ABSTRACT
While vaccines against the pandemic SARS-CoV-2 are currently given intramuscularly, it may be preferable to deliver vaccines in a needle-free manner by inhalation or a nasal spray to secure mucosal protection at the actual site of infection. This will limit the spread of the virus, ease administration and likely improve vaccine acceptance. Here, we report on a subunit vaccine strategy based on engineered human albumin fused to immunogens, which upon intranasal delivery targets FcRn for transport across the mucosa followed by induction of robust local and systemic antibody responses beyond that gained by intramuscular delivery. This needle-free vaccination principle was shown to block infection by both SARS-CoV-2 and influenza A, and as such should be an attractive strategy for design of subunit vaccines targeting respiratory diseases.
ABSTRACT
Introduction: Expert organizations worldwide recommend that all patients with multiple sclerosis (MS) should be vaccinated against acute respiratory syndrome coronavirus 2 disease of 2019 (COVID- 19). However, the effect of disease-modifying therapies (DMTs) on the efficacy to mount an appropriate immune response is unknown. There is increasing evidence of altered protective humoral immunity after mRNA-COVID-19 vaccines among patients treated with fingolimod, rituximab and ocrelizumab. However, the role of cellular immunity is still unknown. Appropriate knowledge regarding the development of protective immunity is of paramount importance in respect to medical, political and public health measures to aid the fight against the COVID-19 pandemic. Objectives and Aims: We aimed to characterize humoral and cellular immunity after mRNA-COVID-19 vaccines in patients with MS treated with high-efficacy DMTs (NEVROVAX). Methods: All patients treated with alemtuzumab, natalizumab, fingolimod, rituximab or cladribine, and vaccinated with BNT162b2- or mRNA-1273-COVID-19 vaccine were invited. We assessed protective humoral immunity by measuring acute respiratory syndrome coronavirus 2 (SARS-CoV-2) IgG response using anti-spike protein-based serology in all included patients before, and 3-6 weeks after full vaccination (NEVROVAX-HUMORAL). Cellular immunity was investigated using high dimensionality multiparameter analyses in 50 pre-selected individuals (10 patients in each treatment group;NEVROVAX-CELLULAR) and in all patients not developing protective humoral immunity in the former group (NEVROVAX-EXTENSION). Results and Conclusions: Over 900 patients were invited and, to date, more than 300 patients have been included in our study. Preliminary results show altered protective humoral immunity in MS patients treated with rituximab and fingolimod. Continuous analysis of cellular immunity is conducted in these patients. The percentage of vaccinated inhabitants in Norway is still under 10%. We expect to complete all analyses by September 2021 and will present our results during ECTRIMS 2021.