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Letter to the Editor

Antibody Kinetics and Durability in SARS-CoV-2 mRNA Vaccinated Solid Organ Transplant Recipients

Boyarsky, Brian J. MD, PhD1; Chiang, Teresa P.-Y. MD, MPH1; Teles, Aura T. BS1; Greenberg, Ross S. BA1; Krach, Michelle R. BA1; Ou, Michael T. BS1; Massie, Allan B. PhD1; Tobian, Aaron A. R. MD, PhD2; Garonzik-Wang, Jacqueline M. MD, PhD1; Segev, Dorry L. MD, PhD1,3; Werbel, and William A. MD4

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doi: 10.1097/TP.0000000000003863
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Decline in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antispike antibodies over time following natural infection and vaccination have been reported,1–3 though kinetics and durability of antispike antibodies in vaccinated transplant recipients are unknown. We sought to quantify antispike antibody titers over a 3 mo period in transplant recipients who completed the mRNA vaccine series.

As previously reported,4,5 serologic testing was undertaken on the Roche Elecsys anti-SARS-CoV-2 S enzyme immunoassay (range <0.4–>250 U/mL [positive ≥0.8 U/mL]) which tests for antibodies against the receptor-binding domain of the spike protein or EUROIMMUN enzyme immunoassay (positive ≥1.1 arbitrary units) which tests for IgG to the S1 domain of the spike protein at 3 time points: before dose 2, 1 mo and 3 mo after dose 2. Participants underwent vaccination between 16 December 2020 and 13 March 2021, and this study was approved by the Johns Hopkins Institutional Review Board.

Overall, 40/305 (13%) had detectable antibody at median (interquartile range [IQR]) 21 (18–25) d after dose 1; 169/305 (55%) had detectable antibody at median (IQR) 29 (28–31) d after dose 2; and 203/305 (67%) had detectable antibody at median (IQR) 90 (88–92) d after dose 2.

Among the participants with detectable antibody at 1 mo, 6/169 (4%) fell below the threshold of positivity at 3 mo (Table 1). Titers decreased in 59/169 (35%), increased in 74/169 (43%), and remained constant in 36/169 (21%).

TABLE 1. - Antispike antibody sero-response 3 mo following SARS-CoV-2 vaccine dose 2 in transplant recipients, stratified by antibody response 1 mo after 2-dose mRNA vaccine series
Sero-response after 3 mo
Negative Low-positive High-positive
Sero-response after 1 mo Negative 96 (70) 31 (23) 9 (7)
Low-positive 5 (7) 35 (47) 35 (47)
High-positive 1 (1) 18 (19) 75 (80)
Negative sero-response was defined per manufacturer data as EUROIMMUN anti-S1 IgG <1.1 arbitrary units (AU) or Roche Elecsys anti-RBD pan Ig <0.8 units/mL. Low-positive sero-response was defined as anti-S1 IgG 1.1–4 AU or anti-RBD pan Ig 0.8–50 units/mL. High-positive sero-response was defined as anti-S1 IgG >4 AU or anti-RBD pan Ig >50 units/mL.
IgG, immunoglobulin G; RBD, receptorbinding domain; SARS-CoV-2, severe acute respiratory syndrome coronavirus 2.

Among those with any positive titer after dose 2, median (IQR [range]) change between 1 mo and 3 mo antibody levels was 0 (0–75 [−166.8.1 to 247.12]; Roche) and −1.19 (−2.04 to 0.55, [−4.2 to 3.02]; EUROIMMUN). Among those with low-positive titers at 1 mo, 35/75 (47%) remained in the low-positive range and 35/75 (47%) became high-positive. Among those with high-positive titers at 1 mo, 18/94 (19%) dropped to the low-positive range and 75/94 (80%) remained high-positive.

In this study of antibody kinetics and durability following SARS-CoV-2 mRNA vaccination, 43% experienced an increase antibody titer, 35% decreased, and 21% remained stable between 1 and 3 mo postvaccination. Though only a small minority (4%) who had detectable antibody at 1 mo fell below the threshold of detectability at 3 mo, 19% with high-positive titers at 1 mo dropped to low-positive.

In the mRNA-1273 trial, binding antibody levels declined slightly over time, but remained elevated at 3 mo after the completion of the 2-dose series.1 It is unknown if antibody decline over time results in higher risk of SARS-CoV-2 infection; however, these results raise the suggestion that additional booster dosing may help augment lower antibody responses in transplant recipients.

This study is limited by convenience sampling, lack of immunocompetent control group, and lack of exploration of neutralizing antibody and memory B immune response. Also, despite clinical screening for incident symptomatic coronavirus disease 2019, antinucleocapsid testing was not performed, precluding analysis of asymptomatic exposure.

In conclusion, we found that antispike antibody sero-response 3 mo following the mRNA vaccine series was largely stable. Understanding longitudinal kinetics of antibody decline among transplant recipients in the context of thresholds for protection may inform need and timing for booster vaccinations.

REFERENCES

1. Widge AT, Rouphael NG, Jackson LA, et al.; mRNA-1273 Study Group. Durability of responses after SARS-CoV-2 mRNA-1273 vaccination. N Engl J Med. 2021;384:80–82.
2. Patel MM, Thornburg NJ, Stubblefield WB, et al. Change in antibodies to SARS-CoV-2 over 60 days among health care personnel in Nashville, tennessee. JAMA. 2020;324:1781–1782.
3. Pegu A, O’Connell S, Schmidt SD, et al. Durability of mRNA-1273-induced antibodies against SARS-CoV-2 variants. bioRxiv. Preprint posted online May 16, 2021. doi:10.1101/2021.05.13.444010
4. Boyarsky BJ, Werbel WA, Avery RK, et al. Immunogenicity of a single dose of SARS-CoV-2 messenger RNA vaccine in solid organ transplant recipients. JAMA. 2021;325:1784–1786.
5. Boyarsky BJ, Werbel WA, Avery RK, et al. Antibody response to 2-dose SARS-CoV-2 mRNA vaccine series in solid organ transplant recipients. JAMA. 2021;325:2204–2206.
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