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Journal article
COVID-19 Vaccine Boosters in People With Multiple Sclerosis: Improved SARS-CoV-2 Cross-Variant Antibody Response and Prediction of Protection
Neurology : neuroimmunology & neuroinflammation, Vol.12(5), e200443
2025
PMID: 40694731
Abstract
Background and Objectives
Although disease-modifying therapies (DMTs) may suppress coronavirus disease 2019 (COVID-19) vaccine responses in people with multiple sclerosis (pwMS), limited data are available on the cumulative effect of additional boosters. Maturation of Spike immunoglobulin G (IgG) to target a greater diversity of SARS-CoV-2 variants, especially past the BA.1 variant, has not been reported. In addition, the prediction of variant-specific protection, given that Spike antibody testing is not performed routinely, remains a challenge. We, therefore, evaluated whether additional vaccine doses improved the breadth of cross-variant recognition to target emerging SARS-CoV-2 variants. Machine learning–based models were designed to predict variant-specific protection status.
Methods
In a prospective observational cohort (n = 442), Spike IgG titers and live virus neutralization against D614, BA.1, BA.2, BA.5, XBB.1.1, XBB.1.5, and EG.5.1 variants were determined in 1,011 serum samples (0–12 months after 2–4 doses). Predictive protection models were developed by K-fold cross-validation on training and test data sets (random split 70:30).
Results
After primary vaccination, pwMS on immunosuppressive disease-modifying therapy (IMM-DMT) had 10-fold and 7.2-fold lower D614 Spike IgG titers than pwMS on low-efficacy (LE)-DMT and cladribine (p < 0.01). After 4 doses, pwMS on IMM-DMT had significantly lower Spike IgG titers, compared with pwMS on low-efficacy disease-modifying therapy, for D614 (p < 0.05), as well as BA.1, BA.2, BA.5, XBB.1, XBB.1.5, and EG.5.1(p < 0.01). The breadth of Spike IgG to recognize variants other than the cognate antigen increased after 4 doses of all DMTs. Although pwMS on IMM-DMT displayed reduced cross-variant recognition, a fourth dose resulted in a 2–4-fold increase in protection against newer variants and a reduction in two-thirds of pwMS without protective Spike IgG (p < 0.0001). Tixagevimab and cilgavimab did not induce additional cross-variant protection. Variant-specific predictive models of vaccine protection were influenced by treatment, time since primary vaccination, and age, with high sensitivity (99.4%, 95% CI 96.8–99.99) and specificity (72.0%, 95% CI 50.6–87.9) for XBB.1.5/EG.5.1 variants.
Discussion
Despite not eliciting adequate antibody response in pwMS on IMM-DMT, COVID-19 boosters improve the breadth of the humoral response against SARS-CoV-2 emerging variants. Vaccine protection can be predicted by statistical modeling.
Details
- Title
- COVID-19 Vaccine Boosters in People With Multiple Sclerosis: Improved SARS-CoV-2 Cross-Variant Antibody Response and Prediction of Protection
- Authors/Creators
- Avani Yeola - The University of SydneySamuel Houston - The University of SydneyAnupriya Aggarwal - UNSW SydneyRashmi Gamage - Children's Hospital at WestmeadVicki E Maltby - John Hunter HospitalMarzena J Fabis-Pedrini - Monash UniversityLinh Le-Kavanagh - Queen Elizabeth II Medical CentreVera Merheb - Children's Hospital at WestmeadKristy Nguyen - Children's Hospital at WestmeadFiona X Z Lee - Children's Hospital at WestmeadSusan Walters - Perron Institute for Neurological and Translational ScienceMarinda Taha - The University of SydneyAnnmaree O'Connell - The University of SydneyVilija G Jokubaitis - Monash UniversityAngie Roldan - Alfred HealthMastura Monif - Monash UniversityHelmut Butzkueven - Alfred HealthSandeep Sampangi - Monash UniversityLouise Rath - Alfred HealthKatherine Fazzolari - The Royal Melbourne HospitalTodd A Hardy - Concord Repatriation General HospitalHeidi N Beadnall - The University of SydneyMichael H Barnett - Mind AustraliaAllan G Kermode - Murdoch University, Institute for Immunology and Infectious DiseasesChristopher DwyerTomas Kalincik - The Royal Melbourne HospitalSimon A Broadley - Gold Coast HospitalStuart G Turville - UNSW SydneyStephen W Reddel - The University of SydneySudarshini Ramanathan - The University of SydneyJeannette Lechner-Scott - John Hunter HospitalAnneke Van Der Walt - Monash UniversityFabienne Brilot - The University of Sydney
- Publication Details
- Neurology : neuroimmunology & neuroinflammation, Vol.12(5), e200443
- Publisher
- American Academy of Neurology
- Number of pages
- 16
- Identifiers
- 991005799071307891
- Copyright
- © 2025 American Academy of Neurology
- Murdoch Affiliation
- Institute for Immunology and Infectious Diseases; Personalised Medicine Centre
- Language
- English
- Resource Type
- Journal article
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- Collaboration types
- Domestic collaboration
- Citation topics
- 1 Clinical & Life Sciences
- 1.203 Neuromuscular Disorders
- 1.203.147 Multiple Sclerosis
- Web Of Science research areas
- Clinical Neurology
- Neurosciences
- ESI research areas
- Neuroscience & Behavior