Vaccine-induced thrombotic thrombocytopenia: Effect of E3 gene elimination from ds-DNA adenovirus vector?

Vaccine Induced Thrombotic Thrombocytopenia (VITT) is a very rare but serious adverse reaction to the Oxford–AstraZeneca and Johnson and Johnson (J&J) vaccines but not observed in the Pfizer and Moderna vaccines. It is immunologically and clinically almost identical to Heparin Induced Thrombocytopenia (HIT). However patients with VITT have no history of heparin exposure. The antigen provocateur has remained elusive. It has been suggested that it is vaccine DNA. However this does not necessarily explain why vaccine RNA is non-causative and why it is not reported as frequently in wild-type virus infection. Evidence suggests that it is the double stranded DNA specifically of the adenovirus vectors used in the Oxford-AstraZeneca and J&J vaccines; combined with the elimination of the E3 gene domain to promote immunity, that are responsible for VITT. We explain why the RNA vaccines are not implicated in the phenomenon. HIT is not exclusive to heparin but rather a patho-immunological response that can occur to others poly-anions of a particular charge and steric configuration. More appropriate terminology for HIT and VITT may be poly-anionic induced thrombotic thrombocytopenia (PITT).