{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T02:02:24Z","timestamp":1788141744605,"version":"build-2803163510"},"reference-count":28,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2020,2,6]],"date-time":"2020-02-06T00:00:00Z","timestamp":1580947200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["HHSN272200800005C; HHSN272201300018I; HHSN272200800004C;5T32AI074492"],"award-info":[{"award-number":["HHSN272200800005C; HHSN272201300018I; HHSN272200800004C;5T32AI074492"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Vaccines"],"abstract":"<jats:p>Background: Vaccinia is known to induce antibody and cellular responses. Plasmablast, circulating follicular helper T (cTFH) cells, cytokine-expressing CD4 T cells, and memory B cells were compared between subcutaneous (SC) and needle-free jet injection (JI) recipients of non-replicating modified vaccinia Ankara (MVA) vaccine. Methods: Vaccinia-na\u00efve adults received MVA SC or by JI on Days 1 and 29. Vaccinia-specific antibodies were quantified by plaque reduction neutralization test (PRNT) and enzyme-linked immunosorbent assay. Plasmablast, cTFH, and cytokine-expressing CD4 T cells were assessed on Days 1, 8, 15, 29, 36, 43 (cTFH and CD4+ only) and 57. Memory B cells were measured on Days 1 and 57. Results: Of the 36 enrolled subjects, only 22 received both vaccinations and had evaluable specimens after the second vaccine. Plasmablasts peaked one week after each vaccine. Day 15 plasmablasts correlated with peak PRNT titers. cTFH peaked on Days 8 and 36 and correlated with Day 36 plasmablasts. CD4+ peaked at Day 29 and one-third produced \u22652 cytokines. Day 57 memory B cells ranged from 0.1% to 0.17% of IgG-secreting B cells. Conclusions: This study provides insights into the cellular responses to non-replicating MVA, currently used as a vector for a variety of novel vaccines.<\/jats:p>","DOI":"10.3390\/vaccines8010069","type":"journal-article","created":{"date-parts":[[2020,2,7]],"date-time":"2020-02-07T03:13:27Z","timestamp":1581045207000},"page":"69","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Plasmablast, Memory B Cell, CD4+ T Cell, and Circulating Follicular Helper T Cell Responses to a Non-Replicating Modified Vaccinia Ankara Vaccine"],"prefix":"10.3390","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1576-4420","authenticated-orcid":false,"given":"Evan J.","family":"Anderson","sequence":"first","affiliation":[{"name":"Departments of Pediatrics and Medicine, Emory University School of Medicine, Atlanta, GA 30322, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lilin","family":"Lai","sequence":"additional","affiliation":[{"name":"Hope Clinic, Department of Medicine, Emory University School of Medicine, Decatur, GA 30030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jens","family":"Wrammert","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Emory University School of Medicine, Atlanta, GA 30322, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah","family":"Kabbani","sequence":"additional","affiliation":[{"name":"Hope Clinic, Department of Medicine, Emory University School of Medicine, Decatur, GA 30030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yongxian","family":"Xu","sequence":"additional","affiliation":[{"name":"Hope Clinic, Department of Medicine, Emory University School of Medicine, Decatur, GA 30030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0479-0164","authenticated-orcid":false,"given":"Lalita","family":"Priyamvada","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Emory University School of Medicine, Atlanta, GA 30322, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heather","family":"Hill","sequence":"additional","affiliation":[{"name":"The Emmes Corporation, Rockville, MD 20850, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9968-4080","authenticated-orcid":false,"given":"Johannes B.","family":"Goll","sequence":"additional","affiliation":[{"name":"The Emmes Corporation, Rockville, MD 20850, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Travis L.","family":"Jensen","sequence":"additional","affiliation":[{"name":"The Emmes Corporation, Rockville, MD 20850, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0295-0785","authenticated-orcid":false,"given":"Carol","family":"Kao","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Emory University School of Medicine, Atlanta, GA 30322, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8631-0020","authenticated-orcid":false,"given":"Inci","family":"Yildirim","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Emory University School of Medicine, Atlanta, GA 30322, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nadine","family":"Rouphael","sequence":"additional","affiliation":[{"name":"Hope