Measurement of pneumococcal IgG response to vaccination is a key test used to investigate humoral immunity, however, the relationship between IgG and IgG subclasses is not firmly established. Here we assessed the IgG and IgG2 responses to pneumococcal vaccination and clinical presentation in antibody-deficient patients.
Pneumococcal responses were measured using the VaccZyme™ pneumococcal capsular polysaccharide (PCP) IgG and IgG2 ELISAs (The Binding Site Group Ltd, Birmingham, UK) in control (median 59 years, range 16-86) and antibody-deficient (66 years, 44-86) patients recruited from the Immunodeficiency Unit at Birmingham Heartlands Hospital UK. Patients were vaccinated with either Prevnar13® (PCV13, n= 16 control, 10 antibody-deficient) or Pneumovax®23 (PPV23, n= 31 control, 18 antibody-deficient) and serum samples collected pre- and 4 weeks post-vaccination.
PCP-Ig responders (+) and non-responders (-) were defined from the lower 95th percentile range of the control population (for PPV23, PCP-IgG: 17.8mg/L and PCP-IgG2: 5.9mg/L; for PCV13, PCP-IgG: 27.5mg/L and PCP-IgG2: 8.9mg/L). Positive correlations between PCP-IgG and IgG2 were observed for both PCV13 (r=0.95, p=0.001) and PPV23 (r=0.92, p=0.001). In antibody-deficient patients, PCP-IgG responders were all IgG2 responders following PCV13 vaccination. However, 3 of 18 PPV23-vaccinated patients were PCP-IgG+/IgG2-. These patients had significantly lower total IgA, median 0.36g/L (range 0.36-0.6g/L) than PCP-IgG+/IgG2+ patients (median 1.09g/L, range 0.66-1.48g/L, p=0.03). Additionally, a greater proportion of PCP-IgG+/IgG2- antibody-deficient patients presented with recurrent infections (100% vs 86%) and required prophylactic antibody treatment (67% vs 57%) than PCP-IgG+/IgG2+ patients.
The identification of PCP-IgG2 non-responders may provide further stratification of patients with a proficient PCP-IgG response.