{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T11:47:00Z","timestamp":1783511220539,"version":"3.55.0"},"reference-count":38,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2022,9,20]],"date-time":"2022-09-20T00:00:00Z","timestamp":1663632000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"name":"COVE","award":["NCT04470427"],"award-info":[{"award-number":["NCT04470427"]}]},{"name":"TeenCOVE","award":["NCT04649151"],"award-info":[{"award-number":["NCT04649151"]}]},{"DOI":"10.13039\/100012399","name":"Biomedical Advanced Research and Development Authority","doi-asserted-by":"publisher","award":["75A50120C00034"],"award-info":[{"award-number":["75A50120C00034"]}],"id":[{"id":"10.13039\/100012399","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Leadership and Operations Center","award":["UM1 AI 68614HVTN"],"award-info":[{"award-number":["UM1 AI 68614HVTN"]}]},{"name":"Statistics and Data Management Center","award":["UM1 AI 68635"],"award-info":[{"award-number":["UM1 AI 68635"]}]},{"name":"HVTN Laboratory Center","award":["UM1 AI 68618"],"award-info":[{"award-number":["UM1 AI 68618"]}]},{"name":"HIV Prevention Trials Network Leadership and Operations Center","award":["UM1 AI 68619"],"award-info":[{"award-number":["UM1 AI 68619"]}]},{"name":"AIDS Clinical Trials Group Leadership and Operations Center","award":["UM1 AI 68636"],"award-info":[{"award-number":["UM1 AI 68636"]}]},{"name":"Infectious Diseases Clinical Research Consortium leadership group 5","award":["UM1 AI148684-03"],"award-info":[{"award-number":["UM1 AI148684-03"]}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,1,13]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>The reactogenicity and immunogenicity of coronavirus disease 2019 (COVID-19) vaccines are well studied. Little is known regarding the relationship between immunogenicity and reactogenicity of COVID-19 vaccines.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>This study assessed the association between immunogenicity and reactogenicity after 2 mRNA-1273 (100 \u00b5g) injections in 1671 total adolescent and adult participants (\u226512 years) from the primary immunogenicity sets of the blinded periods of the Coronavirus Efficacy (COVE) and TeenCOVE trials. Associations between immunogenicity through day 57 and solicited adverse reactions (ARs) after the first and second injections of mRNA-1273 were evaluated among participants with and without solicited ARs using linear mixed-effects models.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>mRNA-1273 reactogenicity in this combined analysis set was similar to that reported for these trials. The vaccine elicited high neutralizing antibody (nAb) geometric mean titers (GMTs) in evaluable participants. GMTs at day 57 were significantly higher in participants who experienced solicited systemic ARs after the second injection (1227.2 [1164.4\u20131293.5]) than those who did not (980.1 [886.8\u20131083.2], P = .001) and were associated with fever, chills, headache, fatigue, myalgia, and arthralgia. Significant associations with local ARs were not found.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>These data show an association of systemic ARs with increased nAb titers following a second mRNA-1273 injection. While these data indicate systemic ARs are associated with increased antibody titers, high nAb titers were observed in participants after both injections, consistent with the immunogenicity and efficacy in these trials. These results add to the body of evidence regarding the relationship of immunogenicity and reactogenicity and can contribute toward the design of future mRNA vaccines.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/cid\/ciac780","type":"journal-article","created":{"date-parts":[[2022,9,21]],"date-time":"2022-09-21T20:12:41Z","timestamp":1663791161000},"page":"271-280","source":"Crossref","is-referenced-by-count":8,"title":["Associations of Immunogenicity and Reactogenicity After Severe Acute Respiratory Syndrome Coronavirus 2 mRNA-1273 Vaccine in the COVE and TeenCOVE Trials"],"prefix":"10.1093","volume":"76","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0560-6314","authenticated-orcid":false,"given":"Uma","family":"Siangphoe","sequence":"first","affiliation":[{"name":"Infectious Disease Development, Moderna , Cambridge, Massachusetts , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lindsey R","family":"Baden","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases, Brigham and Women's Hospital , Boston, Massachusetts , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hana M","family":"El Sahly","sequence":"additional","affiliation":[{"name":"Molecular