Improved antibody breadth with an extended primary dose interval of COVID-19 vaccine is overcome by boosters
IntroductionDuring rollout of mRNA-based COVID-19 vaccines, several jurisdictions extended the interval between the first and second doses to prioritize wider population access to limited vaccine supply. This study evaluated the effects of an extended dose interval on development of antibody and cel...
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Frontiers Media S.A.
2025-03-01
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| author | Jessica I. Ahmed Samantha J. Krosta Mandy N. Reimer Winnie Cheung Christine Mesa Carmen Lopez Rayeil J. Chua Farah Alsattari Alyssia Robinson Kathy Manguiat Naima Jahan Bernard Abrenica Angela Harris Karla Cachero Rissa Fabia Jonathan Walker Myo Minn Oo Derek Stein Derek Stein Hezhao Ji Hezhao Ji Ruey-Chyi Su Ruey-Chyi Su Paul J. McLaren Paul J. McLaren Lyle R. McKinnon Lyle R. McKinnon Lyle R. McKinnon T Blake Ball T Blake Ball Heidi Wood John Kim Sandra A. Kiazyk Sandra A. Kiazyk Catherine M. Card Catherine M. Card |
| author_facet | Jessica I. Ahmed Samantha J. Krosta Mandy N. Reimer Winnie Cheung Christine Mesa Carmen Lopez Rayeil J. Chua Farah Alsattari Alyssia Robinson Kathy Manguiat Naima Jahan Bernard Abrenica Angela Harris Karla Cachero Rissa Fabia Jonathan Walker Myo Minn Oo Derek Stein Derek Stein Hezhao Ji Hezhao Ji Ruey-Chyi Su Ruey-Chyi Su Paul J. McLaren Paul J. McLaren Lyle R. McKinnon Lyle R. McKinnon Lyle R. McKinnon T Blake Ball T Blake Ball Heidi Wood John Kim Sandra A. Kiazyk Sandra A. Kiazyk Catherine M. Card Catherine M. Card |
| author_sort | Jessica I. Ahmed |
| collection | DOAJ |
| description | IntroductionDuring rollout of mRNA-based COVID-19 vaccines, several jurisdictions extended the interval between the first and second doses to prioritize wider population access to limited vaccine supply. This study evaluated the effects of an extended dose interval on development of antibody and cell-mediated responses following the primary dose series and a subsequent booster dose.MethodsBlood samples were collected from mRNA COVID-19 vaccine recipients at baseline and longitudinally after each dose. Samples were analyzed for SARS-CoV-2-specific antibody titers, neutralizing antibodies and memory T cell responses.ResultsAn extended dose interval was associated with improved breadth of neutralizing antibody responses against both ancestral and early SARS-CoV-2 variants, but not Omicron variants. Dose interval had no impact on the development of antigen-specific memory T cell responses, the memory or T helper phenotypes of responding T cells or cytokine production. The effects of the primary dose interval on immune outcomes were no longer evident after a third dose of mRNA vaccine.DiscussionAn extended primary dose interval resulted in short-term benefits to humoral immunity but these were transient in the context of subsequent exposures. However, in addition to the public health benefits of wider population access to vaccines, the short-term immunological benefits of extending the dose interval may have been sustained in the absence of boosters. These findings underscore the importance of evaluating dosing intervals during the development of future vaccine candidates. |
| format | Article |
| id | doaj-art-b95f546d768748e19daec98c31753eb4 |
| institution | DOAJ |
| issn | 1664-3224 |
| language | English |
