Immune responses to SARS-CoV-2 mRNA vaccination in people with idiopathic CD4 lymphopenia

Background: The immunogenicity of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mRNA vaccines is variable in individuals with different inborn errors of immunity or acquired immune deficiencies and is yet unknown in people with idiopathic CD4 lymphopenia (ICL). Objective: We sought to determine the immunogenicity of mRNA vaccines in patients with ICL with a broad range of CD4 T -cell counts. Methods: Samples were collected from 25 patients with ICL and 23 age- and sex -matched healthy volunteers (HVs) after their second or third SARS-CoV-2 mRNA vaccine dose. Anti -spike and anti -receptor binding domain antibodies were measured. T -cell receptor sequencing and stimulation assays were performed to quantify SARS-CoV-2-specific T -cell responses. Results: The median age of ICL participants was 51 years, and their median CD4 count was 150 cells/mu L; 11 participants had CD4 counts <_100 cells/mu L. Anti -spike IgG antibody levels were greater in HVs than in patients with ICL after 2 and 3 doses of mRNA vaccine. There was no detectable significant difference, however, in anti -S IgG between HVs and participants with ICL and CD4 counts >100 cells/mu L. The depth of spike -specific T -cell responses by T -cell receptor sequencing was lower in individuals with ICL. Activation -induced markers and cytokine production of spike -specific CD4 T cells in participants with ICL did not differ significantly compared with HVs after 2 or 3 vaccine doses. Conclusions: Patients with ICL and CD4 counts >100 cells/mu L can mount vigorous humoral and cellular immune responses to SARS-CoV-2 vaccination; however, patients with more severe CD4 lymphopenia have blunted vaccine -induced immunity and may require additional vaccine doses and other risk mitigation strategies. (J Allergy Clin Immunol 2024;153:503-12.)