Virology and Microbiology, Baylor College of Medicine , Houston, Texas , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brandon","family":"Essink","sequence":"additional","affiliation":[{"name":"Meridian Clinical Research , Savannah, Georgia , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kashif","family":"Ali","sequence":"additional","affiliation":[{"name":"Kool Kids Pediatrics, DM Clinical Research , Houston, Texas , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gary","family":"Berman","sequence":"additional","affiliation":[{"name":"The Clinical Research Institute , Minneapolis, Minnesota , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joanne E","family":"Tomassini","sequence":"additional","affiliation":[{"name":"Infectious Disease Development, Moderna , Cambridge, Massachusetts , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weiping","family":"Deng","sequence":"additional","affiliation":[{"name":"Infectious Disease Development, Moderna , Cambridge, Massachusetts , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rolando","family":"Pajon","sequence":"additional","affiliation":[{"name":"Infectious Disease Development, Moderna , Cambridge, Massachusetts , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roderick","family":"McPhee","sequence":"additional","affiliation":[{"name":"Infectious Disease Development, Moderna , Cambridge, Massachusetts , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Avika","family":"Dixit","sequence":"additional","affiliation":[{"name":"Infectious Disease Development, Moderna , Cambridge, Massachusetts , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rituparna","family":"Das","sequence":"additional","affiliation":[{"name":"Infectious Disease Development, Moderna , Cambridge, Massachusetts , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacqueline M","family":"Miller","sequence":"additional","affiliation":[{"name":"Infectious Disease Development, Moderna , Cambridge, Massachusetts , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Honghong","family":"Zhou","sequence":"additional","affiliation":[{"name":"Infectious Disease Development, Moderna , Cambridge, Massachusetts , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"for the COVE and TeenCOVE Study Groups","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2022,9,20]]},"reference":[{"key":"2023053015335866500_ciac780-B1","doi-asserted-by":"crossref","first-page":"1774","DOI":"10.1056\/NEJMoa2113017","article-title":"Efficacy of the mRNA-1273 SARS-CoV-2 vaccine at completion of blinded phase","volume":"385","author":"El Sahly","year":"2021","journal-title":"N Engl J Med"},{"key":"2023053015335866500_ciac780-B2","doi-asserted-by":"crossref","first-page":"1761","DOI":"10.1056\/NEJMoa2110345","article-title":"Safety and efficacy of the BNT162b2 mRNA COVID-19 vaccine through 6 months","volume":"385","author":"Thomas","year":"2021","journal-title":"N Engl J Med"},{"key":"2023053015335866500_ciac780-B3","author":"Moderna, Inc"},{"key":"2023053015335866500_ciac780-B4","doi-asserted-by":"crossref","DOI":"10.1093\/infdis\/jiac188","article-title":"Humoral immunogenicity of the mRNA-1273 vaccine in the phase 3 COVE trial","author":"El Sahly","year":"2022","journal-title":"J Infect Dis"},{"key":"2023053015335866500_ciac780-B5","doi-asserted-by":"crossref","first-page":"2485","DOI":"10.1056\/NEJMc2115597","article-title":"Phase 3 trial of mRNA-1273 during the Delta-variant surge","volume":"385","author":"Baden","year":"2021","journal-title":"N Engl J Med"},{"key":"2023053015335866500_ciac780-B6","doi-asserted-by":"crossref","first-page":"2025","DOI":"10.1038\/s41591-021-01527-y","article-title":"Safety and immunogenicity of SARS-CoV-2 variant mRNA vaccine boosters in healthy adults: an interim analysis","volume":"27","author":"Choi","year":"2021","journal-title":"Nat Med"},{"key":"2023053015335866500_ciac780-B7","doi-asserted-by":"crossref","first-page":"1042","DOI":"10.1038\/s41591-022-01739-w","article-title":"Immune response to SARS-CoV-2 after a booster of mRNA-1273: an open-label phase 2 trial","volume":"28","author":"Chu","year":"2022","journal-title":"Nat Med"},{"key":"2023053015335866500_ciac780-B8","doi-asserted-by":"crossref","first-page":"1088","DOI":"10.1056\/NEJMc2119912","article-title":"SARS-CoV-2 omicron variant neutralization after mRNA-1273 booster vaccination","volume":"386","author":"Pajon","year":"2022","journal-title":"N Engl J Med"},{"key":"2023053015335866500_ciac780-B9","doi-asserted-by":"crossref","first-page":"1372","DOI":"10.1126\/science.abj4176","article-title":"Durability of mRNA-1273 vaccine\u2013induced antibodies against SARS-CoV-2 