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Kinetics of cellular and humoral responses to third BNT162B2 COVID-19 vaccine over six months in heart transplant recipients - implications for the omicron variant.
J Heart Lung Transplant. 2022 10; 41(10):1417-1425.JH

Abstract

BACKGROUND

The durability of the immune response following the 3-dose BNT162b2 vaccination is unknown. The complexity of the situation is enhanced by the threat that highly transmissible variants may further accelerate the decline in the protection afforded by mRNA vaccines.

METHODS

One hundred and three 3-dose-vaccinated heart transplant recipients were longitudinally assessed for the kinetics of variant-specific neutralization (Cohort 1, n = 60) and SARS-CoV-2-specific-T-cell response (Cohort 2, n = 54) over 6 months. Neutralization and T-cell responses were compared between paired samples at 2 time points, using the Kruskal-Wallis test followed by Dunn's multiple comparison test for continuous variables and McNemar's test for dichotomous variables. The Bonferroni method of p values adjustment for multiple comparison was applied.

RESULTS

The third dose induced high neutralization of the wild-type virus and delta variant (geometric mean titer [GMT], 137.2 [95% CI, 84.8-221.9] and 80.6, [95% CI, 49.3-132.0], respectively), and to a lesser degree of the omicron variant (GMT, 10.3 [95% CI, 5.9-17.9]). At 6 months, serum neutralizing activity declined but was still high for the wild-type virus and for the delta variant (GMTs 38.1 [95% CI, 21.2-69.4], p = 0.011; and 28.9 [95% CI, 16.6-52.3], p = 0.022, respectively), but not for the omicron variant (GMT 5.9 [95% CI, 3.4-9.8], p = 0.463). The percentages of neutralizing sera against the wild-type virus, delta and omicron variants increased from 70%, 65%, and 38%, before the third dose, to 93% (p < 0.001), 88% (p < 0.001), and 48% (p = 0.021) at 3 weeks after, respectively; and remained high through the 6 months for the wild-type (80%, p = 0.06) and delta (77%, p = 0.102). The third dose induced the development of a sustained SARS-CoV-2-specific-T-cell population, which persisted through 6 months.

CONCLUSIONS

The third BNT162b2 dose elicited a durable SARS-CoV-2-specific T-cell response and induced effective and durable neutralization of the wild-type virus and the delta variant, and to a lesser degree of the omicron variant.

Authors+Show Affiliations

Leviev Cardiothoracic and Vascular Center, Sheba Medical Center, Israel; Sackler Faculty of Medicine, Tel Aviv University, Israel. Electronic address: Yael.Peled-Potashnik@sheba.health.gov.il.Sackler Faculty of Medicine, Tel Aviv University, Israel; General Management, Sheba Medical Center, Israel.Sackler Faculty of Medicine, Tel Aviv University, Israel; General Management, Sheba Medical Center, Israel.Sackler Faculty of Medicine, Tel Aviv University, Israel; Infectious Disease Unit, Sheba Medical Center, Israel.Central Virology Laboratory, Ministry of Health, Tel-Hashomer, Israel.Sackler Faculty of Medicine, Tel Aviv University, Israel; Central Virology Laboratory, Ministry of Health, Tel-Hashomer, Israel.Central Virology Laboratory, Ministry of Health, Tel-Hashomer, Israel.Leviev Cardiothoracic and Vascular Center, Sheba Medical Center, Israel; Sackler Faculty of Medicine, Tel Aviv University, Israel.Leviev Cardiothoracic and Vascular Center, Sheba Medical Center, Israel; Sackler Faculty of Medicine, Tel Aviv University, Israel.Leviev Cardiothoracic and Vascular Center, Sheba Medical Center, Israel; Sackler Faculty of Medicine, Tel Aviv University, Israel.Leviev Cardiothoracic and Vascular Center, Sheba Medical Center, Israel; Sackler Faculty of Medicine, Tel Aviv University, Israel.Leviev Cardiothoracic and Vascular Center, Sheba Medical Center, Israel; Sackler Faculty of Medicine, Tel Aviv University, Israel.Leviev Cardiothoracic and Vascular Center, Sheba Medical Center, Israel; Sackler Faculty of Medicine, Tel Aviv University, Israel.Sackler Faculty of Medicine, Tel Aviv University, Israel; Central Virology Laboratory, Ministry of Health, Tel-Hashomer, Israel.Cedars-Sinai Heart Institute and David Geffen School of Medicine at the University of California, Los Angeles, California.Sackler Faculty of Medicine, Tel Aviv University, Israel; Central Virology Laboratory, Ministry of Health, Tel-Hashomer, Israel.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

