{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,16]],"date-time":"2026-01-16T09:18:01Z","timestamp":1768555081945,"version":"3.49.0"},"reference-count":39,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2023,5,17]],"date-time":"2023-05-17T00:00:00Z","timestamp":1684281600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100009139","name":"German Center for Infection Research","doi-asserted-by":"publisher","award":["TTU 01.921"],"award-info":[{"award-number":["TTU 01.921"]}],"id":[{"id":"10.13039\/100009139","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009139","name":"German Center for Infection Research","doi-asserted-by":"publisher","award":["TTU 01.712"],"award-info":[{"award-number":["TTU 01.712"]}],"id":[{"id":"10.13039\/100009139","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009139","name":"German Center for Infection Research","doi-asserted-by":"publisher","award":["BMBF 01KI20702"],"award-info":[{"award-number":["BMBF 01KI20702"]}],"id":[{"id":"10.13039\/100009139","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009139","name":"German Center for Infection Research","doi-asserted-by":"publisher","award":["ZOOVAC 01KI1718"],"award-info":[{"award-number":["ZOOVAC 01KI1718"]}],"id":[{"id":"10.13039\/100009139","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002347","name":"Federal Ministry of Education and Research","doi-asserted-by":"publisher","award":["TTU 01.921"],"award-info":[{"award-number":["TTU 01.921"]}],"id":[{"id":"10.13039\/501100002347","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002347","name":"Federal Ministry of Education and Research","doi-asserted-by":"publisher","award":["TTU 01.712"],"award-info":[{"award-number":["TTU 01.712"]}],"id":[{"id":"10.13039\/501100002347","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002347","name":"Federal Ministry of Education and Research","doi-asserted-by":"publisher","award":["BMBF 01KI20702"],"award-info":[{"award-number":["BMBF 01KI20702"]}],"id":[{"id":"10.13039\/501100002347","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002347","name":"Federal Ministry of Education and Research","doi-asserted-by":"publisher","award":["ZOOVAC 01KI1718"],"award-info":[{"award-number":["ZOOVAC 01KI1718"]}],"id":[{"id":"10.13039\/501100002347","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>The COVID-19 pandemic caused significant human health and economic consequences. Due to the ability of SARS-CoV-2 to spread rapidly and to cause severe disease and mortality in certain population groups, vaccines are essential for controlling the pandemic in the future. Several licensed vaccines have shown improved protection against SARS-CoV-2 after extended-interval prime-boost immunizations in humans. Therefore, in this study, we aimed to compare the immunogenicity of our two Modified Vaccinia virus Ankara (MVA) based COVID-19 candidate vaccines MVA-SARS-2-S and MVA-SARS-2-ST after short- and long-interval prime-boost immunization schedules in mice. We immunized BALB\/c mice using 21-day (short-interval) or 56-day (long-interval) prime-boost vaccination protocols and analyzed spike (S)-specific CD8 T cell immunity and humoral immunity. The two schedules induced robust CD8 T cell responses with no significant differences in their magnitude. Furthermore, both candidate vaccines induced comparable levels of total S, and S2-specific IgG binding antibodies. However, MVA-SARS-2-ST consistently elicited higher amounts of S1-, S receptor binding domain (RBD), and SARS-CoV-2 neutralizing antibodies in both vaccination protocols. Overall, we found very comparable immune responses following short- or long-interval immunization. Thus, our results suggest that the chosen time intervals may not be suitable to observe potential differences in antigen-specific immunity when testing different prime-boost intervals with our candidate vaccines in the mouse model. Despite this, our data clearly showed that MVA-SARS-2-ST induced superior humoral immune responses relative to MVA-SARS-2-S after both immunization schedules.<\/jats:p>","DOI":"10.3390\/v15051180","type":"journal-article","created":{"date-parts":[[2023,5,17]],"date-time":"2023-05-17T01:52:41Z","timestamp":1684288361000},"page":"1180","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Short- and Long-Interval Prime-Boost Vaccination with the Candidate Vaccines MVA-SARS-2-ST and MVA-SARS-2-S Induces Comparable Humoral and Cell-Mediated Immunity in Mice"],"prefix":"10.3390","volume":"15","author":[{"given":"Georgia","family":"Kalodimou","sequence":"first","affiliation":[{"name":"Division of Virology, Department of Veterinary Sciences, LMU Munich, 85764 Oberschlei\u00dfheim, Germany"},{"name":"German Center for Infection Research (DZIF), Partner Site Munich, 85764 Oberschlei\u00dfheim, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sylvia","family":"Jany","sequence":"additional","affiliation":[{"name":"Division