Measurement of Typhim Vi IgG as a Diagnostic Tool to Determine Anti-polysaccharide Antibody Production Deficiency in Children

Abstract

Background: The assessment of specific polysaccharide antibody production plays a pivotal role in the diagnosis of humoral primary immunodeficiencies (PID). The response to 23-valent pneumococcal vaccine (PPV) remains the gold standard for the diagnosis of polysaccharide antibodies. However, in Spain, the interpretation of pure polysaccharide 23-valent immunization is hampered by the high endemicity of pneumococcal disease and the generalization of the 13-valent adjuvant pneumococcal vaccination. Specific Typhim Vi vaccination (TV) immunoglobulin G IgG response to immunization is useful in adult PID, but there is no data regarding children. Objectives: To evaluate the clinical utility of TV IgG production as a diagnostic tool to determine anti-polysaccharide antibody production deficiency in children, when the response to PPV is unclear and isolated determination of serotypes is unfeasible. Methods: We conducted a single-institution prospective observational study on 61 children with recurrent infections. Baseline specific antibodies against PPV and TV were evaluated. In 28 children (46%), the response to the production of antibodies confirmed a clinical suspicion of humoral PID, and they were therefore immunized with 23-valent pneumococcal vaccine and Typhim Vi. Both specific antibody responses were measured by ELISA (The Binding Site Group Ltd, Birmingham, UK) using previously published cut-offs. Results: Seventy percent of the 61 children displayed baseline PPV IgG > 27 mg/L, whereas only 8% showed TV IgG > 28 U/mL ( p < 0.0001). Twenty-one of 28 children (75%) achieved a 3-fold increase in post-vaccination TV IgG levels, whereas only 3% achieved a 4-fold increase in PPV IgG post vaccination, mainly due to high baseline PPV IgG titers. When we classified children according to their response to TV as responders or non-responders and compared this with the well-known clinical warning signs of the Jeffrey Modell Foundation. The proportions of children with history of pneumonia and the need for intravenous antibiotics were significantly higher in TV IgG non-responders than in TV IgG responders ( p = 0.02 and p = 0.01, respectively). Conclusion: Response to TV can be considered an ancillary diagnostic tool to determine polysaccharide antibodies in children, particularly when isolated determination of pneumococcal serotypes is not feasible. TV provides a useful asset for clinicians in the era of conjugate PPV vaccination, with clinical relevance. Further research is warranted for validation.

Focusing on Good Responders to Pneumococcal Polysaccharide Vaccination in General Hospital Patients Suspected for Immunodeficiency. A Decision Tree Based on the 23-Valent Pneumococcal IgG Assay

“…Since a majority of childhood vaccination programs now include Pn-C vaccination, and a 20-valent conjugated vaccine is currently investigated with the intent to broaden global protection against pneumococcal disease, the future value of the 23-valent IgG assay as screening method for SPAD will probably become limited. Recent results show promising results for the measurement of the Typhim Vi IgG response as a diagnostic tool for assessing polysaccharide production in Pn-C pre-vaccinated patients (32).…”

The Immune Response to SARS-CoV-2 Vaccination: Insights Learned From Adult Patients With Common Variable Immune Deficiency

“…In a multicenter study, Guevara-Hoyer et al. ( 17 ) demonstrated a lack of response in both Typhim Vi and pneumococcal immunization in a group of CVID patients, suggesting that the evaluation of the specific antibody response to Typhim Vi vaccine may add clinical value to the diagnosis of impaired anti-polysaccharide antibody production in CVID.…”

Vaccination in PADs

“…Sanchez et al [14] demonstrated, in a multicenter study, a similar lack of response in both Typhim Vi and PPSV immunization in a group of CVID patients, suggesting that the evaluation of the specific antibody response to Typhim Vi vaccine adds clinical value to the diagnosis of anti-polysaccharide antibody production deficiency in patients with this immune defect. Another study, conducted by Guevara-Hoyer et al [15], confirmed these data in a pediatric population previously vaccinated with the conjugate pneumococcal vaccine.…”