Resistance towards ChadOx1 nCoV-19 in an 83 Years Old Woman Experiencing Vaccine Induced Thrombosis with Thrombocytopenia Syndrome.

SARS-CoV-2 adenovirus diagnostic resistance vaccine

Journal

Vaccines
ISSN: 2076-393X
Titre abrégé: Vaccines (Basel)
Pays: Switzerland
ID NLM: 101629355

Informations de publication

Date de publication:
30 Nov 2022
Historique:
received: 29 10 2022
revised: 25 11 2022
accepted: 29 11 2022
entrez: 23 12 2022
pubmed: 24 12 2022
medline: 24 12 2022
Statut: epublish

Résumé

in this report, we describe the case of an 83-year-old woman vaccinated with ChadOx1 nCoV-19 who developed a so-called vaccine-induced thrombosis with thrombocytopenia syndrome and who did not develop any antibodies against the spike protein of SARS-CoV-2 at 30 days following the administration of her first dose of ChadOx1 nCoV-19. Experimental section: two serum samples from the patient and 5 serum samples from 5 control individuals having received the two-dose regimen vaccination with ChadOx1 nCoV-19 were evaluated. In order to investigate the lack of response to the vaccination, a cell model was developed. This model permits to evaluate the interaction between responsive cells (A549) possessing the Coxsackievirus and Adenovirus Receptor (CAR), a defined concentration of ChadOx1 nCoV-19 and serial dilution of the patient or the control serum. The aim was to assess the impact of these sera on the production of the spike (S) protein induced by the transfection of the genetic material of ChadOx1 nCoV-19 into the A549 cells. The S protein is measured in the supernatant using an ELISA technique. interestingly, the serum from the patient who developed the vaccine-induced thrombosis with thrombocytopenia syndrome impaired the production of S protein by the A549 cells transfected with ChadOx1 nCoV-19. This was not observed with the controls who did not interfere with the transfection of ChadOx1 nCoV-19 into A549 cells since the S protein is retrieved in the supernatant fraction. based on the data coming from the clinical and the cell model information, we found a possible explanation on the absence of antibody response in our patient. She has, or has developed, characteristics that prevent the production of the S protein in contrast to control subjects. We were not able to investigate the entire mechanism behind this resistance which deserve further investigations. A link between this resistance and the development of the thrombosis with thrombocytopenia syndrome following vaccination with ChadOx1 nCoV-19 cannot be excluded.

Sections du résumé

BACKGROUND BACKGROUND
in this report, we describe the case of an 83-year-old woman vaccinated with ChadOx1 nCoV-19 who developed a so-called vaccine-induced thrombosis with thrombocytopenia syndrome and who did not develop any antibodies against the spike protein of SARS-CoV-2 at 30 days following the administration of her first dose of ChadOx1 nCoV-19. Experimental section: two serum samples from the patient and 5 serum samples from 5 control individuals having received the two-dose regimen vaccination with ChadOx1 nCoV-19 were evaluated. In order to investigate the lack of response to the vaccination, a cell model was developed. This model permits to evaluate the interaction between responsive cells (A549) possessing the Coxsackievirus and Adenovirus Receptor (CAR), a defined concentration of ChadOx1 nCoV-19 and serial dilution of the patient or the control serum. The aim was to assess the impact of these sera on the production of the spike (S) protein induced by the transfection of the genetic material of ChadOx1 nCoV-19 into the A549 cells. The S protein is measured in the supernatant using an ELISA technique.
RESULTS RESULTS
interestingly, the serum from the patient who developed the vaccine-induced thrombosis with thrombocytopenia syndrome impaired the production of S protein by the A549 cells transfected with ChadOx1 nCoV-19. This was not observed with the controls who did not interfere with the transfection of ChadOx1 nCoV-19 into A549 cells since the S protein is retrieved in the supernatant fraction.
CONCLUSION CONCLUSIONS
based on the data coming from the clinical and the cell model information, we found a possible explanation on the absence of antibody response in our patient. She has, or has developed, characteristics that prevent the production of the S protein in contrast to control subjects. We were not able to investigate the entire mechanism behind this resistance which deserve further investigations. A link between this resistance and the development of the thrombosis with thrombocytopenia syndrome following vaccination with ChadOx1 nCoV-19 cannot be excluded.

