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

Alejo, Jennifer L; Mitchell, Jonathan; Chiang, Teresa Po‐Yu; Abedon, Aura T; Sidoti, Carolyn N; Boyarsky, Brian J.; Avery, Robin K.; Tobian, Aaron A.R.; Levan, Macey L; Warren, Daniel; Massie, Allan B.; Garonzik-Wang, Jacqueline M; Segev, Dorry L.; Werbel, William A

doi:10.1097/tp.0000000000003975

Cited by 18 publications

(18 citation statements)

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“…The study found 67% of SOT recipients to have anti-spike IgG antibodies in 4 months after the first dose ( 35 ). Alejo et al ( 27 ) reported data with 7 months of follow-up after the first dose of BNT162b2 or mRNA-1273 vaccine and found 72% of SOT recipients to have anti-spike IgG antibodies. We found 36% of SOT recipients to have a positive humoral response 6 months after the first vaccine dose.…”

Section: Discussionmentioning

confidence: 99%

“…Importantly, while inferior immune responses in SOT recipients have been reported, little is known about risk factors for humoral and cellular non-response ( 5 , 6 , 10 – 18 , 27 , 34 , 35 ). We found increasing age, being less than 1 year from transplantation, use of mycophenolate or corticosteroids, being kidney or lung transplant recipient, and de novo non-skin cancer to be associated with humoral non-response 6 months after the first vaccination.…”

Section: Discussionmentioning

confidence: 99%

“…It has been shown that antibodies after both SARS-CoV-2 infection and vaccination decline over time in immunocompetent populations (24)(25)(26). However, to date, there is only one report on the kinetics of antibodies after vaccination in SOT recipients with 6 months of follow-up (27) without assessment of neutralizing capacity of antibodies, cellular immunity, and a control group. To provide further knowledge on immune responses to the BNT162b2 vaccine in SOT recipients, we aimed to investigate the antibody responses in the first 6 months after vaccination with two doses of BNT162b2 in a large cohort of SOT recipients and compare the antibody responses to that in healthy controls.…”

Section: Introductionmentioning

confidence: 99%

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Decline in Antibody Concentration 6 Months After Two Doses of SARS-CoV-2 BNT162b2 Vaccine in Solid Organ Transplant Recipients and Healthy Controls

et al. 2022

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BackgroundPrevious studies have indicated inferior responses to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) vaccination in solid organ transplant (SOT) recipients. We examined the development of anti-receptor-binding domain (RBD) immunoglobulin G (IgG) after two doses of BNT162b2b in SOT recipients 6 months after vaccination and compared to that of immunocompetent controls.MethodsWe measured anti-RBD IgG after two doses of BNT162b2 in 200 SOT recipients and 200 matched healthy controls up to 6 months after first vaccination. Anti-RBD IgG concentration and neutralizing capacity of antibodies were measured at first and second doses of BNT162b2 and 2 and 6 months after the first dose. T-cell responses were measured 6 months after the first dose.ResultsIn SOT recipients, geometric mean concentration (GMC) of anti-RBD IgG increased from first to second dose (1.14 AU/ml, 95% CI 1.08–1.24 to 11.97 AU/ml, 95% CI 7.73–18.77) and from second dose to 2 months (249.29 AU/ml, 95% CI 153.70–385.19). Six months after the first vaccine, anti-RBD IgG declined (55.85 AU/ml, 95% CI 36.95–83.33). At all time points, anti-RBD IgG was lower in SOT recipients than that in controls. Fewer SOT recipients than controls had a cellular response (13.1% vs. 59.4%, p < 0.001). Risk factors associated with humoral non-response included age [relative risk (RR) 1.23 per 10-year increase, 95% CI 1.11–1.35, p < 0.001], being within 1 year from transplantation (RR 1.55, 95% CI 1.30–1.85, p < 0.001), treatment with mycophenolate (RR 1.54, 95% CI 1.09–2.18, p = 0.015), treatment with corticosteroids (RR 1.45, 95% CI 1.10–1.90, p = 0.009), kidney transplantation (RR 1.70, 95% CI 1.25–2.30, p = 0.001), lung transplantation (RR 1.63, 95% CI 1.16–2.29, p = 0.005), and de novo non-skin cancer comorbidity (RR 1.52, 95% CI, 1.26–1.82, p < 0.001).ConclusionImmune responses to BNT162b2 are inferior in SOT recipients compared to healthy controls, and studies aiming to determine the clinical impact of inferior vaccine responses are warranted.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Decline in Antibody Concentration 6 Months After Two Doses of SARS-CoV-2 BNT162b2 Vaccine in Solid Organ Transplant Recipients and Healthy Controls

et al. 2022

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“…Regarding patients who were seronegative and turned seropositive, we cannot rule out a delayed antibody response for SOT recipients, as also suggested by the two studies described above [ 25 , 26 ]. Peak antibody response has been previously demonstrated at between Day 15 and 45 after natural infection [ 17 , 22 ].…”

