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. 2021 Dec 9:12:781843.
doi: 10.3389/fimmu.2021.781843. eCollection 2021.

Effect of Different Disease-Modifying Therapies on Humoral Response to BNT162b2 Vaccine in Sardinian Multiple Sclerosis Patients

Maristella Pitzalis  1 , Maria Laura Idda  1 , Valeria Lodde  2 , Annalisa Loizedda  1 , Monia Lobina  1 , Magdalena Zoledziewska  1 , Francesca Virdis  1 , Giuseppe Delogu  2 , Federica Pirinu  2 , Maria Giuseppina Marini  1 , Maura Mingoia  1 , Jessica Frau  3 , Lorena Lorefice  3 , Marzia Fronza  4 , Daniele Carmagnini  4 , Elisa Carta  4 , Valeria Orrù  1 , Sergio Uzzau  5 , Paolo Solla  6 , Federica Loi  7 , Marcella Devoto  1   8 , Maristella Steri  1 , Edoardo Fiorillo  1 , Matteo Floris  2 , Ignazio Roberto Zarbo  6 , Eleonora Cocco  3   4 , Francesco Cucca  1   2
Affiliations

Effect of Different Disease-Modifying Therapies on Humoral Response to BNT162b2 Vaccine in Sardinian Multiple Sclerosis Patients

Maristella Pitzalis et al. Front Immunol. .

Abstract

Objectives: Vaccination against COVID-19 is highly recommended to patients affected by multiple sclerosis (MS); however, the impact of MS disease-modifying therapies (DMTs) on the immune response following vaccination has been only partially investigated. Here, we aimed to elucidate the effect of DMTs on the humoral immune response to mRNA-based anti-SARS-CoV-2 vaccines in MS patients.

Methods: We obtained sera from 912 Sardinian MS patients and 63 healthy controls 30 days after the second dose of BNT162b2 vaccine and tested them for SARS-CoV-2 response using anti-Spike (S) protein-based serology. Previous SARS-CoV-2 infection was assessed by anti-Nucleocapsid (N) serology. Patients were either untreated or undergoing treatment with a total of 13 different DMTs. Differences between treatment groups comprised of at least 10 patients were assessed by generalized linear mixed-effects model. Demographic and clinical data and smoking status were analyzed as additional factors potentially influencing humoral immunity from COVID-19 vaccine.

Results: MS patients treated with natalizumab, teriflunomide, azathioprine, fingolimod, ocrelizumab, and rituximab showed significantly lower humoral responses compared to untreated patients. We did not observe a statistically significant difference in response between patients treated with the other drugs (dimethyl fumarate, interferon, alemtuzumab and glatiramer acetate) and untreated patients. In addition, older age, male sex and active smoking were significantly associated with lower antibody titers against SARS-CoV-2. MS patients previously infected with SARS-CoV-2 had significantly higher humoral responses to vaccine than uninfected patients.

Conclusion: Humoral response to BNT162b2 is significantly influenced by the specific DMTs followed by patients, as well as by other factors such as previous SARS-CoV-2 infection, age, sex, and smoking status. These results are important to inform targeted strategies to prevent clinically relevant COVID-19 in MS patients.

Keywords: BNT162b2; COVID-19; SARS-CoV-2; disease-modifying therapy; humoral immunity; multiple sclerosis; vaccine efficacy.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Post-vaccination SARS-CoV-2 antibody response by disease- modifying therapy (DMT). (A) Antibody response to SARS-CoV-2 vaccination by DMT in MS patients (UNT, untreated; ALEM, alemtuzumab; IFN, interferon; GA, glatiramer acetate; DMF, dimethyl fumarate; NAT, natalizumab; CLA, cladribine; TER, teriflunomide; AZA, azathioprine; FTY, fingolimod; RTX, rituximab; OCR, ocrelizumab) and healthy control (HC) negative for anti-N antibodies. The red dotted line indicate a cutoff value of 133 U/ml predictive of the presence of neutralizing antibodies according to Resman et al. (14). (B) Post-vaccination antibody levels in patients treated with anti-CD20 therapies (rituximab and ocrelizumab) according to the time (< 3-month, 3-6 month and > 6-month) between last anti-CD20 treatment and immunization. Results are reported as boxplots, showing the median value (in bold) and the quartiles as box limits; whiskers at the top and bottom sides represent the overall maximum value and the overall minimum value, respectively. Points outside boxes and whiskers represent outliers. (*P< 0.05; ***P<0.001).
Figure 2
Figure 2
Post-vaccination SARS-CoV-2 antibody response by disease- modifying therapy (DMT) in MS patients positive for anti-N antibodies. Antibody response to SARS-CoV-2 vaccination by DMT in MS patients positive for anti-N antibodies (UNT, untreated; ALEM, alemtuzumab; IFN, interferon; GA, glatiramer acetate; DMF, dimethyl fumarate; NAT, natalizumab; CLA, cladribine; TER, teriflunomide; AZA, azathioprine; FTY, fingolimod; RTX, rituximab; OCR, ocrelizumab). The red dotted lines indicate a cutoff value of 133 U/ml predictive of the presence of neutralizing antibodies according to Resman et al. (14). Results are reported as boxplots, showing the median value (in bold) and the quartiles as box limits; whiskers at the top and bottom sides represent the overall maximum value and the overall minimum value, respectively. Points outside boxes and whiskers represent outliers.
Figure 3
Figure 3
Impact of sex, age and smoking on humoral response to BNT162b2 vaccine. Antibody response to SARS-CoV-2 vaccination by age (A), sex (B) and smoking status (C) in MS patients is represented. Results are reported as boxplots, showing the median value (in bold) and the quartiles as box limits; the whiskers at the top and bottom sides represent the overall maximum value and the overall minimum value, respectively. Data outside boxes and whiskers represent outliers. (**P<0.01; ***P<0.001).
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