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An mRNA Vaccine against SARS-CoV-2 - Preliminary Report.

ABSTRACT: BACKGROUND:The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in late 2019 and spread globally, prompting an international effort to accelerate development of a vaccine. The candidate vaccine mRNA-1273 encodes the stabilized prefusion SARS-CoV-2 spike protein. METHODS:We conducted a phase 1, dose-escalation, open-label trial including 45 healthy adults, 18 to 55 years of age, who received two vaccinations, 28 days apart, with mRNA-1273 in a dose of 25 ?g, 100 ?g, or 250 ?g. There were 15 participants in each dose group. RESULTS:After the first vaccination, antibody responses were higher with higher dose (day 29 enzyme-linked immunosorbent assay anti-S-2P antibody geometric mean titer [GMT], 40,227 in the 25-?g group, 109,209 in the 100-?g group, and 213,526 in the 250-?g group). After the second vaccination, the titers increased (day 57 GMT, 299,751, 782,719, and 1,192,154, respectively). After the second vaccination, serum-neutralizing activity was detected by two methods in all participants evaluated, with values generally similar to those in the upper half of the distribution of a panel of control convalescent serum specimens. Solicited adverse events that occurred in more than half the participants included fatigue, chills, headache, myalgia, and pain at the injection site. Systemic adverse events were more common after the second vaccination, particularly with the highest dose, and three participants (21%) in the 250-?g dose group reported one or more severe adverse events. CONCLUSIONS:The mRNA-1273 vaccine induced anti-SARS-CoV-2 immune responses in all participants, and no trial-limiting safety concerns were identified. These findings support further development of this vaccine. (Funded by the National Institute of Allergy and Infectious Diseases and others; mRNA-1273 ClinicalTrials.gov number, NCT04283461).

SUBMITTER: Jackson LA

PROVIDER: S-EPMC7377258 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature

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An mRNA Vaccine against SARS-CoV-2 - Preliminary Report.

Jackson Lisa A LA Anderson Evan J EJ Rouphael Nadine G NG Roberts Paul C PC Makhene Mamodikoe M Coler Rhea N RN McCullough Michele P MP Chappell James D JD Denison Mark R MR Stevens Laura J LJ Pruijssers Andrea J AJ McDermott Adrian A Flach Britta B Doria-Rose Nicole A NA Corbett Kizzmekia S KS Morabito Kaitlyn M KM O'Dell Sijy S Schmidt Stephen D SD Swanson Phillip A PA Padilla Marcelino M Mascola John R JR Neuzil Kathleen M KM Bennett Hamilton H Sun Wellington W Peters Etza E Makowski Mat M Albert Jim J Cross Kaitlyn K Buchanan Wendy W Pikaart-Tautges Rhonda R Ledgerwood Julie E JE Graham Barney S BS Beigel John H JH

The New England journal of medicine 20200714 20

<h4>Background</h4>The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in late 2019 and spread globally, prompting an international effort to accelerate development of a vaccine. The candidate vaccine mRNA-1273 encodes the stabilized prefusion SARS-CoV-2 spike protein.<h4>Methods</h4>We conducted a phase 1, dose-escalation, open-label trial including 45 healthy adults, 18 to 55 years of age, who received two vaccinations, 28 days apart, with mRNA-1273 in a dose of 25 μg, 100 ...[more]

PMID: 32663912

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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:BackgroundA vaccine against SARS-CoV-2 is of high urgency. Here the safety and immunogenicity induced by a DNA vaccine (INO-4800) targeting the full length spike antigen of SARS-CoV-2 are described.MethodsINO-4800 was evaluated in two groups of 20 participants, receiving either 1.0 mg or 2.0 mg of vaccine intradermally followed by CELLECTRA® EP at 0 and 4 weeks. Thirty-nine subjects completed both doses; one subject in the 2.0 mg group discontinued trial participation prior to receiving the second dose. ClinicalTrials.gov identifier: NCT04336410.FindingsThe median age was 34.5, 55% (22/40) were men and 82.5% (33/40) white. Through week 8, only 6 related Grade 1 adverse events in 5 subjects were observed. None of these increased in frequency with the second administration. No serious adverse events were reported. All 38 subjects evaluable for immunogenicity had cellular and/or humoral immune responses following the second dose of INO-4800. By week 6, 95% (36/38) of the participants seroconverted based on their responses by generating binding (ELISA) and/or neutralizing antibodies (PRNT IC50), with responder geometric mean binding antibody titers of 655.5 [95% CI (255.6, 1681.0)] and 994.2 [95% CI (395.3, 2500.3)] in the 1.0 mg and 2.0 mg groups, respectively. For neutralizing antibody, 78% (14/18) and 84% (16/19) generated a response with corresponding geometric mean titers of 102.3 [95% CI (37.4, 280.3)] and 63.5 [95% CI (39.6, 101.8)], in the respective groups. By week 8, 74% (14/19) and 100% (19/19) of subjects generated T cell responses by IFN-ɣ ELISpot assay with the median SFU per 106 PBMC of 46 [95% CI (21.1, 142.2)] and 71 [95% CI (32.2, 194.4)] in the 1.0 mg and 2.0 mg groups, respectively. Flow cytometry demonstrated a T cell response, dominated by CD8+ T cells co-producing IFN-ɣ and TNF-α, without increase in IL-4.InterpretationINO-4800 demonstrated excellent safety and tolerability and was immunogenic in 100% (38/38) of the vaccinated subjects by eliciting either or both humoral or cellular immune responses.FundingCoalition for Epidemic Preparedness Innovations (CEPI).

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An mRNA Vaccine against SARS-CoV-2 - Preliminary Report.

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An mRNA Vaccine against SARS-CoV-2 - Preliminary Report.

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