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Correction: Ziemssen et al. Immune Response to Initial and Booster SARS-CoV-2 mRNA Vaccination in Patients Treated with Siponimod—Final Analysis of a Nonrandomized Controlled Clinical Trial (AMA-VACC). Vaccines 2023, 11, 1374

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The authors would like to make the following corrections to this published paper [...]
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Citation: Ziemssen, T.; Groth, M.;
Winkelmann, V.E.; Bopp, T.
Correction: Ziemssen et al. Immune
Response to Initial and Booster
SARS-CoV-2 mRNA Vaccination in
Patients Treated with
Siponimod—Final Analysis of a
Nonrandomized Controlled Clinical
Trial (AMA-VACC). Vaccines 2023, 11,
1374. Vaccines 2024,12, 911.
https://doi.org/10.3390/
vaccines12080911
Received: 2 July 2024
Accepted: 6 August 2024
Published: 12 August 2024
Copyright: © 2024 by the authors.
Licensee MDPI, Basel, Switzerland.
This article is an open access article
distributed under the terms and
conditions of the Creative Commons
Attribution (CC BY) license (https://
creativecommons.org/licenses/by/
4.0/).
Correction
Correction: Ziemssen et al. Immune Response to Initial and
Booster SARS-CoV-2 mRNA Vaccination in Patients Treated
with Siponimod—Final Analysis of a Nonrandomized
Controlled Clinical Trial (AMA-VACC). Vaccines 2023, 11, 1374
Tjalf Ziemssen 1, * , Marie Groth 2, Veronika Eva Winkelmann 2and Tobias Bopp 3
1Department of Neurology, Center of Clinical Neuroscience, Carl Gustav Carus University Clinic,
University Hospital of Dresden, Technische Universität Dresden, 01307 Dresden, Germany
2Novartis Pharma GmbH, 90429 Nuremberg, Germany; marie.groth@novartis.com (M.G.);
veronika.winkelmann@novartis.com (V.E.W.)
3Institute for Immunology, University Medical Center of the Johannes Gutenberg University, 55131 Mainz,
Germany; boppt@uni-mainz.de
*Correspondence: tjalf.ziemssen@uniklinikum-dresden.de
The authors would like to make the following corrections to this published paper [
1
].
There was a mistake in the legend and picture for Figure 1. For month 6 for the cohort
“siponimod continuous”, one patient’s data were missing. This also affected the number of
booster patients with identical month 6 and month 1 after the booster visit in the figure
legend (old: 10 booster patients with n = 6 in cohort 1; corrected: 11 booster patients with
n = 7 in cohort 1). The correct legend and figure appear below.
There was a mistake in the legend and picture for Figure 2. The number of booster pa-
tients with identical month 6 and month 1 after the booster visit was wrong (old: 10 booster
patients with n = 6 in cohort 1; corrected: 11 booster patients with n = 7 in cohort 1). The
labels of the x-axis of Figure 2A for month 1 after the booster in the cohort “siponimod
continuous” contained an error (old: n = 16; corrected: n = 14). Furthermore, in the analysis
of total anti-spike antibodies (Figure 2B), patients with an invalid control had been erro-
neously included. This has been corrected in accordance with an amendment to the clinical
study report. The correct legend and figure appear below.
There was a mistake in the legend and picture for Supplementary Figure S1. In
Figure S1A,
one patient’s data were missing at month 6 in the cohort “siponimod con-
tinuous” and have since been added. This change also affected the figure legend: the
explanation on the missing data (*) had to be revised (old: *one sample missing for month 1
and month 6; corrected: *one sample missing for month 1), as well as the number of booster
patients with identical month 6 and month 1 after the booster visit (old: 10 booster patients
with n = 6 in cohort 1; corrected: 11 booster patients with n = 7 in cohort 1). Furthermore,
the explanations on missing data in Figure S1 (*, **) were not clearly assigned to part (B) of
the figure legend. The explanations have been moved up. The correct legend and figure
appear below.
