Antibody persistence up to 6 months after the second dose of mRNA-1273 vaccine for Covid-19


To the editor:

Interim results of a phase 3 trial of the Modern mRNA-1273 vaccine for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) indicated 94% efficacy in preventing coronavirus disease 2019 (Covid-19 ).one The durability of the protection is currently unknown. We describe neutralizing and binding antibodies elicited by mRNA1273 in 33 healthy adult participants in an ongoing phase 1 trial,2-4 Stratified by age, at 180 days after the second 100 μg dose (day 209).

Time course of SARS-CoV-2 antibody neutralizing and binding responses after vaccination with mRNA-1273.

All participants received 100 μg of mRNA-1273 on days 1 and 29, indicated by arrows. The number of participants in each age group with data available on day 209 is as follows: 18 to 55 years, 15 participants; 56 to 70 years, 9 participants; and 71 years or more, 9 participants. Titers shown are peak receptor-binding domain protein binding (the end-point dilution titer) evaluated in the enzyme-linked immunosorbent assay (ELISA) on days 1, 15, 29, 36 , 43, 57, 119 and 209 (Panel A); the 50% inhibitory dilution (IDfifty) titer in the pseudovirus neutralization assay on days 1, 15, 29, 36, 43, 57, 119 and 209 (Panel B); and identificationfifty titer in the mNeonGreen Live Virus Focus Reduction Neutralization Test (FRNT-mNG) on days 1, 29, 43, 119, and 209 (Panel C). The lines show geometric mean titles for each age group; Bars indicate 95% confidence intervals. The dashed line indicates the limit of detection for each assay.

Antibody activity remained high in all age groups at day 209. Binding antibodies, measured by enzyme-linked immunosorbent assay against the peak receptor-binding domain of SARS-CoV-2,two had Geometric Mean End Point Titles (GMT) of 92,451 (95% Confidence Interval [CI], 57,148 to 149,562) in participants aged 18 to 55 years, 62,424 (95% CI, 36,765 to 105,990) in those aged 56 to 70 years, and 49,373 (95% CI, 25,171 to 96,849) in those aged 71 or older . Almost all participants had detectable activity in a pseudovirus neutralization assay,two with 50% inhibitory dilution (IDfifty) GMT of 80 (95% CI, 40 to 135), 57 (95% CI, 30 to 106), and 59 (95% CI, 29 to 121), respectively. In the most sensitive live virus focus reduction neutralization test, mNeonGreen,4 all participants had detectable activity, with IDfifty GMT of 406 (95% CI, 286 to 578), 171 (95% CI, 95 to 307), and 131 (95% CI, 69 to 251), respectively; these GMTs were lower in participants aged 56 to 70 years (P = 0.02) and in those aged 71 and over (P = 0.004) than in those aged 18 to 55 (Figure 1; also see the Supplemental Appendix, available with the full text of this letter at NEJM.org).

The estimated half-life of the binding antibodies after day 43 for all participants was 52 days (95% CI, 46 to 58) calculated using an exponential decay model, assuming a constant decay rate at over time, and 109 days (95% CI, 92 to 136) calculated using a power law model (at day 119), which assumes deterioration rates decrease over time. Estimates of the half-life of neutralizing antibodies in the two models were 69 days (95% CI, 61 to 76) and 173 days (95% CI, 144 to 225) for pseudovirus neutralization and 68 days (CI 95%, 61 to 75) and 202 days (95% CI, 159 to 272) for neutralization of live viruses. Measured by ΔAICC (change in Akaike information criterion, corrected for small sample size), the best fit for binding and neutralization were the exponential decay and power law models, respectively (see Supplementary Appendix). These results are consistent with published observations of convalescent Covid-19 patients up to 8 months after the onset of symptoms.5

Although the antibody titers and assays that best correlate with vaccine efficacy are not currently known, antibodies that were elicited by mRNA-1273 persisted for 6 months after the second dose, as detected by three serologic assays. different. Ongoing studies monitor immune responses beyond 6 months and determine the effect of a booster dose to extend the duration and range of activity against emerging viral variants. Our data shows the persistence of antibodies and therefore supports the use of this vaccine to address the Covid-19 pandemic.

