunology and Rheumatology, University Hospital T\u00fcbingen, Otfried-M\u00fcller-Str. 10, 72076 T\u00fcbingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6404-7391","authenticated-orcid":false,"given":"Juliane","family":"Walz","sequence":"additional","affiliation":[{"name":"Department of Immunology, Institute for Cell Biology, University of T\u00fcbingen, Auf der Morgenstelle 15, 72076 T\u00fcbingen, Germany"},{"name":"Cluster of Excellence iFIT (EXC2180) \u201cImage-Guided and Functionally Instructed Tumor Therapies\u201d, University of T\u00fcbingen, 72076 T\u00fcbingen, Germany"},{"name":"German Cancer Consortium (DKTK), Clinical Collaboration Unit Translational Immunology, University Hospital T\u00fcbingen, Otfried-M\u00fcller-Str. 10, 72076 T\u00fcbingen, Germany"},{"name":"Dr. Margarete Fischer-Bosch Institute of Clinical Pharmacology (IKP) and Robert Bosch Center for Tumor Diseases (RBCT), Auerbachstr. 112, 70376 Stuttgart, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8504-8481","authenticated-orcid":false,"given":"Annika","family":"Nelde","sequence":"additional","affiliation":[{"name":"Department of Immunology, Institute for Cell Biology, University of T\u00fcbingen, Auf der Morgenstelle 15, 72076 T\u00fcbingen, Germany"},{"name":"Cluster of Excellence iFIT (EXC2180) \u201cImage-Guided and Functionally Instructed Tumor Therapies\u201d, University of T\u00fcbingen, 72076 T\u00fcbingen, Germany"},{"name":"German Cancer Consortium (DKTK), Clinical Collaboration Unit Translational Immunology, University Hospital T\u00fcbingen, Otfried-M\u00fcller-Str. 10, 72076 T\u00fcbingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sebastian","family":"Haen","sequence":"additional","affiliation":[{"name":"Department of Immunology, Institute for Cell Biology, University of T\u00fcbingen, Auf der Morgenstelle 15, 72076 T\u00fcbingen, Germany"},{"name":"German Cancer Consortium (DKTK) and German Cancer Research Center (DKFZ), Partner Site T\u00fcbingen, 72076 T\u00fcbingen, Germany"},{"name":"Department of Oncology, Hematology and Bone Marrow Transplantation with Section of Pneumology, University Medical Center Hamburg-Eppendorf, Martinistr. 52, 20246 Hamburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1025-7198","authenticated-orcid":false,"given":"Michael","family":"Reth","sequence":"additional","affiliation":[{"name":"Signaling Research Centres BIOSS and CIBSS, Institute of Biology III, Department of Molecular Immunology, University of Freiburg, Sch\u00e4nzlestr. 18, 79104 Freiburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianying","family":"Yang","sequence":"additional","affiliation":[{"name":"Signaling Research Centres BIOSS and CIBSS, Institute of Biology III, Department of Molecular Immunology, University of Freiburg, Sch\u00e4nzlestr. 18, 79104 Freiburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3542-8782","authenticated-orcid":false,"given":"Ghazaleh","family":"Tabatabai","sequence":"additional","affiliation":[{"name":"German Cancer Consortium (DKTK) and German Cancer Research Center (DKFZ), Partner Site T\u00fcbingen, 72076 T\u00fcbingen, Germany"},{"name":"Center for Neuro-Oncology, Comprehensive Cancer Center T\u00fcbingen-Stuttgart, University Hospital T\u00fcbingen, Hoppe-Seyler-Str. 3, 72076 T\u00fcbingen, Germany"},{"name":"Department of Neurology &amp; Interdisciplinary Neuro-Oncology, Hertie Institute for Clinical Brain Research, University Hospital T\u00fcbingen, Hoppe-Seyler-Str. 3, 72076 T\u00fcbingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hans","family":"B\u00f6sm\u00fcller","sequence":"additional","affiliation":[{"name":"Institute of Pathology and Neuropathology, University Hospital T\u00fcbingen, Liebermeisterstr. 8, 72076 T\u00fcbingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helen","family":"Hoffmann","sequence":"additional","affiliation":[{"name":"Department of Immunology, Institute for Cell Biology, University of T\u00fcbingen, Auf der Morgenstelle 15, 72076 T\u00fcbingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8989-5813","authenticated-orcid":false,"given":"Michael","family":"Schindler","sequence":"additional","affiliation":[{"name":"Institute for Medical Virology and Epidemiology of Viral Diseases, University Hospital T\u00fcbingen, Elfriede-Aulhorn-Str. 6, 72076 T\u00fcbingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oliver","family":"Planz","sequence":"additional","affiliation":[{"name":"Department of Immunology, Institute for Cell Biology, University of T\u00fcbingen, Auf der Morgenstelle 15, 72076 T\u00fcbingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karl-Heinz","family":"Wiesm\u00fcller","sequence":"additional","affiliation":[{"name":"EMC