| publishDate | 2025-03-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj-art-b95f546d768748e19daec98c31753eb42025-08-20T02:49:44ZengFrontiers Media S.A.Frontiers in Immunology1664-32242025-03-011610.3389/fimmu.2025.15291341529134Improved antibody breadth with an extended primary dose interval of COVID-19 vaccine is overcome by boostersJessica I. Ahmed0Samantha J. Krosta1Mandy N. Reimer2Winnie Cheung3Christine Mesa4Carmen Lopez5Rayeil J. Chua6Farah Alsattari7Alyssia Robinson8Kathy Manguiat9Naima Jahan10Bernard Abrenica11Angela Harris12Karla Cachero13Rissa Fabia14Jonathan Walker15Myo Minn Oo16Derek Stein17Derek Stein18Hezhao Ji19Hezhao Ji20Ruey-Chyi Su21Ruey-Chyi Su22Paul J. McLaren23Paul J. McLaren24Lyle R. McKinnon25Lyle R. McKinnon26Lyle R. McKinnon27T Blake Ball28T Blake Ball29Heidi Wood30John Kim31Sandra A. Kiazyk32Sandra A. Kiazyk33Catherine M. Card34Catherine M. Card35Division of Sexually-Transmitted and Blood-Borne Infections, Public Health Agency of Canada, Winnipeg, MB, CanadaDivision of Sexually-Transmitted and Blood-Borne Infections, Public Health Agency of Canada, Winnipeg, MB, CanadaDivision of Sexually-Transmitted and Blood-Borne Infections, Public Health Agency of Canada, Winnipeg, MB, CanadaDivision of Sexually-Transmitted and Blood-Borne Infections, Public Health Agency of Canada, Winnipeg, MB, CanadaDivision of Sexually-Transmitted and Blood-Borne Infections, Public Health Agency of Canada, Winnipeg, MB, CanadaDivision of Sexually-Transmitted and Blood-Borne Infections, Public Health Agency of Canada, Winnipeg, MB, CanadaDivision of Sexually-Transmitted and Blood-Borne Infections, Public Health Agency of Canada, Winnipeg, MB, CanadaDivision of Sexually-Transmitted and Blood-Borne Infections, Public Health Agency of Canada, Winnipeg, MB, CanadaDivision of Mycobacteriology, Vector-borne and Prion Diseases, Public Health Agency of Canada, Winnipeg, MB, CanadaDivision of Mycobacteriology, Vector-borne and Prion Diseases, Public Health Agency of Canada, Winnipeg, MB, CanadaDepartment of Medical Microbiology and Infectious Diseases, University of Manitoba, Winnipeg, MB, CanadaDivision of Sexually-Transmitted and Blood-Borne Infections, Public Health Agency of Canada, Winnipeg, MB, CanadaDivision of Sexually-Transmitted and Blood-Borne Infections, Public Health Agency of Canada, Winnipeg, MB, CanadaDivision of Sexually-Transmitted and Blood-Borne Infections, Public Health Agency of Canada, Winnipeg, MB, CanadaDivision of Sexually-Transmitted and Blood-Borne Infections, Public Health Agency of Canada, Winnipeg, MB, CanadaDivision of Sexually-Transmitted and Blood-Borne Infections, Public Health Agency of Canada, Winnipeg, MB, CanadaDepartment of Medical Microbiology and Infectious Diseases, University of Manitoba, Winnipeg, MB, CanadaDepartment of Medical Microbiology and Infectious Diseases, University of Manitoba, Winnipeg, MB, CanadaDepartment of Serology and Parasitology, Cadham Provincial Laboratory, Winnipeg, MB, CanadaDivision of Sexually-Transmitted and Blood-Borne Infections, Public Health Agency of Canada, Winnipeg, MB, CanadaDepartment of Medical Microbiology and Infectious Diseases, University of Manitoba, Winnipeg, MB, CanadaDivision of Sexually-Transmitted and Blood-Borne Infections, Public Health Agency of Canada, Winnipeg, MB, CanadaDepartment of Medical Microbiology and Infectious Diseases, University of Manitoba, Winnipeg, MB, CanadaDivision of Sexually-Transmitted and Blood-Borne Infections, Public Health Agency of Canada, Winnipeg, MB, CanadaDepartment of Medical Microbiology and Infectious Diseases, University of Manitoba, Winnipeg, MB, CanadaDivision of Sexually-Transmitted and Blood-Borne Infections, Public Health Agency of Canada, Winnipeg, MB, CanadaDepartment of Medical Microbiology and Infectious Diseases, University of Manitoba, Winnipeg, MB, CanadaDepartment of Serology and Parasitology, Centre for the AIDS Programme of Research in South Africa (CAPRISA), Durban, South AfricaDivision of Sexually-Transmitted and Blood-Borne Infections, Public Health Agency of Canada, Winnipeg, MB, CanadaDepartment of Medical Microbiology and Infectious Diseases, University of Manitoba, Winnipeg, MB, CanadaDivision of Mycobacteriology, Vector-borne and Prion Diseases, Public Health Agency of Canada, Winnipeg, MB, CanadaDivision of Sexually-Transmitted and Blood-Borne Infections, Public Health