Serum levels of anti-PF4 IgG after AZD1222 (ChAdOx1 nCoV-19) vaccination

Abstract

Rare cases of thrombosis with thrombocytopenia syndrome (TTS) have been reported after AZD1222. Anti-platelet factor-4 (PF4) antibodies were observed in patients following presentation of TTS, however it is unclear if AZD1222 was responsible for inducing production of anti-PF4. Paired samples (baseline and day-15) from a phase 3 trial of AZD1222 vs placebo were analyzed for anti-PF4 levels; 19/1727 (1.1%, AZD1222) vs 7/857 (0.8%, placebo) participants were anti-PF4-IgG-negative at baseline but had moderate Day-15 levels (P = 0.676) and 0/35 and 1/20 (5.0%) had moderate levels at baseline but high Day-15 levels. These data indicate that AZD1222 does not induce a clinically relevant general increase in anti-PF4 IgG.

Temporal changes in biomarkers of neutrophil extracellular traps and NET‐promoting autoantibodies following adenovirus‐vectored, mRNA, and recombinant protein COVID‐19 vaccination

“…Consequently, we conducted a comparative discussion based on the aforementioned relevant literature. As per a study funded by AstraZeneca and the US Government, HDs with a male predominance (60.3%) and young adults' predominance (≥18 and <56 years old, 51.0%) did not exhibit statistically significant elevation of anti‐HPF4 after one shot of AZ vaccine 33,34 . However, our study also identified an increase in anti‐PF4 in some individuals (75.68%, 28 in 37) who received two adenoviral vector vaccines without clinical VITT.…”

“…Government, HDs with a male predominance (60.3%) and young adults' predominance (≥18 and <56 years old, 51.0%) did not exhibit statistically significant elevation of anti-HPF4 after one shot of AZ vaccine. 33,34 However, our study also identified an increase in anti-PF4 in some individuals (75.68%, 28 in 37) who received two adenoviral vector vaccines without clinical VITT. Furthermore, an increase in anti-HPF4 (43.24%, 16 in 37) was observed in HDs after receiving an mRNA booster in our cohort.…”

Understanding thrombosis with thrombocytopenia syndrome after COVID-19 vaccination

“…The presence of low level anti-PF4 antibodies and platelet activation does not predict the induction of TTS. Indeed 1-2% of individuals are positive for low levels of anti-PF4 IgG and these individuals do not develop TTS post-vaccination 32,33 . Also, vaccination with Vaxzevria does not generally increase anti-PF4 levels in healthy vaccine recipients who did not develop VITT 32 .…”

“…Indeed 1-2% of individuals are positive for low levels of anti-PF4 IgG and these individuals do not develop TTS post-vaccination 32,33 . Also, vaccination with Vaxzevria does not generally increase anti-PF4 levels in healthy vaccine recipients who did not develop VITT 32 . According to the company's working hypothesis, the nature of the individual host response determines whether TTS is induced upon exposure to the ChAdOx1-PF4 complex.…”

Potential mechanisms of vaccine-induced thrombosis

“…Moreover, a post-hoc analysis of sera from subjects recruited in a phase 3 trial of ChAdOx1-SARS-COV-2 vaccine found no increased rate of detection of anti-PF4 IgG post-vaccination compared to placebo during the period of highest TTS risk. Indeed, 19/1727 (1.1%, ChA-dOx1) vs 7/857 (0.8%, placebo) participants were anti-PF4-IgGnegative at baseline, but had moderate Day-15 levels (P = 0.676) and 0/35 and 1/20 (5.0%) had moderate levels at baseline but high Day-15 levels [54]. None of the participants to the trial experienced VITT following administration of vaccine or placebo.…”