of Virology, Department of Veterinary Sciences, LMU Munich, 85764 Oberschlei\u00dfheim, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Astrid","family":"Freudenstein","sequence":"additional","affiliation":[{"name":"Division of Virology, Department of Veterinary Sciences, LMU Munich, 85764 Oberschlei\u00dfheim, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jan Hendrik","family":"Schwarz","sequence":"additional","affiliation":[{"name":"Division of Virology, Department of Veterinary Sciences, LMU Munich, 85764 Oberschlei\u00dfheim, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Leonard","family":"Limpinsel","sequence":"additional","affiliation":[{"name":"Division of Virology, Department of Veterinary Sciences, LMU Munich, 85764 Oberschlei\u00dfheim, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4752-8326","authenticated-orcid":false,"given":"Cornelius","family":"Rohde","sequence":"additional","affiliation":[{"name":"Institute of Virology, Philipps University of Marburg, 35043 Marburg, Germany"},{"name":"German Center for Infection Research (DZIF), Partner Site Gie\u00dfen-Marburg-Langen, 35043 Marburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8517-4779","authenticated-orcid":false,"given":"Alexandra","family":"Kupke","sequence":"additional","affiliation":[{"name":"Institute of Virology, Philipps University of Marburg, 35043 Marburg, Germany"},{"name":"German Center for Infection Research (DZIF), Partner Site Gie\u00dfen-Marburg-Langen, 35043 Marburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6621-9350","authenticated-orcid":false,"given":"Stephan","family":"Becker","sequence":"additional","affiliation":[{"name":"Institute of Virology, Philipps University of Marburg, 35043 Marburg, Germany"},{"name":"German Center for Infection Research (DZIF), Partner Site Gie\u00dfen-Marburg-Langen, 35043 Marburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Asisa","family":"Volz","sequence":"additional","affiliation":[{"name":"Institute of Virology, University of Veterinary Medicine Hannover, 30559 Hannover, Germany"},{"name":"German Center for Infection Research (DZIF), Partner Site Hannover-Braunschweig, 30559 Hannover, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6066-8246","authenticated-orcid":false,"given":"Alina","family":"Tscherne","sequence":"additional","affiliation":[{"name":"Division of Virology, Department of Veterinary Sciences, LMU Munich, 85764 Oberschlei\u00dfheim, Germany"},{"name":"German Center for Infection Research (DZIF), Partner Site Munich, 85764 Oberschlei\u00dfheim, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6143-082X","authenticated-orcid":false,"given":"Gerd","family":"Sutter","sequence":"additional","affiliation":[{"name":"Division of Virology, Department of Veterinary Sciences, LMU Munich, 85764 Oberschlei\u00dfheim, Germany"},{"name":"German Center for Infection Research (DZIF), Partner Site Munich, 85764 Oberschlei\u00dfheim, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,5,17]]},"reference":[{"key":"ref_1","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_2","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1016\/S0140-6736(20)32661-1","article-title":"Safety and efficacy of the ChAdOx1 nCoV-19 vaccine (AZD1222) against SARS-CoV-2: An interim analysis of four randomised controlled trials in Brazil, South Africa, and the UK","volume":"397","author":"Voysey","year":"2021","journal-title":"Lancet"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"2187","DOI":"10.1056\/NEJMoa2101544","article-title":"Safety and Efficacy of Single-Dose Ad26.COV2.S Vaccine against COVID-19","volume":"384","author":"Sadoff","year":"2021","journal-title":"N. Engl. J. Med."},{"key":"ref_4","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":"2020","journal-title":"N. Engl. J. Med."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1001\/jama.2021.8565","article-title":"Effect of 2 Inactivated SARS-CoV-2 Vaccines on Symptomatic COVID-19 Infection in Adults: A Randomized Clinical Trial","volume":"326","author":"Zhang","year":"2021","journal-title":"J. Am. Med. Assoc."},{"key":"ref_6","unstructured":"STIKO (2021). STIKO-Empfehlung zur COVID-19-Impfung. Epidemiol. Bull., 19."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"7123","DOI":"10.1016\/j.vaccine.2021.10.050","article-title":"The influence of interval between doses on response to vaccines","volume":"39","author":"Rodrigues","year":"2021","journal-title":"Vaccine"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"568","DOI":"10.7326\/M20-7866","article-title":"Speed Versus Efficacy: Quantifying Potential Tradeoffs in COVID-19 Vaccine Deployment","volume":"174","author":"Paltiel","year":"2021","journal-title":"Ann. Intern. Med."