The total IgM, IgA and IgG antibody responses to pneumococcal polysaccharide vaccination (Pneumovax®23) in a healthy adult population and patients diagnosed with primary immunodeficiencies

Background: Interpretation of the responses to the pneumococcal polysaccharide vaccine (Pneumovax®23, PPV) has proven challenging. In addition, there are few studies documenting the longevity of these responses. Methods: The age-specific PPV IgM, IgA, IgG and IgG2 concentrations were determined pre, 4–6 weeks and 6 years post-vaccination in the serum of Prevnar®-naïve adults using VaccZyme™ pneumococcal capsular polysaccharide ELISAs. Results: The median pre-vaccination concentrations were; PPV IgM 53 U/mL (5–95% CI: 16-169 U/mL), IgA 23 U/mL (6-103 U/mL), IgG 41 mg/L (10-184 U/mL) and IgG2 18 mg/L (3-95 U/mL). 4–6 weeks post-vaccination there was a median 6-fold (5–95% CI: 2–24) increase in PPV IgM (median 315 U/mL (5–95% CI: 60-1133 U/mL), 18-fold (4–74) increase in IgA (369 U/mL (78-1802 U/mL)), 9-fold (2–19) increase in IgG (375 mg/L (77–1238 mg/L)) and 8-fold (1–20) increase in IgG2 (141 mg/L (25–573 mg/L)). This was significant for all isotypes in all age ranges (p < 0.0001). Six years post-vaccination median PPV concentrations were; IgM 54 U/mL (17–128), IgA 85 U/mL (19–279), IgG 148 mg/L (30–997) and IgG2 57 mg/L (9–437). The median concentrations for all ages 6 years post-vaccination were significantly elevated compared to the pre-vaccination titres for PPV IgA, IgG and IgG2 isotypes only. The PPV IgM and IgA responses were influenced by age. At 6 years post vaccination, in individuals with normal PPV IgG, 34 individuals had PPV IgM and/or IgA concentrations below the lower limit of the healthy adult ranges. We also used the healthy adult reference ranges developed in this study to assess a cohort of primary immunodeficiency (PID) patients. Conclusion: These ranges will help to provide a framework for assessment and definition of normal response to PPV, which will facilitate clinical interpretation of a deficient polysaccharide response in those suspected of antibody deficiency.