• Booster of mRNA-1273 Vaccine Reduces SARS-CoV-2 Omicron Escape from Neutralizing Antibodies.

      Doria-Rose, Nicole A; Shen, Xiaoying; Schmidt, Stephen D; O'Dell, Sijy; McDanal, Charlene; Feng, Wenhong; Tong, Jin; Eaton, Amanda; Maglinao, Maha; Tang, Haili; et al. (Cold Spring Harbor Laboratory, 2021-12-15)
      The Omicron variant of SARS-CoV-2 is raising concerns because of its increased transmissibility and potential for reduced susceptibility to antibody neutralization. To assess the potential risk of this variant to existing vaccines, serum samples from mRNA-1273 vaccine recipients were tested for neutralizing activity against Omicron and compared to neutralization titers against D614G and Beta in live virus and pseudovirus assays. Omicron was 41-84-fold less sensitive to neutralization than D614G and 5.3-7.4-fold less sensitive than Beta when assayed with serum samples obtained 4 weeks after 2 standard inoculations with 100 µg mRNA-1273. A 50 µg boost increased Omicron neutralization titers and may substantially reduce the risk of symptomatic vaccine breakthrough infections.
    • Efficacy and Safety of the mRNA-1273 SARS-CoV-2 Vaccine

      Baden, Lindsey R; El Sahly, Hana M; Essink, Brandon; Kotloff, Karen; Frey, Sharon; Novak, Rick; Diemert, David; Spector, Stephen A; Rouphael, Nadine; Creech, C Buddy; et al. (Massachusetts Medical Society, 2020-12-30)
      BACKGROUND Vaccines 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. METHODS This 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 μg) 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. RESULTS The 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. CONCLUSIONS The 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.
    • Evaluation of mRNA-1273 Covid-19 Vaccine in Children 6 to 11 Years of Age.

      Creech, C Buddy; Anderson, Evan; Berthaud, Vladimir; Yildirim, Inci; Atz, Andrew M; Melendez Baez, Ivan; Finkelstein, Daniel; Pickrell, Paul; Kirstein, Judith; Yut, Clifford; et al. (Massachusetts Medical Society, 2022-05-11)
      Background: Vaccination of children to prevent coronavirus disease 2019 (Covid-19) is an urgent public health need. The safety, immunogenicity, and efficacy of the mRNA-1273 vaccine in children 6 to 11 years of age are unknown. Methods: Part 1 of this ongoing phase 2-3 trial was open label for dose selection; part 2 was an observer-blinded, placebo-controlled expansion evaluation of the selected dose. In part 2, we randomly assigned children (6 to 11 years of age) in a 3:1 ratio to receive two injections of mRNA-1273 (50 μg each) or placebo, administered 28 days apart. The primary objectives were evaluation of the safety of the vaccine in children and the noninferiority of the immune response in these children to that in young adults (18 to 25 years of age) in a related phase 3 trial. Secondary objectives included determination of the incidences of confirmed Covid-19 and severe acute respiratory syndrome coronavirus 2 infection, regardless of symptoms. Interim analysis results are reported. Results: In part 1 of the trial, 751 children received 50-μg or 100-μg injections of the mRNA- 1273 vaccine, and on the basis of safety and immunogenicity results, the 50-μg dose level was selected for part 2. In part 2 of the trial, 4016 children were randomly assigned to receive two injections of mRNA-1273 (50 μg each) or placebo and were followed for a median of 82 days (interquartile range, 14 to 94) after the first injection. This dose level was associated with mainly low-grade, transient adverse events, most commonly injection-site pain, headache, and fatigue. No vaccine-related serious adverse events, multisystem inflammatory syndrome in children, myocarditis, or pericarditis were reported as of the data-cutoff date. One month after the second injection (day 57), the neutralizing antibody titer in children who received mRNA-1273 at a 50-μg level was 1610 (95% confidence interval [CI], 1457 to 1780), as compared with 1300 (95% CI, 1171 to 1443) at the 100-μg level in young adults, with serologic responses in at least 99.0% of the participants in both age groups, findings that met the prespecified noninferiority success criterion. Estimated vaccine efficacy was 88.0% (95% CI, 70.0 to 95.8) against Covid-19 occurring 14 days or more after the first injection, at a time when B.1.617.2 (delta) was the dominant circulating variant. Conclusions: Two 50-μg doses of the mRNA-1273 vaccine were found to be safe and effective in inducing immune responses and preventing Covid-19 in children 6 to 11 years of age; these responses were noninferior to those in young adults. Copyright © 2022 Massachusetts Medical Society.
    • Immune correlates analysis of the mRNA-1273 COVID-19 vaccine efficacy clinical trial.

      Gilbert, Peter B; Montefiori, David C; McDermott, Adrian B; Fong, Youyi; Benkeser, David; Deng, Weiping; Zhou, Honghong; Houchens, Christopher R; Martins, Karen; Jayashankar, Lakshmi; et al. (American Association for the Advancement of Science, 2021-11-23)
    • Phase 3 Trial of mRNA-1273 during the Delta-Variant Surge

      Baden, Lindsey R; El Sahly, Hana M; Essink, Brandon; Follmann, Dean; Neuzil, Kathleen M; August, Allison; Clouting, Heather; Fortier, Gabrielle; Deng, Weiping; Han, Shu; et al. (Massachusetts Medical Society, 2021-11-03)
    • SARS-CoV-2 Omicron Variant Neutralization after mRNA-1273 Booster Vaccination.

      Pajon, Rolando; Doria-Rose, Nicole A; Shen, Xiaoying; Schmidt, Stephen D; O'Dell, Sijy; McDanal, Charlene; Feng, Wenhong; Tong, Jin; Eaton, Amanda; Maglinao, Maha; et al. (Massachusetts Medical Society, 2022-01-26)