35710484

Citation

Peled, Yael, et al. "Kinetics of Cellular and Humoral Responses to Third BNT162B2 COVID-19 Vaccine Over Six Months in Heart Transplant Recipients - Implications for the Omicron Variant." The Journal of Heart and Lung Transplantation : the Official Publication of the International Society for Heart Transplantation, vol. 41, no. 10, 2022, pp. 1417-1425.
Peled Y, Afek A, Kreiss Y, et al. Kinetics of cellular and humoral responses to third BNT162B2 COVID-19 vaccine over six months in heart transplant recipients - implications for the omicron variant. J Heart Lung Transplant. 2022;41(10):1417-1425.
Peled, Y., Afek, A., Kreiss, Y., Rahav, G., Nemet, I., Kliker, L., Indenbaum, V., Ram, E., Lavee, J., Segev, A., Matezki, S., Sternik, L., Raanani, E., Lustig, Y., Patel, J. K., & Mandelboim, M. (2022). Kinetics of cellular and humoral responses to third BNT162B2 COVID-19 vaccine over six months in heart transplant recipients - implications for the omicron variant. The Journal of Heart and Lung Transplantation : the Official Publication of the International Society for Heart Transplantation, 41(10), 1417-1425. https://doi.org/10.1016/j.healun.2022.05.014
Peled Y, et al. Kinetics of Cellular and Humoral Responses to Third BNT162B2 COVID-19 Vaccine Over Six Months in Heart Transplant Recipients - Implications for the Omicron Variant. J Heart Lung Transplant. 2022;41(10):1417-1425. PubMed PMID: 35710484.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Kinetics of cellular and humoral responses to third BNT162B2 COVID-19 vaccine over six months in heart transplant recipients - implications for the omicron variant. AU - Peled,Yael, AU - Afek,Arnon, AU - Kreiss,Yitshak, AU - Rahav,Galia, AU - Nemet,Ital, AU - Kliker,Limor, AU - Indenbaum,Victoria, AU - Ram,Eilon, AU - Lavee,Jacob, AU - Segev,Amit, AU - Matezki,Shlomi, AU - Sternik,Leonid, AU - Raanani,Ehud, AU - Lustig,Yaniv, AU - Patel,Jignesh K, AU - Mandelboim,Michal, Y1 - 2022/05/24/ PY - 2022/01/30/received PY - 2022/04/21/revised PY - 2022/05/20/accepted PY - 2022/6/17/pubmed PY - 2022/10/5/medline PY - 2022/6/16/entrez KW - BNT162b2 vaccine KW - SARS-CoV-2-specificT-cell KW - heart transplantation KW - neutralization KW - omicron SP - 1417 EP - 1425 JF - The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation JO - J Heart Lung Transplant VL - 41 IS - 10 N2 - BACKGROUND: The durability of the immune response following the 3-dose BNT162b2 vaccination is unknown. The complexity of the situation is enhanced by the threat that highly transmissible variants may further accelerate the decline in the protection afforded by mRNA vaccines. METHODS: One hundred and three 3-dose-vaccinated heart transplant recipients were longitudinally assessed for the kinetics of variant-specific neutralization (Cohort 1, n = 60) and SARS-CoV-2-specific-T-cell response (Cohort 2, n = 54) over 6 months. Neutralization and T-cell responses were compared between paired samples at 2 time points, using the Kruskal-Wallis test followed by Dunn's multiple comparison test for continuous variables and McNemar's test for dichotomous variables. The Bonferroni method of p values adjustment for multiple comparison was applied. RESULTS: The third dose induced high neutralization of the wild-type virus and delta variant (geometric mean titer [GMT], 137.2 [95% CI, 84.8-221.9] and 80.6, [95% CI, 49.3-132.0], respectively), and to a lesser degree of the omicron variant (GMT, 10.3 [95% CI, 5.9-17.9]). At 6 months, serum neutralizing activity declined but was still high for the wild-type virus and for the delta variant (GMTs 38.1 [95% CI, 21.2-69.4], p = 0.011; and 28.9 [95% CI, 16.6-52.3], p = 0.022, respectively), but not for the omicron variant (GMT 5.9 [95% CI, 3.4-9.8], p = 0.463). The percentages of neutralizing sera against the wild-type virus, delta and omicron variants increased from 70%, 65%, and 38%, before the third dose, to 93% (p < 0.001), 88% (p < 0.001), and 48% (p = 0.021) at 3 weeks after, respectively; and remained high through the 6 months for the wild-type (80%, p = 0.06) and delta (77%, p = 0.102). The third dose induced the development of a sustained SARS-CoV-2-specific-T-cell population, which persisted through 6 months. CONCLUSIONS: The third BNT162b2 dose elicited a durable SARS-CoV-2-specific T-cell response and induced effective and durable neutralization of the wild-type virus and the delta variant, and to a lesser degree of the omicron variant. SN - 1557-3117 UR - https://www.unboundmedicine.com/medline/citation/35710484/Kinetics_of_cellular_and_humoral_responses_to_third_BNT162B2_COVID_19_vaccine_over_six_months_in_heart_transplant_recipients___implications_for_the_omicron_variant_ DB - PRIME DP - Unbound Medicine ER -