Delta or Omicron BA.1/2-neutralizing antibody levels and T-cell reactivity after triple-vaccination or infection

Rose, Ruben; Neumann, Franziska; Müller, S; Bäumler, Carina; Schäfer, Miriam R.; Schön, Frieda; Römpke, Janine; Schulze, Simone; Weyer, Dirk; Grobe, Olaf; Lorentz, Thomas; Fickenscher, Helmut; Krumbholz, Andi

doi:10.22541/au.164854470.08362985/v1

Cited by 2 publications

(18 citation statements)

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“…Six months after second vaccination, BA.2 NAs were not detected in any of the three study groups, suggesting that the S antigen of this VOC is relevantly different from that of wt and derived VOCs, consistent with recent studies. (10,24) The loss of IgG avidity was unexpected as anti-TNFα patients displayed similarly high IgG avidity as the other groups at day 14 post second vaccination. Conversely, other studies have shown, that the avidity of anti-SARS-CoV-2 IgG increases during the subsequent months after vaccination.…”

Section: Discussionmentioning

confidence: 95%

“…After surface staining with CD4-APC-Vio770 (M-T466), CD8-VioGreen (REA734), Measurement of neutralising antibodies against a pre-VOC strain and a BA.2 strain Sera were tested in triplicate using a Vero cell-based live virus neutralisation test (cVNT) in 96-well format under biosafety level 3 conditions, as previously reported. (10,22) In brief, sera were diluted 1:10 to 1:1280 in cell culture medium free of fetal calf serum. As antigens for the cVNT, we used either 50 plaque-forming units per well of a B.1 strain (pre-VOC of 2020) or an Omicron BA.2 strain, which we had previously isolated (23) and characterised by whole-genome sequencing.…”

Section: Measurement Of Antibody Secreting Cells By Three-colour Fluo...mentioning

confidence: 99%

“…Serum dilutions (titres) > 1:10 that prevented the formation of a cytopathic effect in ≥2 wells were considered to contain neutralising antibodies (NA); if no exact titre could be given, the geometric mean of the two adjacent titres was calculated. (10,22) Data analysis and statistics…”

Section: Measurement Of Antibody Secreting Cells By Three-colour Fluo...mentioning

confidence: 99%

“…(8) Sera from vaccinated healthy individuals show only limited neutralisation capacity against Omicron (B.1.1.529) VOC. (9,10) This variant, consisting of several sublineages, including BA.1 and BA.2, is considered a separate serotype that is antigenically distinct from the original Wuhan strain (designated here as wild-type, wt, or pre-VOC) and other VOCs. (11) The marked immune escape of BA.1 and BA.2 and the importance of booster vaccination for the development of NA against both sublineages have recently been demonstrated, (10) especially the need of mRNA boost immunisations for persons vaccinated with inactivated viruses.…”

Section: Introductionmentioning

confidence: 99%

“…(9,10) This variant, consisting of several sublineages, including BA.1 and BA.2, is considered a separate serotype that is antigenically distinct from the original Wuhan strain (designated here as wild-type, wt, or pre-VOC) and other VOCs. (11) The marked immune escape of BA.1 and BA.2 and the importance of booster vaccination for the development of NA against both sublineages have recently been demonstrated, (10) especially the need of mRNA boost immunisations for persons vaccinated with inactivated viruses. (12) Only limited data are available on the persistence of NA against various SARS-CoV-2 lineages (including Omicron) in CID patients receiving anti-TNFα therapy after double vaccination.…”

Section: Introductionmentioning

confidence: 99%

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Multiple effects of TNFα inhibitors on the development of the adaptive immune response after SARS-CoV-2 vaccination

