Safety and Immunogenicity of SARS-CoV-2 mRNA-1273 Vaccine in Older Adults
Copyright © 2020 Massachusetts Medical Society..
BACKGROUND: Testing of vaccine candidates to prevent infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in an older population is important, since increased incidences of illness and death from coronavirus disease 2019 (Covid-19) have been associated with an older age.
METHODS: We conducted a phase 1, dose-escalation, open-label trial of a messenger RNA vaccine, mRNA-1273, which encodes the stabilized prefusion SARS-CoV-2 spike protein (S-2P) in healthy adults. The trial was expanded to include 40 older adults, who were stratified according to age (56 to 70 years or ≥71 years). All the participants were assigned sequentially to receive two doses of either 25 μg or 100 μg of vaccine administered 28 days apart.
RESULTS: Solicited adverse events were predominantly mild or moderate in severity and most frequently included fatigue, chills, headache, myalgia, and pain at the injection site. Such adverse events were dose-dependent and were more common after the second immunization. Binding-antibody responses increased rapidly after the first immunization. By day 57, among the participants who received the 25-μg dose, the anti-S-2P geometric mean titer (GMT) was 323,945 among those between the ages of 56 and 70 years and 1,128,391 among those who were 71 years of age or older; among the participants who received the 100-μg dose, the GMT in the two age subgroups was 1,183,066 and 3,638,522, respectively. After the second immunization, serum neutralizing activity was detected in all the participants by multiple methods. Binding- and neutralizing-antibody responses appeared to be similar to those previously reported among vaccine recipients between the ages of 18 and 55 years and were above the median of a panel of controls who had donated convalescent serum. The vaccine elicited a strong CD4 cytokine response involving type 1 helper T cells.
CONCLUSIONS: In this small study involving older adults, adverse events associated with the mRNA-1273 vaccine were mainly mild or moderate. The 100-μg dose induced higher binding- and neutralizing-antibody titers than the 25-μg dose, which supports the use of the 100-μg dose in a phase 3 vaccine trial. (Funded by the National Institute of Allergy and Infectious Diseases and others; mRNA-1273 Study ClinicalTrials.gov number, NCT04283461.).
| Errataetall: |
CommentIn: Tidsskr Nor Laegeforen. 2021 Nov 15;141(18):. - PMID 34911279 |
|---|---|
| Medienart: |
E-Artikel |
| Erscheinungsjahr: |
2020 |
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| Erschienen: |
2020 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:383 |
|---|---|
| Enthalten in: |
The New England journal of medicine - 383(2020), 25 vom: 17. Dez., Seite 2427-2438 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Anderson, Evan J [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 23.12.2020 Date Revised 17.12.2021 published: Print-Electronic ClinicalTrials.gov: NCT04283461 CommentIn: Tidsskr Nor Laegeforen. 2021 Nov 15;141(18):. - PMID 34911279 Citation Status MEDLINE |
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| doi: |
10.1056/NEJMoa2028436 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| 245 | 1 | 0 | |a Safety and Immunogenicity of SARS-CoV-2 mRNA-1273 Vaccine in Older Adults |
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| 500 | |a Date Completed 23.12.2020 | ||
| 500 | |a Date Revised 17.12.2021 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a ClinicalTrials.gov: NCT04283461 | ||
| 500 | |a CommentIn: Tidsskr Nor Laegeforen. 2021 Nov 15;141(18):. - PMID 34911279 | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2020 Massachusetts Medical Society. | ||
| 520 | |a BACKGROUND: Testing of vaccine candidates to prevent infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in an older population is important, since increased incidences of illness and death from coronavirus disease 2019 (Covid-19) have been associated with an older age | ||
| 520 | |a METHODS: We conducted a phase 1, dose-escalation, open-label trial of a messenger RNA vaccine, mRNA-1273, which encodes the stabilized prefusion SARS-CoV-2 spike protein (S-2P) in healthy adults. The trial was expanded to include 40 older adults, who were stratified according to age (56 to 70 years or ≥71 years). All the participants were assigned sequentially to receive two doses of either 25 μg or 100 μg of vaccine administered 28 days apart | ||
