{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T23:54:25Z","timestamp":1792886065652,"version":"4.5.0"},"reference-count":33,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,3,24]],"date-time":"2025-03-24T00:00:00Z","timestamp":1742774400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Vaccination against COVID-19 has been pivotal in reducing the global burden of the disease. However, Phase III trial results and observational studies underscore differences in efficacy across vaccine technologies and dosing regimens. Notably, mRNA vaccines have exhibited superior effectiveness compared to Adenovirus (AdV) vaccines, especially with extended dosing intervals.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Using in-host mechanistic modelling, this study elucidates these variations and unravels the biological mechanisms shaping the immune responses at the cellular level. We used data on the change in memory B cells, plasmablasts, and antibody titres after the second dose of a COVID-19 vaccine for Australian healthcare workers. Alongside this dataset, we constructed a kinetic model of humoral immunity which jointly captured the dynamics of multiple immune markers, and integrated hierarchical effects into this kinetics model, including age, dosing schedule, and vaccine type.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Our analysis estimated that mRNA vaccines induced 2.1 times higher memory B cell proliferation than AdV vaccines after adjusting for age, interval between doses and priming dose. Additionally, extending the duration between the second vaccine dose and priming dose beyond 28 days boosted neutralising antibody production per plasmablast concentration by 30%. We also found that antibody responses after the second dose were more persistent when mRNA vaccines were used over AdV vaccines and for longer dosing regimens.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>Reconstructing in-host kinetics in response to vaccination could help optimise vaccine dosing regimens, improve vaccine efficacy in different population groups, and inform the design of future vaccines for enhanced protection against emerging pathogens.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2025.1487066","type":"journal-article","created":{"date-parts":[[2025,3,24]],"date-time":"2025-03-24T11:15:48Z","timestamp":1742814948000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":9,"title":["Memory B cell proliferation drives differences in neutralising responses between ChAdOx1 and BNT162b2 SARS-CoV-2 vaccines"],"prefix":"10.3389","volume":"16","author":[{"given":"David","family":"Hodgson","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Louise","family":"Carolan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Siddhartha","family":"Mahanty","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kanta","family":"Subbarao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sheena G.","family":"Sullivan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annette","family":"Fox","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adam","family":"Kucharski","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,3,24]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmi.2021.10.005","article-title":"Comparing COVID-19 vaccines for their characteristics, efficacy and effectiveness against SARS-CoV-2 and variants of concern: a narrative review","volume":"28","author":"Fiolet","year":"2022","journal-title":"Clin Microbiol Infect"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2034577","article-title":"Safety and efficacy of the BNT162b2 mRNA Covid-19 vaccine","volume":"383","author":"Polack Fernando","year":"2020","journal-title":"N Engl J Med"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2110345","article-title":"Safety and Efficacy of the BNT162b2 mRNA Covid-19 Vaccine through 6 Months","volume":"385","author":"Thomas Stephen","year":"2021","journal-title":"N Engl J Med"},{"key":"B4","doi-asserted-by":"publisher","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":"B5","doi-asserted-by":"publisher","first-page":"78","DOI":"10.1186\/s12916-023-02795-w","article-title":"Comparative effectiveness of BNT162b2 and ChAdOx1 nCoV-19 vaccines against COVID-19","volume":"21","author":"Wei","year":"2023","journal-title":"BMC Med"},{"key":"B6","doi-asserted-by":"publisher","first-page":"1214","DOI":"10.1038\/s41467-024-45334-8","article-title":"Comparative effectiveness of alternative intervals between first and second doses of the mRNA COVID-19 vaccines","volume":"15","author":"Shioda","year":"2024","journal-title":"Nat Commun"},{"key":"B7","doi-asserted-by":"publisher","first-page":"e13345","DOI":"10.1111\/sji.13345","article-title":"To be remembered: B cell memory response against SARS-CoV-2 and its variants in vaccinated and unvaccinated individuals","volume":"99","author":"Ahmed","year":"2024","journal-title":"Scand J Immunol"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1016\/j.vaccine.2023.10.034","article-title":"Superior immunogenicity of mRNA over adenoviral vectored COVID-19 vaccines reflects B cell dynamics independent of anti-vector immunity: Implications for future pandemic vaccines","volume":"41","author":"Liu","year":"2023","journal-title":"Vaccine"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-020-01194-5","article-title":"T cell and antibody responses induced by a single dose of ChAdOx1 nCoV-19 (AZD1222) vaccine in a phase 1\/2 clinical trial","volume":"27","author":"Ewer","year":"2021","journal-title":"Nat Med"},{"key":"B10","doi-asserted-by":"publisher","first-page":"29","DOI":"10.1186\/s12916-022-02240-4","article-title":"Single-dose SARS-CoV-2 vaccinations with either BNT162b2 or AZD1222 induce disparate Th1 responses and IgA production","volume":"20","author":"M\u00fcller","year":"2022","journal-title":"BMC Med"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1038\/s41590-021-01126-6","article-title":"Delayed-interval BNT162b2 mRNA COVID-19 vaccination enhances humoral immunity and induces robust T cell responses","volume":"23","author":"Hall","year":"2022","journal-title":"Nat Immunol"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2024.1330549","article-title":"The effect of dose-interval on antibody response to mRNA COVID-19 