{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,10]],"date-time":"2026-08-10T10:49:57Z","timestamp":1786358997478,"version":"build-2736575974"},"reference-count":26,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2025,3,9]],"date-time":"2025-03-09T00:00:00Z","timestamp":1741478400000},"content-version":"vor","delay-in-days":8,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"Australian National Health and Medical Research Council","award":["2004398"],"award-info":[{"award-number":["2004398"]}]},{"name":"Australian Medical Research Future Fund","award":["2005544"],"award-info":[{"award-number":["2005544"]}]},{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Charles and Sylvia Viertel Senior Medical Research"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,3,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Human clinical trials have reported immunological outcomes can differ between ipsilateral (same side) and contralateral (alternate sides) prime-boost vaccination. However, our mechanistic understanding of how keeping or shifting the anatomical sites of immunization impacts the resultant germinal centers (GCs) and antibody responses is limited. Here, we use an adjuvanted SARS-CoV-2 spike vaccine to dissect GC dynamics in draining lymph nodes and serological outcomes following ipsilateral or contralateral prime-boost vaccination in C57BL\/6 mice. Contralateral vaccination elicited independent GCs at distinct lymph nodes, where robust secondary GCs only appeared upon secondary distal vaccination, while ongoing GCs from the primary site were not boosted. In contrast, ipsilateral vaccination resulted in sustained GC activity. Ipsilateral vaccination accelerated the development of antibody titers against ancestral (wild-type [WT]), Beta, and BA.1 but were later comparable between ipsilateral and contralateral groups in terms of magnitude, durability, and neutralization capacity beyond 28\u2009d. Using a heterologous SARS-CoV-2 WT\/BA.1 spike prime-boost model, cross-reactive GC responses were generated against WT and BA.1 spike, with analogous serological and GC dynamics to our homologous model. Within the cross-reactive GC B cells, differential recognition of WT and BA.1 antigens was observed and were further compartmentalized in primary or secondary GCs, depending on ipsilateral or contralateral regimes. Collectively, maintaining a common prime-boost site augments the kinetics of memory B cell recall and transiently drive higher antibody titers, but longer-term serological outcomes are unaffected by the anatomical localization of immunization.<\/jats:p>","DOI":"10.1093\/jimmun\/vkae067","type":"journal-article","created":{"date-parts":[[2025,3,9]],"date-time":"2025-03-09T19:51:34Z","timestamp":1741549894000},"page":"335-346","source":"Crossref","is-referenced-by-count":4,"title":["Modulation of germinal center and antibody dynamics via ipsilateral versus contralateral immunization against SARS-CoV-2"],"prefix":"10.1093","volume":"214","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-4293-7984","authenticated-orcid":false,"given":"Lauren","family":"Burmas","sequence":"first","affiliation":[{"name":"Department of Microbiology and Immunology, University of Melbourne, Peter Doherty Institute for Infection and Immunity , Melbourne, Victoria,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wen Shi","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, University of Melbourne, Peter Doherty Institute for Infection and Immunity , Melbourne, Victoria,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2719-6544","authenticated-orcid":false,"given":"Andrew","family":"Kelly","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, University of Melbourne, Peter Doherty Institute for Infection and Immunity , Melbourne, Victoria,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rosela","family":"Webster","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, University of Melbourne, Peter Doherty Institute for Infection and Immunity , Melbourne, Victoria,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robyn","family":"Esterbauer","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, University of Melbourne, Peter Doherty Institute for Infection and Immunity , Melbourne, Victoria,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8539-4891","authenticated-orcid":false,"given":"Stephen J","family":"Kent","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, University of Melbourne, Peter Doherty Institute for Infection and Immunity , Melbourne, Victoria,","place":["Australia"]},{"name":"Melbourne Sexual Health Centre and Department of Infectious Diseases, Alfred