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"570","DOI":"10.7326\/M20-8137","article-title":"Alternative Dose Allocation Strategies to Increase Benefits From Constrained COVID-19 Vaccine Supply","volume":"174","author":"Tuite","year":"2021","journal-title":"Ann. Intern. Med."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"n18","DOI":"10.1136\/bmj.n18","article-title":"COVID-19 vaccination: What\u2019s the evidence for extending the dosing interval?","volume":"372","author":"Iacobucci","year":"2021","journal-title":"Br. Med. J."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"5699","DOI":"10.1016\/j.cell.2021.10.011","article-title":"Immunogenicity of standard and extended dosing intervals of BNT162b2 mRNA vaccine","volume":"184","author":"Payne","year":"2021","journal-title":"Cell"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"7217","DOI":"10.1038\/s41467-021-27410-5","article-title":"Serological responses and vaccine effectiveness for extended COVID-19 vaccine schedules in England","volume":"12","author":"Amirthalingam","year":"2021","journal-title":"Nat. Commun."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1980","DOI":"10.1093\/cid\/ciac290","article-title":"Two-Dose Severe Acute Respiratory Syndrome Coronavirus 2 Vaccine Effectiveness With Mixed Schedules and Extended Dosing Intervals: Test-Negative Design Studies From British Columbia and Quebec, Canada","volume":"75","author":"Skowronski","year":"2022","journal-title":"Clin. Infect. Dis."},{"key":"ref_14","first-page":"187","article-title":"Chapter Five\u2014Modified Vaccinia Virus Ankara: History, Value in Basic Research, and Current Perspectives for Vaccine Development","volume":"Volume 97","author":"Kielian","year":"2017","journal-title":"Advances in Virus Research"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"447","DOI":"10.1586\/erv.09.4","article-title":"Candidate influenza vaccines based on recombinant modified vaccinia virus Ankara","volume":"8","author":"Rimmelzwaan","year":"2009","journal-title":"Expert Rev. Vaccines"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"10847","DOI":"10.1073\/pnas.89.22.10847","article-title":"Nonreplicating vaccinia vector efficiently expresses recombinant genes","volume":"89","author":"Sutter","year":"1992","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"827","DOI":"10.1016\/S1473-3099(20)30248-6","article-title":"Safety and immunogenicity of a modified vaccinia virus Ankara vector vaccine candidate for Middle East respiratory syndrome: An open-label, phase 1 trial","volume":"20","author":"Koch","year":"2020","journal-title":"Lancet Infect. Dis."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1196","DOI":"10.1016\/S1473-3099(14)70963-6","article-title":"Safety and immunogenicity of a modified-vaccinia-virus-Ankara-based influenza A H5N1 vaccine: A randomised, double-blind phase 1\/2a clinical trial","volume":"14","author":"Kreijtz","year":"2014","journal-title":"Lancet Infect. Dis."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"e2026207118","DOI":"10.1073\/pnas.2026207118","article-title":"Immunogenicity and efficacy of the COVID-19 candidate vector vaccine MVA-SARS-2-S in preclinical vaccination","volume":"118","author":"Tscherne","year":"2021","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"e159895","DOI":"10.1172\/JCI159895","article-title":"Stabilized recombinant SARS-CoV-2 spike antigen enhances vaccine immunogenicity and protective capacity","volume":"132","author":"Tscherne","year":"2022","journal-title":"J. Clin. Investig."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"767","DOI":"10.1016\/0092-8674(84)90412-4","article-title":"The structure of an antigenic determinant in a protein","volume":"37","author":"Wilson","year":"1984","journal-title":"Cell"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1451","DOI":"10.1016\/S0264-410X(96)00072-2","article-title":"Development of a replication-deficient recombinant vaccinia virus vaccine effective against parainfluenza virus 3 infection in an animal model","volume":"14","author":"Wyatt","year":"1996","journal-title":"Vaccine"},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Isaacs, S.N. (2012). Vaccinia Virus and Poxvirology: Methods and Protocols, Humana Press.","DOI":"10.1007\/978-1-61779-876-4"},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Kalodimou, G., Veit, S., Jany, S., Kalinke, U., Broder, C.C., Sutter, G., and Volz, A. (2020). A Soluble Version of Nipah Virus Glycoprotein G Delivered by Vaccinia Virus MVA Activates Specific CD8 and CD4 T Cells in Mice. Viruses, 12.","DOI":"10.3390\/v12010026"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"843","DOI":"10.1016\/j.cell.2020.06.044","article-title":"Longitudinal Isolation of Potent Near-Germline SARS-CoV-2-Neutralizing Antibodies from COVID-19 Patients","volume":"182","author":"Kreer","year":"2020","journal-title":"Cell"},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Veit, S., Jany, S., Fux, R., Sutter, G., and