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Durability of Responses after SARS-CoV-2 mRNA-1273 Vaccination


to the Editor:

We recently reported the Phase I results of mRNA-1273, a messenger RNA vaccine to prevent infection with SARS-COV-2; Those interim results covered a period of 57 days after the first vaccination.1,2 Here, we describe immunogenicity data 119 days after the first vaccination (90 days after the second vaccination) in 34 healthy adult participants in the same trial who received two injections of the vaccine at a dose of 100 μg. Injections were received 28 days apart. The recipients were stratified according to age (18 to 55 years, 56 to 70 years, or years71), and the donkeys used have been described previously.1,2

Time course of SARS-COV-2 antibody ligation and neutralization reactions after MRAN-1273 vaccination.

Shown are data from 34 participants who were stratified by age: 18 to 55 years (15 participants), 56 to 70 years of age (9 participants), and 71 years or older (10 participants). All participants received 100 μg of mRNA-1273 on days 1 and 29, indicated by arrows. The titers shown are binding on days 1, 15, 29, 36, 43, 57 and 119 of the enzyme-linked immunosorbent assay (ELISA) for the spike receptor-binding domain (RBD) protein (end-point dilution titer). (Panel A); 50% inhibitory dilution (ID50) Titer on pseudovirus neutralization assay at 1, 15, 29, 36, 43, 57, and 119 (panel); Id50 Concentration Reduction Neutralization Test mNeonGreen (FRNT-mNG) assay on days 1, 29, 43 and 119 (panel C); And 80% inhibitory dilution (ID)80) Titer on the plaque-minimization reduction test (PRNT) assay on days 1, 43, and 119 (panel D). Data from 43 and 57 days are missing for 1 participant in the 18- to 55-year stratum, for which samples were not obtained at those time points. Each line represents a single participant over time.

At a dose of 100-μg, mRNA-1273 produced a high level of antibodies and neutralized antibodies, which decreased slightly over time, but they remained elevated in all participants 3 months after booster vaccination. Responses that respond to the spike receptor-binding domain were evaluated by enzyme-linked immunosorbent assay. At 119 time points, the geometric mean titer (GMT) was 235,228 (95% confidence interval) [CI], 1, ,, 236 to 312,195) in the age group of 55 to 55 years, 151.161 (95% CI,%%, 5 CI1 to 23,030,333) in the age group of 56 to 60 years. In, and in those years 1 years of age 15,9,949 (95% CI, 79,335 to 26,720). or older (Figure 1).

Serum neutralizing antibodies continued to be detected in all participants over 119 days. On pseudovirus virus neutralization assay, 50% inhibitory dilution (ID)50) 12 (95% CI, 112 to 299) between the ages of 58 and 0 among the participants, 1 CI and 55 years, 14 CI (95%) among those between 58 and 20 years of age. CI, 88) to 31)) were among those 71 years or older, 95% CI, 68 to 175). Live-Virus Focus Reduce Neutralization Test on mNeonGreen Assay, ID50 GMT was 775 (95% CI, 560 to 1071), 685 (95% CI, 436 to 1077), and 552 (95% CI, 321 to 947) in 775, respectively. 80% inhibitory dilution GMT on live-virus plaque-minimization test assay, similarly in 430 (95% CI, 277 to 667), 269 (95% CI, 134 to 542) and 165 (95% CI) Was elevated. , 3 to 332 respectively in three groups)Figure 1).

Binding and neutralizing GMTs, at day 119, was higher than mean GMTs in a panel of 41 controls who were believing with Kovid-19 with a mean of 34 days since diagnosis (range, 23 to 54).2 No serious adverse events were noted in the trial, no prescribed test-stay rules were found, and no new adverse events considered to be vaccine-related by investigators occurred after 57 days.

Although the relationship of protection against SARS-CoV-2 infection in humans has not yet been established, these results suggest that despite modestly decreasing the binding and neutralization of antibodies, mRNA-1273 provides durable humoral immunity. Has the potential. Natural infection produces variable antibody longevity3,4 And may induce strong memory B-cell responses despite reduced plasma neutralizing activity.4,5 Although the memory cellular response to mRNA-1273 is not yet defined, this vaccine revealed primary CD4 type 1 helper T responses 43 days after primary immunization,2 And vaccine-induced B cells continue to be studied. Longitudinal vaccine responses are critically important, and a follow-up analysis continues to assess safety and immunogenicity in participants for a period of 13 months. Our findings provide support for the use of a 100-μg dose of mRNA-1273 in a continuous phase 3 trial, which recently showed a 94.5% efficacy rate in an interim analysis.