| 520 | |a RESULTS: Solicited adverse events were predominantly mild or moderate in severity and most frequently included fatigue, chills, headache, myalgia, and pain at the injection site. Such adverse events were dose-dependent and were more common after the second immunization. Binding-antibody responses increased rapidly after the first immunization. By day 57, among the participants who received the 25-μg dose, the anti-S-2P geometric mean titer (GMT) was 323,945 among those between the ages of 56 and 70 years and 1,128,391 among those who were 71 years of age or older; among the participants who received the 100-μg dose, the GMT in the two age subgroups was 1,183,066 and 3,638,522, respectively. After the second immunization, serum neutralizing activity was detected in all the participants by multiple methods. Binding- and neutralizing-antibody responses appeared to be similar to those previously reported among vaccine recipients between the ages of 18 and 55 years and were above the median of a panel of controls who had donated convalescent serum. The vaccine elicited a strong CD4 cytokine response involving type 1 helper T cells | ||
| 520 | |a CONCLUSIONS: In this small study involving older adults, adverse events associated with the mRNA-1273 vaccine were mainly mild or moderate. The 100-μg dose induced higher binding- and neutralizing-antibody titers than the 25-μg dose, which supports the use of the 100-μg dose in a phase 3 vaccine trial. (Funded by the National Institute of Allergy and Infectious Diseases and others; mRNA-1273 Study ClinicalTrials.gov number, NCT04283461.) | ||
| 650 | 4 | |a Clinical Trial, Phase I | |
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, N.I.H., Extramural | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 7 | |a Antibodies, Neutralizing |2 NLM | |
| 650 | 7 | |a Antibodies, Viral |2 NLM | |
| 650 | 7 | |a COVID-19 Vaccines |2 NLM | |
| 650 | 7 | |a Spike Glycoprotein, Coronavirus |2 NLM | |
| 650 | 7 | |a spike protein, SARS-CoV-2 |2 NLM | |
| 650 | 7 | |a 2019-nCoV Vaccine mRNA-1273 |2 NLM | |
| 650 | 7 | |a EPK39PL4R4 |2 NLM | |
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| 700 | 1 | |a Edara, Venkata Viswanadh |e verfasserin |4 aut | |
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| 700 | 1 | |a Suthar, Mehul S |e verfasserin |4 aut | |
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| 700 | 1 | |a Elsafy, Mohammed |e investigator |4 oth | |
| 700 | 1 | |a Hoang, Binh |e investigator |4 oth | |
| 700 | 1 | |a Kim, Sonnie |e investigator |4 oth | |
| 700 | 1 | |a Kolhekar, Aparna |e investigator |4 oth | |
| 700 | 1 | |a Koo, Hyung |e investigator |4 oth | |
| 700 | 1 | |a Luke, Catherine |e investigator |4 oth | |
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| 700 | 1 | |a Edara, Venkata Viswanadh |e investigator |4 oth | |
| 700 | 1 | |a Edupuganti, Srilatha |e investigator |4 oth | |
| 700 | 1 | |a Floyd, Katharine |e investigator |4 oth | |
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| 700 | 1 | |a Kao, Carol |e investigator |4 oth | |
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| 700 | 1 | |a Rostad, Christina A |e investigator |4 oth | |
| 700 | 1 | |a Rouphael, Nadine |e investigator |4 oth | |
| 700 | 1 | |a Scherer, Erin |e investigator |4 oth | |
| 700 | 1 | |a Sherman, Amy |e investigator |4 oth | |
| 700 | 1 | |a Stephens, Kathy |e investigator |4 oth | |
| 700 | 1 | |a Suthar, Mehul S |e investigator |4 oth | |
| 700 | 1 | |a Teherani, Mehgan |e investigator |4 oth | |
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| 700 | 1 | |a Yildirim, Inci |e investigator |4 oth | |
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| 700 | 1 | |a Bennett, Hamilton |e investigator |4 oth | |
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| 700 | 1 | |a Hurley, Marjorie |e investigator |4 oth | |
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| 700 | 1 | |a Wang, Lingshu |e investigator |4 oth | |
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| 700 | 1 | |a Zhang, Yi |e investigator |4 oth | |
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