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

Abstract

Background and Aim: Recently, the 23-valent IgG-assay was suggested as screening assay to identify poor responders to pneumococcal polysaccharide (PnPS)-vaccination with the serotype-specific assay as a second-line test. However, in a low pre-test probability general hospital setting predicting good responders could be more valuable to reduce the number of samples needing serotyping.Methods: Serotype-specific PnPS antibody-assays were performed for suspected immunodeficiency in two Dutch general hospitals (Jeroen Bosch Hospital, 's-Hertogenbosch; Elisabeth Tweesteden Hospital, Tilburg). 23-Valent PnPS antibody-assays were subsequently performed in archived material. Data were analyzed using receiver operating characteristic curves (AUC) and agreement indices (ICC).Results: Sera of 284 patients (348 samples) were included; 23-valent IgG-titres and the corresponding sum of PnPS-serotype specific antibodies showed moderate correlation (ICC = 0.63). In 232 conjugated-pneumococcal-vaccine-naïve patients (270 samples), a random 23-valent IgG-titer could discriminate between samples with and without ≥7/11, ≥7/13, or ≥6/9 pneumococcal serotypes when both cut-off values 0.35 and 1.0 μg/ml were used (AUC 0.86 and 0.92, respectively). All patients with a pre-immunization-titer ≥38.2 μg/ml and/or post-immunization-titer ≥96.1 μg/ml and none with a post-immunization-titer ≤38.5 μg/ml exhibited a good response to PnPS vaccination. Using these breakpoints as screening test to predict good responders, only 24% of patients would require further serotyping, as opposed to 68% if breakpoints to predict poor responders would have been used.Conclusion: In a low pre-test probability setting, the 23-valent IgG-assay proved to be a reliable screening test for good responders in conjugated-pneumococcal-vaccine-naïve patients, reducing the overall number of patient samples needing further serotyping, thus reducing overall costs of pneumococcal vaccination response assessment.

The clinical relevance of IgM and IgA anti-pneumococcal polysaccharide ELISA assays in patients with suspected antibody deficiency

“…To investigate whether patients from our cohort with recurrent -0.97 and 0.80, 95% = CI = 0.62-0.98, respectively). However, the discriminative power of using the anti-PnPS IgG assay alone was higher (ROC analysis; pre-immunization: AUC = 0.84, 95% CI = 0.76-0.91 and post-immunization: AUC = 0.93, 95% CI = 0.85-1.00 [10]).…”

“…Of these, 61 samples were from 49 patients who were previously vaccinated with the Pn‐C vaccine. Residual samples were stored at ≤−80°C and later retrieved from the laboratory to perform anti‐PnPS IgA and IgM assays between September and November 2019; anti‐PnPS IgG assays were previously performed (and published) between August and September 2018 [ 10 ]. Most patients ( n = 84) were diagnosed with unclassified primary antibody deficiency (unPAD): deficiency of IgG, and/or combination(s) of deficiency of IgG‐subclass(es), IgM, IgA or specific antibodies.…”

“…The Luminex multiplex immunoassay was used to measure serotype‐specific IgG antibodies against PnPS, as previously described [ 10 ], including CPS 22F adsorption to block anti‐CWPS antibodies [ 4 ]. For assessing the response to PnPS vaccination a blood sample was drawn 4–8 weeks after intramuscular vaccination with one dose of 23‐valent PnPS vaccine (Pneumovax 23; Merck, Sharp & Dohme BV, Haarlem, the Netherlands).…”

“…Such serotype‐specific PnPS IgG testing is expensive, not widely available, and interpretation of the results has proved to be challenging [ 7 , 8 ]. The anti‐PnPS IgG assay has been shown to be a reliable screening test for poor [ 9 ] as well as for good [ 10 ] serotype‐specific PnPS IgG responders to PnPS vaccine in conjugated pneumococcal (Pn‐C) vaccine‐naive patients. This reduces the number of patients needing serotype‐specific PnPS IgG testing, thus reducing the costs while maintaining the quality of the diagnostic assessment for potential SPAD.…”

“…In this study, we investigated the clinical relevance of anti‐PnPS IgM and IgA assays in addition to the anti‐PnPS IgG assay when analysing patients for potential PAD in a general hospital population. Our first objective was to investigate whether there were patients in our cohort with recurrent ENT and/or respiratory tract infections labelled as ‘no PAD’ based on a good response in serotype‐specific PnPS IgG assays [ 10 ] with a reduced anti‐PnPS IgA and/or IgM response. Secondly, we investigated whether adding anti‐PnPS IgA and/or IgM assays to the anti‐PnPS IgG assay could reduce the need for serotype‐specific PnPS testing.…”