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Immune Response to Third Dose BNT162b2 COVID-19 Vaccine Among Kidney Transplant Recipients-A Prospective Study.

ABSTRACT: Immune response to two SARS-CoV-2 mRNA vaccine doses among kidney transplant recipients (KTRs) is limited. We aimed to evaluate humoral and cellular response to a third BNT162b2 dose. In this prospective study, 190 KTRs were evaluated before and ∼3 weeks after the third vaccine dose. The primary outcomes were anti-spike antibody level >4160 AU/ml (neutralization-associated cutoff) and any seropositivity. Univariate and multivariate analyses were conducted to identify variables associated with antibody response. T-cell response was evaluated in a subset of participants. Results were compared to a control group of 56 healthcare workers. Among KTRs, we found a seropositivity rate of 70% (133/190) after the third dose (37%, 70/190, after the second vaccine dose); and 27% (52/190) achieved levels above 4160 AU/ml after the third dose, compared to 93% of controls. Variables associated with antibody response included higher antibody levels after the second dose (odds ratio [OR] 30.8 per log AU/ml, 95% confidence interval [CI]11-86.4, p < 0.001); and discontinuation of antimetabolite prior to vaccination (OR 9.1,95% CI 1.8-46.5, p = 0.008). T-cell response was demonstrated in 13% (7/53). In conclusion, third dose BNT162b2 improved immune response among KTRs, however 30% still remained seronegative. Pre-vaccination temporary immunosuppression reduction improved antibody response.

SUBMITTER: Yahav D

PROVIDER: S-EPMC9068869 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature

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Immune Response to Third Dose BNT162b2 COVID-19 Vaccine Among Kidney Transplant Recipients-A Prospective Study.

Yahav Dafna D Rahamimov Ruth R Mashraki Tiki T Ben-Dor Naomi N Steinmetz Tali T Agur Timna T Zingerman Boris B Herman-Edelstein Michal M Lichtenberg Shelly S Ben-Zvi Haim H Bar-Haim Erez E Cohen Hila H Rotem Shahar S Elia Uri U Margalit Ili I Zvi Benaya Rozen BR

Transplant international : official journal of the European Society for Organ Transplantation 20220421

Immune response to two SARS-CoV-2 mRNA vaccine doses among kidney transplant recipients (KTRs) is limited. We aimed to evaluate humoral and cellular response to a third BNT162b2 dose. In this prospective study, 190 KTRs were evaluated before and ∼3 weeks after the third vaccine dose. The primary outcomes were anti-spike antibody level >4160 AU/ml (neutralization-associated cutoff) and any seropositivity. Univariate and multivariate analyses were conducted to identify variables associated with an ...[more]

PMID: 35529596

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Project description:Background & aimsImmune responses of solid organ transplant recipients to 2 doses of the BNT162b2 mRNA anti-SARS-CoV-2 vaccine are impaired. The immunogenicity and safety of a third dose among liver transplant (LT) recipients are unknown. This work aimed to evaluate the immune response of LT recipients to a third dose of the BNT162b2 mRNA vaccine.MethodsConsecutive LT recipients (n = 61) in follow-up at Sheba Medical Center were included. Receptor binding domain (RBD) IgG, neutralizing antibody (NA) titers, and T-cell levels before and 21-28 days after a third vaccine dose were determined. Adverse effects after the third dose were monitored.ResultsThe median age of LT recipients was 65 years and 57.4% were male. The humoral immune response rate improved significantly, with 56% of patients showing a response before the third vaccine dose compared to 98% after the third dose. The cellular response in 12 evaluated patients improved significantly (p = 0.008). The geometric mean of anti-RBD IgG levels, NA levels, and T-cell count also increased significantly after the third dose. NA titers after the third dose negatively correlated with age (p = 0.03), mycophenolate mofetil treatment (p = 0.005), and combined immunosuppression as opposed to calcineurin inhibitor monotherapy (p = 0.001). After the third dose, adverse effects were reported by 37% of recipients and were mostly mild (local pain and fatigue).ConclusionAfter a third BNT162b2 mRNA vaccine, the immune response improved significantly among LT recipients, without serious adverse effects. Further studies are needed to evaluate immune response durability and to determine the optimal number and schedule of booster vaccine doses.Lay summaryThe Pfizer-Biotech BNT162b2SARS-CoV-2 vaccine induced significant immunity among liver transplant recipients after a third dose. The majority of the patients developed sufficient levels of both humoral and cellular immune responses. Factors that predict non-response were older age and immunosuppressive medications.

