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Volume 13
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10.3390/vaccines13010003
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Article

Recombinant Anti-PF4 Antibodies Derived from Patients with Vaccine-Induced Immune Thrombocytopenia and Thrombosis (VITT) Facilitate Research and Laboratory Diagnosis of VITT

by
Luisa Müller
1,†,
Venkata A. S. Dabbiru
1,†,
Lucy Rutten
2,
Rinke Bos
2,
Roland Zahn
2,
Stefan Handtke
1,
Thomas Thiele
1,
Marta Palicio
3,
Olga Esteban
3,
Marta Broto
3,
Tom Paul Gordon
4,
Andreas Greinacher
1,
Jing Jing Wang
4,‡ and
Linda Schönborn
1,*,‡
1
Institut für Transfusionsmedizin, Universitätsmedizin Greifswald, 17489 Greifswald, Germany
2
Janssen Vaccines & Prevention BV, 2333 CN Leiden, The Netherlands
3
Werfen, Lliçà d’Amunt, 08186 Barcelona, Spain
4
Department of Immunology, College of Medicine and Public Health, Flinders University and SA Pathology, Bedford Park, Adelaide, SA 5042, Australia
*
Author to whom correspondence should be addressed.
†
These authors contributed equally to this work.
‡
These authors also contributed equally to this work.
Vaccines 2025, 13(1), 3; https://doi.org/10.3390/vaccines13010003
Submission received: 14 November 2024 / Revised: 13 December 2024 / Accepted: 20 December 2024 / Published: 24 December 2024
(This article belongs to the Special Issue Vaccine-Induced Immune Thrombotic Thrombocytopenia)
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Abstract

Background/Objectives: Adenoviral vector-based vaccines against COVID-19 rarely cause vaccine-induced immune thrombocytopenia and thrombosis (VITT), a severe adverse reaction caused by IgG antibodies against platelet factor 4 (PF4). To study VITT, patient samples are crucial but have become a scarce resource. Recombinant antibodies (rAbs) derived from VITT patient characteristic amino acid sequences of anti-PF4 IgG are an alternative to study VITT pathophysiology. Methods: Amino acid sequences of the variable region of immunoglobulin light and heavy chain of anti-PF4 IgG derived from VITT patients were obtained by mass spectrometry sequencing and rAbs were synthetized by reverse-engineering. Six different rAbs were produced: CR23003, CR23004, and CR23005 (from a patient vaccinated with Jcovden, Johnson & Johnson-Janssen (Beerse, Belgium)), CR22046, and CR22050 and CR22066 (from two different patients vaccinated with Vaxzevria, AstraZeneca (Cambridge, UK)). These rAbs were further characterized using anti-PF4 and anti-PF4/heparin IgG ELISAs, rapid anti-PF4 and anti-PF4/polyanion chemiluminescence assays, and PF4-induced platelet activation assay (PIPA) and their capacity to induce procoagulant platelets. Results: rAbs bound to PF4 alone, but not to PF4/polyanion complexes in rapid chemiluminescence assays. Chemiluminescence assays and both anti-PF4 IgG and anti-PF4 IgG/heparin ELISA showed concentration-dependent PF4 binding of all six rAbs, however, with different reactivities among them. PIPA showed a similar, concentration-dependent platelet activation pattern. rAbs varied in their reactivity and the majority of the tested rAbs were able to induce procoagulant platelets. Conclusions: The six rAbs derived from VITT patients reflect VITT-typical binding capacities and the ability to activate platelets. Therefore, these rAbs offer an attractive new option to study VITT pathophysiology.
Keywords: vaccine-induced immune thrombocytopenia and thrombosis (VITT); platelet-factor 4; recombinant antibodies; platelet activation assay vaccine-induced immune thrombocytopenia and thrombosis (VITT); platelet-factor 4; recombinant antibodies; platelet activation assay

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MDPI and ACS Style

Müller, L.; Dabbiru, V.A.S.; Rutten, L.; Bos, R.; Zahn, R.; Handtke, S.; Thiele, T.; Palicio, M.; Esteban, O.; Broto, M.; et al. Recombinant Anti-PF4 Antibodies Derived from Patients with Vaccine-Induced Immune Thrombocytopenia and Thrombosis (VITT) Facilitate Research and Laboratory Diagnosis of VITT. Vaccines 2025, 13, 3. https://doi.org/10.3390/vaccines13010003

AMA Style

Müller L, Dabbiru VAS, Rutten L, Bos R, Zahn R, Handtke S, Thiele T, Palicio M, Esteban O, Broto M, et al. Recombinant Anti-PF4 Antibodies Derived from Patients with Vaccine-Induced Immune Thrombocytopenia and Thrombosis (VITT) Facilitate Research and Laboratory Diagnosis of VITT. Vaccines. 2025; 13(1):3. https://doi.org/10.3390/vaccines13010003

Chicago/Turabian Style

Müller, Luisa, Venkata A. S. Dabbiru, Lucy Rutten, Rinke Bos, Roland Zahn, Stefan Handtke, Thomas Thiele, Marta Palicio, Olga Esteban, Marta Broto, and et al. 2025. "Recombinant Anti-PF4 Antibodies Derived from Patients with Vaccine-Induced Immune Thrombocytopenia and Thrombosis (VITT) Facilitate Research and Laboratory Diagnosis of VITT" Vaccines 13, no. 1: 3. https://doi.org/10.3390/vaccines13010003

APA Style

Müller, L., Dabbiru, V. A. S., Rutten, L., Bos, R., Zahn, R., Handtke, S., Thiele, T., Palicio, M., Esteban, O., Broto, M., Gordon, T. P., Greinacher, A., Wang, J. J., & Schönborn, L. (2025). Recombinant Anti-PF4 Antibodies Derived from Patients with Vaccine-Induced Immune Thrombocytopenia and Thrombosis (VITT) Facilitate Research and Laboratory Diagnosis of VITT. Vaccines, 13(1), 3. https://doi.org/10.3390/vaccines13010003

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