Geisen¹,

Rose

Neumann³

et al. 2022

Preprint

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Objectives: The humoral immune response to SARS-CoV-2 vaccination in patients with chronic inflammatory disease (CID) declines more rapidly with TNFα inhibition. Furthermore, the efficacy of current vaccines against Omicron variants of concern (VOC) including BA.2 is limited. Alterations within immune cell populations, changes in IgG affinity and the ability to neutralise a pre-VOC strain and the BA.2 virus were investigated in these at-risk patients. Methods: Serum levels of anti-SARS-CoV-2 IgG, IgG avidity and neutralising antibodies (NA) were determined in anti-TNFα patients (n=10) and controls (n=24 healthy individuals; n=12 patients under other disease-modifying anti-rheumatic drugs, oDMARD) before and after the second and third vaccination by ELISA, immunoblot and live virus neutralisation assay. SARS-CoV-2-specific B- and T cell subsets were analysed by multicolour flow cytometry. Results: IgG avidity and anti-pre-VOC NA titres decreased faster in anti-TNFα recipients than in controls 6 months after the second vaccination (healthy individuals: avidity: p≤0.0001; NA: p=0.0347; oDMARDs: avidity: p=0.0012; NA: p=0.0293). Total plasma cell counts were increased in anti-TNFα patients (Healthy individuals: p=0.0344; oDMARDs: p=0.0254), whereas absolute numbers of SARS-CoV-2-specific cells were comparable 7 days after vaccination. These patients had lower BA.2 NA titres compared to both other groups, even after the third vaccination. Conclusions: We show a reduced SARS-CoV-2 neutralising capacity in patients under TNFα blockade. In this cohort, the plasma cell response appears to be less specific and show stronger bystander activation. While these effects were observable after the first two vaccinations and with older VOC, the differences in responses to BA.2 were magnified.

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Section: Discussionmentioning

confidence: 95%

Section: Measurement Of Antibody Secreting Cells By Three-colour Fluo...mentioning

confidence: 99%

Section: Measurement Of Antibody Secreting Cells By Three-colour Fluo...mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Multiple effects of TNFα inhibitors on the development of the adaptive immune response after SARS-CoV-2 vaccination

Geisen¹,

Rose

Neumann³

et al. 2022

Preprint

Self Cite

View full text Add to dashboard Cite

show abstract

The long term vaccine‐induced anti‐SARS‐CoV‐2 immune response is impaired in quantity and quality under TNFα blockade

Geisen¹,

Rose

Neumann³

et al. 2022

Journal of Medical Virology

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The humoral immune response to severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) vaccination in patients with chronic inflammatory disease (CID) declines more rapidly with tumor necrosis factor‐α (TNF‐α) inhibition. Furthermore, the efficacy of current vaccines against Omicron variants of concern (VOC) including BA.2 is limited. Alterations within immune cell populations, changes in IgG affinity, and the ability to neutralize a pre‐VOC strain and the BA.2 virus were investigated in these at‐risk patients. Serum levels of anti‐SARS‐CoV‐2 IgG, IgG avidity, and neutralizing antibodies (NA) were determined in anti‐TNF‐α patients ( n = 10) and controls ( n = 24 healthy individuals; n = 12 patients under other disease‐modifying antirheumatic drugs, oDMARD) before and after the second and third vaccination by ELISA, immunoblot and live virus neutralization assay. SARS‐CoV‐2‐specific B‐ and T cell subsets were analysed by multicolor flow cytometry. Six months after the second vaccination, anti‐SARS‐CoV‐2 IgG levels, IgG avidity and anti‐pre‐VOC NA titres were significantly reduced in anti‐TNF‐α recipients compared to controls (healthy individuals: avidity: p ≤ 0.0001; NA: p = 0.0347; oDMARDs: avidity: p = 0.0012; NA: p = 0.0293). The number of plasma cells was increased in anti‐TNF‐α patients (Healthy individuals: p = 0.0344; oDMARDs: p = 0.0254), while the absolute number of SARS‐CoV‐2‐specific plasma cells 7 days after 2nd vaccination were comparable. Even after a third vaccination, these patients had lower anti‐BA.2 NA titres compared to both other groups. We show a reduced SARS‐CoV‐2 neutralizing capacity in patients under TNF‐α blockade. In this cohort, the plasma cell response appears to be less specific and shows stronger bystander activation. While these effects were observable after the first two vaccinations and with older VOC, the differences in responses to BA.2 were enhanced.

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Delta or Omicron BA.1/2-neutralizing antibody levels and T-cell reactivity after triple-vaccination or infection

Cited by 2 publications

References 0 publications

Multiple effects of TNFα inhibitors on the development of the adaptive immune response after SARS-CoV-2 vaccination

Multiple effects of TNFα inhibitors on the development of the adaptive immune response after SARS-CoV-2 vaccination

The long term vaccine‐induced anti‐SARS‐CoV‐2 immune response is impaired in quantity and quality under TNFα blockade

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