Project description:Abstract BACKGROUND AND AIMS Mortality due to SARS-COV-2 infection in hemodialysis (HD) patients and kidney transplant recipients(KTRs) is high. Despite increased rates of administration of two doses of mRNA vaccines among these vulnerable populations, the adequacy of the respective generated immune responses is reported lower than general population, especially in KTRs. A third booster dose has been officially recommended in these immunocompromised patients while the humoral and cellular immune responses to SARS-COV-2 vaccination remains to be elucidated in HD patients and KTRs. The aim of our study was to investigate the antibody (Ab) response status together with vaccine-induced alterations in circulating lymphocytes subsets, following the administration of three doses of the BNT162b2 vaccine in a cohort of maintenance HD patients and KTRs. METHOD The initial cohort of this prospective study (ClinicalTrials.gov, NCT04932876) included 34 HD patients and 54 KTRs who received two doses of the BNT162b2 (Pfizer–BioNTech). Of this cohort, 24 HD patients and 30 KTRs, who remained free of SARS-CoV2 infection and receive a third dose 6 months after the second dose, were finally analyzed. Lymphocyte subpopulations, including B cells, CD4+and CD8+T cells as well as naïve and memory T lymphocytes subpopulations among others, were analyzed by flow cytometry at four time points, before vaccination (T0), before the second dose (T1), 2 weeks after the second dose (T2) and 2–3 weeks after the third dose (T3). The anti-SARS-CoV2 antibody (Ab) response was assessed by using the ARCHITECT IgG II Quant test (Abbott). Titers >50 arbitrary units (AU)/mL were considered positive for seroconversion at T1 and at T2 and T3. RESULTS Of the initial cohort 31 HD patients (91.8%) and 16 KTRs (29.6%) became seropositive at T2. Of the final cohort (24 HD and 30 KTRs), almost all HD patients (23, 96%) became seropositive since T2 and this finding remained at T3 (Figure 1). In KTRs the percentage of responders was doubled between T2 and T3, T2 9 KTRs (30%) versus T3 18 KTRs (60%) (Figure 1). KTRs who developed Ab at T1 ``respond'' better to the third dose, maximizing the levels of Ab. HD patients who became seropositive at T1 displayed higher CD19+B lymphocytes compared with their seronegative HD counterparts. In HD patients, a positive correlation was established between CD19+B cells counts and Ab titers at all time-points (P < 0.001). In KTRs, Ab at T1 showed an inverse correlation with T+B+NK at T1 (P = 0.006). T2-Ab showed inverse correlation with CD45RA+CD45RO at T0 (P = 0.01) and with CD3+at T3 (P = 0.02). T3-Ab showed positive correlation with CD3+CD16+56+at T2 (P = 0.003) and with CD3-CD16+56+at T3 (P = 0.01). CD19+at T3 correlated positively with Ab at T1 and T3 (P = 0.003 and P = 0.03, respectively). CONCLUSION Our study confirms the improved immunogenicity after the third dose of BNT162b2 vaccine in KTRs. The positive correlation between CD19+B cells and Ab in both groups of patients, more stable and constant in HD patients in comparison with KTR, possibly reflects successful humoral immunity. However, a big proportion of kidney patients remain at high risk for COVID-19 infection considering the new more transmissible variants such as the Omicron variant.

Dataset Information

Immune Response to Third Dose BNT162b2 COVID-19 Vaccine Among Kidney Transplant Recipients-A Prospective Study.

Publications

Immune Response to Third Dose BNT162b2 COVID-19 Vaccine Among Kidney Transplant Recipients-A Prospective Study.

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