tetano
Editor, Senior Moderator
J Allergy Clin Immunol
. 2024 Feb;153(2):503-512.
doi: 10.1016/j.jaci.2023.10.012. Epub 2023 Oct 28. Immune responses to SARS-CoV-2 mRNA vaccination in people with idiopathic CD4 lymphopenia
Joseph M Rocco[SUP] 1 [/SUP], Kristin L Boswell[SUP] 2 [/SUP], Elizabeth Laidlaw[SUP] 1 [/SUP], Brian Epling[SUP] 1 [/SUP], Megan Anderson[SUP] 1 [/SUP], Leonid Serebryannyy[SUP] 2 [/SUP], Sandeep Narpala[SUP] 2 [/SUP], Sarah O'Connell[SUP] 2 [/SUP], Heather Kalish[SUP] 3 [/SUP], Sophie Kelly[SUP] 3 [/SUP], Sarah Porche[SUP] 3 [/SUP], Cihan Oguz[SUP] 4 [/SUP], Adrian McDermott[SUP] 2 [/SUP], Maura Manion[SUP] 1 [/SUP], Richard A Koup[SUP] 2 [/SUP], Andrea Lisco[SUP] 1 [/SUP], Irini Sereti[SUP] 5 [/SUP]
Affiliations
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/μL; 11 participants had CD4 counts ≤100 cells/μL. 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/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 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/μL 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.
Keywords: COVID-19; Idiopathic CD4 lymphopenia; SARS-CoV-2; immune response; mRNA vaccines.
. 2024 Feb;153(2):503-512.
doi: 10.1016/j.jaci.2023.10.012. Epub 2023 Oct 28. Immune responses to SARS-CoV-2 mRNA vaccination in people with idiopathic CD4 lymphopenia
Joseph M Rocco[SUP] 1 [/SUP], Kristin L Boswell[SUP] 2 [/SUP], Elizabeth Laidlaw[SUP] 1 [/SUP], Brian Epling[SUP] 1 [/SUP], Megan Anderson[SUP] 1 [/SUP], Leonid Serebryannyy[SUP] 2 [/SUP], Sandeep Narpala[SUP] 2 [/SUP], Sarah O'Connell[SUP] 2 [/SUP], Heather Kalish[SUP] 3 [/SUP], Sophie Kelly[SUP] 3 [/SUP], Sarah Porche[SUP] 3 [/SUP], Cihan Oguz[SUP] 4 [/SUP], Adrian McDermott[SUP] 2 [/SUP], Maura Manion[SUP] 1 [/SUP], Richard A Koup[SUP] 2 [/SUP], Andrea Lisco[SUP] 1 [/SUP], Irini Sereti[SUP] 5 [/SUP]
Affiliations
- PMID: 38344971
- DOI: 10.1016/j.jaci.2023.10.012
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/μL; 11 participants had CD4 counts ≤100 cells/μL. 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/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 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/μL 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.
Keywords: COVID-19; Idiopathic CD4 lymphopenia; SARS-CoV-2; immune response; mRNA vaccines.