mRNA versus inactivated virus COVID-19 vaccines in multiple sclerosis: Humoral responses and protectivity-Does it matter?

Abstract

Background: COVID-19 vaccines are recommended for people with multiple sclerosis (pwMS). Adequate humoral responses are obtained in pwMS receiving disease-modifying therapies (DMTs) after vaccination, with the exception of those receiving B-cell-depleting therapies and non-selective S1P modulators. However, most of the reported studies on the immunity of COVID-19 vaccinations have included mRNA vaccines, and information on inactivated virus vaccine responses, long-term protectivity, and comparative studies with mRNA vaccines are very limited. Here, we aimed to investigate the association between humoral vaccine responses and COVID-19 infection outcomes following mRNA and inactivated virus vaccines in a large national cohort of pwMS receiving DMTs.

Methods: This is a cross-sectional and prospective multicenter study on COVID-19-vaccinated pwMS. Blood samples of pwMS with or without DMTs and healthy controls were collected after two doses of inactivated virus (Sinovac) or mRNA (Pfizer-BioNTech) vaccines. PwMS were sub-grouped according to the mode of action of the DMTs that they were receiving. SARS-CoV-2 IgG titers were evaluated by chemiluminescent microparticle immunoassay. A representative sample of this study cohort was followed up for a year. COVID-19 infection status and clinical outcomes were compared between the mRNA and inactivated virus groups as well as among pwMS subgroups.

Results: A total of 1484 pwMS (1387 treated, 97 untreated) and 185 healthy controls were included in the analyses (male/female: 544/1125). Of those, 852 (51.05%) received BioNTech, and 817 (48.95%) received Sinovac. mRNA and inactivated virus vaccines result in similar seropositivity; however, the BioNTech vaccination group had significantly higher antibody titers (7.175±10.074) compared with the Sinovac vaccination group (823±1.774) (p<0.001). PwMS under ocrelizumab, fingolimod, and cladribine treatments had lower humoral responses compared with the healthy controls in both vaccine types. After a mean of 327±16 days, 246/704 (34.9%) of pwMS who were contacted had COVID-19 infection, among whom 83% had asymptomatic or mild disease. There was no significant difference in infection rates of COVID-19 between participants vaccinated with BioNTech or Sinovac vaccines. Furthermore, regression analyses show that no association was found regarding age, sex, Expanded Disability Status Scale score (EDSS), the number of vaccination, DMT type, or humoral antibody responses with COVID-19 infection rate and disease severity, except BMI Body mass index (BMI).

Conclusion: mRNA and inactivated virus vaccines had similar seropositivity; however, mRNA vaccines appeared to be more effective in producing SARS-CoV-2 IgG antibodies. B-cell-depleting therapies fingolimod and cladribine were associated with attenuated antibody titer. mRNA and inactive virus vaccines had equal long-term protectivity against COVID-19 infection regardless of the antibody status.

Keywords: COVID-19; Humoral response; Inactivated virus vaccine; Multiple sclerosis; mRNA vaccine.

Fig. 1

A) Comparison of the antibody levels (log₁₀) among healthy controls, untreated pwMS, and pwMS receiving DMTs. pwMS, people with multiple sclerosis; DMT, disease-modifying therapy; ***p<0.001: compared with healthy controls; ⁺⁺⁺p<0.001: compared with untreated pwMS.

Fig. 2

Percentage of seropositivity (antibody titer ≥ 50 AU/ml) among the groups.

Fig. 3

Comparison of the antibody levels (log₁₀) among the groups. PwMS w/o DMT: People with MS without disease-modifying therapies. *p<0.05, ^⁎⁎⁎p<0.001: compared with healthy controls (BioNTech) ^&&&p<0.001: compared with untreated pwMS (BioNTech) ⁺⁺p<0.01, ⁺⁺⁺p<0.001: compared with healthy controls (Sinovac) ^###p<0.001: compared with untreated pwMS (Sinovac).

Fig. 4

Comparison of the antibody levels (log₁₀) among MS types. RRMS: relapsing-remitting multiple sclerosis, SPMS: secondary progressive multiple sclerosis, PPMS: primary progressive multiple sclerosis. ***p<0.001: compared with healthy controls; ⁺⁺⁺p<0.001: compared with the RRMS group.

Fig. 5

The effect of lymphocyte distribution on antibody titers in patients receiving fingolimod treatment.

Fig. 6

Correlations between antibody levels (log₁₀) and the time between the second vaccine dose and sample collection date (TVBS) in the A) entire population, B) BioNTech group, and C) Sinovac group. Partial correlations between antibody levels (log₁₀) and age, after controlling for TVBS, in the D) entire population, E) BioNTech group, and F) Sinovac group. Partial correlations between antibody levels (log₁₀) and body mass index (BMI), after controlling for TVBS, in the G) entire population, H) BioNTech group, and I) Sinovac group.

Fig. 7

Decision tree shows on the top node that the average antibody count for the entire cohort is 4066. Those who received Sinovac–the bottom left leaf of the tree–consists of 817 participants, yielding the lowest average antibody count of 823. The second lowest antibody response group–the second leaf from the bottom left of the tree–consists of pwMS who received BioNTech and were on ocrelizumab or fingolimod, with 356 participants with an average of 1199 antibody count. The highest antibody group consists of healthy controls and pwMS on interferon beta who received BioNTech, with 167 participants with an average of 14,901 antibody count.