Limitations in the clinical utility of vaccine challenge responses in the evaluation of primary antibody deficiency including Common Variable Immunodeficiency Disorders

• Published in: Clinical immunology (Orlando, Fla.) Fla.), 2024-09, Vol.266, p.110320, Article 110320
• Main Authors: Ameratunga, Rohan, Longhurst, Hilary, Leung, Euphemia, Steele, Richard, Lehnert, Klaus, Woon, See-Tarn
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; Agammaglobulinemia - diagnosis; Agammaglobulinemia - immunology; Aged; Antibodies, Bacterial - blood; Antibodies, Bacterial - immunology; Child; Cohort studies; Common Variable Immunodeficiency - immunology; CVID; Female; Haemophilus influenzae type b - immunology; Haemophilus Vaccines - administration & dosage; Haemophilus Vaccines - immunology; Haemophilus Vaccines - therapeutic use; Humans; Hypogammaglobulinemia; Immunoglobulins, Intravenous - therapeutic use; Male; Middle Aged; New Zealand; Pneumococcal Vaccines - immunology; Pneumococcal Vaccines - therapeutic use; Prospective Studies; SCIG/IVIG; Tetanus Toxoid - immunology; Vaccine challenge responses; Young Adult
• ISSN: 1521-6616; 1521-7035; 1521-7035
• DOI: 10.1016/j.clim.2024.110320

Vaccine challenge responses are an integral component in the diagnostic evaluation of patients with primary antibody deficiency, including Common Variable Immunodeficiency Disorders (CVID). There are no studies of vaccine challenge responses in primary hypogammaglobulinemia patients not accepted for subcutaneous/intravenous immunoglobulin (SCIG/IVIG) replacement compared to those accepted for such treatment. Vaccine challenge responses in patients enrolled in two long-term prospective cohorts, the New Zealand Hypogammaglobulinemia Study (NZHS) and the New Zealand CVID study (NZCS), were compared in this analysis. Almost all patients in the more severely affected SCIG/IVIG treatment group achieved protective antibody levels to tetanus toxoid and H. influenzae type B (HIB). Although there was a highly significant statistical difference in vaccine responses to HIB, tetanus and diphtheria toxoids, there was substantial overlap in both groups. In contrast, there was no significant difference in Pneumococcal Polysaccharide antibody responses to Pneumovax® (PPV23). This analysis illustrates the limitations of evaluating vaccine challenge responses in patients with primary hypogammaglobulinemia to establish the diagnosis of CVID and in making decisions to treat with SCIG/IVIG. The conclusion from this study is that patients with symptoms attributable to primary hypogammaglobulinemia with reduced IgG should not be denied SCIG/IVIG if they have normal vaccine responses. •This study illustrates the limitations of vaccine challenge responses in the evaluation of primary antibody deficiency disorders.•Current consensus is that impaired vaccine challenge responses support a diagnosis of Common Variable Immunodeficiency Disorders (CVID) in patients with primary hypogammaglobulinemia.•Vaccine challenge responses were compared in two long-term prospective primary antibody deficiency cohorts in New Zealand (NZ): The NZ hypogammaglobulinemia study (NZHS) and the NZ Common Variable Immunodeficiency Disorders study (NZCS).•This analysis failed to demonstrate differences in antibody responses to Pneumovax® (PPV23) in patients accepted for treatment with SCIG/IVG compared to those who were not.Although there were highly significant statistical differences in protein-based vaccine antigens (H. influenzae type B [HIB], diphtheria and tetanus toxoids) there was considerable overlap in antibody responses between the two groups.•The clinical implications of this study are that patien