Antibody Persistence through 6 Months after the Second Dose of mRNA-1273 Vaccine for Covid-19

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

Antibody activity remained high in all age groups at day 209. Binding antibodies, measured by means of an enzyme-linked immunosorbent assay against SARS-CoV-2 spike receptor–binding domain,² had geometric mean end-point titers (GMTs) of 92,451 (95% confidence interval [CI], 57,148 to 149,562) in participants 18 to 55 years of age, 62,424 (95% CI, 36,765 to 105,990) in those 56 to 70 years of age, and 49,373 (95% CI, 25,171 to 96,849) in those 71 years of age or older. Nearly all participants had detectable activity in a pseudovirus neutralization assay,² with 50% inhibitory dilution (ID₅₀) GMTs of 80 (95% CI, 40 to 135), 57 (95% CI, 30 to 106), and 59 (95% CI, 29 to 121), respectively. On the more sensitive live-virus focus-reduction neutralization mNeonGreen test,⁴ all the participants had detectable activity, with ID₅₀ GMTs of 361 (95% CI, 258 to 504), 171 (95% CI, 95 to 307), and 131 (95% CI, 69 to 251), respectively; these GMTs were lower in participants 56 to 70 years of age (P=0.03) and in those 71 years of age or older (P=0.005) than in those 18 to 55 years of age (Figure 1; also see the Supplementary Appendix, available with the full text of this letter at NEJM.org).

Figure 1. Time Course of SARS-CoV-2 Antibody Binding and Neutralization Responses after mRNA-1273 Vaccination.

All the participants received 100 μg of mRNA-1273 on days 1 and 29, indicated by arrows. The numbers of participants in each age group with data available at day 209 are as follows: 18 to 55 years, 15 participants; 56 to 70 years, 9 participants; and 71 years or older, 9 participants. The titers shown are the binding to spike receptor–binding domain protein (the end-point dilution titer) assessed on enzyme-linked immunosorbent assay (ELISA) on days 1, 15, 29, 36, 43, 57, 119, and 209 (Panel A); the 50% inhibitory dilution (ID₅₀) titer on pseudovirus neutralization assay on days 1, 15, 29, 36, 43, 57, 119, and 209 (Panel B); and the ID₅₀ titer on the live-virus focus-reduction neutralization mNeonGreen test (FRNT-mNG) on days 1, 29, 43, 119, and 209 (Panel C). Lines show geometric mean titers for each age group; 𝙸 bars indicate 95% confidence intervals. The dashed line indicates the limit of detection for each assay.

The estimated half-life of binding antibodies after day 43 for all the participants was 52 days (95% CI, 46 to 58) calculated with the use of an exponential decay model, which assumes a steady decay rate over time, and 109 days (95% CI, 92 to 136) calculated with the use of a power-law model (at day 119), which assumes that decay rates decrease over time. The neutralizing antibody half-life estimates in the two models were 69 days (95% CI, 61 to 76) and 173 days (95% CI, 144 to 225) for pseudovirus neutralization and 66 days (95% CI, 59 to 72) and 182 days (95% CI, 153 to 254) for live-virus neutralization. As measured by ΔAIC_c (change in Akaike information criterion, corrected for small sample size), the best fit for binding and neutralization were the power-law and exponential decay models, respectively (see the Supplementary Appendix). These results are consistent with published observations of convalescent patients with Covid-19 through 8 months after symptom onset.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 through 6 months after the second dose, as detected by three distinct serologic assays. Ongoing studies are monitoring immune responses beyond 6 months as well as determining the effect of a booster dose to extend the duration and breadth of activity against emerging viral variants. Our data show antibody persistence and thus support the use of this vaccine in addressing the Covid-19 pandemic.

This letter was published on April 6, 2021, and last updated on January 19, 2022, at NEJM.org.