Hospital and Central Clinical School, Monash University , Melbourne, Victoria,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adam K","family":"Wheatley","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, University of Melbourne, Peter Doherty Institute for Infection and Immunity , Melbourne, Victoria,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9072-1017","authenticated-orcid":false,"given":"Jennifer A","family":"Juno","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, University of Melbourne, Peter Doherty Institute for Infection and Immunity , Melbourne, Victoria,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1064-3934","authenticated-orcid":false,"given":"Hyon-Xhi","family":"Tan","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, University of Melbourne, Peter Doherty Institute for Infection and Immunity , Melbourne, Victoria,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2025,3,9]]},"reference":[{"key":"2025032923542570800_vkae067-B1","first-page":"399","article-title":"Deltoid versus buttock as preferred site of injection for hepatitis B vaccine","volume":"76","author":"Hellgren","year":"1989","journal-title":"J Florida Med Assoc"},{"key":"2025032923542570800_vkae067-B2","doi-asserted-by":"crossref","first-page":"1237","DOI":"10.1136\/bmj.321.7271.1237","article-title":"The importance of injecting vaccines into muscle. Different patients need different needle sizes","volume":"321","author":"Zuckerman","year":"2000","journal-title":"BMJ"},{"key":"2025032923542570800_vkae067-B3","doi-asserted-by":"crossref","first-page":"540.540.e1","DOI":"10.1016\/j.cmi.2022.11.009","article-title":"Effect of same-arm versus cross-arm administration of sequential doses of BNT162b2 on short-term vaccine effectiveness-a retrospective cohort study","volume":"29","author":"Grupel","year":"2023","journal-title":"Clin Microbiol Infect"},{"key":"2025032923542570800_vkae067-B4","first-page":"17","article-title":"Pre-exposure rabies prophylaxis problems and procedures","volume":"33","author":"Peck","year":"1964","journal-title":"J Med Ind"},{"key":"2025032923542570800_vkae067-B5","doi-asserted-by":"crossref","first-page":"172","DOI":"10.1016\/S1473-3099(14)71057-6","article-title":"Immunological effect of administration of sequential doses of Haemophilus influenzae type b and pneumococcal conjugate vaccines in the same versus alternating limbs in the routine infant immunisation schedule: an open-label randomised controlled trial","volume":"15","author":"Iro","year":"2015","journal-title":"Lancet Infect Dis"},{"key":"2025032923542570800_vkae067-B6","doi-asserted-by":"crossref","first-page":"104743","DOI":"10.1016\/j.ebiom.2023.104743","article-title":"Differences in SARS-CoV-2 specific humoral and cellular immune responses after contralateral and ipsilateral COVID-19 vaccination","volume":"95","author":"Ziegler","year":"2023","journal-title":"EBioMedicine"},{"key":"2025032923542570800_vkae067-B7","doi-asserted-by":"crossref","first-page":"e176411","DOI":"10.1172\/JCI176411","article-title":"Contralateral second dose improves antibody responses to a 2-dose mRNA vaccination regimen","volume":"134","author":"Fazli","year":"2024","journal-title":"J Clin Invest"},{"key":"2025032923542570800_vkae067-B8","doi-asserted-by":"crossref","first-page":"eadd3075","DOI":"10.1126\/sciimmunol.add3075","article-title":"Route of self-amplifying mRNA vaccination modulates the establishment of pulmonary resident memory CD8 and CD4 T cells","volume":"7","author":"K\u00fcnzli","year":"2022","journal-title":"Sci Immunol"},{"key":"2025032923542570800_vkae067-B9","doi-asserted-by":"crossref","first-page":"eabn5311","DOI":"10.1126\/sciimmunol.abn5311","article-title":"Recall of B cell memory depends on relative locations of prime and boost immunization","volume":"7","author":"Kuraoka","year":"2022","journal-title":"Sci Immunol"},{"key":"2025032923542570800_vkae067-B10","doi-asserted-by":"crossref","first-page":"113665","DOI":"10.1016\/j.celrep.2023.113665","article-title":"Ipsilateral immunization after a prior SARS-CoV-2 mRNA vaccination elicits superior B cell responses compared with contralateral immunization","volume":"43","author":"Jiang","year":"2024","journal-title":"Cell Rep"},{"key":"2025032923542570800_vkae067-B11","doi-asserted-by":"crossref","first-page":"1260","DOI":"10.1126\/science.abb2507","article-title":"Cryo-EM structure of the 2019-nCoV spike in the prefusion conformation","volume":"367","author":"Wrapp","year":"2020","journal-title":"Science"},{"key":"2025032923542570800_vkae067-B12","doi-asserted-by":"crossref","first-page":"1403","DOI":"10.1038\/s41467-021-21665-8","article-title":"Immunogenicity