Multiple sclerosis therapies differentially affect SARS-CoV-2 vaccine–induced antibody and T cell immunity and function

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Abstract

BACKGROUND

Vaccine-elicited adaptive immunity is a prerequisite for control of SARS-CoV-2 infection. Multiple sclerosis (MS) disease-modifying therapies (DMTs) differentially target humoral and cellular immunity. A comprehensive comparison of the effects of MS DMTs on SARS-CoV-2 vaccine–specific immunity is needed, including quantitative and functional B and T cell responses.

METHODS

Spike-specific Ab and T cell responses were measured before and following SARS-CoV-2 vaccination in a cohort of 80 study participants, including healthy controls and patients with MS in 6 DMT groups: untreated and treated with glatiramer acetate (GA), dimethyl fumarate (DMF), natalizumab (NTZ), sphingosine-1-phosphate (S1P) receptor modulators, and anti-CD20 mAbs. Anti–spike-Ab responses were assessed by Luminex assay, VirScan, and pseudovirus neutralization. Spike-specific CD4 ⁺ and CD8 ⁺ T cell responses were characterized by activation-induced marker and cytokine expression and tetramer.

RESULTS

Anti-spike IgG levels were similar between healthy control participants and patients with untreated MS and those receiving GA, DMF, or NTZ but were reduced in anti-CD20 mAb– and S1P-treated patients. Anti-spike seropositivity in anti-CD20 mAb–treated patients was correlated with CD19 ⁺ B cell levels and inversely correlated with cumulative treatment duration. Spike epitope reactivity and pseudovirus neutralization were reduced in anti-CD20 mAb– and S1P-treated patients. Spike-specific CD4 ⁺ and CD8 ⁺ T cell reactivity remained robust across all groups, except in S1P-treated patients, in whom postvaccine CD4 ⁺ T cell responses were attenuated.

CONCLUSION

These findings from a large cohort of patients with MS exposed to a wide spectrum of MS immunotherapies have important implications for treatment-specific COVID-19 clinical guidelines.

FUNDING

NIH grants 1K08NS107619, K08NS096117, R01AI159260, R01NS092835, R01AI131624, and R21NS108159; NMSS grants TA-1903-33713 and RG1701-26628; Westridge Foundation; Chan Zuckerberg Biohub; Maisin Foundation.

Abstract

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Alba Grifoni, Daniela Weiskopf, Sydney Ramirez … (2020)

Summary Understanding adaptive immunity to SARS-CoV-2 is important for vaccine development, interpreting coronavirus disease 2019 (COVID-19) pathogenesis, and calibration of pandemic control measures. Using HLA class I and II predicted peptide ‘megapools’, circulating SARS-CoV-2−specific CD8+ and CD4+ T cells were identified in ∼70% and 100% of COVID-19 convalescent patients, respectively. CD4+ T cell responses to spike, the main target of most vaccine efforts, were robust and correlated with the magnitude of the anti-SARS-CoV-2 IgG and IgA titers. The M, spike and N proteins each accounted for 11-27% of the total CD4+ response, with additional responses commonly targeting nsp3, nsp4, ORF3a and ORF8, among others. For CD8+ T cells, spike and M were recognized, with at least eight SARS-CoV-2 ORFs targeted. Importantly, we detected SARS-CoV-2−reactive CD4+ T cells in ∼40-60% of unexposed individuals, suggesting cross-reactive T cell recognition between circulating ‘common cold’ coronaviruses and SARS-CoV-2.

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Predictive models of immune protection from COVID-19 are urgently needed to identify correlates of protection to assist in the future deployment of vaccines. To address this, we analyzed the relationship between in vitro neutralization levels and the observed protection from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection using data from seven current vaccines and from convalescent cohorts. We estimated the neutralization level for 50% protection against detectable SARS-CoV-2 infection to be 20.2% of the mean convalescent level (95% confidence interval (CI) = 14.4-28.4%). The estimated neutralization level required for 50% protection from severe infection was significantly lower (3% of the mean convalescent level; 95% CI = 0.7-13%, P = 0.0004). Modeling of the decay of the neutralization titer over the first 250 d after immunization predicts that a significant loss in protection from SARS-CoV-2 infection will occur, although protection from severe disease should be largely retained. Neutralization titers against some SARS-CoV-2 variants of concern are reduced compared with the vaccine strain, and our model predicts the relationship between neutralization and efficacy against viral variants. Here, we show that neutralization level is highly predictive of immune protection, and provide an evidence-based model of SARS-CoV-2 immune protection that will assist in developing vaccine strategies to control the future trajectory of the pandemic.