Clinic, Department of Medicine, Emory University School of Medicine, Decatur, GA 30030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lisa","family":"Jackson","sequence":"additional","affiliation":[{"name":"Kaiser Permanente, Seattle, WA 98101, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark J.","family":"Mulligan","sequence":"additional","affiliation":[{"name":"Hope Clinic, Department of Medicine, Emory University School of Medicine, Decatur, GA 30030, USA"},{"name":"Langone Vaccine Center, New York University, New York, NY 10016, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,2,6]]},"reference":[{"key":"ref_1","first-page":"397","article-title":"Smallpox: Emergence, global spread, and eradication","volume":"15","author":"Fenner","year":"1993","journal-title":"Hist. Philos. Life Sci."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"2127","DOI":"10.1001\/jama.281.22.2127","article-title":"Smallpox as a biological weapon: Medical and public health management. Working Group on Civilian Biodefense","volume":"281","author":"Henderson","year":"1999","journal-title":"JAMA"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1201","DOI":"10.1056\/NEJM196911272812201","article-title":"Complications of smallpox vaccination, 1968","volume":"281","author":"Lane","year":"1969","journal-title":"N. Engl. J. Med."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"3278","DOI":"10.1001\/jama.289.24.3278","article-title":"US military smallpox vaccination program experience","volume":"289","author":"Grabenstein","year":"2003","journal-title":"JAMA"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1209","DOI":"10.1016\/j.vaccine.2009.11.030","article-title":"A randomized, double-blind, dose-finding Phase II study to evaluate immunogenicity and safety of the third generation smallpox vaccine candidate IMVAMUNE","volume":"28","author":"Vollmar","year":"2010","journal-title":"Vaccine"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1897","DOI":"10.1056\/NEJMoa1817307","article-title":"Phase 3 Efficacy Trial of Modified Vaccinia Ankara as a Vaccine against Smallpox","volume":"381","author":"Pittman","year":"2019","journal-title":"N. Engl. J. Med."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"363","DOI":"10.1016\/S1074-7613(00)80541-5","article-title":"Humoral immunity due to long-lived plasma cells","volume":"8","author":"Slifka","year":"1998","journal-title":"Immunity"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"4969","DOI":"10.4049\/jimmunol.171.10.4969","article-title":"Cutting edge: Long-term B cell memory in humans after smallpox vaccination","volume":"171","author":"Crotty","year":"2003","journal-title":"J. Immunol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"4590","DOI":"10.1073\/pnas.0401165101","article-title":"Highly attenuated smallpox vaccine protects mice with and without immune deficiencies against pathogenic vaccinia virus challenge","volume":"101","author":"Wyatt","year":"2004","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"176ra132","DOI":"10.1126\/scitranslmed.3005191","article-title":"Induction of ICOS+CXCR3+CXCR5+TH cells correlates with antibody responses to influenza vaccination","volume":"5","author":"Bentebibel","year":"2013","journal-title":"Sci. Transl. Med."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1016\/j.immuni.2010.12.012","article-title":"Human blood CXCR5(+)CD4(+) T cells are counterparts of T follicular cells and contain specific subsets that differentially support antibody secretion","volume":"34","author":"Morita","year":"2011","journal-title":"Immunity"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"770","DOI":"10.1016\/j.immuni.2013.09.007","article-title":"Circulating precursor CCR7(lo)PD-1(hi) CXCR5(+) CD4(+) T cells indicate Tfh cell activity and promote antibody responses upon antigen reexposure","volume":"39","author":"He","year":"2013","journal-title":"Immunity"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"3528","DOI":"10.4049\/jimmunol.1302503","article-title":"Circulating CXCR5+PD-1+ response predicts influenza vaccine antibody responses in young adults but not elderly adults","volume":"193","author":"Herati","year":"2014","journal-title":"J. Immunol."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Matsui, K., Adelsberger, J.W., Kemp, T.J., Baseler, M.W., Ledgerwood, J.E., and Pinto, L.A. (2015). Circulating CXCR5(+)CD4(+) T Follicular-Like Helper Cell and Memory B Cell Responses to Human Papillomavirus Vaccines. