2
views
0
recommends
+1 Recommend
1 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

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

      research-article

      Read this article at

      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          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

          Related collections

          Most cited references50

          • Record: found
          • Abstract: found
          • Article: not found

          Targets of T cell responses to SARS-CoV-2 coronavirus in humans with COVID-19 disease and unexposed individuals

          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.
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            Neutralizing antibody levels are highly predictive of immune protection from symptomatic SARS-CoV-2 infection

            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.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              Safety and Immunogenicity of Two RNA-Based Covid-19 Vaccine Candidates

              Abstract Background Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections and the resulting disease, coronavirus disease 2019 (Covid-19), have spread to millions of persons worldwide. Multiple vaccine candidates are under development, but no vaccine is currently available. Interim safety and immunogenicity data about the vaccine candidate BNT162b1 in younger adults have been reported previously from trials in Germany and the United States. Methods In an ongoing, placebo-controlled, observer-blinded, dose-escalation, phase 1 trial conducted in the United States, we randomly assigned healthy adults 18 to 55 years of age and those 65 to 85 years of age to receive either placebo or one of two lipid nanoparticle–formulated, nucleoside-modified RNA vaccine candidates: BNT162b1, which encodes a secreted trimerized SARS-CoV-2 receptor–binding domain; or BNT162b2, which encodes a membrane-anchored SARS-CoV-2 full-length spike, stabilized in the prefusion conformation. The primary outcome was safety (e.g., local and systemic reactions and adverse events); immunogenicity was a secondary outcome. Trial groups were defined according to vaccine candidate, age of the participants, and vaccine dose level (10 μg, 20 μg, 30 μg, and 100 μg). In all groups but one, participants received two doses, with a 21-day interval between doses; in one group (100 μg of BNT162b1), participants received one dose. Results A total of 195 participants underwent randomization. In each of 13 groups of 15 participants, 12 participants received vaccine and 3 received placebo. BNT162b2 was associated with a lower incidence and severity of systemic reactions than BNT162b1, particularly in older adults. In both younger and older adults, the two vaccine candidates elicited similar dose-dependent SARS-CoV-2–neutralizing geometric mean titers, which were similar to or higher than the geometric mean titer of a panel of SARS-CoV-2 convalescent serum samples. Conclusions The safety and immunogenicity data from this U.S. phase 1 trial of two vaccine candidates in younger and older adults, added to earlier interim safety and immunogenicity data regarding BNT162b1 in younger adults from trials in Germany and the United States, support the selection of BNT162b2 for advancement to a pivotal phase 2–3 safety and efficacy evaluation. (Funded by BioNTech and Pfizer; ClinicalTrials.gov number, NCT04368728.)
                Bookmark

                Author and article information

                Contributors
                Journal
                JCI Insight
                JCI Insight
                JCI Insight
                JCI Insight
                American Society for Clinical Investigation
                2379-3708
                22 February 2022
                22 February 2022
                22 February 2022
                : 7
                : 4
                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).
                Article
                156978
                10.1172/jci.insight.156978
                8876469
                35030101
                de6a733f-4540-43c7-9f30-225309a8dd9d
                © 2022 Sabatino et al.

                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/.

                Funding
                Funded by: Office of Extramural Research, National Institutes of Health, https://doi.org/10.13039/100006955;
                Award ID: 1K08NS107619
                Funded by: Office of Extramural Research, National Institutes of Health, https://doi.org/10.13039/100006955;
                Award ID: K08NS096117
                Funded by: Westridge Foundation
                Award ID: N/A
                Funded by: Chan Zuckerberg Biohub
                Award ID: N/A
                Funded by: Office of Extramural Research, National Institutes of Health, https://doi.org/10.13039/100006955;
                Award ID: R01AI159260
                Funded by: Office of Extramural Research, National Institutes of Health, https://doi.org/10.13039/100006955;
                Award ID: R01NS092835
                Funded by: Office of Extramural Research, National Institutes of Health, https://doi.org/10.13039/100006955;
                Award ID: R01AI131624
                Funded by: Office of Extramural Research, National Institutes of Health, https://doi.org/10.13039/100006955;
                Award ID: R21NS108159
                Funded by: National Multiple Sclerosis Society, https://doi.org/10.13039/100000890;
                Award ID: TA-1903-33713
                Funded by: National Multiple Sclerosis Society, https://doi.org/10.13039/100000890;
                Award ID: RG1701-26628
                Funded by: Maisin Foundation
                Award ID: N/A
                Categories
                Clinical Medicine

                autoimmunity,covid-19,adaptive immunity,multiple sclerosis

                Comments

                Comment on this article