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

Abstract

BackgroundThe immunogenicity of 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). ObjectiveDetermine the immunogenicity of mRNA vaccines in patients with ICL with a broad range of CD4 T-cell counts. MethodsSamples 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. ResultsThe median age of ICL participants was 51-years and their CD4 count was 150 cells/μl; eleven individuals had CD4 ≤100 cells/μL. Anti-spike IgG antibody levels were greater in HVs than in patients with ICL after 2-doses and 3-doses of mRNA vaccine. There was no detectable significant difference, however, in anti-spike IgG between HVs and those with ICL and CD4 >100 cells/μL. 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 ICL did not differ significantly compared to HVs after two or three vaccine doses. ConclusionPatients with ICL and CD4 count >100 cells/μL can mount vigorous humoral and cellular immune responses to SARS-CoV-2 vaccination, however, those with more severe CD4 lymphopenia have blunted vaccine-induced immunity and may require additional vaccine doses and other risk mitigation strategies.