We previously reported overall stability of SARS-CoV-2 anti-spike antibodies in vaccinated solid organ transplant recipients (SOTRs) three months after receiving two doses of BNT162b2 or mRNA-1237 vaccines 1. In the interim, the FDA fully authorized the BNT162b2 vaccine for people 16 years and older and expanded Emergency Use Authorization to allow for a third dose in immunocompromised individuals 2. The CDC currently recommends an additional dose for mild to moderately immunocompromised patients at least 28 days following mRNA dose two, but optimal timing for booster doses in SOTRs has not been determined 3. Declines in SARS-CoV-2 antibodies over time were observed three months post-vaccination in the general population 4, but antibody longevity in SOTRs is unknown. We measured anti-spike antibody titers in SOTRs for 6 months after completing a two-dose mRNA series. The assays, (previously described) (1), were performed 1, 3, and 6 months after dose two. Participants provided informed consent, and this study was approved by the Johns Hopkins Institutional Review Board (IRB00248540).
312 SOTRs received a second mRNA vaccine between January 6th, 2021, and April 14th, 2021. None reported a third dose during the study period. Median (interquartile range, IQR) age was 62 (48, 69) years, 65% were female, and 92% were white. 156 (50%) were kidney transplant recipients, median time from transplant was 7.2 (3.3, 14.3) years. Regarding immunosuppression, 224 (72%) were taking an anti-metabolite, 250/312 (80%) tacrolimus, and 169/312 (54%) steroids. At median 29 (28-32) days after dose 2, 198/312 (63%) patients had positive titers; at median 91 (89, 94) days post-dose 2, 178/246 (72%) had positive titers, and at 181 (174, 186) days after dose 2, 227/312 (72%) had positive titers. 43/114 (38%) patients with negative 1-month titers developed positive titers by 6 months; 12/43 had high-positive titer levels at 6 months. Among 198 patients with positive titers at 1 month, 14 (7.1%) fell below the threshold of positivity at 6 months (Table 1). The 4 patients whose titers fell from high-positive to negative experienced this by 3 months.
Table 1.
Anti-spike antibody sero-response 6 months after receiving second mRNA SARS-CoV-2 vaccine, stratified by antibody response 1 month after receiving second mRNA vaccine. N (%)
| Sero-response after 6 months | |||||
|---|---|---|---|---|---|
| Negative | Low-Positive | High-Positive | Totals (1 month) |
||
| Sero-response after 1 month | Negative | 71 (62.3) | 31 (27.2) | 12 (10.5) | 114 (36.5) |
| Low-Positive | 9 (12.0) | 24 (32.0) | 42 (56.0) | 75 (24.0) | |
| High-Positive | 5 (4.1) | 23 (18.7) | 95 (77.2) | 123 (39.4) | |
| Totals (6 month) | 85 (27.2) | 77 (25.6) | 140 (46.5) | 312 (100) | |
In this study of SARS-CoV-2 antibody kinetics and durability, 73% of SOTRs had positive antibody titers 6 months following mRNA vaccination; titers increased in 27% over 6 months, decreased in 12%, and remained stable in 61% of patients over 6 months. This differs from healthy individuals, who had overall stability of antibody positivity over 6 months 5. It is unknown what degree of antibody titer decline confers increased risk of breakthrough infection.
This study is limited by the lack of an immunocompetent control group, unknown correlation with neutralizing antibody, and absence of anti-nucleocapsid testing, prohibiting analysis of asymptomatic exposure. The presence of COVID infection would likely increase antibody levels.
In conclusion, anti-spike antibody levels against SARS-CoV-2 in SOTRs are relatively stable 6 months after receipt of the second vaccine. Further investigation into the effect of booster vaccination on antibody titers, as well as understanding B and T cell responses against emerging variants of concern, are needed to better inform timing of booster vaccination.
ACKNOWLEDGEMENTS
The authors thank the Johns Hopkins transplant vaccine study team, including Mayan Teles, BS; Julia Lopez, BS; Michael T. Ou, BS; Ross S. Greenberg, BA; Jake A. Ruddy, BS; Muhammad Asad Munir, MBBS; Michelle R. Krach, MS; Iulia Barbur, BSE. They also thank Andrew H. Karaba, MD, PhD; and Ms. Yolanda Eby for project support and guidance.
FUNDING/GRANT/AWARD INFORMATION
This research was made possible with the generous support of the Ben-Dov family. This work was supported by grants T32DK007713 (Dr. Alejo), The ASTS Fryer Resident Scientist Award (Dr. Mitchell), F32DK124941 (Dr. Boyarsky), K01DK114388-03 (Dr. Levan), K01DK101677 (Dr. Massie), and K23DK115908 (Dr. Garonzik-Wang) from the National Institute of Diabetes and Digestive and Kidney Diseases; grant K24AI144954 (Dr. Segev) from the National Institute of Allergy and Infectious Disease; grant K23AI157893 (Dr. Werbel). The analyses described here are the responsibility of the authors alone and do not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products or organizations imply endorsement by the US government.
ABBREVIATIONS
- CDC
Centers for Disease Control and Prevention
- FDA
U.S. Food & Drug Administration
- mRNA
messenger RNA
- J&J
Johnson and Johnson/Janssen viral vector vaccine
- SOTRs
Solid Organ Transplant Recipients
Footnotes
DISCLOSURE
DL Segev has the following financial disclosures: consulting and speaking honoraria from Sanofi, Novartis, CLS Behring, Jazz Pharmaceuticals, Veloxis, Mallinckrodt, Thermo Fisher Scientific. Dr. Levan is the Social Media Editor for Transplantation. Dr. Avery has grant/research support from Aicuris, Astellas, Chimerix, Merck, Oxford Immunotec, Qiagen, and Takeda/Shire. The remaining authors of this manuscript have no financial disclosures or conflicts of interest to disclose as described by Transplantation.
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