Neutralising Antibody Responses to Bivalent SARS-CoV-2 Vaccines and Hybrid Immunity in Patients on TNF Inhibitors: A Prospective Cohort Study

Hilde S. Ørbo¹, Taissa M. Kasahara², Asia-Sophia Wolf³, Kristin H. Bjørlykke⁴, Joseph Sexton⁵, Ingrid Jyssum⁵, Anne Therese Tveter⁵, Guri Solum³, Ingrid Fadum Kjønstad³, Andreas Lind⁶, Veselka Petrova Dimova-Svetoslavova⁶, Tore K. Kvien⁷, Jørgen Jahnsen⁸, Espen A. Haavardsholm¹, Ludvig A. Munthe⁹, Sella A. Provan⁵, John Torgils Vaage⁹, Siri Mjaaland³, Kristin K. Jørgensen⁴, Gunnveig Grødeland⁹, Silje W. Syversen¹⁰ and Guro L. Goll¹⁰, ¹Center for treatment of Rheumatic and Musculoskeletal Diseases (REMEDY), Diakonhjemmet Hospital, Oslo, Norway, and University of Oslo (UiO), Institute of Clinical Medicine, Oslo, Norway, Oslo, Norway, ²University of Oslo (UiO), Institute of Clinical Medicine, Oslo, Norway, Oslo, Norway, ³Norwegian Institute of Public Health, Section for Immunology, Oslo, Norway, Oslo, Norway, ⁴Akershus University Hospital, Department of Gastroenterology, Lørenskog, Norway, ⁵Center for treatment of Rheumatic and Musculoskeletal Diseases (REMEDY), Diakonhjemmet Hospital, Oslo, Norway, Oslo, Norway, ⁶Oslo University Hospital, Department of Microbiology, Oslo, Norway, Oslo, Norway, ⁷Center for treatment of Rheumatic and Musculoskeletal Diseases (REMEDY), Diakonhjemmet Hospital, Oslo, Norway and University of Oslo (UiO), Institute of Clinical Medicine, Oslo, Norway, Oslo, Norway, ⁸Akershus University Hospital, Department of Gastroenterology, Lørenskog, Norway and University of Oslo (UiO), Institute of Clinical Medicine, Oslo, Norway, ⁹Oslo University Hospital, Department of Immunology, Oslo, Norway, and University of Oslo (UiO), Institute of Clinical Medicine, Oslo, Norway, Oslo, Norway, ¹⁰Center for treatment of Rheumatic and Musculoskeletal Diseases (REMEDY), Diakonhjemmet Hospital, Oslo, Norway, and University of Oslo (UiO), Institute of Health and Society, Oslo, Norway, Oslo, Norway

Meeting: ACR Convergence 2024

Keywords: Anti-TNF Drugs, Cohort Study, COVID-19, immunology, prevention

Session Information

Date: Saturday, November 16, 2024

Title: Infection-related Rheumatic Disease Poster

Session Type: Poster Session A

Session Time: 10:30AM-12:30PM

Background/Purpose: The SARS-CoV-2 virus mutates continuously, posing challenges for patients with immune-mediated inflammatory diseases (IMIDs) on tumour necrosis factor inhibitors (TNFi). These patients often have diminished vaccine responses and are at a higher risk of severe infections. The efficacy of the recommended mono- and bivalent vaccine boosters in this patient population remains unclear.

The objective of this study was to assess the neutralizing capacity and anti-spike antibody responses to SARS-CoV-2 in TNFi-treated IMID patients, after receiving a monovalent 4th vaccine dose and a bivalent 5th vaccine dose, compared to those with hybrid immunity.

Methods: These analyses from the ongoing observational Nor-vaC study included TNFi-treated IMID patients who received either a 5th vaccine dose or experienced SARS-CoV-2 infection following a 4th vaccine dose (hybrid immunity).

Blood samples were collected 2-4 weeks after the 4th monovalent vaccine dose and after either subsequent COVID-19 or a 5th bivalent dose (BA.1 or BA.4/5).

Neutralizing antibody titres against three viral variants (Wuhan (WT), Omicron BA.1, and Omicron BA.4), and IgG anti-spike antibody levels, were analysed. Group comparisons were performed with Mann Whitney U test.

Results: From December 17, 2021, to June 20, 2023, 371 IMID patients (86 rheumatoid arthritis, 72 psoriatic arthritis, 95 spondyloarthritis, 75 Crohn’s disease, 43 ulcerative colitis) on TNFi in mono- (60%) or combination (40%) therapy received a 4th and a 5th vaccine dose or had a SARS-CoV-2 infection after the 4th vaccine dose, median age 58 (IQR 48-67), 53 % female.

In total, 322 patients, received a 5th bivalent vaccine dose, either BA.1 (40%), BA.4/5 vaccine (60%). Overall, 180 (49%) had COVID-19 following a 4th vaccine dose (4th hybrid). All infections occurred while BA.1, BA.4 and BA.5 were the circulating variants.