Section: Discussionmentioning

confidence: 96%

“…At ∼1 month following a second dose of mRNA vaccine, 63% were seropositive; at ∼3 months, 72% were seropositive; and at 6 months, 72% as well. Seven percent of seropositive patients at 1 month became seronegative at 6 months [ 26 ].…”

Section: Discussionmentioning

confidence: 99%

SARS-CoV-2 antibody dynamics among kidney transplant recipients 3 months after BNT162b2 vaccination: a prospective cohort study

Yelin

Rozen‐Zvi

Yahav

et al. 2022

Clinical Kidney Journal

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Data regarding immunogenicity of mRNA SARS-CoV-2 vaccines among kidney transplant recipients in the months following vaccination are lacking. We aimed to investigate humoral immune response at 3–4 months post vaccination among a cohort of kidney transplant recipients, compared to control group of dialysis patients. Anti-spike antibodies were tested at 1 and 3–4 months after vaccination. Of 259 kidney transplant recipients tested at median time of 110 days from second vaccine dose, 99 (38%) were seropositive, compared with 83% (101/122) control patients. Younger age, better renal function, and lower immunosuppression levels were associated with seropositivity. 14% (13/94) of participants seropositive at 1 month became seronegative at follow up, and 12% (18/165) became seropositive. The latter were mainly individuals with higher antibody levels at 1 month. Antibody levels at 3–4 months were significantly reduced in both study groups, though the decline was more pronounced in the control group. Kidney transplant recipients present poor antibody response to mRNA SARS-CoV-2 vaccination, with only 38% seropositive at 3–4 months. Nevertheless, the decay in antibody response over time is modest, and some patients may present delayed response, reaching adequate antibody levels at 3–4 months. Low seropositivity rates in this group call for investigating other immunization strategies.

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Third dose of the BNT162b2 vaccine in cardiothoracic transplant recipients: predictive factors for humoral response

et al. 2022

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Background We report the results of a prospective study on the immunogenicity of a 3rd dose of BNT162b2 in thoracic organ recipients with no or minimal response following a two-dose BNT162b2 vaccination scheme. Methods A total of 243 transplant recipients received a homologue 3rd dose. Anti-SARS-CoV2-immunoglobulins (IgGs) were monitored immediately before (T1), 4 weeks (T2) as well as 2 and 4 months after the 3rd dose. Neutralizing antibody capacity (NAC) was determined at T2. To reveal predictors for detectable humoral response, patients were divided into a positive response group (n = 129) based on the combined criteria of IgGs and NAC above the defined cut-offs at T2—and a group with negative response (n = 114), with both, IgGs and NAC beyond the cut-offs. Results The 3rd dose induced a positive humoral response in 53% of patients at T2, 47% were still non-responsive. Sero-positivity was significantly stronger in patients who presented with weak, but detectable IgGs already prior to the booster (T1), when compared to those with no detectable response at T1. Multivariable analysis identified age > 55 years, a period since transplantation < 2 years, a reduced glomerular filtration rate, a triple immunosuppressive regimen, and the use of tacrolimus and of mycophenolate as independent risk factors for lack of humoral response. Conclusions Our data indicate that a lack of immunogenicity is linked to the type and extent of maintenance immunosuppression. The necessity of the cumulative immunosuppressive regimen might individually be questioned and possibly be reduced to enhance the chance of an immune response following an additional booster dose.

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

Abstract: This research was made possible with the generous support of the Ben-Dov family. This work was supported by the ASTS Fryer Resident Scientist Award

Cited by 18 publications

References 3 publications

Decline in Antibody Concentration 6 Months After Two Doses of SARS-CoV-2 BNT162b2 Vaccine in Solid Organ Transplant Recipients and Healthy Controls

Decline in Antibody Concentration 6 Months After Two Doses of SARS-CoV-2 BNT162b2 Vaccine in Solid Organ Transplant Recipients and Healthy Controls

SARS-CoV-2 antibody dynamics among kidney transplant recipients 3 months after BNT162b2 vaccination: a prospective cohort study

Third dose of the BNT162b2 vaccine in cardiothoracic transplant recipients: predictive factors for humoral response

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