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0137195"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"2729","DOI":"10.1038\/s41598-018-20740-3","article-title":"Activated T follicular helper-like cells are released into blood after oral vaccination and correlate with vaccine specific mucosal B-cell memory","volume":"8","author":"Cardeno","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"667","DOI":"10.1038\/nature06890","article-title":"Rapid cloning of high-affinity human monoclonal antibodies against influenza virus","volume":"453","author":"Wrammert","year":"2008","journal-title":"Nature"},{"key":"ref_17","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_18","doi-asserted-by":"crossref","first-page":"3025","DOI":"10.1016\/j.vaccine.2013.04.050","article-title":"Safety and immunogenicity of IMVAMUNE(R) smallpox vaccine using different strategies for a post event scenario","volume":"31","author":"Frey","year":"2013","journal-title":"Vaccine"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"ofv040","DOI":"10.1093\/ofid\/ofv040","article-title":"Safety and immunogenicity of modified vaccinia Ankara-Bavarian Nordic smallpox vaccine in vaccinia-naive and experienced human immunodeficiency virus-infected individuals: An open-label, controlled clinical Phase II trial","volume":"2","author":"Overton","year":"2015","journal-title":"Open Forum Infect. Dis."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1084\/jem.20101352","article-title":"Broadly cross-reactive antibodies dominate the human B cell response against 2009 pandemic H1N1 influenza virus infection","volume":"208","author":"Wrammert","year":"2011","journal-title":"J. Exp. Med."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1016\/j.jim.2003.12.015","article-title":"Tracking human antigen-specific memory B cells: A sensitive and generalized ELISPOT system","volume":"286","author":"Crotty","year":"2004","journal-title":"J. Immunol. Methods"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1111\/j.1600-065X.2010.00975.x","article-title":"Smallpox vaccines: Targets of protective immunity","volume":"239","author":"Moss","year":"2011","journal-title":"Immunol. Rev."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"621","DOI":"10.1146\/annurev-immunol-031210-101400","article-title":"Follicular helper CD4 T cells (TFH)","volume":"29","author":"Crotty","year":"2011","journal-title":"Annu. Rev. Immunol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"5574","DOI":"10.1128\/JVI.03203-15","article-title":"B Cell Responses during Secondary Dengue Virus Infection Are Dominated by Highly Cross-Reactive, Memory-Derived Plasmablasts","volume":"90","author":"Priyamvada","year":"2016","journal-title":"J. Virol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"2911","DOI":"10.1128\/JVI.06075-11","article-title":"Rapid and massive virus-specific plasmablast responses during acute dengue virus infection in humans","volume":"86","author":"Wrammert","year":"2012","journal-title":"J. Virol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"4719","DOI":"10.1016\/j.vaccine.2015.03.074","article-title":"A randomized clinical trial in adults and newborns in South Africa to compare the safety and immunogenicity of bacille Calmette-Guerin (BCG) vaccine administration via a disposable-syringe jet injector to conventional technique with needle and syringe","volume":"33","author":"Geldenhuys","year":"2015","journal-title":"Vaccine"},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Graham, B.S., Enama, M.E., Nason, M.C., Gordon, I.J., Peel, S.A., Ledgerwood, J.E., Plummer, S.A., Mascola, J.R., Bailer, R.T., and Roederer, M. (2013). DNA vaccine delivered by a needle-free injection device improves potency of priming for antibody and CD8+ T-cell responses after rAd5 boost in a randomized clinical trial. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0059340"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"552","DOI":"10.1016\/S0140-6736(17)33105-7","article-title":"Safety, tolerability, and immunogenicity of two Zika virus DNA vaccine candidates in healthy adults: Randomised, open-label, phase 1 clinical trials","volume":"391","author":"Gaudinski","year":"2018","journal-title":"Lancet"}],"container-title":["Vaccines"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-393X\/8\/1\/69\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T08:55:09Z","timestamp":1760172909000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-393X\/8\/1\/69"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,2,6]]},"references-count":28,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2020,3]]}},"alternative-id":["vaccines8010069"],"URL":"https:\/\/doi.org\/10.3390\/vaccines8010069","relation":{},"ISSN":["2076-393X"],"issn-type":[{"value":"2076-393X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,2,6]]}}}