Durability of mRNA-1273 vaccine-induced antibodies against SARS-CoV-2 variants

Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mutations may diminish vaccine-induced protective immune responses, particularly as antibody titers wane over time. Here, we assess the effect of SARS-CoV-2 variants B.1.1.7 (Alpha), B.1.351 (Beta), P.1 (Gamma), B.1.429 (Epsilon), B.1.526 (Iota), and B.1.617.2 (Delta) on binding, neutralizing, and angiotensin-converting enzyme 2 (ACE2)–competing antibodies elicited by the messenger RNA (mRNA) vaccine mRNA-1273 over 7 months. Cross-reactive neutralizing responses were rare after a single dose. At the peak of response to the second vaccine dose, all individuals had responses to all variants. Binding and functional antibodies against variants persisted in most subjects, albeit at low levels, for 6 months after the primary series of the mRNA-1273 vaccine. Across all assays, B.1.351 had the lowest antibody recognition. These data complement ongoing studies to inform the potential need for additional boost vaccinations.

Fig. 1.. Binding and functional antibodies persist for 6 months after the second dose of the mRNA-1273 vaccine.

(A) Pseudovirus neutralization, expressed as 50% inhibitory dilution (ID₅₀). Dotted line indicates the limit of detection (>20). Pseudoviruses included WA1, D614G, B.1.1.7, B.1.351, P.1, B.1.429, B.1.526, and B.1.617.2. (B) Live-virus FRNT neutralization, expressed as ID₅₀. Dotted line indicates the limit of detection (>20). Viruses included WA1, 83E (spike is D614G), B.1.1.7, and B.1.351. (C) Competition of ACE2 binding to RBD, measured by MSD-ECLIA and expressed as fold reduction of ACE2 binding in the presence of serum compared with no-serum control. Dotted line indicates the limit of detection (>2). RBD proteins included WA1, B.1.1.7, and B.1.351. (D) Binding to cell surface–expressed full-length spike, measured by flow cytometry and expressed as median fluorescence intensity (MFI). Spikes included WA1, D614G, B.1.1.7, B.1.351, P.1, B.1.429, B.1.526, and B.1.617.2. (E) Binding to soluble spike protein S-2P, measured by MSD-ECLIA and expressed as area under the curve (AUC). S-2P proteins included WA1, B.1.1.7, B.1.351, and P.1. (F) Binding to RBD protein, measured by MSD-ECLIA and expressed as AUC. RBD proteins included WA1, B.1.1.7, B.1.351, and P.1. For all assays, sera from n = 24 individuals were sampled at four time points. Individuals were vaccinated with 100 μg mRNA-1273 at days 1 and 29 (arrows). Symbols show the geometric mean value, and error bars show 95% confidence intervals.

Fig. 2.. The relative effect of each SARS-CoV-2 viral variant is similar across assays.

(A) ID₅₀ in pseudovirus neutralization assays. Dotted line indicates the limit of detection (>20). (B) ID₅₀ in live virus FRNT neutralization. Dotted line indicates the limit of detection (>20). (C) Competition of ACE2 binding to RBD of WA1, B.1.1.7, and B.1.351, expressed as fold reduction of signal in the presence of serum compared with no-serum control. Dotted line indicates the limit of detection (>2). (D) Binding to cell surface–expressed full-length spike, expressed as MFI. (E) Binding to S-2P, expressed as AUC. (F) Binding to RBD protein, expressed as AUC. (G) Geometric mean of ratios of values. na, not applicable. In (A) to (F), symbols show data for all samples at all time points, light gray lines connect data from each sample for the variants, and black lines show geometric mean of all samples. All viruses are color coded as in Fig. 1.

Fig. 3.. All individuals had binding antibodies to SARS-CoV-2 variants, and the majority of individuals maintained functional activity against viral variants at 6 months after the second vaccination.

Values are the percentage of sera (n = 24 at each time point) for which antibodies were detected for each variant. For pseudovirus and live-virus neutralization, samples were called detectable at ID₅₀ > 20; for ACE2 blocking, at a twofold decrease in signal compared with no-serum control; for S-2P and RBD binding, at AUC > 100; and for cell surface spike binding, at MFI > 100.

Fig. 4.. Binding antibodies to viral variants decayed faster than antibodies to WA1, but the functional antibodies to variants diminished more slowly.

(A) S-2P binding. (B) RBD binding. (C) ACE2 competition. (D) Live-virus neutralization. Symbols show the value for WA1 divided by the value for the indicated variant for each sample. P values are from paired t tests.