SARS-CoV-2 Vaccine-Elicited Immunity After B Cell Depletion in Multiple Sclerosis

Overview

Journal Immunohorizons

Specialty Allergy & Immunology

Date 2024 Mar 14

PMID 38483384

Authors

Ryan M Baxter

Berenice Cabrera-Martinez

Tusharkanti Ghosh

Cody Rester

Miguel Guerrero Moreno

Tyler L Borko

Sean Selva

Chelsie L Fleischer

Nicola Haakonsen

Ariana Mayher

Emily Bowhay

Courtney Evans

Todd M Miller

Leah Huey

Jennifer McWilliams

Adrie Van Bokhoven

Kevin D Deane

Vijaya Knight

Kimberly R Jordan

Debashis Ghosh

Jared Klarquist

Ross M Kedl

Amanda L Piquet

Elena W Y Hsieh

Affiliations

Soon will be listed here.

Abstract

The impact of B cell deficiency on the humoral and cellular responses to SARS-CoV2 mRNA vaccination remains a challenging and significant clinical management question. We evaluated vaccine-elicited serological and cellular responses in 1) healthy individuals who were pre-exposed to SARS-CoV-2 (n = 21), 2) healthy individuals who received a homologous booster (mRNA, n = 19; or Novavax, n = 19), and 3) persons with multiple sclerosis on B cell depletion therapy (MS-αCD20) receiving mRNA homologous boosting (n = 36). Pre-exposure increased humoral and CD4 T cellular responses in immunocompetent individuals. Novavax homologous boosting induced a significantly more robust serological response than mRNA boosting. MS-α CD20 had an intact IgA mucosal response and an enhanced CD8 T cell response to mRNA boosting compared with immunocompetent individuals. This enhanced cellular response was characterized by the expansion of only effector, not memory, T cells. The enhancement of CD8 T cells in the setting of B cell depletion suggests a regulatory mechanism between B and CD8 T cell vaccine responses.

References

Bates T, McBride S, Leier H, Guzman G, Lyski Z, Schoen D . Vaccination before or after SARS-CoV-2 infection leads to robust humoral response and antibodies that effectively neutralize variants. Sci Immunol. 2022; 7(68):eabn8014. PMC: 8939472. DOI: 10.1126/sciimmunol.abn8014. View

B Gilbert P, Donis R, Koup R, Fong Y, Plotkin S, Follmann D . A Covid-19 Milestone Attained - A Correlate of Protection for Vaccines. N Engl J Med. 2022; 387(24):2203-2206. DOI: 10.1056/NEJMp2211314. View

Wratil P, Stern M, Priller A, Willmann A, Almanzar G, Vogel E . Three exposures to the spike protein of SARS-CoV-2 by either infection or vaccination elicit superior neutralizing immunity to all variants of concern. Nat Med. 2022; 28(3):496-503. DOI: 10.1038/s41591-022-01715-4. View

Schultz J, McCarthy M, Rester C, Sabourin K, Annen K, DomBourian M . Development and Validation of a Multiplex Microsphere Immunoassay Using Dried Blood Spots for SARS-CoV-2 Seroprevalence: Application in First Responders in Colorado, USA. J Clin Microbiol. 2021; 59(6). PMC: 8315929. DOI: 10.1128/JCM.00290-21. View

Garcia-Beltran W, Denis K, Hoelzemer A, Lam E, Nitido A, Sheehan M . mRNA-based COVID-19 vaccine boosters induce neutralizing immunity against SARS-CoV-2 Omicron variant. Cell. 2022; 185(3):457-466.e4. PMC: 8733787. DOI: 10.1016/j.cell.2021.12.033. View

Mei H, Frolich D, Giesecke C, Loddenkemper C, Reiter K, Schmidt S . Steady-state generation of mucosal IgA+ plasmablasts is not abrogated by B-cell depletion therapy with rituximab. Blood. 2010; 116(24):5181-90. DOI: 10.1182/blood-2010-01-266536. View

Perry C, Luttwak E, Balaban R, Shefer G, Morales M, Aharon A . Efficacy of the BNT162b2 mRNA COVID-19 vaccine in patients with B-cell non-Hodgkin lymphoma. Blood Adv. 2021; 5(16):3053-3061. PMC: 8362658. DOI: 10.1182/bloodadvances.2021005094. View