Agency of Canada, Winnipeg, MB, CanadaDivision of Sexually-Transmitted and Blood-Borne Infections, Public Health Agency of Canada, Winnipeg, MB, CanadaDepartment of Medical Microbiology and Infectious Diseases, University of Manitoba, Winnipeg, MB, CanadaDivision of Sexually-Transmitted and Blood-Borne Infections, Public Health Agency of Canada, Winnipeg, MB, CanadaDepartment of Medical Microbiology and Infectious Diseases, University of Manitoba, Winnipeg, MB, CanadaIntroductionDuring rollout of mRNA-based COVID-19 vaccines, several jurisdictions extended the interval between the first and second doses to prioritize wider population access to limited vaccine supply. This study evaluated the effects of an extended dose interval on development of antibody and cell-mediated responses following the primary dose series and a subsequent booster dose.MethodsBlood samples were collected from mRNA COVID-19 vaccine recipients at baseline and longitudinally after each dose. Samples were analyzed for SARS-CoV-2-specific antibody titers, neutralizing antibodies and memory T cell responses.ResultsAn extended dose interval was associated with improved breadth of neutralizing antibody responses against both ancestral and early SARS-CoV-2 variants, but not Omicron variants. Dose interval had no impact on the development of antigen-specific memory T cell responses, the memory or T helper phenotypes of responding T cells or cytokine production. The effects of the primary dose interval on immune outcomes were no longer evident after a third dose of mRNA vaccine.DiscussionAn extended primary dose interval resulted in short-term benefits to humoral immunity but these were transient in the context of subsequent exposures. However, in addition to the public health benefits of wider population access to vaccines, the short-term immunological benefits of extending the dose interval may have been sustained in the absence of boosters. These findings underscore the importance of evaluating dosing intervals during the development of future vaccine candidates.https://www.frontiersin.org/articles/10.3389/fimmu.2025.1529134/fullCOVID-19mRNA vaccinedose intervalantibodybreadthneutralization |
| spellingShingle | Jessica I. Ahmed Samantha J. Krosta Mandy N. Reimer Winnie Cheung Christine Mesa Carmen Lopez Rayeil J. Chua Farah Alsattari Alyssia Robinson Kathy Manguiat Naima Jahan Bernard Abrenica Angela Harris Karla Cachero Rissa Fabia Jonathan Walker Myo Minn Oo Derek Stein Derek Stein Hezhao Ji Hezhao Ji Ruey-Chyi Su Ruey-Chyi Su Paul J. McLaren Paul J. McLaren Lyle R. McKinnon Lyle R. McKinnon Lyle R. McKinnon T Blake Ball T Blake Ball Heidi Wood John Kim Sandra A. Kiazyk Sandra A. Kiazyk Catherine M. Card Catherine M. Card Improved antibody breadth with an extended primary dose interval of COVID-19 vaccine is overcome by boosters Frontiers in Immunology COVID-19 mRNA vaccine dose interval antibody breadth neutralization |
| title | Improved antibody breadth with an extended primary dose interval of COVID-19 vaccine is overcome by boosters |
| title_full | Improved antibody breadth with an extended primary dose interval of COVID-19 vaccine is overcome by boosters |
| title_fullStr | Improved antibody breadth with an extended primary dose interval of COVID-19 vaccine is overcome by boosters |
| title_full_unstemmed | Improved antibody breadth with an extended primary dose interval of COVID-19 vaccine is overcome by boosters |
| title_short | Improved antibody breadth with an extended primary dose interval of COVID-19 vaccine is overcome by boosters |
| title_sort | improved antibody breadth with an extended primary dose interval of covid 19 vaccine is overcome by boosters |
| topic | COVID-19 mRNA vaccine dose interval antibody breadth neutralization |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2025.1529134/full |
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