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Ann Rheum Dis. 2021 Oct 04; doi: 10.1136/annrheumdis-2021-221097. Epub 2021 Oct 04.

BNT162b2 vaccine-induced humoral and cellular responses against SARS-CoV-2 variants in systemic lupus erythematosus.

Annals of the rheumatic diseases

Quentin Moyon, Delphine Sterlin, Makoto Miyara, François Anna, Alexis Mathian, Raphael Lhote, Pascale Ghillani-Dalbin, Paul Breillat, Sasi Mudumba, Sophia de Alba, Fleur Cohen-Aubart, Julien Haroche, Micheline Pha, Thi Huong Du Boutin, Hedi Chaieb, Pedro Macedo Flores, Pierre Charneau, Guy Gorochov, Zahir Amoura

Affiliations

  1. Inserm, Centre d'Immunologie et des Maladies Infectieuses (CIMI-Paris), Sorbonne Université, Paris, France.
  2. Assistance Publique-Hôpitaux de Paris (AP-HP), Groupement Hospitalier Pitié-Salpêtrière (GHPS), French National Reference Center for Systemic Lupus Erythematosus, Antiphospholipid Antibody Syndrome and Other Autoimmune Disorders, Service de Médecine Interne 2, Institut E3M, Sorbonne Université, Paris, France.
  3. Assistance Publique Hôpitaux de Paris (AP-HP), Département d'Immunologie, Hôpital Pitié-Salpêtrière, Sorbonne Université, Paris, France.
  4. Virology Department, Institut Pasteur-TheraVectys Joint Lab, Paris, France.
  5. Unité de Virologie Moléculaire et Vaccinologie, Institut Pasteur, Paris, France.
  6. Assay Development Department, Genalyte Inc, San Diego, California, USA.
  7. Mathématiques appliquées, Sorbonne Universite Faculte des Sciences et Ingenierie, Paris, France.
  8. Inserm, Centre d'Immunologie et des Maladies Infectieuses (CIMI-Paris), Sorbonne Université, Paris, France [email protected] [email protected].

PMID: 34607791 PMCID: PMC8494536 DOI: 10.1136/annrheumdis-2021-221097

Abstract

OBJECTIVES: Our aim was to evaluate systemic lupus erythematosus (SLE) disease activity and SARS-CoV-2-specific immune responses after BNT162b2 vaccination.

METHODS: In this prospective study, disease activity and clinical assessments were recorded from the first dose of vaccine until day 15 after the second dose in 126 patients with SLE. SARS-CoV-2 antibody responses were measured against wild-type spike antigen, while serum-neutralising activity was assessed against the SARS-CoV-2 historical strain and variants of concerns (VOCs). Vaccine-specific T cell responses were quantified by interferon-γ release assay after the second dose.

RESULTS: BNT162b2 was well tolerated and no statistically significant variations of BILAG (British Isles Lupus Assessment Group) and SLEDAI (SLE Disease Activity Index) scores were observed throughout the study in patients with SLE with active and inactive disease at baseline. Mycophenolate mofetil (MMF) and methotrexate (MTX) treatments were associated with drastically reduced BNT162b2 antibody response (β=-78, p=0.007; β=-122, p<0.001, respectively). Anti-spike antibody response was positively associated with baseline total immunoglobulin G serum levels, naïve B cell frequencies (β=2, p=0.018; β=2.5, p=0.003) and SARS-CoV-2-specific T cell response (r=0.462, p=0.003). In responders, serum neutralisation activity decreased against VOCs bearing the E484K mutation but remained detectable in a majority of patients.

CONCLUSION: MMF, MTX and poor baseline humoral immune status, particularly low naïve B cell frequencies, are independently associated with impaired BNT162b2 mRNA antibody response, delineating patients with SLE who might need adapted vaccine regimens and follow-up.

© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

Keywords: COVID-19; lupus erythematosus; systemic; vaccination

Conflict of interest statement

Competing interests: ZA has received research grants from Amgen, AstraZeneca, GSK and Roche; fees for consultancy from AstraZeneca, GSK and Kezar. MM received consulting fees from Genalyte Inc. 3 year

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