Identifiants

pubmed: 36560466
pii: vaccines10122056
doi: 10.3390/vaccines10122056
pmc: PMC9781243
pii:
doi:

Types de publication

Case Reports

Langues

eng

Références

Lancet. 2021 Jan 9;397(10269):99-111
pubmed: 33306989
Gene Ther. 2002 Sep;9(18):1262-70
pubmed: 12215894
J Virol. 2007 Jun;81(12):6594-604
pubmed: 17428852
J Gen Virol. 2012 Jan;93(Pt 1):155-158
pubmed: 21918008
Haematologica. 2021 Dec 01;106(12):3249-3252
pubmed: 34847660
Proc Natl Acad Sci U S A. 2018 Oct 9;115(41):10440-10445
pubmed: 30209217
Front Immunol. 2021 Jun 23;12:612910
pubmed: 34248928
PLoS One. 2015 Jul 06;10(7):e0131571
pubmed: 26148007
Immune Netw. 2021 Feb 15;21(1):e6
pubmed: 33728099
Front Immunol. 2019 Apr 05;10:730
pubmed: 31024558
J Immunol. 2005 Jun 1;174(11):7179-85
pubmed: 15905562
J Thromb Haemost. 2016 Dec;14(12):2548-2552
pubmed: 27864862
Clin Chem. 2020 Aug 1;66(8):1104-1106
pubmed: 32484887
Vaccine. 2007 Aug 29;25(35):6501-10
pubmed: 17646036
J Virol. 2012 Jan;86(1):625-9
pubmed: 22072776
PLoS One. 2011 Apr 13;6(4):e18526
pubmed: 21533229
J Virol. 2002 Jun;76(11):5711-9
pubmed: 11991999
Immunol Rev. 2000 Feb;173:89-97
pubmed: 10719670
Mol Pharm. 2010 Feb 1;7(1):105-15
pubmed: 19968324
Lancet. 2020 Aug 15;396(10249):479-488
pubmed: 32702299
FEBS Lett. 2020 Jun;594(12):1828-1837
pubmed: 32298477
Mol Ther. 2011 Oct;19(10):1858-66
pubmed: 21792178
Front Immunol. 2020 Oct 02;11:579250
pubmed: 33123165
Virology. 2017 Feb;502:144-151
pubmed: 28049062
Lancet. 2021 Dec 19;396(10267):1979-1993
pubmed: 33220855
Lancet. 2021 Jan 9;397(10269):72-74
pubmed: 33306990
Mol Ther. 2004 Oct;10(4):616-29
pubmed: 15451446

Auteurs

Constant Gillot (C)

Department of Pharmacy, Namur Research Institute for Life Sciences, Namur Thrombosis and Hemostasis Center, University of Namur, B-5000 Namur, Belgium.

Julien Favresse (J)

Department of Pharmacy, Namur Research Institute for Life Sciences, Namur Thrombosis and Hemostasis Center, University of Namur, B-5000 Namur, Belgium.
Department of Laboratory Medicine, Clinique St-Luc Bouge, B-5000 Namur, Belgium.

Vincent Maloteau (V)

Department of Pharmacy, Namur Research Institute for Life Sciences, Namur Thrombosis and Hemostasis Center, University of Namur, B-5000 Namur, Belgium.

Valérie Mathieux (V)

Service d'Hématologie, CHU UCL NAMUR-Site Sainte Elisabeth, Namur Thrombosis and Hemostasis Center, B-5000 Namur, Belgium.

Jean-Michel Dogné (JM)

Department of Pharmacy, Namur Research Institute for Life Sciences, Namur Thrombosis and Hemostasis Center, University of Namur, B-5000 Namur, Belgium.

François Mullier (F)

Department of Pharmacy, Namur Research Institute for Life Sciences, Namur Thrombosis and Hemostasis Center, University of Namur, B-5000 Namur, Belgium.
Université Catholique de Louvain, CHU UCL NAMUR, Department of Laboratory Medicine, B-5300 Yvoir, Belgium.

Jonathan Douxfils (J)

Department of Pharmacy, Namur Research Institute for Life Sciences, Namur Thrombosis and Hemostasis Center, University of Namur, B-5000 Namur, Belgium.
Qualiblood sa, Research and Development Department, B-5000 Namur, Belgium.

Classifications MeSH