An investigation of three SARS-CoV-2 mRNA doses in multiple sclerosis vaccine non-responders
Multiple sclerosis (MS) patients
don't have an increased risk of SARS-CoV-2 infection or severe COVID-19 disease
per se. Still, the risk is elevated if there are comorbidities such as older
age, higher disability levels, and ongoing treatment with specific
disease-modifying therapies (DMTs).
One of the most critical factors in
reducing long-term disability in MS patients is early initiation of treatment
with high-efficacy DMT. However, some DMTs are associated with an increased
risk of infection. Vaccinating all patients with MS against COVID-19 is highly
recommended by experts worldwide.
Among patients treated with
anti-CD20 therapy (rituximab, ocrelizumab) or fingolimod, there is increasing
evidence of reduced humoral immunity after two doses of mRNA-COVID-19 vaccines.
In solid-organ transplant recipients, three doses of mRNA-COVID-19 vaccines
seem to be beneficial. However, whether a third vaccine dose will affect
anti-SARS-Cov 2 IgG antibody levels in MS patients is unclear.
A clinical study by a team of
scientists from Norway aimed to assess the immunogenicity and safety of a third
dose of COVID-19 mRNA vaccine in MS patients treated with anti-CD20 therapy or
fingolimod. A preprint version of the study, which is yet to undergo peer
review, is available on the medRxiv* server.
Multiple sclerosis
In MS, the body's immune system
attacks the protective covering of nerves. This causes permanent nerve damage.
Treatment options include medications that suppress the immune system. In
addition, immunosuppression helps to manage symptoms and slows disease
progression. Specifically, patients may be treated with anti-CD20 therapy or
fingolimod. Anti-CD20 is a monoclonal antibody against the protein CD20, which
is present on B-cells of the immune system. It reduces the number of B-cells by
triggering cell death. Fingolimod is a sphingosine 1-phosphate receptor
modulator. It is an immunomodulator that sequesters immune cells called
lymphocytes in lymph nodes. This ultimately prevents an autoimmune reaction.
COVID-19 vaccination of MS patients
Studies have shown that the humoral
immunity of patients treated with anti-CD20 therapy or fingolimod after two
doses of mRNA-COVID-19 vaccines is reduced. Approximately 80% of MS patients
treated with anti-CD20 therapy or fingolimod have low or absent humoral
immunity after two doses of mRNA-COVID-19 vaccines.
Humoral immune response in MS
patients
A total of 130 MS patients treated
with anti-CD20 or fingolimod with low or absent humoral immunity despite full
vaccination against SARS-CoV-2 were administered a third dose of mRNA-COVID-19
vaccine (BNT162b2 or mRNA-1273). Inclusion criteria were MS diagnosis, signed
informed consent, full COVID-19-vaccination and SARS-CoV-2 Spike RBD IgG <70
AU 3-12 weeks after full vaccination.
The IgG antibody response against
SARS-CoV2 Spike receptor-binding domain (RBD), i.e., humoral immunity, was
measured using a bead-based flow cytometric assay. Low/absent humoral immunity
was assumed when anti-SARS-CoV-2 Spike RBD IgG was <70 AU 3-5 weeks after
revaccination.
The frequency and characteristics
of side effects were collected from all participants 3-5 weeks after revaccination.
Patient- and treatment-specific variables were acquired through a digital
questionnaire, the Norwegian Immunization Registry and hospital journals.
Revaccination improves humoral
immunity
Most MS patients received full
vaccination (two doses) with the Pfizer-BioNTech BNT162b2 vaccine - 83% as the
first and 85% as the second dose. With the third dose, 85% received the Moderna
mRNA-1273 vaccine. The mean time between the last dose of full vaccination (two
doses) and booster shot (third dose) was 94 days in anti-CD20-treated and 78
days in fingolimod-treated patients.
The third dose of SARS-CoV-2 mRNA
vaccine increased anti-SARS-CoV-2 Spike RBD IgG levels significantly. After the
third dose, 25% of anti-CD20-treated patients and 7% of fingolimod-treated
patients assumed protective humoral immunity (anti-SARS-CoV-2 Spike RBD IgG
> 70 AU).
Higher absolute lymphocyte and
CD19-B-cell counts (in patients receiving anti-CD20 therapy) were significantly
associated with developing protective humoral immunity.
Sixty-three percent of
anti-CD20-treated and 38% of fingolimod-treated MS patients reported side
effects. The most common side effects were transient local pain and fatigue.
None of the patients experienced serious adverse effects after revaccination.
The lymphocyte count was significantly higher in patients reporting side
effects compared to those who did not.
Conclusion and relevance
The third dose of mRNA-COVID-19
vaccine improved protective humoral immunity in anti-CD20-treated or
fingolimod-treated MS patients with low or absent humoral immunity despite full
vaccination. The effect of a third dose was limited but more prominent among
those treated with anti-CD20 therapy. These results indicate that revaccination
can be considered safe and can be indicated to reduce the risk of severe
COVID-19 in MS patients on immunosuppressive medications.
Limitations of the study
This study involves a short-term
follow-up of a limited number of patients. A long-term follow-up would be of
greater importance in such a study.
This study reports IgG responses as
a correlate of humoral immunity. However, the adaptive immune response to
SARS-CoV-2 depends on cellular responses too.
This study does not comment on the durability of the antibody response or the clinical effect of revaccinations.
출처: News Medical