Nicole Doria-Rose, Ph.D.
National Institute of Allergy and Infectious Diseases (NIAID), Bethesda, MD

Mehul S. Suthar, Ph.D.
Emory University School of Medicine, Decatur, GA
[email protected]

Mat Makowski, Ph.D.
Emmes Company, Rockville, MD

Sarah O’Connell, MS
Adrian B. McDermott, Ph.D.
Britta Flach, Ph.D.
Julie E. Ledgerwood, DO
John R. Mascola, MD
Barney S. Graham, MD
Bob C. Lin, Bachelor of Laws
Sijy O’Dell, MS
Stephen D. Schmidt, Bachelor of Science
Alicia T. Widge, MD
NIAID, Bethesda, MD

Venkata-Viswanadh Edara, Ph.D.
Evan J. Anderson, MD
Lilin Lai, MD
Katharine Floyd, BA
Nadine G. Rouphael, MD
Veronika Zarnitsyna, Ph.D.
Emory University School of Medicine, Decatur, GA

Paul C. Roberts, Ph.D.
Mamodikoe Makhene, MD, MPH
Wendy Buchanan, BSN, MS
Catherine J. Luke, Ph.D.
John H. Beigel, physician
NIAID, Bethesda, MD

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

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

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

Jim Albert, MS
Pratap Kunwar, MS
Emmes Company, Rockville, MD

for study group mRNA-1273

Supported by grants (UM1AI148373, to Kaiser Washington; UM1AI148576 and UM1AI148684, to Emory University; NIH AID AI149644, to the University of North Carolina; UM1Al148684-01S1, to the Vanderbilt University Medical Center ,2201500002C27; and HHSNC272) the National Institute of Emory) Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH); by a grant (UL1 TR002243, to Vanderbilt University Medical Center) from the National Center for the Advancement of Translational Sciences, NIH; and by the Dolly Parton Covid-19 Research Fund (to Vanderbilt University Medical Center). Laboratory efforts were supported in part by the Emory Executive Vice President for Health Affairs Synergy Fund Award, the Center for Childhood Infections and Vaccines, Children’s Healthcare of Atlanta, a Woodruff Health Sciences Center 2020 COVID-19 CURE Award, the Georgia Research Alliance , and North Carolina Policy Fellow at the University of North Carolina at Chapel Hill, with funding from the North Carolina Coronavirus Relief Fund established and allocated by the North Carolina General Assembly. The Intramural Research Program of the Vaccine Research Center, NIAID, NIH provided additional support. The Coalition for Innovation in Epidemic Preparedness provided funding for the manufacture of phase 1 mRNA-1273 material.

Disclosure forms provided by the authors are available with the full text of this letter at NEJM.org.

This letter was posted on April 6, 2021, on NEJM.org.

Members of the mRNA-1273 Study Group are listed in the Supplemental Appendix, available with the full text of this letter at NEJM.org.

Drs. Doria-Rose and Suthar contributed equally to this letter.

  1. one. Baden LR, The Sahly HM, Essink B, et al. Efficacy and safety of the mRNA-1273 SARS-CoV-2 vaccine. N Engl J Med 2021; 384:403416.

  2. two. Jackson LA, Anderson EJ, Rouphael NG, et al. An mRNA vaccine against SARS-CoV-2 – preliminary report. N Engl J Med 2020; 383:19201931.

  3. 3. Widge AT, Rouphael NG, Jackson LA, et al. Durability of responses after vaccination with SARS-CoV-2 mRNA-1273. N Engl J Med 2021; 384:8082.

  4. Four. Anderson EJ, Rouphael NG, Widge AT, et al. Safety and immunogenicity of the SARS-CoV-2 mRNA-1273 vaccine in older adults. N Engl J Med 2020; 383:24272438.

  5. 5. Dan JM, Mateus J, Kato Y, et al. Immunological memory to SARS-CoV-2 was evaluated up to 8 months after infection. Science 2021; 371 (6529):eabf4063eabf4063.

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