Belik M, Jalkanen P, Lundberg R, Reinholm A, Laine L, Vaisanen E . Comparative analysis of COVID-19 vaccine responses and third booster dose-induced neutralizing antibodies against Delta and Omicron variants. Nat Commun. 2022; 13(1):2476. PMC: 9072399. DOI: 10.1038/s41467-022-30162-5. View

Lucchini M, Bianco A, Del Giacomo P, De Fino C, Nociti V, Mirabella M . Is serological response to SARS-CoV-2 preserved in MS patients on ocrelizumab treatment? A case report. Mult Scler Relat Disord. 2020; 44:102323. PMC: 7307994. DOI: 10.1016/j.msard.2020.102323. View

10.

He Y, Shimoda M, Ono Y, Villalobos I, Mitra A, Konia T . Persistence of Autoreactive IgA-Secreting B Cells Despite Multiple Immunosuppressive Medications Including Rituximab. JAMA Dermatol. 2015; 151(6):646-50. DOI: 10.1001/jamadermatol.2015.59. View

11.

Sadoff J, Gray G, Vandebosch A, Cardenas V, Shukarev G, Grinsztejn B . Safety and Efficacy of Single-Dose Ad26.COV2.S Vaccine against Covid-19. N Engl J Med. 2021; 384(23):2187-2201. PMC: 8220996. DOI: 10.1056/NEJMoa2101544. View

12.

Pilz S, Theiler-Schwetz V, Trummer C, Krause R, Ioannidis J . SARS-CoV-2 reinfections: Overview of efficacy and duration of natural and hybrid immunity. Environ Res. 2022; 209:112911. PMC: 8824301. DOI: 10.1016/j.envres.2022.112911. View

13.

Muller R, Maier R, Hoschler K, Zambon M, Ludewig B, Herrmann M . Efficient boosting of the antiviral T cell response in B cell-depleted patients with autoimmune rheumatic diseases following influenza vaccination. Clin Exp Rheumatol. 2013; 31(5):723-30. View

14.

Tartof S, Slezak J, Fischer H, Hong V, Ackerson B, Ranasinghe O . Effectiveness of mRNA BNT162b2 COVID-19 vaccine up to 6 months in a large integrated health system in the USA: a retrospective cohort study. Lancet. 2021; 398(10309):1407-1416. PMC: 8489881. DOI: 10.1016/S0140-6736(21)02183-8. View

15.

Grant M, Bentley K, Fielding C, Hatfield K, Ings D, Harnum D . Combined anti-S1 and anti-S2 antibodies from hybrid immunity elicit potent cross-variant ADCC against SARS-CoV-2. JCI Insight. 2023; 8(15). PMC: 10445686. DOI: 10.1172/jci.insight.170681. View

16.

Eisenberg R, Jawad A, Boyer J, Maurer K, McDonald K, Luning Prak E . Rituximab-treated patients have a poor response to influenza vaccination. J Clin Immunol. 2012; 33(2):388-96. PMC: 3565069. DOI: 10.1007/s10875-012-9813-x. View

17.

Jackson L, Anderson E, Rouphael N, Roberts P, Makhene M, Coler R . An mRNA Vaccine against SARS-CoV-2 - Preliminary Report. N Engl J Med. 2020; 383(20):1920-1931. PMC: 7377258. DOI: 10.1056/NEJMoa2022483. View

18.

Grifoni A, Weiskopf D, Ramirez S, Mateus J, Dan J, Rydyznski Moderbacher C . Targets of T Cell Responses to SARS-CoV-2 Coronavirus in Humans with COVID-19 Disease and Unexposed Individuals. Cell. 2020; 181(7):1489-1501.e15. PMC: 7237901. DOI: 10.1016/j.cell.2020.05.015. View

19.

Sheikh-Mohamed S, Sanders E, Gommerman J, Tal M . Guardians of the oral and nasopharyngeal galaxy: IgA and protection against SARS-CoV-2 infection. Immunol Rev. 2022; 309(1):75-85. PMC: 9349649. DOI: 10.1111/imr.13118. View

20.

Murray S, Ansari A, Frater J, Klenerman P, Dunachie S, Barnes E . The impact of pre-existing cross-reactive immunity on SARS-CoV-2 infection and vaccine responses. Nat Rev Immunol. 2022; 23(5):304-316. PMC: 9765363. DOI: 10.1038/s41577-022-00809-x. View