The proportion of patients with SARS-CoV-2-specific T-cell responses in cohort 1
mentioned within the text (Abstract and Results) was inconsistent with the data in Figure 2A
(old text version: 28.5%; corrected text version: 26.7%). The original sentence in the Abstract,
“T-cell responses were seen in 28.5%, 25.0%, and 73.7% at month 6 and in 28.6%, 50.0%, and
83.3% after the booster (cohorts 1, 2, and 3, respectively)”, should be changed to “T-cell
responses were seen in 26.7%, 25.0%, and 73.7% at month 6 and in 28.6%, 50.0%, and 83.3%
after the booster (cohorts 1, 2, and 3, respectively).” The first sentence in Paragraph 3,
Results Section, “SARS-CoV-2-specific T-cell responses were seen in only 28.5% (cohort
1) and 25.0% (cohort 2) at month 6, as well as in 28.6% (cohort 1) and 50.0% (cohort 2) at
month 1 after the booster”, should be updated to “SARS-CoV-2-specific T-cell responses
Vaccines 2024,12, 911. https://doi.org/10.3390/vaccines12080911 https://www.mdpi.com/journal/vaccines
Vaccines 2024,12, 911 2 of 4
were seen in only 26.7% (cohort 1) and 25.0% (cohort 2) at month 6, as well as in 28.6%
(cohort 1) and 50.0% (cohort 2) at month 1 after the booster”.
The authors state that the scientific conclusions are unaffected.
These corrections were approved by the Academic Editor. The original publication
has also been updated.
Vaccines2024,12,xFORPEERREVIEW2of4
Figure1.(A)SARSCoV2specicneutralizingantibodylevelsinU/mL.(B)SARSCoV2specic
serumtotalantibodylevelsinU/mL.Allthepatientswithavailabledatawereincludedinthe
analysis,andindividualvaluesarerepresentedbydots.For11boosterpatients,themonth6visit
andthemonth1aftertheboostervisitwereidentical(cohort1:n=7;cohort2:n=1;cohort3:n=3).
Thebarsshowthemedianvalues;theblackdoedlinesindicateassayspeciccutosfor
seropositivity;andthegraydoedlinesindicatethemaximalvalueofthequanticationrange.
DMF:dimethylfumarate;GA:glatirameracetate;IFN:interferonbeta;n:numberofpatientswith
assessments;TF:teriunomide;andU:units.
Figure 1.
(
A
) SARS-CoV-2-specific neutralizing antibody levels in U/mL. (
B
) SARS-CoV-2-specific
serum total antibody levels in U/mL. All the patients with available data were included in the
analysis, and individual values are represented by dots. For 11 booster patients, the month 6 visit and
the month 1 after the booster visit were identical (cohort 1: n = 7; cohort 2: n = 1; cohort 3: n = 3). The
bars show the median values; the black dotted lines indicate assay-specific cut-offs for seropositivity;
and the gray dotted lines indicate the maximal value of the quantification range. DMF: dimethyl
fumarate; GA: glatiramer acetate; IFN: interferon-beta; n: number of patients with assessments; TF:
teriflunomide; and U: units.
Vaccines 2024,12, 911 3 of 4
Vaccines2024,12,xFORPEERREVIEW3of4
Figure2.(A)T-cellresponsedenedasthepresenceofSARS-CoV-2-reactiveT-cellsmeasuredby
thesecretionofeitherIFN-,IL-2,orboth(anylevelabovebasalactivity);(B)ELISpot-based
quanticationofT-cellreactivitybycalculationofIFN-stimulationindicestowardsSARS-CoV-2.