Alicia T. Wise, MD
National Institute of Allergy and Infectious Diseases (NIAID), Bethesda, MD

Nadine G. Ruffel, MD
Emory University School of Medicine, Decatur, GA

Lisa A. Jackson, MD, MPH
Kaiser Permanente Washington Health Research Institute, Seattle, WA

Evan J. Anderson, MD
Emory University School of Medicine, Decatur, GA

Paul C. Roberts, Ph.D.
Mamodiko Makhin, MD, MPH
NIAID, Bethesda, MD

James D. Chappell, M.D., Ph.D.
Mark R. Dennison, MD
Laura J. Stevens, M.S.
Andrea J. Prowessors, Ph.D.
Vanderbilt University Medical Center, Nashville, TN

Adrian b. McDermott, Ph.D.
Britta Flack, Ph.D.
Bob C. Lin, B.S.
Nicole A. Doria-Rose, Ph.D.
Sizzi O’Dell, M.S.
Stephen D. Schmidt, B.S.
NIAID, Bethesda, MD

Kathleen M. Newzill, MD
University of Maryland School of Medicine, Baltimore, MD

Hamilton Bennett, M.Sc.
Brett Leeuw, MD
Modern, Cambridge, MA

Matt Makowski, Ph.D.
Jim Albert, M.S.
Catiline Cross, M.S.
Ames Company, Rockville, MD

Venkata-Viswanadh Edara, Ph.D.
Kathryn Floyd, B.S.
Mehul S. Suthar, Ph.D.
Emory University School of Medicine, Decatur, GA

Wendy Buchanan, B.S.N., M.S.
Catherine J. Luke, Ph.D.
Julie E. Leisurewood, DO
John R. Mascola, MD
Barney S. Graham, MD
John H. Begel, MD
NIAID, Bethesda, MD

mRNA-1273 for study group

Funded for (UM1AI148373, Kaiser Washington; UM1AI148576, UM1AI148684, and NIH P51 OD011132, Emory University, NIH AID AI149644, University of North Carolina; UM1Al148684-01S1; supported by Vanderbilt University Medical Center, HHS) . From the National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH); From the grant (UL1 TR002243, to Vanderbilt University Medical Center) National Center for Advanced Translational Sciences, NIH; And by Dolly Parton Kovid-19 Research Fund (For Vanderbilt University Medical Center). Laboratory efforts were supported by Emory Executive Vice President for Synergy Fund Award for Health Affairs, To Center for Childhood Infections and Vaccines, Atlanta Children’s Healthcare, Covid-Trigger-I3 Funds from the Woodruff Health Sciences Center and Emory School of Medicine, and North Carolina Policy Cooperation at the University of North Carolina at Chapel Hill, raising funds from the North Carolina Coronavirus Relief Fund and appropriated by the North Carolina General Assembly. Additional support was provided by the Internal Research Program of the Vaccine Research Center, NIAID, NIH. Funding was provided for the manufacture of MRNA-1273 Phase 1 material Epidemic preparations combine for innovation.

Disclosure forms The full text of this paper is available at NEJM.org provided by the authors.

The paper was published on December 3, 2020 on NEJM.org.

Members of the MRNA-1273 study group are listed Supplementary Addendum, With full text of this paper available at NEJM.org.

DRS. Graham and Begel contributed equally to this paper.

  1. 1. Jackson la, Anderson EJ, Raufel N.G., and others. An mRNA vaccine against SARS-CoV-2 – preliminary report. N angle j med 2020; 383:19201931.

  2. 2. Anderson EJ, Raufel N.G., Weight at, and others. Safety and immunity of the SARS-CoV-2 mRNA-1273 vaccine in older adults. Ann Engl J Med. 10.1056 / NEJMoa2028436.

  3. 3. Gudbjartson DF, Norddl GL, Melstead P, and others. Hummer immune response to SARS-CoV-2 in Iceland. N angle j med 2020; 383:17241734.

  4. 4. Dan JM, Mateus J, Cut it, and others. Immunological memory for SARS-COV-2 for more than six months after infection. November 16, 2020 (https://www.biorxiv.org/content/10.1101/2020.11.15.383323v1). Preprint.

  5. 5. Robney df, Gabler Sea, Muecksch f, and others. Convergent antibody responses of SARS-CoV-2 in SARS-constable individuals. Nature 2020; 584:437442.



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