vaccines: a prospective cohort study","volume":"15","author":"Almeida","year":"2024","journal-title":"Front Immunol"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1016\/j.vaccine.2023.04.030","article-title":"Within-host modeling to measure dynamics of antibody responses after natural infection or vaccination: A systematic review","volume":"41","author":"Garcia-Fogeda","year":"2023","journal-title":"Vaccine"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1038\/s41592-024-02265-y","article-title":"Decoding immune kinetics: unveiling secrets using custom-built mathematical models","volume":"21","author":"Smith","year":"2024","journal-title":"Nat Methods"},{"key":"B15","doi-asserted-by":"publisher","first-page":"110254","DOI":"10.1016\/j.jtbi.2020.110254","article-title":"A model for establishment, maintenance and reactivation of the immune response after vaccination against Ebola virus","volume":"495","author":"Balelli","year":"2020","journal-title":"J Theor Biol"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1038\/s41587-020-0631-z","article-title":"A SARS-CoV-2 surrogate virus neutralization test based on antibody-mediated blockage of ACE2-spike protein-protein interaction","volume":"38","author":"Tan","year":"2020","journal-title":"Nat Biotechnol"},{"key":"B17","doi-asserted-by":"publisher","first-page":"104","DOI":"10.1038\/s41541-021-00369-6","article-title":"Distinguishing features of current COVID-19 vaccines: knowns and unknowns of antigen presentation and modes of action","volume":"6","author":"Heinz","year":"2021","journal-title":"NPJ Vaccines"},{"key":"B18","doi-asserted-by":"publisher","first-page":"25","DOI":"10.1038\/s41590-020-00826-9","article-title":"Distinct antibody responses to SARS-CoV-2 in children and adults across the COVID-19 clinical spectrum","volume":"22","author":"Weisberg","year":"2021","journal-title":"Nat Immunol"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1038\/s41590-021-01089-8","article-title":"Children develop robust and sustained cross-reactive spike-specific immune responses to SARS-CoV-2 infection","volume":"23","author":"Dowell","year":"2022","journal-title":"Nat Immunol"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-021-03739-1","article-title":"Age-related immune response heterogeneity to SARS-CoV-2 vaccine BNT162b2","volume":"596","author":"Collier","year":"2021","journal-title":"Nature"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1038\/s41564-021-00947-3","article-title":"Antibody responses to SARS-CoV-2 vaccines in 45,965 adults from the general population of the United Kingdom","volume":"6","author":"Wei","year":"2021","journal-title":"Nat Microbiol"},{"key":"B22","doi-asserted-by":"publisher","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":"B23","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-021-03696-9","article-title":"Naturally enhanced neutralizing breadth against SARS-CoV-2 one year after infection","volume":"595","author":"Wang","year":"2021","journal-title":"Nature"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1126\/sciimmunol.abg6916","article-title":"Prolonged evolution of the human B cell response to SARS-CoV-2 infection","volume":"6","author":"Sakharkar","year":"2021","journal-title":"Sci Immunol"},{"key":"B25","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1111\/imr.v310.1","article-title":"Immunological memory to SARS-CoV-2 infection and COVID-19 vaccines","volume":"310","author":"Sette","year":"2022","journal-title":"Immunol Rev"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.169860","article-title":"A modeling-based approach to optimize COVID-19 vaccine dosing schedules for improved protection","volume":"8","author":"Dogra","year":"2023","journal-title":"JCI Insight"},{"key":"B27","doi-asserted-by":"publisher","first-page":"109823","DOI":"10.1016\/j.celrep.2021.109823","article-title":"High-affinity memory B cells induced by SARS-CoV-2 infection produce more plasmablasts and atypical memory B cells than those primed by mRNA vaccines","volume":"37","author":"Pape","year":"2021","journal-title":"Cell Rep"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-021-03738-2","article-title":"SARS-CoV-2 mRNA vaccines induce persistent human germinal centre responses","volume":"596","author":"Turner","year":"2021","journal-title":"Nature"},{"key":"B29","doi-asserted-by":"publisher","first-page":"100898","DOI":"10.1016\/j.xcrm.2022.100898","article-title":"Impact of SARS-CoV-2 exposure history on the T cell and IgG response","volume":"4","author":"Keeton","year":"2023","journal-title":"Cell Rep Med"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1016\/j.it.2020.04.001","article-title":"Improving vaccine-induced immunity: can baseline predict outcome","volume":"41","author":"Tsang","year":"2020","journal-title":"Trends Immunol"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1080\/21645515.2017.1338547","article-title":"Factors affecting immune responses to the influenza vaccine","volume":"14","author":"Castrucci","year":"2018","journal-title":"Hum Vaccin Immunother"},{"key":"B32","doi-asserted-by":"publisher","first-page":"22","DOI":"10.1038\/s41541-022-00455-3","article-title":"Calibrated comparison of SARS-CoV-2 neutralizing antibody levels in response to protein-, mRNA-, and vector-based COVID-19 vaccines","volume":"7","author":"Karbiener","year":"2022","journal-title":"NPJ Vaccines"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.3201\/eid2903.221142","article-title":"The 100 days mission\u20142022 global pandemic preparedness summit","volume":"29","author":"Gouglas","year":"2023","journal-title":"Emerg Infect Dis"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2025.1487066\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,3,24]],"date-time":"2025-03-24T11:15:51Z","timestamp":1742814951000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2025.1487066\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,3,24]]},"references-count":33,"alternative-id":["10.3389\/fimmu.2025.1487066"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2025.1487066","relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/2024.07.11.24310221","asserted-by":"object"}]},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,3,24]]},"article-number":"1487066"}}