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. 2024 Dec;22(12):3532-3541.
doi: 10.1016/j.jtha.2024.08.019. Epub 2024 Sep 13.

Assessment of antibodies against platelet factor 4 following vaccination with adenovirus type 26-vectored vaccines

Hendy Kristyanto  1 , Leen Slaets  2 , Esmée Braams  1 , Ilse Scheys  2 , Roy Heesbeen  1 , Vicky Cárdenas  3 , Georgi Shukarev  1 , Gert Scheper  1 , Jerald Sadoff  1 , Kerstin Lühn  1 , Hanneke Schuitemaker  1 , Frank Struyf  2 , Jenny Hendriks  4
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Free article

Assessment of antibodies against platelet factor 4 following vaccination with adenovirus type 26-vectored vaccines

Hendy Kristyanto et al. J Thromb Haemost. 2024 Dec.
Free article

Abstract

Background: Vaccine-induced immune thrombotic thrombocytopenia (VITT) is a rare adverse event identified following vaccination with some adenovirus-vectored COVID-19 vaccines, including Ad26.COV2.S. VITT is characterized by the presence of antibodies against platelet factor 4 (PF4).

Objectives: To evaluate whether PF4 antibodies were generally induced following vaccination with adenovirus type 26 (Ad26)-vectored vaccines.

Methods: The study included 913 and 991 healthy participants without thromboembolic (TE) events in Ad26.COV2.S and non-COVID-19 Ad26-vectored vaccine clinical studies, respectively, and 1 participant with VITT following Ad26.COV2.S vaccination. PF4 antibody levels were measured in prevaccination and postvaccination sera. PF4 antibody positivity rates were assessed in a case-control setting in participants who developed TE events during participation in Ad26-vectored vaccine clinical studies.

Results: In the 1 VITT patient, PF4 antibodies were negative before vaccination. Seroconversion for platelet-activating PF4 antibodies was observed upon Ad26.COV2.S vaccination. In participants without TE events, the PF4 antibody levels and positivity rates were similar before and after Ad26 vaccination. Ad26 vaccination did not increase PF4 antibody levels in participants who were PF4 antibody-positive at baseline (n = 47). Lastly, 1 out of 28 TE cases and 2 out of 156 non-TE controls seroconverted after Ad26.COV2.S vaccination. None of the 15 TE cases and 3 of the 77 non-TE controls seroconverted following non-COVID-19 Ad26 vaccination.

Conclusion: Ad26.COV2.S and the other Ad26-vectored vaccines studied did not generally induce PF4 antibodies or increase preexisting PF4 antibody levels. Moreover, unlike VITT, TE events that occurred at any time following Ad26 vaccination were not associated with PF4 antibodies.

Keywords: COVID-19 vaccines; platelet factor 4; thrombocytopenia; thrombosis.

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Conflict of interest statement

Declaration of competing interests All authors were full-time employees of Johnson & Johnson at the time of the study and may have equity or stocks in Johnson & Johnson. F.S. is a former employee of GlaxoSmithKline and holds GlaxoSmithKline equity or stocks.

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