Vaccine-Induced Immune Thrombotic Thrombocytopenia Two Years Later: Should It Still Be on the Scientific Agenda?

Petito, Eleonora; Gresele, Paolo

doi:10.1055/a-2107-0891

Cited by 3 publications

(1 citation statement)

References 98 publications

(299 reference statements)

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“…The overall safety profile of licensed vaccines is typically thoroughly established, and their risk–benefit ratio is well in favor of the latter. As of January 2023, the administration of over 13.2 billion of vaccine doses against COVID-19 inevitably associated vaccines with undesirable rare adverse events (AEs) [ 1 , 2 , 3 , 4 , 5 ]. The background incidence rates of various conditions in the population and the large numbers of individuals being vaccinated placed some of these AEs in the post-vaccination time window by chance.…”

Section: Introductionmentioning

confidence: 99%

Adenovirus Transcriptome in Human Cells Infected with ChAdOx1-Vectored Candidate HIV-1 Vaccine Is Dominated by High Levels of Correctly Spliced HIVconsv1&62 Transgene RNA

et al. 2023

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We develop candidate HIV-1 vaccines, of which two components, ChAdOx1.tHIVconsv1 (C1) and ChAdOx1.HIVconsv62 (C62), are delivered by the simian adenovirus-derived vaccine vector ChAdOx1. Aberrant adenovirus RNA splicing involving transgene(s) coding for the SARS-CoV-2 spike was suggested as an aetiology of rare adverse events temporarily associated with the initial deployment of adenovirus-vectored vaccines during the COVID-19 pandemic. Here, to eliminate this theoretically plausible splicing phenomenon from the list of possible pathomechanisms for our HIV-1 vaccine candidates, we directly sequenced mRNAs in C1- and C62-infected nonpermissive MRC-5 and A549 and permissive HEK293 human cell lines. Our two main observations in nonpermissive human cells, which are most similar to those which become infected after the intramuscular administration of vaccines into human volunteers, were that (i) the dominant adenovirus vector-derived mRNAs were the expected transcripts coding for the HIVconsvX immunogens and (ii) atypical splicing events within the synthetic open reading frame of the two transgenes are rare. We conclude that inadvertent RNA splicing is not a safety concern for the two tested candidate HIV-1 vaccines.

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Section: Introductionmentioning

confidence: 99%

Adenovirus Transcriptome in Human Cells Infected with ChAdOx1-Vectored Candidate HIV-1 Vaccine Is Dominated by High Levels of Correctly Spliced HIVconsv1&62 Transgene RNA

et al. 2023

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Emerging Thrombotic Disorders Associated with Virus-Based Innovative Therapies: From VITT to AAV Gene Therapy–Related Thrombotic Microangiopathy

Benemei,

Gatto,

Marcucci

et al. 2024

Thromb Haemost

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Gene therapy is a promising therapeutic approach for treating life-threatening disorders. Despite the clinical improvements observed with gene therapy, immune responses either innate or adaptive against the vector used for gene delivery, can affect treatment efficacy and lead to adverse reactions. Thrombotic microangiopathy (TMA) is a thrombosis with thrombocytopenia syndrome (TTS) characterized by microangiopathic hemolytic anemia, thrombocytopenia, and small vessel occlusion known to be elicited by several drugs, that has been recently reported as an adverse event of adeno-associated virus (AAV)-based gene therapy. TMA encompasses a heterogenous group of disorders, its classification and underlining mechanisms are still uncertain, and still lacks validated biomarkers. The identification of predictors of TMA, such as vector dose and patient characteristics, is a pressing need to recognize patients at risk before and after AAV-based gene therapy administration. This review aims to explore the literature on TMA associated with AAV-based gene therapy in the larger context of TMA (i.e., hemolytic-uremic syndrome, thrombotic thrombocytopenic purpura, and other drug-related TMAs). Considering the wide attention recently gained by another TTS associated with a non-gene therapy viral platform (adenovirus, AV COVID-19 vaccine), namely vaccine-induced immune thrombocytopenia and thrombosis (VITT), AAV gene therapy–related TMA mechanisms will be discussed and differentiated from those of VITT to avoid recency bias and favor a correct positioning of these two recently emerged syndromes within the heterogenous group of drug-related TTS. Finally, the review will discuss strategies for enhancing the safety and optimize the management of AAV-based gene therapy that is emerging as an efficacious therapeutic option for disparate, severe, and often orphan conditions.

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Cranioplasty after Decompressive Craniectomy (DC) in a Patient with Intracerebral Hemorrhage after SARS-CoV-2 Vaccination-Related Vaccine-Induced Thrombotic Thrombocytopenia (VITT)—Proposal of a Management Protocol for This Rare Pathological Condition

Spanehl,

Walter,

Thiele

et al. 2024

JCM

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The COVID-19 (coronavirus disease) pandemic had a severe impact on public health worldwide. A rare but serious complication after administration of adenoviral vaccines against SARS-CoV-2 (AstraZeneca–Oxford and Johnson & Johnson) is vaccine-induced immune thrombotic thrombocytopenia and thrombosis (VITT), which can lead to serious complications such as cerebral venous sinus thrombosis (CVST). CVST itself can cause subarachnoid hemorrhage (SAH) and/or intracerebral hemorrhage (ICH), leading to high mortality due to herniation of brain parenchyma. In those patients, an emergent decompressive hemicraniectomy (DC) is regularly performed. Herein, the authors want to focus on the patients who survive DC following VITT-associated CVST and shed light on the neurosurgical considerations in those patients. We herein propose a treatment algorithm regarding the timing and the perioperative management of cranioplasty. We describe an exemplary case highlighting that special circumstances may result in a more urgent need for autologous cranioplasty than usual, based on individual risk assessment.

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Vaccine-Induced Immune Thrombotic Thrombocytopenia Two Years Later: Should It Still Be on the Scientific Agenda?

Cited by 3 publications

References 98 publications

Adenovirus Transcriptome in Human Cells Infected with ChAdOx1-Vectored Candidate HIV-1 Vaccine Is Dominated by High Levels of Correctly Spliced HIVconsv1&62 Transgene RNA

Adenovirus Transcriptome in Human Cells Infected with ChAdOx1-Vectored Candidate HIV-1 Vaccine Is Dominated by High Levels of Correctly Spliced HIVconsv1&62 Transgene RNA

Emerging Thrombotic Disorders Associated with Virus-Based Innovative Therapies: From VITT to AAV Gene Therapy–Related Thrombotic Microangiopathy

Cranioplasty after Decompressive Craniectomy (DC) in a Patient with Intracerebral Hemorrhage after SARS-CoV-2 Vaccination-Related Vaccine-Induced Thrombotic Thrombocytopenia (VITT)—Proposal of a Management Protocol for This Rare Pathological Condition

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