variants","volume":"373","author":"Pegu","year":"2021","journal-title":"Science"},{"key":"2023053015335866500_ciac780-B10","doi-asserted-by":"crossref","article-title":"A bivalent omicron-containing booster vaccine against Covid-19","author":"Chalkias","DOI":"10.1056\/NEJMoa2208343"},{"key":"2023053015335866500_ciac780-B11","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1038\/s41541-019-0132-6","article-title":"The how's and what's of vaccine reactogenicity","volume":"4","author":"Herve","year":"2019","journal-title":"NPJ Vaccines"},{"key":"2023053015335866500_ciac780-B12","article-title":"Adverse events of active and placebo groups in SARS-CoV-2 vaccine randomized trials: a systematic review","volume":"12","author":"Amanzio","year":"2022","journal-title":"Lancet Reg Health Eur"},{"key":"2023053015335866500_ciac780-B13","doi-asserted-by":"crossref","first-page":"248","DOI":"10.1111\/j.1600-065X.2008.00733.x","article-title":"Microbe sensing, positive feedback loops, and the pathogenesis of inflammatory diseases","volume":"227","author":"Beutler","year":"2009","journal-title":"Immunol Rev"},{"key":"2023053015335866500_ciac780-B14","doi-asserted-by":"crossref","DOI":"10.1172\/jci.insight.96031","article-title":"Early molecular correlates of adverse events following yellow fever vaccination","volume":"2","author":"Chan","year":"2017","journal-title":"JCI Insight"},{"key":"2023053015335866500_ciac780-B15","doi-asserted-by":"crossref","first-page":"2201","DOI":"10.1001\/jama.2021.5374","article-title":"Reactogenicity following receipt of mRNA-based COVID-19 vaccines","volume":"325","author":"Chapin-Bardales","year":"2021","journal-title":"JAMA"},{"key":"2023053015335866500_ciac780-B16","article-title":"Clinical development of mRNA vaccines: challenges and opportunities","author":"August","journal-title":"Curr Top Microbiol"},{"key":"2023053015335866500_ciac780-B17","doi-asserted-by":"crossref","first-page":"1436","DOI":"10.1056\/NEJMcibr2111445","article-title":"In gratitude for mRNA vaccines","volume":"385","author":"Stuart","year":"2021","journal-title":"N Engl J Med"},{"key":"2023053015335866500_ciac780-B18","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1038\/s41577-021-00526-x","article-title":"COVID-19 vaccines: modes of immune activation and future challenges","volume":"21","author":"Teijaro","year":"2021","journal-title":"Nat Rev Immunol"},{"key":"2023053015335866500_ciac780-B19","article-title":"Adverse effects and antibody titers in response to the BNT162b2 mRNA COVID-19 vaccine in a prospective study of healthcare workers","volume":"9","author":"Coggins","year":"2021","journal-title":"Open Forum Infect Dis"},{"key":"2023053015335866500_ciac780-B20","doi-asserted-by":"crossref","first-page":"1486","DOI":"10.3904\/kjim.2021.210","article-title":"Can reactogenicity predict immunogenicity after COVID-19 vaccination?","volume":"36","author":"Hwang","year":"2021","journal-title":"Korean J Intern Med"},{"key":"2023053015335866500_ciac780-B21","doi-asserted-by":"crossref","first-page":"1063","DOI":"10.3390\/vaccines9101063","article-title":"Reactogenicity correlates only weakly with humoral immunogenicity after COVID-19 vaccination with BNT162b2 mRNA (Comirnaty\u00ae)","volume":"10","author":"Held","year":"2021","journal-title":"Vaccines"},{"key":"2023053015335866500_ciac780-B22","doi-asserted-by":"crossref","first-page":"1019","DOI":"10.1016\/j.vaccine.2022.01.002","article-title":"Young age, female sex, and presence of systemic adverse reactions are associated with high post-vaccination antibody titer after two doses of BNT162b2 mRNA SARS-CoV-2 vaccination: an observational study of 646 Japanese healthcare workers and university staff","volume":"40","author":"Uwamino","year":"2022","journal-title":"Vaccine"},{"key":"2023053015335866500_ciac780-B23","doi-asserted-by":"crossref","first-page":"2241","DOI":"10.1056\/NEJMoa2109522","article-title":"Evaluation of mRNA-1273 SARS-CoV-2 vaccine in adolescents","volume":"385","author":"Ali","year":"2021","journal-title":"N Engl J Med"},{"key":"2023053015335866500_ciac780-B24","author":"Department of Health and Human Services (DHHS)"},{"key":"2023053015335866500_ciac780-B25","doi-asserted-by":"crossref","DOI":"10.1126\/scitranslmed.abi8961","article-title":"Robust immune responses are observed after one dose of BNT162b2 mRNA vaccine dose in SARS-CoV-2\u2013experienced individuals","volume":"14","author":"Samanovic","year":"2022","journal-title":"Sci Transl Med"},{"key":"2023053015335866500_ciac780-B26","doi-asserted-by":"crossref","DOI":"10.1126\/sciimmunol.abi6950","article-title":"Distinct antibody and memory B cell responses in SARS-CoV-2 na\u00efve