Dataset Information

Safety and Immunogenicity of SARS-CoV-2 mRNA-1273 Vaccine in Older Adults.

ABSTRACT: 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 ?g or 100 ?g 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-?g 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-?g 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-?g dose induced higher binding- and neutralizing-antibody titers than the 25-?g dose, which supports the use of the 100-?g 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.).

SUBMITTER: Anderson EJ

PROVIDER: S-EPMC7556339 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Safety and Immunogenicity of SARS-CoV-2 mRNA-1273 Vaccine in Older Adults.

Anderson Evan J EJ Rouphael Nadine G NG Widge Alicia T AT Jackson Lisa A LA Roberts Paul C PC Makhene Mamodikoe M Chappell James D JD Denison Mark R MR Stevens Laura J LJ Pruijssers Andrea J AJ McDermott Adrian B AB Flach Britta B Lin Bob C BC Doria-Rose Nicole A NA O'Dell Sijy S Schmidt Stephen D SD Corbett Kizzmekia S KS Swanson Phillip A PA Padilla Marcelino M Neuzil Kathy M KM Bennett Hamilton H Leav Brett B Makowski Mat M Albert Jim J Cross Kaitlyn K Edara Venkata Viswanadh VV Floyd Katharine K Suthar Mehul S MS Martinez David R DR Baric Ralph R Buchanan Wendy W Luke Catherine J CJ Phadke Varun K VK Rostad Christina A CA Ledgerwood Julie E JE Graham Barney S BS Beigel John H JH

The New England journal of medicine 20200929 25

<h4>Background</h4>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.<h4>Methods</h4>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 adul ...[more]

PMID: 32991794

Similar Datasets

Project description:BackgroundVaccines are needed to prevent coronavirus disease 2019 (Covid-19) and to protect persons who are at high risk for complications. The mRNA-1273 vaccine is a lipid nanoparticle-encapsulated mRNA-based vaccine that encodes the prefusion stabilized full-length spike protein of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes Covid-19.MethodsThis phase 3 randomized, observer-blinded, placebo-controlled trial was conducted at 99 centers across the United States. Persons at high risk for SARS-CoV-2 infection or its complications were randomly assigned in a 1:1 ratio to receive two intramuscular injections of mRNA-1273 (100 ?g) or placebo 28 days apart. The primary end point was prevention of Covid-19 illness with onset at least 14 days after the second injection in participants who had not previously been infected with SARS-CoV-2.ResultsThe trial enrolled 30,420 volunteers who were randomly assigned in a 1:1 ratio to receive either vaccine or placebo (15,210 participants in each group). More than 96% of participants received both injections, and 2.2% had evidence (serologic, virologic, or both) of SARS-CoV-2 infection at baseline. Symptomatic Covid-19 illness was confirmed in 185 participants in the placebo group (56.5 per 1000 person-years; 95% confidence interval [CI], 48.7 to 65.3) and in 11 participants in the mRNA-1273 group (3.3 per 1000 person-years; 95% CI, 1.7 to 6.0); vaccine efficacy was 94.1% (95% CI, 89.3 to 96.8%; P<0.001). Efficacy was similar across key secondary analyses, including assessment 14 days after the first dose, analyses that included participants who had evidence of SARS-CoV-2 infection at baseline, and analyses in participants 65 years of age or older. Severe Covid-19 occurred in 30 participants, with one fatality; all 30 were in the placebo group. Moderate, transient reactogenicity after vaccination occurred more frequently in the mRNA-1273 group. Serious adverse events were rare, and the incidence was similar in the two groups.ConclusionsThe mRNA-1273 vaccine showed 94.1% efficacy at preventing Covid-19 illness, including severe disease. Aside from transient local and systemic reactions, no safety concerns were identified. (Funded by the Biomedical Advanced Research and Development Authority and the National Institute of Allergy and Infectious Diseases; COVE ClinicalTrials.gov number, NCT04470427.).

Project description:BackgroundVaccines are urgently needed to prevent the global spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We assessed the safety and immunogenicity of vaccine candidate mRNA-1273, encoding the prefusion-stabilized spike protein of SARS-CoV-2.MethodsThis phase 2, randomized, observer-blind, placebo-controlled trial was conducted at 8 sites in the USA, in healthy adults aged ≥18 years with no known history or risk of SARS-CoV-2 infection, and had not previously received an investigational CoV vaccine or treatment. Participants were stratified into two age cohorts (≥18-<55 and ≥55) and were randomly assigned (1:1:1) to either 50 or 100 µg of mRNA-1273, or placebo administered as two intramuscular injections 28 days apart. The primary outcomes were safety, reactogenicity, and immunogenicity assessed by anti-SARS-CoV-2-spike binding antibody level (bAb). Secondary outcome was immunogenicity assessed by SARS-CoV-2 neutralizing antibody (nAb) response.ResultsBetween 29 May and 8 July 2020, 600 participants were randomized, 300 per age cohort. The most common solicited adverse reactions were pain at injection site, headache, and fatigue following each vaccination in both age cohorts. One serious adverse event deemed unrelated by the site investigator occurred 33 days post-vaccination one. mRNA-1273 induced bAb and nAb by 28 days post-vaccination one that were higher at the 100 µg dose relative to the 50 µg dose; this difference was less apparent post-vaccination two. Binding antibodies and nAb increased substantially by 14 days following the second vaccination (day 43) to levels exceeding those of convalescent sera and remained elevated through day 57.ConclusionsVaccination with mRNA-1273 resulted in significant immune responses to SARS-CoV-2 in participants 18 years and older, with an acceptable safety profile, confirming the safety and immunogenicity of 50 and 100 µg mRNA-1273 given as a 2 dose-regimen. ClinicalTrials.gov; NCT04405076.