microcollections GmbH, Sindelfinger Str. 3, 72070 T\u00fcbingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2513-1317","authenticated-orcid":false,"given":"Markus","family":"L\u00f6ffler","sequence":"additional","affiliation":[{"name":"Department of Immunology, Institute for Cell Biology, University of T\u00fcbingen, Auf der Morgenstelle 15, 72076 T\u00fcbingen, Germany"},{"name":"German Cancer Consortium (DKTK) and German Cancer Research Center (DKFZ), Partner Site T\u00fcbingen, 72076 T\u00fcbingen, Germany"},{"name":"Cluster of Excellence iFIT (EXC2180) \u201cImage-Guided and Functionally Instructed Tumor Therapies\u201d, University of T\u00fcbingen, 72076 T\u00fcbingen, Germany"},{"name":"Department of General, Visceral and Transplant Surgery, University Hospital T\u00fcbingen, Hoppe-Seyler-Str. 3, 72076 T\u00fcbingen, Germany"},{"name":"Department of Clinical Pharmacology, University Hospital T\u00fcbingen, Auf der Morgenstelle 8, 72076 T\u00fcbingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,4,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"727","DOI":"10.1056\/NEJMoa2001017","article-title":"A Novel Coronavirus from Patients with Pneumonia in China, 2019","volume":"382","author":"Zhu","year":"2020","journal-title":"N. Engl. J. Med."},{"key":"ref_2","first-page":"157","article-title":"WHO Declares COVID-19 a Pandemic","volume":"91","author":"Cucinotta","year":"2020","journal-title":"Acta Biomed."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"403","DOI":"10.1056\/NEJMoa2035389","article-title":"Efficacy and Safety of the mRNA-1273 SARS-CoV-2 Vaccine","volume":"384","author":"Baden","year":"2021","journal-title":"N. Engl. J. Med."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"2603","DOI":"10.1056\/NEJMoa2034577","article-title":"Safety and Efficacy of the BNT162b2 mRNA Covid-19 Vaccine","volume":"383","author":"Polack","year":"2020","journal-title":"N. Engl. J. Med."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Prendecki, M., Clarke, C., Brown, J., Cox, A., Gleeson, S., Guckian, M., Randell, P., Pria, A.D., Lightstone, L., and Xu, X.N. (2021). Effect of previous SARS-CoV-2 infection on humoral and T-cell responses to single-dose BNT162b2 vaccine. Lancet.","DOI":"10.1016\/S0140-6736(21)00502-X"},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Panagiotou, O.A., Kosar, C.M., White, E.M., Bantis, L.E., Yang, X., Santostefano, C.M., Feifer, R.A., Blackman, C., Rudolph, J.L., and Gravenstein, S. (2021). Risk Factors Associated With All-Cause 30-Day Mortality in Nursing Home Residents With COVID-19. JAMA Intern. Med.","DOI":"10.1001\/jamainternmed.2020.7968"},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Guan, W.J., Liang, W.H., Zhao, Y., Liang, H.R., Chen, Z.S., Li, Y.M., Liu, X.Q., Chen, R.C., Tang, C.L., and Wang, T. (2020). Comorbidity and its impact on 1590 patients with COVID-19 in China: A nationwide analysis. Eur. Respir. J., 55.","DOI":"10.1183\/13993003.01227-2020"},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Erdal, G.S., Polat, O., Erdem, G.U., Korkusuz, R., Hindilerden, F., Yilmaz, M., Yasar, K.K., Isiksacan, N., and Tural, D. (2021). The mortality rate of COVID-19 was high in cancer patients: A retrospective single-center study. Int. J. Clin. Oncol.","DOI":"10.1007\/s10147-021-01863-6"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1089\/rej.2018.2059","article-title":"Review of Scientific Self-Experimentation: Ethics History, Regulation, Scenarios, and Views Among Ethics Committees and Prominent Scientists","volume":"22","author":"Hanley","year":"2019","journal-title":"Rejuvenation Res."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1186\/s40425-019-0796-5","article-title":"A new synthetic toll-like receptor 1\/2 ligand is an efficient adjuvant for peptide vaccination in a human volunteer","volume":"7","author":"Rammensee","year":"2019","journal-title":"J. Immunother. Cancer"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"w20415","DOI":"10.4414\/smw.2020.20415","article-title":"Going first: The ethics of vaccine self-experimentation in coronavirus times","volume":"150","year":"2020","journal-title":"Swiss Med. Wkly."