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Interdependencies of cellular and humoral immune responses in heterologous and homologous SARS-CoV-2 vaccination.
Allergy. 2022 08; 77(8):2381-2392.A

Abstract

BACKGROUND

Homologous and heterologous SARS-CoV-2 vaccinations yield different spike protein-directed humoral and cellular immune responses. This study aimed to explore their currently unknown interdependencies.

METHODS

COV-ADAPT is a prospective, observational cohort study of 417 healthcare workers who received vaccination with homologous ChAdOx1 nCoV-19, homologous BNT162b2 or with heterologous ChAdOx1 nCoV-19/BNT162b2. We assessed humoral (anti-spike-RBD-IgG, neutralizing antibodies, and avidity) and cellular (spike-induced T-cell interferon-γ release) immune responses in blood samples up to 2 weeks before (T1) and 2-12 weeks following secondary immunization (T2).

RESULTS

Initial vaccination with ChAdOx1 nCoV-19 resulted in lower anti-spike-RBD-IgG compared with BNT162b2 (70 ± 114 vs. 226 ± 279 BAU/ml, p < .01) at T1. Booster vaccination with BNT162b2 proved superior to ChAdOx1 nCoV-19 at T2 (anti-spike-RBD-IgG: ChAdOx1 nCoV-19/BNT162b2 2387 ± 1627 and homologous BNT162b2 3202 ± 2184 vs. homologous ChAdOx1 nCoV-19 413 ± 461 BAU/ml, both p < .001; spike-induced T-cell interferon-γ release: ChAdOx1 nCoV-19/BNT162b2 5069 ± 6733 and homologous BNT162b2 4880 ± 7570 vs. homologous ChAdOx1 nCoV-19 1152 ± 2243 mIU/ml, both p < .001). No significant differences were detected between BNT162b2-boostered groups at T2. For ChAdOx1 nCoV-19, no booster effect on T-cell activation could be observed. We found associations between anti-spike-RBD-IgG levels (ChAdOx1 nCoV-19/BNT162b2 and homologous BNT162b2) and T-cell responses (homologous ChAdOx1 nCoV-19 and ChAdOx1 nCoV-19/BNT162b2) from T1 to T2. Additionally, anti-spike-RBD-IgG and T-cell response were linked at both time points (all groups combined). All regimes yielded neutralizing antibodies and increased antibody avidity at T2.

CONCLUSIONS

Interdependencies between humoral and cellular immune responses differ between common SARS-CoV-2 vaccination regimes. T-cell activation is unlikely to compensate for poor humoral responses.

Authors+Show Affiliations

Department of Dermatology, Venereology and Allergology, University Medical Center Göttingen, Göttingen, Germany.Institute of Medical Microbiology and Virology, University Medical Center Göttingen, Göttingen, Germany.Department of Dermatology, Venereology and Allergology, University Medical Center Göttingen, Göttingen, Germany. Lower Saxony Institute of Occupational Dermatology, University Medical Center Göttingen, Göttingen, Germany.Department of Dermatology, Venereology and Allergology, University Medical Center Göttingen, Göttingen, Germany.Department of Dermatology, Venereology and Allergology, University Medical Center Göttingen, Göttingen, Germany.Institute for Clinical Chemistry, University Medical Center Göttingen, Göttingen, Germany.Institute for Clinical Chemistry, University Medical Center Göttingen, Göttingen, Germany.Department of Dermatology, Venereology and Allergology, University Medical Center Göttingen, Göttingen, Germany.Department of Dermatology, Venereology and Allergology, University Medical Center Göttingen, Göttingen, Germany.Department of Dermatology, University of Münster, Münster, Germany.Department of Dermatology, University of Münster, Münster, Germany.Department of Dermatology, Venereology and Allergology, University Medical Center Göttingen, Göttingen, Germany.Institute for Clinical Chemistry, University Medical Center Göttingen, Göttingen, Germany. Department of Hematology and Medical Oncology, University Medical Center Göttingen, Göttingen, Germany.Institute for Clinical Chemistry, University Medical Center Göttingen, Göttingen, Germany. Division Vascular Signaling and Cancer, German Cancer Research Center (DKFZ), Heidelberg, Germany.Institute of Medical Microbiology and Virology, University Medical Center Göttingen, Göttingen, Germany.Department of Medical Statistics, University Medical Center Göttingen, Göttingen, Germany.Institute of Medical Microbiology and Virology, University Medical Center Göttingen, Göttingen, Germany. Institute of Medical Microbiology and Hospital Hygiene, Medical Faculty, Otto-von-Guericke University Magdeburg, Magdeburg, Germany.Institute for Clinical Chemistry, University Medical Center Göttingen, Göttingen, Germany.Department of Dermatology, Venereology and Allergology, University Medical Center Göttingen, Göttingen, Germany. Department of Dermatology, University of Münster, Münster, Germany.