Eachdotrepresentsonepatient,andthemediansareindicatedbyhorizontallines.DMF:dimethyl
fumarate;GA:glatirameracetate;IFN:interferon-beta;IFN-:interferon-;n:numberofpatientswith
assessments;PBMC:peripheralbloodmononuclearcell;andTF:teriunomide.TheT-cellresponse
couldnotbeassessedinthreepatientswiththecontinuedsiponimodtreatment,onepatientinthe
controlgroupatthemonth6visit,andtwopatientsofcohort3atmonth1aftertheboosterbecause
ofinsucientcellcountsafterPBMCisolation.For11boosterpatients,themonth6visitandthe
month1aftertheboostervisitwereidentical(cohort1:n=7;cohort2:n=1;cohort3:n=3).
Figure 2.
(
A
) T-cell response defined as the presence of SARS-CoV-2-reactive T-cells measured
by the secretion of either IFN-, IL-2, or both (any level above basal activity); (
B
) ELISpot-based
quantification of T-cell reactivity by calculation of IFN- stimulation indices towards SARS-CoV-
2. Each dot represents one patient, and the medians are indicated by horizontal lines. DMF:
dimethyl fumarate; GA: glatiramer acetate; IFN: interferon-beta; IFN-: interferon-; n: number of
patients with assessments; PBMC: peripheral blood mononuclear cell; and TF: teriflunomide. The
T-cell response could not be assessed in three patients with the continued siponimod treatment,
one patient in the control group at the month 6 visit, and two patients of cohort 3 at month 1 after
the booster because of insufficient cell counts after PBMC isolation. For 11 booster patients, the
month 6 visit and the month 1 after the booster visit were identical (cohort 1: n = 7; cohort 2: n = 1;
cohort 3: n = 3).
Vaccines 2024,12, 911 4 of 4
Vaccines2024,12,xFORPEERREVIEW4of4
FigureS1.SARS-CoV-2-specicneutralizingantibodylevelsinU/mLbythetimingofbooster
vaccination.(A)Boostervaccinationbeforemonth6;*onesamplemissingformonth1.(B)Booster
vaccinationaftermonth6;*onesamplemissingformonth6andmonth1afterbooster;and**two
patientsdidnotreceiveaboostervaccination.Allthepatientswithavailabledatawereincludedin
theanalysis,andtheindividualvaluesarerepresentedbydots.For11boosterpatients,themonth
6visitandthemonth1afterboostervisitwereidentical(cohort1:n=7;cohort2:n=1;cohort3:n
=3).Thebarsshowthemedianvalues,andtheblackdoedlinesindicatetheassay-speciccut-off
forseropositivity.DMF:dimethylfumarate;GA:glatirameracetate,IFN:interferon-beta;IU:
internationalunits;n:numberofpatientswithassessments;andTF:teriunomide.
TheproportionofpatientswithSARS-CoV-2-specicT-cellresponsesincohort1
mentionedwithinthetext(AbstractandResults)wasinconsistentwiththedatainFigure
2A(oldtextversion:28.5%;correctedtextversion:26.7%).Theoriginalsentenceinthe
Abstract,“T-cellresponseswereseenin28.5%,25.0%,and73.7%atmonth6andin28.6%,
50.0%,and83.3%afterthebooster(cohorts1,2,and3,respectively)”,shouldbechanged
to“T-cellresponseswereseenin26.7%,25.0%,and73.7%atmonth6andin28.6%,50.0%,
and83.3%afterthebooster(cohorts1,2,and3,respectively).”Therstsentencein
Paragraph3,ResultsSection,“SARS-CoV-2-specicT-cellresponseswereseeninonly
28.5%(cohort1)and25.0%(cohort2)atmonth6,aswellasin28.6%(cohort1)and50.0%
(cohort2)atmonth1afterthebooster”,shouldbeupdatedto“SARS-CoV-2-specicT-
cellresponseswereseeninonly26.7%(cohort1)and25.0%(cohort2)atmonth6,aswell
asin28.6%(cohort1)and50.0%(cohort2)atmonth1afterthebooster.”
Theauthorsstatethatthescienticconclusionsareunaected.
