OC 55.3 - Inflammasome activation in vaccine-induced thrombotic thrombocytopenia (VITT) after immunization with adenovirus-based SARS-CoV-2 vaccines

Tuesday, June 27, 2023

11:15 – 11:30 ET

Room: 510

Session Available As: On-Demand

Presenting Author(s)

Remy Martins-Gonçalves, MD (he/him/his)

PhD Student
Fiocruz, Rio de Janeiro, Brazil
Rio de Janeiro, Espirito Santo, Brazil

Co-Author(s)

DP

Daniela P. Mendes-De-Almeida

researcher
Department of Medical Affairs, Clinical Studies, and Post-Registration Surveillance (DEAME), Institute of Technology in Immunobiologicals/Bio-Manguinhos, Fundação Oswaldo Cruz (FIOCRUZ), Rio de Janeiro, Brazil
Rio de Janeiro, Rio de Janeiro, Brazil
CQ

Carolina Q. Sacramento

researcher
National Institute for Science and Technology on Innovation on Neglected Diseases (INCT/IDN), Center for Technological Development in Health (CDTS), Fiocruz, Rio de Janeiro, RJ, Brazil.
Rio de Janeiro, Rio de Janeiro, Brazil
SV

Stephane Vicente Rozini

Masters Student
- Laboratory of Immunothrombosis, Department of Biochemistry, Federal University of Juiz de Fora, Juiz de Fora, Brazil
Rio de Janeiro, Rio de Janeiro, Brazil
JB

Joanna Bokel

MD
Instituto Nacional de Infectologia Evandro Chagas (INI), Fundação Oswaldo Cruz (FIOCRUZ), Rio de Janeiro, Brazil
rio de janeiro, Rio de Janeiro, Brazil
GV

Gabriellen Vitiello Teixeira

researcher
- Institute of Technology in Immunobiologicals/Bio-Manguinhos/Fiocruz, Rio de Janeiro, Brazil
Rio de Janeiro, Rio de Janeiro, Brazil
VB

Victor Bertollo Gomes Porto

researcher
- General Coordination of the National Immunization Program/National Immunization Program/ Brazilian Ministry of Health, Brazil
Rio de Janeiro, Rio de Janeiro, Brazil
SW

Sandra Wagner Cardoso

researcher
- Instituto de Pesquisa Clínica Evandro Chagas, Fundação Oswaldo Cruz, Rio de Janeiro, RJ, Brazil.
Rio de Janiero, Rio de Janeiro, Brazil
BH

Brenda Hoagland

researcher
- Instituto de Pesquisa Clínica Evandro Chagas, Fundação Oswaldo Cruz, Rio de Janeiro, RJ, Brazil.
Rio de Janeiro, Rio de Janeiro, Brazil
PM

Patricia Mouta Nunes De Oliveira

researcher
- Institute of Technology in Immunobiologicals/Bio-Manguinhos/Fiocruz, Rio de Janeiro, Brazil
Rio de Janeiro, Rio de Janeiro, Brazil
LA

Luiz Amorim Filho

researcher
- Hemorio, Rio de Janeiro, Brazil.
Rio de Janeiro, Rio de Janeiro, Brazil
BG

Beatriz Grinsztejn

researcher
- Instituto Nacional de Infectologia Evandro Chagas, Fundação Oswaldo Cruz (FIOCRUZ), Rio de Janeiro, Brazil
Rio de Janeiro, Rio de Janeiro, Brazil
ED

Eugênio D. Hottz

researcher
Laboratory of Immunothrombosis, Department of Biochemistry, Federal University of Juiz de Fora, Juiz de Fora, Brazil
Rio de Janeiro, Rio de Janeiro, Brazil
MD

Maria de Lourdes De Sousa Maia

researcher
- Institute of Technology in Immunobiologicals/Bio-Manguinhos/Fiocruz, Rio de Janeiro, Brazil
Rio de Janeiro, Rio de Janeiro, Brazil
PT

Patricia T. Bozza

researcher
- Laboratory of Immunopharmacology, Oswaldo Cruz Institute, FIOCRUZ, Rio de Janeiro, Brazil.
Rio de Janeiro, Rio de Janeiro, Brazil

Background: The development of immunizers changed the SARS-CoV-2 pandemic’s course, reducing severity/mortality and allowing for reduced social distancing. Nevertheless, with billions of doses administered, a rare adverse effect associated with adenovector vaccines became concerning. In individuals affected, adenovector particles aggregates with Platelet Factor 4 (PF4), forming neoepitopes, leading to high anti-PF4 antibodies titers. The immunocomplexes formed activates platelets through FCγ receptors, leading to thrombus formation, a condition known as Vaccine Induced Thrombotic Thrombocytopenia (VITT). Inflammasome activation is a common feature of Immunothrombosis. Here we hypothesized that inflammasome activation might be involved in the development of VITT.

Aims: This study aims to characterize inflammasome activation patients with VITT.

Methods: Forty patients with post-vaccine thrombosis (PVT) and 39 age/sex matched unvaccinated individuals were included (CAAE-48532621.8.0000.5262 and CAAE-52396621.0.0000.5262). Cohort characteristics are described in Table-1. Anti-PF4 IgGs (immucor), Tissue Factor (TF), CD62p (p-selectin), PF4, IL-1β, IL-18 and activated p20-Caspase-1 subunit (R&D) were evaluated through ELISA.

Results: PVTs were classified as possible (n=16), probable (n=8) or definite VITT (n=16) according Pavord et al., 2021 criteria. Besides variables used in the classification (d-dimer, thrombocytopenia and Anti-PF4 IgGs), patients displayed elevated plasmatic levels of TF and CD62p (Figure-1A, B). Patients presented lower detectable PF4 (Figure-1C), which could be due to the presence of Anti-PF4 antibodies in the patients’ plasma. Patients also presented elevated plasmatic levels of IL-1β and IL-18 (Figure-1D, E), cytokines primed by Caspase-1 upon inflammasome activation. Indeed, PTV patients present detectable levels of activated caspase-1, and among them, definite VITT cases presented higher Caspase-1 levels (Figure-1F), confirming inflammasome activation in VITT.

Conclusion(s): Our data shows that inflammasome activation occurs in VITT patients and may be associated with VITT development and severity, requiring further investigation. As NLRP3 inhibitors are under clinical trials, a better understanding of inflammasome activation in the development of VITT could be beneficial for future clinical management.

Learning Objectives:

Upon completion, participant will be able to identify the main characteristics that indicate that an thrombotic event may be related to Vaccine Induced Thrombotic thrombocytopenia (VITT).
Upon completion, participant will be able to understand the main described mechanism of Vaccine Induced Thrombotic thrombocytopenia (VITT) associatd primarely with adenovector COVID-19 vaccines.
Upon completion, participant will be able to understand the main gaps in knowledge of VITT mechanisms.