Pub Type(s)

Journal Article
Observational Study
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

35124800

Citation

Hollstein, Moritz M., et al. "Interdependencies of Cellular and Humoral Immune Responses in Heterologous and Homologous SARS-CoV-2 Vaccination." Allergy, vol. 77, no. 8, 2022, pp. 2381-2392.
Hollstein MM, Münsterkötter L, Schön MP, et al. Interdependencies of cellular and humoral immune responses in heterologous and homologous SARS-CoV-2 vaccination. Allergy. 2022;77(8):2381-2392.
Hollstein, M. M., Münsterkötter, L., Schön, M. P., Bergmann, A., Husar, T. M., Abratis, A., Eidizadeh, A., Schaffrinski, M., Zachmann, K., Schmitz, A., Holsapple, J. S., Stanisz-Bogeski, H., Schanz, J., Fischer, A., Groβ, U., Leha, A., Zautner, A. E., Schnelle, M., & Erpenbeck, L. (2022). Interdependencies of cellular and humoral immune responses in heterologous and homologous SARS-CoV-2 vaccination. Allergy, 77(8), 2381-2392. https://doi.org/10.1111/all.15247
Hollstein MM, et al. Interdependencies of Cellular and Humoral Immune Responses in Heterologous and Homologous SARS-CoV-2 Vaccination. Allergy. 2022;77(8):2381-2392. PubMed PMID: 35124800.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Interdependencies of cellular and humoral immune responses in heterologous and homologous SARS-CoV-2 vaccination. AU - Hollstein,Moritz M, AU - Münsterkötter,Lennart, AU - Schön,Michael P, AU - Bergmann,Armin, AU - Husar,Thea M, AU - Abratis,Anna, AU - Eidizadeh,Abass, AU - Schaffrinski,Meike, AU - Zachmann,Karolin, AU - Schmitz,Anne, AU - Holsapple,Jason S, AU - Stanisz-Bogeski,Hedwig, AU - Schanz,Julie, AU - Fischer,Andreas, AU - Groβ,Uwe, AU - Leha,Andreas, AU - Zautner,Andreas E, AU - Schnelle,Moritz, AU - Erpenbeck,Luise, Y1 - 2022/02/16/ PY - 2022/01/17/revised PY - 2021/12/23/received PY - 2022/01/23/accepted PY - 2022/2/7/pubmed PY - 2022/8/10/medline PY - 2022/2/6/entrez KW - BNT162b2 KW - ChAdOx1 nCoV-19 KW - SARS-CoV-2 KW - immune response KW - vaccination SP - 2381 EP - 2392 JF - Allergy JO - Allergy VL - 77 IS - 8 N2 - BACKGROUND: Homologous and heterologous SARS-CoV-2 vaccinations yield different spike protein-directed humoral and cellular immune responses. This study aimed to explore their currently unknown interdependencies. METHODS: COV-ADAPT is a prospective, observational cohort study of 417 healthcare workers who received vaccination with homologous ChAdOx1 nCoV-19, homologous BNT162b2 or with heterologous ChAdOx1 nCoV-19/BNT162b2. We assessed humoral (anti-spike-RBD-IgG, neutralizing antibodies, and avidity) and cellular (spike-induced T-cell interferon-γ release) immune responses in blood samples up to 2 weeks before (T1) and 2-12 weeks following secondary immunization (T2). RESULTS: Initial vaccination with ChAdOx1 nCoV-19 resulted in lower anti-spike-RBD-IgG compared with BNT162b2 (70 ± 114 vs. 226 ± 279 BAU/ml, p < .01) at T1. Booster vaccination with BNT162b2 proved superior to ChAdOx1 nCoV-19 at T2 (anti-spike-RBD-IgG: ChAdOx1 nCoV-19/BNT162b2 2387 ± 1627 and homologous BNT162b2 3202 ± 2184 vs. homologous ChAdOx1 nCoV-19 413 ± 461 BAU/ml, both p < .001; spike-induced T-cell interferon-γ release: ChAdOx1 nCoV-19/BNT162b2 5069 ± 6733 and homologous BNT162b2 4880 ± 7570 vs. homologous ChAdOx1 nCoV-19 1152 ± 2243 mIU/ml, both p < .001). No significant differences were detected between BNT162b2-boostered groups at T2. For ChAdOx1 nCoV-19, no booster effect on T-cell activation could be observed. We found associations between anti-spike-RBD-IgG levels (ChAdOx1 nCoV-19/BNT162b2 and homologous BNT162b2) and T-cell responses (homologous ChAdOx1 nCoV-19 and ChAdOx1 nCoV-19/BNT162b2) from T1 to T2. Additionally, anti-spike-RBD-IgG and T-cell response were linked at both time points (all groups combined). All regimes yielded neutralizing antibodies and increased antibody avidity at T2. CONCLUSIONS: Interdependencies between humoral and cellular immune responses differ between common SARS-CoV-2 vaccination regimes. T-cell activation is unlikely to compensate for poor humoral responses. SN - 1398-9995 UR - https://www.unboundmedicine.com/medline/citation/35124800/Interdependencies_of_cellular_and_humoral_immune_responses_in_heterologous_and_homologous_SARS_CoV_2_vaccination_ DB - PRIME DP - Unbound Medicine ER -