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Rammensee, H.G., Stevanovi\u0107, S., Gouttefangeas, C., Heidu, S., Klein, R., Preu\u00df, B., Walz, J.S., Nelde, A., Haen, S.P., and Reth, M. (2021). Designing a therapeutic SARS-CoV-2 T-cell-inducing vaccine for high-risk patient groups. Res. Sq.","DOI":"10.21203\/rs.3.rs-27316\/v1"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1038\/s41586-020-2008-3","article-title":"A new coronavirus associated with human respiratory disease in China","volume":"579","author":"Wu","year":"2020","journal-title":"Nature"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"92","DOI":"10.3389\/fimmu.2014.00092","article-title":"Early BCR Events and Antigen Capture, Processing, and Loading on MHC Class II on B Cells","volume":"5","author":"Avalos","year":"2014","journal-title":"Front. Immunol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1007\/s002510050595","article-title":"SYFPEITHI: Database for MHC ligands and peptide motifs","volume":"50","author":"Rammensee","year":"1999","journal-title":"Immunogenetics"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1038\/s41590-020-00808-x","article-title":"SARS-CoV-2-derived peptides define heterologous and COVID-19-induced T cell recognition","volume":"22","author":"Nelde","year":"2021","journal-title":"Nat. Immunol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"L651","DOI":"10.1152\/ajplung.00133.2017","article-title":"The beginnings of cardiac catheterization and the resulting impact on pulmonary medicine","volume":"313","author":"West","year":"2017","journal-title":"Am. J. Physiol. Lung Cell Mol. Physiol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"330","DOI":"10.7326\/0003-4819-134-4-200102200-00017","article-title":"In defense of case reports and case series","volume":"134","author":"Vandenbroucke","year":"2001","journal-title":"Ann. Intern. Med."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"140","DOI":"10.1002\/ijc.26365","article-title":"Promiscuous survivin peptide induces robust CD4+ T-cell responses in the majority of vaccinated cancer patients","volume":"131","author":"Widenmeyer","year":"2012","journal-title":"Int. J. Cancer"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"849","DOI":"10.1016\/j.jhep.2016.06.027","article-title":"Personalized peptide vaccine-induced immune response associated with long-term survival of a metastatic cholangiocarcinoma patient","volume":"65","author":"Chandran","year":"2016","journal-title":"J. Hepatol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"2995","DOI":"10.1128\/JVI.02980-14","article-title":"Severe acute respiratory syndrome-associated coronavirus vaccines formulated with delta inulin adjuvants provide enhanced protection while ameliorating lung eosinophilic immunopathology","volume":"89","author":"Barnard","year":"2015","journal-title":"J. Virol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"745","DOI":"10.1126\/science.1185181","article-title":"Cross-reacting antibodies enhance dengue virus infection in humans","volume":"328","author":"Dejnirattisai","year":"2010","journal-title":"Science"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1315","DOI":"10.1292\/jvms.70.1315","article-title":"Antibody-dependent enhancement occurs upon re-infection with the identical serotype virus in feline infectious peritonitis virus infection","volume":"70","author":"Takano","year":"2008","journal-title":"J. Vet. Med. Sci."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1016\/j.micinf.2020.02.006","article-title":"Is COVID-19 receiving ADE from other coronaviruses?","volume":"22","author":"Tetro","year":"2020","journal-title":"Microbes Infect."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"797","DOI":"10.1073\/pnas.0409065102","article-title":"Evasion of antibody neutralization in emerging severe acute respiratory syndrome coronaviruses","volume":"102","author":"Yang","year":"2005","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"118","DOI":"10.1007\/s12026-014-8534-z","article-title":"T cell-mediated immune response to respiratory coronaviruses","volume":"59","author":"Channappanavar","year":"2014","journal-title":"Immunol. Res."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1016\/j.jneuroim.2005.07.014","article-title":"High level of cross-reactivity in influenza virus hemagglutinin-specific CD4+ T-cell response: Implications for the initiation of autoimmune response in multiple sclerosis","volume":"169","author":"Hemmer","year":"2005","journal-title":"J. Neuroimmunol."}],"container-title":["Vaccines"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-393X\/9\/5\/428\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T05:52:27Z","timestamp":1760161947000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-393X\/9\/5\/428"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,4,24]]},"references-count":27,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2021,5]]}},"alternative-id":["vaccines9050428"],"URL":"https:\/\/doi.org\/10.3390\/vaccines9050428","relation":{},"ISSN":["2076-393X"],"issn-type":[{"value":"2076-393X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,4,24]]}}}