Linda Thole (Berlin/ DE), Dr. Arne Sattler (Berlin/ DE), Prof. Dr. Katja Kotsch (Berlin/ DE), Laura Tóth (Berlin/ DE), Janine Siegle (Berlin/ DE), Carolin Stahl (Berlin/ DE), Georg Hermsdorf (Berlin/ DE), Anette Knabe (Berlin/ DE), Annika Winkler (Berlin/ DE), PD Dr. Eva Vanessa Schrezenmeier (Berlin/ DE), Carolin Ludwig (Ulm/ DE), Prof. Dr. Hubert Schrezenmeier (Ulm/ DE), Prof. Dr. Johannes Schulte (Berlin/ DE)
Background
Stem cell transplant recipients (SCTR) suffer from increased COVID-19-associated risks and higher mortality rate than determined for the general population, supporting the need for effective vaccination strategies. Data on immunogenicity of SARS-CoV2 mRNA-based vaccination is limited and it remains largely unaddressed whether and how SARS-CoV2-vaccination-specific humoral and cellular immunity is altered in stem cell transplant recipients, particularly in pediatric cohorts.
Methods
In this observational study we comprehensively analyzed mRNA vaccine induced humoral and cellular responses after second and third vaccination in pediatric SCTR aged 2-19 years and age-matched healthy children 5 weeks post-vaccination. Vaccine-specific IgG, IgA and Omicron variant neutralizing capacity was assessed by ELISA together with extensive quantification and functional characterization of spike protein-specific B- and T cells by flow cytometry. Spike-specific CD4+ T cells were identified according to the co-expression of CD137 and CD154 after peptide mix stimulation and vaccine-specific B cells were detected by co-staining with fluorescently labeled recombinant receptor binding domain protein and recombinant full spike protein.
Results
After third vaccination, SCTR reached similar levels of vaccine-specific IgG, IgA and neutralizing antibodies against omicron variant as controls. Although patients showed an increase in frequencies of SARS-CoV2 specific B cells after this booster vaccination, overall frequencies were still fourfold reduced compared to controls. While the majority of individuals enrolled mounted SARS-CoV2 Spike protein-specific CD4+ T helper cell responses, SCTR were characterized by elevated frequencies of vaccine-specific CD4+ T cells compared to controls. Functional analysis revealed significantly diminished portions of specific CD4+IFNγ+ T cells along with an increase in IL-2 producers after the second and third dose in patients compared to controls.
Conclusion
Our data show multiple quantitative and functional impairments of SARS-CoV2 specific cellular immunity in pediatric SCTR. Moreover, they underline the need of a third vaccine dose for SCTR for mounting sufficient humoral responses, particularly with respect to development of neutralizing antibodies. On the background of vaccination hesitancy amongst parents of SCTR, transplant pediatricians are urged to provide COVID-19-related education and information to protect this vulnerable patient group.
Offenlegung Interessenkonflikt:
All authors have nothing to disclose.