ThesecorrectionswereapprovedbytheAcademicEditor.Theoriginalpublication
hasalsobeenupdated.
Reference
1. Ziemssen,T.;Groth,M.;Winkelmann,V.E.;Bopp,T.ImmuneResponsetoInitialandBoosterSARS-CoV-2mRNAVaccination
inPatientsTreatedwithSiponimodFinalAnalysisofaNonrandomizedControlledClinicalTrial(AMA-VACC).Vaccines2023,
11,1374.https://doi.org/10.3390/vaccines11081374.
Disclaimer/PublishersNote:Thestatements,opinionsanddatacontainedinallpublicationsaresolelythoseoftheindividual
author(s)andcontributor(s)andnotofMDPIand/ortheeditor(s).MDPIand/ortheeditor(s)disclaimresponsibilityforanyinjury
topeopleorpropertyresultingfromanyideas,methods,instructionsorproductsreferredtointhecontent.
Figure S1.
SARS-CoV-2-specific neutralizing antibody levels in U/mL by the timing of booster vacci-
nation. (
A
) Booster vaccination before month 6; * one sample missing for month 1. (
B
) Booster vacci-
nation after month 6; * one sample missing for month 6 and month 1 after booster; and
** two patients
did not receive a booster vaccination. All the patients with available data were included in the
analysis, and the individual values are represented by dots. For 11 booster patients, the month
6 visit and the month 1 after booster visit were identical (cohort 1: n = 7; cohort 2: n = 1; cohort
3: n = 3). The bars show the median values, and the black dotted lines indicate the assay-specific
cut-off for seropositivity. DMF: dimethyl fumarate; GA: glatiramer acetate, IFN: interferon-beta; IU:
international units; n: number of patients with assessments; and TF: teriflunomide.
Reference
1.
Ziemssen, T.; Groth, M.; Winkelmann, V.E.; Bopp, T. Immune Response to Initial and Booster SARS-CoV-2 mRNA Vaccination in
Patients Treated with Siponimod—Final Analysis of a Nonrandomized Controlled Clinical Trial (AMA-VACC). Vaccines
2023
,
11, 1374. [CrossRef]
Disclaimer/Publisher’s Note:
The statements, opinions and data contained in all publications are solely those of the individual
author(s) and contributor(s) and not of MDPI and/or the editor(s). MDPI and/or the editor(s) disclaim responsibility for any injury to
people or property resulting from any ideas, methods, instructions or products referred to in the content.
ResearchGate has not been able to resolve any citations for this publication.
Article
Full-text available
Background: Evidence on SARS-CoV-2 mRNA vaccination under siponimod treatment is rare. Methods: AMA-VACC is a prospective, open-label clinical study on SARS-CoV-2 mRNA vaccination during ongoing siponimod treatment (cohort 1), during siponimod interruption (cohort 2), or during treatment with other disease-modifying therapies or without therapy (cohort 3). SARS-CoV-2-specific antibodies and T-cell reactivity were measured six months after the initial vaccination and one month after the booster. Results: 41 patients were recruited into cohort 1 (n = 17), cohort 2 (n = 4), and cohort 3 (n = 20). Seroconversion for SARS-CoV-2 neutralizing antibodies was reached by 50.0%, 100.0%, and 90.0% of patients at month 6 and by 81.3%, 100.0%, and 100.0% one month after booster (cohorts 1, 2, and 3, respectively). Antibody levels in cohort 1 increased after the booster compared to month 6 but remained lower compared to cohorts 2 and 3. T-cell responses were seen in 28.5%, 25.0%, and 73.7% at month 6 and in 28.6%, 50.0%, and 83.3% after the booster (cohorts 1, 2, and 3, respectively). In cohort 1, the extent of T-cell response was lower at month 6 compared to cohorts 2 and 3 but reached almost similar levels after the booster. Conclusions: The antibody and T-cell responses support SARS-CoV-2 (booster) vaccines in siponimod-treated patients.