What lab test is ordered for an immunocompromised patient with suspected antibody deficiency after receiving Prevnar (pneumococcal conjugate vaccine)?

Pneumococcal Serotype-Specific IgG Antibody Testing

For an immunocompromised patient with suspected antibody deficiency after receiving Prevnar (pneumococcal conjugate vaccine), order serotype-specific IgG antibody levels to pneumococcal capsular polysaccharides, measured 3-4 weeks post-vaccination. 1

Specific Test to Order

• Measure serotype-specific pneumococcal IgG antibodies using a standardized ELISA method, expressed in micrograms per milliliter (μg/mL), with results compared to the reference standard serum (US FDA SF89). 1

• Test antibody levels to at least 6-12 pneumococcal serotypes included in the vaccine, ensuring adequate assessment of the antibody response. 1, 2

• The test should be performed 3-4 weeks (or up to 4-6 weeks) after vaccination to allow adequate time for antibody production. 1, 3

Critical Context: Prevnar is a Conjugate Vaccine

• Prevnar (PCV7 or PCV13) couples polysaccharides to a protein carrier, making the antibody response indicative of protein antigen response rather than pure polysaccharide immunity. 1

• This is fundamentally different from the 23-valent pneumococcal polysaccharide vaccine (PPSV-23), which tests pure polysaccharide responses and is the preferred vaccine for diagnosing specific antibody deficiency (SAD). 1, 2

• Normal antibody responses to conjugate vaccines do NOT exclude the diagnosis of SAD, because patients with SAD typically have normal protein antigen responses but impaired polysaccharide responses. 1

Interpretation Criteria

• Protective antibody concentration is ≥1.3 μg/mL per serotype, which is associated with protection against invasive pneumococcal infections. 1, 3

• For adults and children >6 years: An adequate response requires concentration >1.3 μg/mL for ≥70% of serotypes tested. 1, 2

• For **children <6 years**: An adequate response requires concentration >1.3 μg/mL for ≥50% of serotypes tested. 1, 2

• Some experts also consider a 4-fold increase from baseline as part of the criteria, though absolute post-vaccination titers ≥1.3 μg/mL are more clinically relevant for protection. 1, 3

Additional Baseline Testing Required

Before interpreting pneumococcal antibody responses, you must establish:

• Total serum immunoglobulin levels (IgG, IgA, IgM) to distinguish SAD from other antibody deficiencies like CVID or hypogammaglobulinemia. 2, 4

• IgG subclass levels (IgG1, IgG2, IgG3, IgG4), as IgG2 and IgG3 deficiencies commonly coexist with impaired pneumococcal responses. 2, 5

• Pre-vaccination pneumococcal antibody titers to assess the magnitude of response, since patients with high baseline levels may not demonstrate significant increases post-vaccination. 1

Important Diagnostic Pitfalls

• Do not diagnose antibody deficiency based solely on conjugate vaccine responses. If antibody deficiency is suspected, the patient should subsequently receive the 23-valent polysaccharide vaccine (PPSV-23) to properly assess polysaccharide immunity. 1, 2, 4

• ELISA-measured antibody concentrations reflect protein quantity, not functional antibody activity. Opsonophagocytic assays provide more accurate functional assessment but are not yet widely available for clinical use. 1

• Laboratory assays vary significantly between facilities in terms of standards, methodology, and reliability, making cross-laboratory comparisons challenging. 1, 3

• Immunocompromised patients may have blunted responses to conjugate vaccines. Studies in ataxia-telangiectasia patients showed 96% failed to respond adequately to conjugate vaccines, and patients with chronic kidney disease on dialysis showed only 37.5% adequate response using strict criteria. 6, 7

• Patients with IgG2 deficiency frequently fail to develop protective antibody levels to all pneumococcal serotypes and may have deficient immunologic memory for anti-pneumococcal antibodies. 5, 8