CD19+IgD+CD27- Naïve B Cells as Predictors of Humoral Response to COVID 19 mRNA Vaccination in Immunocompromised Patients

• Published in: Frontiers in immunology Vol. 12; p. 803742
• Main Authors: Schulz, Eduard, Hodl, Isabel, Forstner, Patrick, Hatzl, Stefan, Sareban, Nazanin, Moritz, Martina, Fessler, Johannes, Dreo, Barbara, Uhl, Barbara, Url, Claudia, Grisold, Andrea J, Khalil, Michael, Kleinhappl, Barbara, Enzinger, Christian, Stradner, Martin H, Greinix, Hildegard T, Schlenke, Peter, Steinmetz, Ivo
• Format: Journal Article
• Language: English
• Published: Switzerland Frontiers Media S.A 07.12.2021
• Subjects: Adult; Aged; Antibodies, Neutralizing - immunology; Antibodies, Viral - immunology; B cells; B-Lymphocyte Subsets - immunology; cancer; COVID-19; COVID-19 - prevention & control; COVID-19 Vaccines - immunology; Female; Humans; Immunocompromised Host - immunology; immunodeficiencies; Immunogenicity, Vaccine - immunology; Immunology; Male; Middle Aged; mRNA vaccine; mRNA Vaccines - immunology; SARS-CoV-2; Vaccines, Synthetic - immunology; COVID-19; immunodeficiencies; cancer; B cells; mRNA vaccine
• ISSN: 1664-3224; 1664-3224
• DOI: 10.3389/fimmu.2021.803742

Immunocompromised patients are considered high-risk and prioritized for vaccination against COVID-19. We aimed to analyze B-cell subsets in these patients to identify potential predictors of humoral vaccination response. Patients (n=120) suffering from hematologic malignancies or other causes of immunodeficiency and healthy controls (n=79) received a full vaccination series with an mRNA vaccine. B-cell subsets were analyzed prior to vaccination. Two independent anti-SARS-CoV-2 immunoassays targeting the receptor-binding domain (RBD) or trimeric S protein (TSP) were performed three to four weeks after the second vaccination. Seroconversion occurred in 100% of healthy controls, in contrast to 67% (RBD) and 82% (TSP) of immunocompromised patients, while only 32% (RBD) and 22% (TSP) achieved antibody levels comparable to those of healthy controls. The number of circulating CD19 IgD CD27 naïve B cells was strongly associated with antibody levels (ρ=0.761, P<0.001) and the only independent predictor for achieving antibody levels comparable to healthy controls (OR 1.07 per 10-µL increase, 95%CI 1.02-1.12, P=0.009). Receiver operating characteristic analysis identified a cut-off at ≥61 naïve B cells per µl to discriminate between patients with and without an optimal antibody response. Consequently, measuring of naïve B cells in immunocompromised hematologic patients could be useful in predicting their humoral vaccination response.