Project description:BackgroundThe incidence of coronavirus disease 2019 (Covid-19) among adolescents between 12 and 17 years of age was approximately 900 per 100,000 population from April 1 through June 11, 2021. The safety, immunogenicity, and efficacy of the mRNA-1273 vaccine in adolescents are unknown.MethodsIn this ongoing phase 2-3, placebo-controlled trial, we randomly assigned healthy adolescents (12 to 17 years of age) in a 2:1 ratio to receive two injections of the mRNA-1273 vaccine (100 μg in each) or placebo, administered 28 days apart. The primary objectives were evaluation of the safety of mRNA-1273 in adolescents and the noninferiority of the immune response in adolescents as compared with that in young adults (18 to 25 years of age) in a phase 3 trial. Secondary objectives included the efficacy of mRNA-1273 in preventing Covid-19 or asymptomatic severe acute respiratory syndrome coronavirus 2 infection.ResultsA total of 3732 participants were randomly assigned to receive mRNA-1273 (2489 participants) or placebo (1243 participants). In the mRNA-1273 group, the most common solicited adverse reactions after the first or second injections were injection-site pain (in 93.1% and 92.4%, respectively), headache (in 44.6% and 70.2%, respectively), and fatigue (in 47.9% and 67.8%, respectively); in the placebo group, the most common solicited adverse reactions after the first or second injections were injection-site pain (in 34.8% or 30.3%, respectively), headache (in 38.5% and 30.2%, respectively), and fatigue (in 36.6% and 28.9%, respectively). No serious adverse events related to mRNA-1273 or placebo were noted. The geometric mean titer ratio of pseudovirus neutralizing antibody titers in adolescents relative to young adults was 1.08 (95% confidence interval [CI], 0.94 to 1.24), and the absolute difference in serologic response was 0.2 percentage points (95% CI, -1.8 to 2.4), which met the noninferiority criterion. No cases of Covid-19 with an onset of 14 days after the second injection were reported in the mRNA-1273 group, and four cases occurred in the placebo group.ConclusionsThe mRNA-1273 vaccine had an acceptable safety profile in adolescents. The immune response was similar to that in young adults, and the vaccine was efficacious in preventing Covid-19. (Funded by Moderna and the Biomedical Advanced Research and Development Authority; Teen COVE ClinicalTrials.gov number, NCT04649151.).

Project description:BackgroundDifferences in immunogenicity between mRNA SARS-CoV-2 vaccines have not been well characterized in patients undergoing dialysis. We compared the serologic response in patients undergoing maintenance hemodialysis after vaccination against SARS-CoV-2 with BNT162b2 (Pfizer-BioNTech) and mRNA-1273 (Moderna).MethodsWe conducted a prospective observational cohort study at 2 academic centres in Toronto, Canada, from Feb. 2, 2021, to July 20, 2021, which included 129 and 95 patients who received the BNT162b2 and mRNA-1273 SARS-CoV-2 vaccines, respectively. We measured SARS-CoV-2 immunoglobulin G antibodies to the spike protein (anti-spike), receptor binding domain (anti-RBD) and nucleocapsid protein (anti-NP) at 6-7 and 12 weeks after the second dose of vaccine and compared those levels with the median convalescent serum antibody levels from 211 controls who were previously infected with SARS-CoV-2.ResultsAt 6-7 weeks after 2-dose vaccination, we found that 51 of 70 patients (73%) who received BNT162b2 and 83 of 87 (95%) who received mRNA-1273 attained convalescent levels of anti-spike antibody (p < 0.001). In those who received BNT162b2, 35 of 70 (50%) reached the convalescent level for anti-RBD compared with 69 of 87 (79%) who received mRNA-1273 (p < 0.001). At 12 weeks after the second dose, anti-spike and anti-RBD levels were significantly lower in patients who received BNT162b2 than in those who received mRNA-1273. For anti-spike, 70 of 122 patients (57.4%) who received BNT162b2 maintained the convalescent level versus 68 of 71 (96%) of those who received mRNA-1273 (p < 0.001). For anti-RBD, 47 of 122 patients (38.5%) who received BNT162b2 maintained the anti-RBD convalescent level versus 45 of 71 (63%) of those who received mRNA-1273 (p = 0.002).InterpretationIn patients undergoing hemodialysis, mRNA-1273 elicited a stronger humoral response than BNT162b2. Given the rapid decline in immunogenicity at 12 weeks in patients who received BNT162b2, a third dose is recommended in patients undergoing dialysis as a primary series, similar to recommendations for other vulnerable populations.

Dataset Information

Safety and Immunogenicity of SARS-CoV-2 mRNA-1273 Vaccine in Older Adults.

Publications

Safety and Immunogenicity of SARS-CoV-2 mRNA-1273 Vaccine in Older Adults.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets