The impact of hybrid immunity on immune responses after SARS-CoV-2 vaccination in persons with multiple sclerosis treated with disease-modifying therapies

Eur J Neurol. 2023 Dec;30(12):3789-3798. doi: 10.1111/ene.16015. Epub 2023 Aug 24.

Abstract

Background and purpose: Hybrid immunity to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) develops from a combination of natural infection and vaccine-generated immunity. Multiple sclerosis (MS) disease-modifying therapies (DMTs) have the potential to impact humoral and cellular immunity induced by SARS-CoV-2 vaccination and infection. The aims were to compare antibody and T-cell responses after SARS-CoV-2 mRNA vaccination in persons with MS (pwMS) treated with different DMTs and to assess differences between naïvely vaccinated pwMS and pwMS with hybrid immunity vaccinated following a previous SARS-CoV-2 infection.

Methods: Antibody and T-cell responses were determined in pwMS at baseline and 4 and 12 weeks after the second dose of SARS-CoV-2 vaccination in 143 pwMS with or without previous SARS-CoV-2 infection and 40 healthy controls (HCs). The MS cohort comprised natalizumab (n = 22), dimethylfumarate (n = 23), fingolimod (n = 38), cladribine (n = 30), alemtuzumab (n = 17) and teriflunomide (n = 13) treated pwMS. Immunoglobulin G antibody responses to SARS-CoV-2 antigens were measured using a multiplex bead assay and FluoroSpot was used to assess T-cell responses (interferon γ and interleukin 13).

Results: Humoral and T-cell responses to vaccination were comparable between naïvely vaccinated HCs and pwMS treated with natalizumab, dimethylfumarate, cladribine, alemtuzumab and teriflunomide, but were suppressed in fingolimod-treated pwMS. Both fingolimod-treated pwMS and HCs vaccinated following a previous SARS-CoV-2 infection had higher antibody levels 4 weeks after vaccination compared to naïvely vaccinated individuals. Antibody and interferon γ levels 12 weeks after vaccination were positively correlated with time from last treatment course of cladribine.

Conclusion: These findings are of relevance for infection risk mitigation and for vaccination strategies amongst pwMS undergoing DMT.

Keywords: SARS-CoV-2; cellular immunity; humoral immunity; multiple sclerosis; vaccination.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptive Immunity
  • Alemtuzumab
  • Antibodies
  • Antibodies, Viral
  • COVID-19 Vaccines / therapeutic use
  • COVID-19* / prevention & control
  • Cladribine
  • Dimethyl Fumarate
  • Fingolimod Hydrochloride
  • Humans
  • Interferon-gamma
  • Multiple Sclerosis* / drug therapy
  • Natalizumab
  • SARS-CoV-2
  • Vaccination

Substances

  • teriflunomide
  • Cladribine
  • Natalizumab
  • COVID-19 Vaccines
  • Interferon-gamma
  • Alemtuzumab
  • Dimethyl Fumarate
  • Fingolimod Hydrochloride
  • Antibodies
  • Antibodies, Viral