Volz, A. (2018). CD8+ T Cells Responding to the Middle East Respiratory Syndrome Coronavirus Nucleocapsid Protein Delivered by Vaccinia Virus MVA in Mice. Viruses, 10.","DOI":"10.3390\/v10120718"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"6318","DOI":"10.1128\/JVI.00427-06","article-title":"Poxvirus CD8+ T-Cell Determinants and Cross-Reactivity in BALB\/c Mice","volume":"80","author":"Tscharke","year":"2006","journal-title":"J. Virol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"e238","DOI":"10.1016\/S2352-3018(19)30406-0","article-title":"Late boosting of the RV144 regimen with AIDSVAX B\/E and ALVAC-HIV in HIV-uninfected Thai volunteers: A double-blind, randomised controlled trial","volume":"7","author":"Pitisuttithum","year":"2020","journal-title":"Lancet HIV"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1038\/s41541-020-0175-8","article-title":"Innate and secondary humoral responses are improved by increasing the time between MVA vaccine immunizations","volume":"5","author":"Palgen","year":"2020","journal-title":"NPJ Vaccines"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1675","DOI":"10.1016\/j.vaccine.2017.02.032","article-title":"Safety and immunogenicity of a modified vaccinia Ankara vaccine using three immunization schedules and two modes of delivery: A randomized clinical non-inferiority trial","volume":"35","author":"Jackson","year":"2017","journal-title":"Vaccine"},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Pettini, E., Pastore, G., Fiorino, F., Medaglini, D., and Ciabattini, A. (2021). Short or Long Interval between Priming and Boosting: Does It Impact on the Vaccine Immunogenicity?. Vaccines, 9.","DOI":"10.3390\/vaccines9030289"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"105904","DOI":"10.1016\/j.isci.2022.105904","article-title":"An extended SARS-CoV-2 mRNA vaccine prime-boost interval enhances B cell immunity with limited impact on T cells","volume":"26","author":"Nicolas","year":"2023","journal-title":"iScience"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"579761","DOI":"10.3389\/fimmu.2020.579761","article-title":"Vaccine Adjuvants Differentially Affect Kinetics of Antibody and Germinal Center Responses","volume":"11","author":"Pedersen","year":"2020","journal-title":"Front. Immunol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1242","DOI":"10.4049\/jimmunol.1502472","article-title":"Germinal Center B Cell and T Follicular Helper Cell Responses to Viral Vector and Protein-in-Adjuvant Vaccines","volume":"197","author":"Wang","year":"2016","journal-title":"J. Immunol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1281","DOI":"10.1016\/j.immuni.2020.11.009","article-title":"SARS-CoV-2 mRNA Vaccines Foster Potent Antigen-Specific Germinal Center Responses Associated with Neutralizing Antibody Generation","volume":"53","author":"Lederer","year":"2020","journal-title":"Immunity"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"881","DOI":"10.1016\/S0140-6736(21)00432-3","article-title":"Single-dose administration and the influence of the timing of the booster dose on immunogenicity and efficacy of ChAdOx1 nCoV-19 (AZD1222) vaccine: A pooled analysis of four randomised trials","volume":"397","author":"Voysey","year":"2021","journal-title":"Lancet"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"12438","DOI":"10.1128\/JVI.02223-14","article-title":"Kinetic and Phenotypic Analysis of CD8+ T Cell Responses after Priming with Alphavirus Replicons and Homologous or Heterologous Booster Immunizations","volume":"88","author":"Knudsen","year":"2014","journal-title":"J. Virol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"710","DOI":"10.1016\/j.immuni.2008.02.020","article-title":"Human Effector and Memory CD8+ T Cell Responses to Smallpox and Yellow Fever Vaccines","volume":"28","author":"Miller","year":"2008","journal-title":"Immunity"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"11491","DOI":"10.1073\/pnas.191380898","article-title":"Complete, long-lasting protection against malaria of mice primed and boosted with two distinct viral vectors expressing the same plasmodial antigen","volume":"98","author":"Hafalla","year":"2001","journal-title":"Proc. Natl. Acad. Sci. USA"}],"container-title":["Viruses"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4915\/15\/5\/1180\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T19:36:30Z","timestamp":1760124990000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4915\/15\/5\/1180"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,5,17]]},"references-count":39,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2023,5]]}},"alternative-id":["v15051180"],"URL":"https:\/\/doi.org\/10.3390\/v15051180","relation":{},"ISSN":["1999-4915"],"issn-type":[{"value":"1999-4915","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,5,17]]}}}