tetano
Editor, Senior Moderator
Front Immunol
. 2024 Sep 5:15:1432348.
doi: 10.3389/fimmu.2024.1432348. eCollection 2024. Humoral and cellular immune response from first to fourth SARS-CoV-2 mRNA vaccination in anti-CD20-treated multiple sclerosis patients-a longitudinal cohort study
Frederik Novak[SUP] 1 2 [/SUP], Anna Christine Nilsson[SUP] 3 4 [/SUP], Emil Birch Christensen[SUP] 3 4 5 [/SUP], Caroline Louise Stougaard[SUP] 3 4 5 [/SUP], Mike Bogetofte Barnkob[SUP] 3 4 5 [/SUP], Dorte K Holm[SUP] 3 [/SUP], Agnes Hauschultz Witt[SUP] 6 [/SUP], Keld-Erik Byg[SUP] 5 7 [/SUP], Isik S Johansen[SUP] 4 8 [/SUP], Christian Nielsen[SUP] 3 4 5 [/SUP], Tobias Sejbaek[SUP] 1 2 [/SUP]
Affiliations
Background: This study examines the humoral and cellular response in multiple sclerosis (MS) patients on anti-CD20 therapy before and after the 1st to 4th BNT162b2 mRNA SARS-CoV-2 vaccination and the relationship with breakthrough infection.
Methods: Participants with McDonald 2017 MS that were treated with ocrelizumab were included. The study duration was throughout the COVID-19 pandemic until four months after fourth mRNA SARS-CoV-2 vaccination (BNT162b2). Longitudinal blood samples were analysed for: IgG antibodies of SARS-CoV-2 spike anti-receptor binding domain (anti-RBD), nucleocapsid IgG antibodies (anti-N) and activation induced marker expressing CD4+, CD8+ T-cells and concentration of ocrelizumab and anti-drug antibodies. Incidences of breakthrough infection were confirmed with SARS-CoV-2 PCR tests.
Results: The rate of anti-RBD positive participants increased substantially between the third and fourth vaccination from 22.2% to 55.9% (median 54.7 BAU/mL; IQR: 14.5 - 221.2 BAU/mL and 607.7 BAU/mL; IQR: 29.4 - 784.6 BAU/mL, respectively). Within the same period 75% of participants experienced breakthrough infection. The fourth vaccination resulted in an additional increase in seropositive individuals (64.3%) (median 541.8 BAU/mL (IQR: 19.1-1007 BAU/mL). Breakthrough infection did not influence the cellular response without a significant change after the fourth vaccination. During the study period two participants had detectable anti-N, both after the fourth vaccination. No correlation was found between serum concentration of ocrelizumab and the humoral and cellular response.
Discussion: Low levels or absence of specific anti-RBD following vaccination, with a significant increase after breakthrough infections and boosted by the fourth vaccination. T-cell reactivity remained sustained and unaffected by breakthrough infections.
Keywords: SARS-CoV-2; anti-CD20; breakthrough infection; cellular immune activation; humoral immune response; mRNA vaccination vulnerable population; multiple sclerosis; ocrelizumab concentration.
. 2024 Sep 5:15:1432348.
doi: 10.3389/fimmu.2024.1432348. eCollection 2024. Humoral and cellular immune response from first to fourth SARS-CoV-2 mRNA vaccination in anti-CD20-treated multiple sclerosis patients-a longitudinal cohort study
Frederik Novak[SUP] 1 2 [/SUP], Anna Christine Nilsson[SUP] 3 4 [/SUP], Emil Birch Christensen[SUP] 3 4 5 [/SUP], Caroline Louise Stougaard[SUP] 3 4 5 [/SUP], Mike Bogetofte Barnkob[SUP] 3 4 5 [/SUP], Dorte K Holm[SUP] 3 [/SUP], Agnes Hauschultz Witt[SUP] 6 [/SUP], Keld-Erik Byg[SUP] 5 7 [/SUP], Isik S Johansen[SUP] 4 8 [/SUP], Christian Nielsen[SUP] 3 4 5 [/SUP], Tobias Sejbaek[SUP] 1 2 [/SUP]
Affiliations
- PMID: 39301017
- PMCID: PMC11410621
- DOI: 10.3389/fimmu.2024.1432348
Background: This study examines the humoral and cellular response in multiple sclerosis (MS) patients on anti-CD20 therapy before and after the 1st to 4th BNT162b2 mRNA SARS-CoV-2 vaccination and the relationship with breakthrough infection.
Methods: Participants with McDonald 2017 MS that were treated with ocrelizumab were included. The study duration was throughout the COVID-19 pandemic until four months after fourth mRNA SARS-CoV-2 vaccination (BNT162b2). Longitudinal blood samples were analysed for: IgG antibodies of SARS-CoV-2 spike anti-receptor binding domain (anti-RBD), nucleocapsid IgG antibodies (anti-N) and activation induced marker expressing CD4+, CD8+ T-cells and concentration of ocrelizumab and anti-drug antibodies. Incidences of breakthrough infection were confirmed with SARS-CoV-2 PCR tests.
Results: The rate of anti-RBD positive participants increased substantially between the third and fourth vaccination from 22.2% to 55.9% (median 54.7 BAU/mL; IQR: 14.5 - 221.2 BAU/mL and 607.7 BAU/mL; IQR: 29.4 - 784.6 BAU/mL, respectively). Within the same period 75% of participants experienced breakthrough infection. The fourth vaccination resulted in an additional increase in seropositive individuals (64.3%) (median 541.8 BAU/mL (IQR: 19.1-1007 BAU/mL). Breakthrough infection did not influence the cellular response without a significant change after the fourth vaccination. During the study period two participants had detectable anti-N, both after the fourth vaccination. No correlation was found between serum concentration of ocrelizumab and the humoral and cellular response.
Discussion: Low levels or absence of specific anti-RBD following vaccination, with a significant increase after breakthrough infections and boosted by the fourth vaccination. T-cell reactivity remained sustained and unaffected by breakthrough infections.
Keywords: SARS-CoV-2; anti-CD20; breakthrough infection; cellular immune activation; humoral immune response; mRNA vaccination vulnerable population; multiple sclerosis; ocrelizumab concentration.