and recovered individuals after mRNA vaccination","volume":"6","author":"Goel","year":"2021","journal-title":"Sci Immunol"},{"key":"2023053015335866500_ciac780-B27","article-title":"Impact of age, ethnicity, sex and prior infection status on immunogenicity following a single dose of the BNT162b2 mRNA COVID-19 vaccine: real-world evidence from healthcare workers, Israel, December 2020 to January 2021","volume":"26","author":"Jabal","year":"2021","journal-title":"Eurosurveillance"},{"key":"2023053015335866500_ciac780-B28","doi-asserted-by":"crossref","first-page":"951","DOI":"10.1056\/NEJMoa2116747","article-title":"Immunogenicity and reactogenicity of vaccine boosters after Ad26.COV2.S priming","volume":"386","author":"Sablerolles","year":"2022","journal-title":"N Engl J Med"},{"key":"2023053015335866500_ciac780-B29","doi-asserted-by":"crossref","first-page":"1910","DOI":"10.1056\/NEJMoa2200674","article-title":"Safety and efficacy of a third dose of BNT162b2 COVID-19 vaccine","volume":"386","author":"Moreira","year":"2022","journal-title":"N Engl J Med"},{"key":"2023053015335866500_ciac780-B30","doi-asserted-by":"crossref","first-page":"2065","DOI":"10.1093\/cid\/ciab381","article-title":"Age-dependent immune response to the biontech\/pfizer BNT162b2 coronavirus disease 2019 vaccination","volume":"73","author":"M\u00fcller","year":"2021","journal-title":"Clin Infect Dis"},{"key":"2023053015335866500_ciac780-B31","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1056\/NEJMoa2115463","article-title":"Comparative effectiveness of BNT162b2 and mRNA-1273 vaccines in U.S. Veterans","volume":"386","author":"Dickerman","year":"2022","journal-title":"N Engl J Med"},{"key":"2023053015335866500_ciac780-B32","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1126\/science.abm3425","article-title":"Immune correlates analysis of the mRNA-1273 COVID-19 vaccine efficacy clinical trial","volume":"375","author":"Gilbert","year":"2022","journal-title":"Science"},{"key":"2023053015335866500_ciac780-B33","doi-asserted-by":"crossref","first-page":"1205","DOI":"10.1038\/s41591-021-01377-8","article-title":"Neutralizing antibody levels are highly predictive of immune protection from symptomatic SARS-CoV-2 infection","volume":"27","author":"Khoury","year":"2021","journal-title":"Nat Med"},{"key":"2023053015335866500_ciac780-B34","doi-asserted-by":"crossref","first-page":"2250","DOI":"10.1016\/j.vaccine.2019.10.046","article-title":"Updates on immunologic correlates of vaccine-induced protection","volume":"38","author":"Plotkin","year":"2020","journal-title":"Vaccine"},{"key":"2023053015335866500_ciac780-B35","doi-asserted-by":"crossref","first-page":"e585","DOI":"10.1093\/cid\/ciac169","article-title":"Antibody response in immunocompromised patients after the administration of SARS-CoV-2 vaccine BNT162b2 or mRNA-1273: a randomised controlled trial","volume":"75","author":"Speich","year":"2022","journal-title":"Clin Infect Dis"},{"key":"2023053015335866500_ciac780-B36","doi-asserted-by":"crossref","first-page":"2011","DOI":"10.1056\/NEJMoa2203315","article-title":"Evaluation of mRNA-1273 COVID-19 vaccine in children 6 to 11 years of age","volume":"386","author":"Creech","year":"2022","journal-title":"N Engl J Med"},{"key":"2023053015335866500_ciac780-B37","doi-asserted-by":"crossref","first-page":"2370","DOI":"10.1001\/jama.2021.7563","article-title":"Immunogenicity of COVID-19 mRNA vaccines in pregnant and lactating women","volume":"325","author":"Collier","year":"2021","journal-title":"JAMA"},{"key":"2023053015335866500_ciac780-B38","author":"US Food and Drug Administration"}],"container-title":["Clinical Infectious Diseases"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/cid\/advance-article-pdf\/doi\/10.1093\/cid\/ciac780\/46538900\/ciac780.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/cid\/article-pdf\/76\/2\/271\/50488770\/ciac780.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/cid\/article-pdf\/76\/2\/271\/50488770\/ciac780.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,5,30]],"date-time":"2023-05-30T15:35:11Z","timestamp":1685460911000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/cid\/article\/76\/2\/271\/6708263"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,9,20]]},"references-count":38,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2022,9,20]]},"published-print":{"date-parts":[[2023,1,13]]}},"URL":"https:\/\/doi.org\/10.1093\/cid\/ciac780","relation":{},"ISSN":["1058-4838","1537-6591"],"issn-type":[{"value":"1058-4838","type":"print"},{"value":"1537-6591","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2023,1,15]]},"published":{"date-parts":[[2022,9,20]]}}}