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Safety and Immunogenicity of a 100 μg mRNA-1273 Vaccine Booster for Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2).

ABSTRACT: Due to the emergence of highly transmissible SARS-CoV-2 variants, evaluation of boosters is needed. Evaluate safety and immunogenicity of 100-µg of mRNA-1273 booster dose in adults. Open-label, Phase 2/3 study. Multicenter study at 8 sites in the U.S. The mRNA-1273 100-µg booster was administered to adults who previously received a two dose primary series of 100-µg mRNA-1273 in the phase 3 Coronavirus Efficacy (COVE) trial, at least 6 months earlier. Lipid nanoparticle containing 100-µg of mRNA encoding the spike glycoprotein of SARS-CoV-2 (Wuhan-HU-1). Solicited local and systemic adverse reactions, and unsolicited adverse events were collected after vaccination. Primary immunogenicity objectives were to demonstrate non-inferiority of the neutralizing antibody (nAb) response against SARS-CoV-2 based on the geometric mean titer (GMTs) and the seroresponse rates (SRRs) (booster dose vs. primary series in a historical control group). nAbs against SARS-CoV-2 variants were also evaluated. The 100-µg booster dose had a greater incidence of local and systemic adverse reactions compared to the second dose of mRNA-1273 as well as the 50-µg mRNA-1273 booster in separate studies. The geometric mean titers (GMTs; 95% CI) of SARS-CoV-2 nAbs against the ancestral SARS-CoV-2 at 28 days after the 100-µg booster dose were 4039.5 (3592.7,4541.8) and 1132.0 (1046.7,1224.2) at 28 days after the second dose in the historical control group [GMT ratio=3.6 (3.1,4.2)]. SRRs (95% CI) were 100% (98.6,100) at 28 days after the booster and 98.1% (96.7,99.1) 28 days after the second dose in the historical control group [percentage difference=1.9% (0.4,3.3)]. The GMT ratio (GMR) and SRR difference for the booster as compared to the primary series met the pre-specified non-inferiority criteria. Delta-specific nAbs also increased (GMT fold-rise=233.3) after the 100-µg booster of mRNA-1273. The 100-µg mRNA-1273 booster induced a robust neutralizing antibody response against SARS-CoV-2, and reactogenicity was higher with the 100-µg booster dose compared to the authorized booster dose level in adults (50-µg). mRNA-1273 100-µg booster dose can be considered when eliciting an antibody response might be challenging such as in moderately or severely immunocompromised hosts. Trial Registration: NCT04927065. Question: What is the safety and immunogenicity of a booster dose of 100 µg of mRNA-1273 in adults who previously received the primary series of mRNA-1273?Findings: In this open-label, Phase 2/3 study, the 100 µg booster dose of mRNA-1273 had a greater incidence of local and systemic adverse reactions compared to a 50 µg booster dose of mRNA- 1273 or after the second dose of mRNA-1273 during the primary series. The 100 µg booster dose of mRNA-1273 induced a robust antibody response against the ancestral SARS-CoV-2 and variants.Meaning: mRNA-1273 100 µg booster dose might be considered when eliciting an antibody response might be challenging, such as in moderately or severely immunocompromised hosts.

SUBMITTER: Chalkias S

PROVIDER: S-EPMC8923111 | biostudies-literature | 2022 Mar

REPOSITORIES: biostudies-literature

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Safety and Immunogenicity of a 100 μg mRNA-1273 Vaccine Booster for Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2).

Chalkias Spyros S Schwartz Howard H Nestorova Biliana B Feng Jing J Chang Ying Y Zhou Honghong H Dutko Frank J FJ Edwards Darin K DK Montefiori David D Pajon Rolando R Leav Brett B Miller Jacqueline M JM Das Rituparna R

medRxiv : the preprint server for health sciences 20220307

<h4>Importance</h4>Due to the emergence of highly transmissible SARS-CoV-2 variants, evaluation of boosters is needed.<h4>Objectives</h4>Evaluate safety and immunogenicity of 100-μg of mRNA-1273 booster dose in adults.<h4>Design</h4>Open-label, Phase 2/3 study.<h4>Setting</h4>Multicenter study at 8 sites in the U.S.<h4>Participants</h4>The mRNA-1273 100-μg booster was administered to adults who previously received a two dose primary series of 100-μg mRNA-1273 in the phase 3 Coronavirus Efficacy ...[more]

PMID: 35291289

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Project description:BackgroundTesting 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.MethodsWe 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.ResultsSolicited 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.ConclusionsIn 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.).

Dataset Information

Safety and Immunogenicity of a 100 μg mRNA-1273 Vaccine Booster for Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2).

Publications

Safety and Immunogenicity of a 100 μg mRNA-1273 Vaccine Booster for Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2).

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