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Alan Thompson, Brenda Banwell, Frederik Barkhof … (2018)

The 2010 McDonald criteria for the diagnosis of multiple sclerosis are widely used in research and clinical practice. Scientific advances in the past 7 years suggest that they might no longer provide the most up-to-date guidance for clinicians and researchers. The International Panel on Diagnosis of Multiple Sclerosis reviewed the 2010 McDonald criteria and recommended revisions. The 2017 McDonald criteria continue to apply primarily to patients experiencing a typical clinically isolated syndrome, define what is needed to fulfil dissemination in time and space of lesions in the CNS, and stress the need for no better explanation for the presentation. The following changes were made: in patients with a typical clinically isolated syndrome and clinical or MRI demonstration of dissemination in space, the presence of CSF-specific oligoclonal bands allows a diagnosis of multiple sclerosis; symptomatic lesions can be used to demonstrate dissemination in space or time in patients with supratentorial, infratentorial, or spinal cord syndrome; and cortical lesions can be used to demonstrate dissemination in space. Research to further refine the criteria should focus on optic nerve involvement, validation in diverse populations, and incorporation of advanced imaging, neurophysiological, and body fluid markers.

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Author and article information

Contributors

Joseph J. Sabatino Jr.:

ORCID: http://orcid.org/0000-0002-6804-7441

Kristen Mittl

William M. Rowles:

ORCID: http://orcid.org/0000-0002-5613-0483

Jayant V. Rajan

Matthew T. Laurie:

ORCID: http://orcid.org/0000-0002-3526-7368

Colin R. Zamecnik:

ORCID: http://orcid.org/0000-0002-9477-1388

Ravi Dandekar

Bonny D. Alvarenga:

ORCID: http://orcid.org/0000-0001-7922-9454

Rita P. Loudermilk:

ORCID: http://orcid.org/0000-0001-9970-5112

Chloe Gerungan

Collin M. Spencer:

ORCID: http://orcid.org/0000-0002-3999-7499

Sharon A. Sagan

Danillo G. Augusto:

ORCID: http://orcid.org/0000-0001-5665-8547

Jessa R. Alexander:

ORCID: http://orcid.org/0000-0003-4461-2060

Joseph L. DeRisi:

ORCID: http://orcid.org/0000-0002-4611-9205

Jill A. Hollenbach:

ORCID: http://orcid.org/0000-0001-6572-7962

Michael R. Wilson:

ORCID: http://orcid.org/0000-0002-8705-5084

Scott S. Zamvil:

ORCID: http://orcid.org/0000-0003-2720-9915

Riley Bove:

ORCID: http://orcid.org/0000-0002-2034-8800

Journal

Journal ID (nlm-ta): JCI Insight

Journal ID (iso-abbrev): JCI Insight

Journal ID (publisher-id): JCI Insight

Title: JCI Insight

Publisher: American Society for Clinical Investigation

ISSN (Electronic): 2379-3708

Publication date (Electronic, pub): 22 February 2022

Publication date (Electronic, collection): 22 February 2022

Publication date PMC-release: 22 February 2022

Volume: 7

Issue: 4

Electronic Location Identifier: e156978

Affiliations

[1 ]Weill Institute for Neurosciences, Department of Neurology,

[2 ]Division of Experimental Medicine, Department of Medicine, Zuckerberg San Francisco General Hospital, and

[3 ]Department of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, California, USA.

[4 ]Postgraduate Program in Genetics, Federal University of Paraná, Curitiba, Brazil.

[5 ]Chan Zuckerberg Biohub, San Francisco, California, USA.

[6 ]Department of Epidemiology and Biostatistics and

[7 ]Program in Immunology, University of California, San Francisco, San Francisco, California, USA.

Author notes

Address correspondence to: Joseph Sabatino or Riley Bove, 1651 4th St, San Francisco, California 94158, USA. Phone: 415.353.2069; Email: joseph.sabatinojr@ 123456ucsf.edu (JS); Email: riley.bove@ 123456ucsf.edu (RB).

Author information

Joseph J. Sabatino Jr. http://orcid.org/0000-0002-6804-7441

William M. Rowles http://orcid.org/0000-0002-5613-0483

Matthew T. Laurie http://orcid.org/0000-0002-3526-7368

Colin R. Zamecnik http://orcid.org/0000-0002-9477-1388

Bonny D. Alvarenga http://orcid.org/0000-0001-7922-9454

Rita P. Loudermilk http://orcid.org/0000-0001-9970-5112

Collin M. Spencer http://orcid.org/0000-0002-3999-7499

Danillo G. Augusto http://orcid.org/0000-0001-5665-8547

Jessa R. Alexander http://orcid.org/0000-0003-4461-2060

Joseph L. DeRisi http://orcid.org/0000-0002-4611-9205

Jill A. Hollenbach http://orcid.org/0000-0001-6572-7962

Michael R. Wilson http://orcid.org/0000-0002-8705-5084

Scott S. Zamvil http://orcid.org/0000-0003-2720-9915

Riley Bove http://orcid.org/0000-0002-2034-8800

Article

Publisher ID: 156978

DOI: 10.1172/jci.insight.156978

PMC ID: 8876469

PubMed ID: 35030101

SO-VID: de6a733f-4540-43c7-9f30-225309a8dd9d

License:

This work is licensed under the Creative Commons Attribution 4.0 International License. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.