Altering the mRNA-1273 dosing interval impacts the kinetics, quality, and magnitude of immune responses in mice
For a vaccine to achieve durable immunity and optimal efficacy, many require a multi-dose primary vaccination schedule that acts to first “prime” naive immune systems and then “boost” initial immune responses by repeated immunizations (ie, prime-boost regimens). In the context of the global coronavi...
| Main Authors: | , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-11-01
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| Series: | Frontiers in Immunology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2022.948335/full |
| _version_ | 1798023388322594816 |
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| author | Dario Garcia-Dominguez Carole Henry LingZhi Ma Hardik Jani Nicholas J. Amato Taylor Manning Alec Freyn Heather Davis Chiaowen Joyce Hsiao Mengying Li Hillary Koch Sayda Elbashir Anthony DiPiazza Andrea Carfi Darin Edwards Kapil Bahl |
| author_facet | Dario Garcia-Dominguez Carole Henry LingZhi Ma Hardik Jani Nicholas J. Amato Taylor Manning Alec Freyn Heather Davis Chiaowen Joyce Hsiao Mengying Li Hillary Koch Sayda Elbashir Anthony DiPiazza Andrea Carfi Darin Edwards Kapil Bahl |
| author_sort | Dario Garcia-Dominguez |
| collection | DOAJ |
| description | For a vaccine to achieve durable immunity and optimal efficacy, many require a multi-dose primary vaccination schedule that acts to first “prime” naive immune systems and then “boost” initial immune responses by repeated immunizations (ie, prime-boost regimens). In the context of the global coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), 2-dose primary vaccination regimens were often selected with short intervals between doses to provide rapid protection while still inducing robust immunity. However, emerging post-authorization evidence has suggested that longer intervals between doses 1 and 2 for SARS-CoV-2 vaccines may positively impact robustness and durability of immune responses. Here, the dosing interval for mRNA-1273, a messenger RNA based SARS-CoV-2 vaccine administered on a 2-dose primary schedule with 4 weeks between doses, was evaluated in mice by varying the dose interval between 1 and 8 weeks and examining immune responses through 24 weeks after dose 2. A dosing interval of 6 to 8 weeks generated the highest level of antigen-specific serum immunoglobulin G binding antibody titers. Differences in binding antibody titers between mRNA-1273 1 µg and 10 µg decreased over time for dosing intervals of ≥4 weeks, suggesting a potential dose-sparing effect. Longer intervals (≥4 weeks) also increased antibody-dependent cellular cytotoxicity activity and numbers of antibody-secreting cells (including long-lived plasma cells) after the second dose. An interval of 6 to 8 weeks elicited the strongest CD8+ T-cell responses, while an interval of 3 weeks elicited the strongest CD4+ T-cell response. Overall, these results suggest that in a non-pandemic setting, a longer interval (≥6 weeks) between the doses of the primary series for mRNA-1273 may induce more durable immune responses. |
| first_indexed | 2024-04-11T17:45:33Z |
| format | Article |
| id | doaj.art-7ceed16ea2d0483aa3c331e1bda0099f |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-04-11T17:45:33Z |
| publishDate | 2022-11-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-7ceed16ea2d0483aa3c331e1bda0099f2022-12-22T04:11:23ZengFrontiers Media S.A.Frontiers in Immunology1664-32242022-11-011310.3389/fimmu.2022.948335948335Altering the mRNA-1273 dosing interval impacts the kinetics, quality, and magnitude of immune responses in miceDario Garcia-DominguezCarole HenryLingZhi MaHardik JaniNicholas J. AmatoTaylor ManningAlec FreynHeather DavisChiaowen Joyce HsiaoMengying LiHillary KochSayda ElbashirAnthony DiPiazzaAndrea CarfiDarin EdwardsKapil BahlFor a vaccine to achieve durable immunity and optimal efficacy, many require a multi-dose primary vaccination schedule that acts to first “prime” naive immune systems and then “boost” initial immune responses by repeated immunizations (ie, prime-boost regimens). In the context of the global coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), 2-dose primary vaccination regimens were often selected with short intervals between doses to provide rapid protection while still inducing robust immunity. However, emerging post-authorization evidence has suggested that longer intervals between doses 1 and 2 for SARS-CoV-2 vaccines may positively impact robustness and durability of immune responses. Here, the dosing interval for mRNA-1273, a messenger RNA based SARS-CoV-2 vaccine administered on a 2-dose primary schedule with 4 weeks between doses, was evaluated in mice by varying the dose interval between 1 and 8 weeks and examining immune responses through 24 weeks after dose 2. A dosing interval of 6 to 8 weeks generated the highest level of antigen-specific serum immunoglobulin G binding antibody titers. Differences in binding antibody titers between mRNA-1273 1 µg and 10 µg decreased over time for dosing intervals of ≥4 weeks, suggesting a potential dose-sparing effect. Longer intervals (≥4 weeks) also increased antibody-dependent cellular cytotoxicity activity and numbers of antibody-secreting cells (including long-lived plasma cells) after the second dose. An interval of 6 to 8 weeks elicited the strongest CD8+ T-cell responses, while an interval of 3 weeks elicited the strongest CD4+ T-cell response. Overall, these results suggest that in a non-pandemic setting, a longer interval (≥6 weeks) between the doses of the primary series for mRNA-1273 may induce more durable immune responses.https://www.frontiersin.org/articles/10.3389/fimmu.2022.948335/fullSARS-CoV-2mRNA-1273COVID-19dosing intervaldosing regimen |
| spellingShingle | Dario Garcia-Dominguez Carole Henry LingZhi Ma Hardik Jani Nicholas J. Amato Taylor Manning Alec Freyn Heather Davis Chiaowen Joyce Hsiao Mengying Li Hillary Koch Sayda Elbashir Anthony DiPiazza Andrea Carfi Darin Edwards Kapil Bahl Altering the mRNA-1273 dosing interval impacts the kinetics, quality, and magnitude of immune responses in mice Frontiers in Immunology SARS-CoV-2 mRNA-1273 COVID-19 dosing interval dosing regimen |
| title | Altering the mRNA-1273 dosing interval impacts the kinetics, quality, and magnitude of immune responses in mice |
| title_full | Altering the mRNA-1273 dosing interval impacts the kinetics, quality, and magnitude of immune responses in mice |
| title_fullStr | Altering the mRNA-1273 dosing interval impacts the kinetics, quality, and magnitude of immune responses in mice |
| title_full_unstemmed | Altering the mRNA-1273 dosing interval impacts the kinetics, quality, and magnitude of immune responses in mice |
| title_short | Altering the mRNA-1273 dosing interval impacts the kinetics, quality, and magnitude of immune responses in mice |
| title_sort | altering the mrna 1273 dosing interval impacts the kinetics quality and magnitude of immune responses in mice |
| topic | SARS-CoV-2 mRNA-1273 COVID-19 dosing interval dosing regimen |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2022.948335/full |
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