of prime-boost protein subunit vaccine strategies against SARS-CoV-2 in mice and macaques","volume":"12","author":"Tan","year":"2021","journal-title":"Nat Commun"},{"key":"2025032923542570800_vkae067-B13","doi-asserted-by":"crossref","first-page":"735","DOI":"10.4049\/jimmunol.2001299","article-title":"Coformulation with tattoo ink for immunological assessment of vaccine immunogenicity in the draining lymph node","volume":"207","author":"Barber-Axthelm","year":"2021","journal-title":"J Immunol"},{"key":"2025032923542570800_vkae067-B14","doi-asserted-by":"crossref","first-page":"eadg5301","DOI":"10.1126\/sciadv.adg5301","article-title":"Durable reprogramming of neutralizing antibody responses following Omicron breakthrough infection","volume":"9","author":"Lee","year":"2023","journal-title":"Sci Adv"},{"key":"2025032923542570800_vkae067-B15","doi-asserted-by":"crossref","first-page":"1908","DOI":"10.1038\/nprot.2016.102","article-title":"Sequencing and cloning of antigen-specific antibodies from mouse memory B cells","volume":"11","author":"von Boehmer","year":"2016","journal-title":"Nat Protoc"},{"key":"2025032923542570800_vkae067-B16","doi-asserted-by":"crossref","first-page":"569","DOI":"10.1007\/978-1-61779-842-9_32","article-title":"IMGT(\u00ae) tools for the nucleotide analysis of immunoglobulin (IG) and T cell receptor (TR) V-(D)-J repertoires, polymorphisms, and IG mutations: IMGT\/V-QUEST and IMGT\/HighV-QUEST for NGS","volume":"882","author":"Alamyar","year":"2012","journal-title":"Methods Mol Biol"},{"key":"2025032923542570800_vkae067-B17","doi-asserted-by":"crossref","first-page":"1618","DOI":"10.1016\/j.immuni.2024.05.009","article-title":"Opposing effects of pre-existing antibody and memory T cell help on the dynamics of recall germinal centers","volume":"57","author":"Schiepers","year":"2024","journal-title":"Immunity"},{"key":"2025032923542570800_vkae067-B18","doi-asserted-by":"crossref","first-page":"457","DOI":"10.1084\/jem.20120150","article-title":"Germinal center B cells govern their own fate via antibody feedback","volume":"210","author":"Zhang","year":"2013","journal-title":"J Exp Med"},{"key":"2025032923542570800_vkae067-B19","doi-asserted-by":"crossref","first-page":"1856","DOI":"10.1016\/j.immuni.2022.07.020","article-title":"Antibodies from primary humoral responses modulate the recruitment of naive B cells during secondary 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immunization","volume":"615","author":"Schiepers","year":"2023","journal-title":"Nature"},{"key":"2025032923542570800_vkae067-B23","doi-asserted-by":"crossref","first-page":"3372","DOI":"10.1038\/s41467-018-05772-7","article-title":"Memory B cells are reactivated in subcapsular proliferative foci of lymph nodes","volume":"9","author":"Moran","year":"2018","journal-title":"Nat Commun"},{"key":"2025032923542570800_vkae067-B24","doi-asserted-by":"crossref","first-page":"1214","DOI":"10.1084\/jem.20181365","article-title":"CD4(+) resident memory T cells dominate immunosurveillance and orchestrate local recall responses","volume":"216","author":"Beura","year":"2019","journal-title":"J Exp Med"},{"key":"2025032923542570800_vkae067-B25","doi-asserted-by":"crossref","first-page":"4821","DOI":"10.1038\/ncomms5821","article-title":"Resident CD4+ T cells accumulate in lymphoid organs after prolonged antigen exposure","volume":"5","author":"Ugur","year":"2014","journal-title":"Nat Commun"},{"key":"2025032923542570800_vkae067-B26","doi-asserted-by":"crossref","first-page":"406","DOI":"10.1016\/j.celrep.2016.12.038","article-title":"Infection programs sustained lymphoid stromal cell responses and shapes lymph node remodeling upon secondary challenge","volume":"18","author":"Gregory","year":"2017","journal-title":"Cell Rep"}],"container-title":["The Journal of Immunology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/jimmunol\/article-pdf\/214\/3\/335\/62351680\/vkae067.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jimmunol\/article-pdf\/214\/3\/335\/62351680\/vkae067.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,3,31]],"date-time":"2025-03-31T18:27:14Z","timestamp":1743445634000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jimmunol\/article\/214\/3\/335\/8064669"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,3,1]]},"references-count":26,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2025,3,1]]}},"URL":"https:\/\/doi.org\/10.1093\/jimmun\/vkae067","relation":{},"ISSN":["0022-1767","1550-6606"],"issn-type":[{"value":"0022-1767","type":"print"},{"value":"1550-6606","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2025,3]]},"published":{"date-parts":[[2025,3,1]]}}}