Patients with hybrid immunity had a higher median anti-spike antibody level than did infection-naïve patients following the 5th dose BA.1 vaccine (p=0.0015), but comparable to levels after a 5th BA.4/5 vaccine dose (p=0.24) (figure A, table). Hybrid immunity increased neutralizing antibody titres against all tested variants compared to a 4th vaccine dose (WT: p< 0.0001), BA1: p< 0.0001, BA4: p< 0.0001) and 5th vaccine dose with BA.1 (WT: p< 0.0001, BA1: p=0.0002, BA4: p< 0.0001) (figure B, table).

In infection-naïve patients, a 5th BA.4/5 vaccine increased neutralizing antibody titres against all viral variants tested (WT, BA.1 and BA.4), compared to post-4th dose levels (WT: p=0.011, BA.1: p=0.001, BA.4: p=0.0001) (figure B, table). In infection-naïve patients, a 5th BA.4/5 vaccine gave higher neutralizing antibody responses against BA.4 than a 5th BA.1 vaccine (p=0.023) and comparable to that after hybrid immunity (p=0.16) (figure B, table).

Conclusion: In IMID patients on TNFi who reported COVID-19 as a fifth antigenic exposure, neutralising antibody capacity was superior to that following a fifth updated, bivalent vaccine in patients that were infection-naïve. Infection-naïve patients benefit from the most updated vaccine, providing a humoral response almost comparable to that following infection.

Figure: Anti-spike antibody levels (A) in infection-naïve patients following a 4th monovalent dose (4th dose), and a 5th bivalent dose distributed by type of vaccine (5th BA.1 vs 5th BA4.5), and in patients with COVID_19 following a 4th dose (4th dose hybrid) and neutralising titres (B) following these immunisations. # <0.05 (compared to 4th dose) † <0.05 (compared to 5th dose BA.4/5). *p<0.05, ***p<0.001, **** p<0.0001.

Table: Comparisons of anti-spike antibodies and neutralizing antibodies (NAb) following four monovalent vaccine doses in infection-naïve individuals (4th dose), following a 5th bivalent vaccine dose with either BA.1 (5th dose BA.1) or BA.4/5 (5th dose BA.4/5) in patients without prior infection, and in patients with prior infection between the 4th monovalent and the 5th bivalent vaccine dose (4th dose hybrid).

Disclosures: H. Ørbo: None; T. Kasahara: None; A. Wolf: None; K. Bjørlykke: Janssen-Cilag, 6; J. Sexton: None; I. Jyssum: None; A. Tveter: None; G. Solum: None; I. Kjønstad: None; A. Lind: None; V. Dimova-Svetoslavova: None; T. Kvien: AbbVie/Abbott, 1, 2, 5, Bristol-Myers Squibb(BMS), 5, Galapagos, 5, Gilead, 2, Grünenthal, 6, Janssen, 2, 6, Novartis, 2, 5, Pfizer, 2, 5, Sandoz, 2, 6, UCB, 2, 5; J. Jahnsen: AbbVie/Abbott, 1, 3, 6, Bristol-Myers Squibb(BMS), 1, 6, Galapagos, 1, 6, Gilead, 1, 6, Janssen, 1, 6, Pfizer, 1, 2, 5, Roche, 1, 6, Sandoz, 1, 6, Takeda, 1, 6; E. Haavardsholm: AbbVie/Abbott, 2, Celgene, 2, Eli Lilly, 2, Gilead, 2, Janssen, 2, Pfizer, 2, UCB, 2; L. Munthe: Incyte, 6, Janssen, 6; S. Provan: Boehringer-Ingelheim, 2; J. Vaage: None; S. Mjaaland: None; K. Jørgensen: Bristol-Myers Squibb(BMS), 6, Roche, 6; G. Grødeland: AstraZeneca, 1, Bayer, 6, GlaxoSmithKlein(GSK), 6, Janssen, 1, Moderna, 1, Pfizer, 6, Sanofi, 6, Seqirus, 1, ThermoFisher, 6; S. Syversen: AstraZeneca, 1; G. Goll: AbbVie/Abbott, 1, 6, Galapagos, 1, 6, Novartis, 1, Pfizer, 1, 6, UCB, 1, 6.

To cite this abstract in AMA style:

Ørbo H, Kasahara T, Wolf A, Bjørlykke K, Sexton J, Jyssum I, Tveter A, Solum G, Kjønstad I, Lind A, Dimova-Svetoslavova V, Kvien T, Jahnsen J, Haavardsholm E, Munthe L, Provan S, Vaage J, Mjaaland S, Jørgensen K, Grødeland G, Syversen S, Goll G. Neutralising Antibody Responses to Bivalent SARS-CoV-2 Vaccines and Hybrid Immunity in Patients on TNF Inhibitors: A Prospective Cohort Study [abstract]. Arthritis Rheumatol. 2024; 76 (suppl 9). https://acrabstracts.org/abstract/neutralising-antibody-responses-to-bivalent-sars-cov-2-vaccines-and-hybrid-immunity-in-patients-on-tnf-inhibitors-a-prospective-cohort-study/. Accessed .

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