Ampath Chat No. 96 – April 2025
Dr Lizelle Nagel, Dr Sylvia van den Berg
DIAGNOSTIC VACCINATION AS AN IMMUNOLOGICAL INVESTIGATION
Patients with inborn errors of immunity (IEI) often suffer from infections and immune regulation disorders. Most have impaired antibody-mediated immunity. 🧫
Key assessments include:
- Serum immunoglobulins (IgA, IgM, IgG, IgE)
- Lymphocyte subpopulations
- Diagnostic vaccination
Poor antigen-specific antibody production or memory formation is common in IEIs and secondary immunodeficiencies.
Diagnostic vaccination involves measuring antibodies before and after stimulation with a vaccine. It helps identify defects in B cell and T cell interactions.
PROTEIN VS POLYSACCHARIDE VACCINES
Protein vaccines (e.g., tetanus, diphtheria):
- Stimulate T cell-dependent responses
- Require functional CD4+ T cells and B cells
Conjugate vaccines (e.g., Prevenar 13):
- Polysaccharides bound to proteins
- Also stimulate T cell-B cell cooperation
Pure polysaccharide vaccines (e.g., Pneumovax 23):
- Stimulate T cell-independent responses
- Directly activate B cells
- Less immunogenic, poor memory formation
- Not reliable in children ≤ 2–3 years
IMMUNE RESPONSE MECHANISMS
Figure 1: illustrates how protein, conjugate, and polysaccharide vaccines activate the immune system.
(Source: Pollard AJ et al., Nature Reviews Immunology, 2021)
PNEUMOCOCCAL VACCINE SEROTYPES
Recommended for:
- Children (EPISA)
- Adults >65
- High-risk groups
Key facts:
- 23 serotypes targeted
- IgG peaks at 4–6 weeks, wanes in 2–5 years
- Protection thresholds:
- Adults: ≥1.3 µg/ml
- Children ≤2 years: ≥0.35 µg/ml
Higher levels needed for mucosal protection (e.g., sinusitis, otitis).
Post-PCV era: non-vaccine serotypes dominate. Common ones include:
- 8 (18%), 12F (6%), 15B/C (5%), 16F (5%), 19F (8%)
- Others: 3, 4, 6C, 11A, 19A, 21, 22F, 23A/B, 35B/D, 35F
INTERPRETING PNEUMOVAX 23 RESPONSES
Timing matters:
- Blood collection at baseline, peak (4–6 weeks), and 6 months
Expected response:
- ≥1.3 µg/ml + 2-fold increase in:
- ≥70% of serotypes (age >6)
- ≥50% of serotypes (age 2–6)
Inadequate response → possible B cell dysfunction
Also test with protein vaccine (e.g., tetanus toxoid)
Pure polysaccharide serotypes (marked):
2, 8*, 9N*, 10A*, 11A*, 12F*, 15B*, 17F*, 20*, 22F*, 33F*
CHILDREN < 2–3 YEARS
Polysaccharide response not routinely assessed due to immaturity.
If IEI suspected:
- Look for ≥2-fold increase in ≥50% of serotypes post-Prevenar 13
- Levels <0.35 µg/ml in ≥50% → prompt IEI work-up
WHEN TO CONSIDER DIAGNOSTIC VACCINATION
• Recurrent infections (e.g. sinusitis, otitis media, pneumonia)
• A history of invasive pneumococcal disease
• If a primary immunodeficiency is strongly suspected on clinical grounds
• Risk factors for secondary immunodeficiency (e.g. immunosuppressive therapy, chronic illness, diabetes mellitus, post-splenectomy, etc.)
NEXT STEPS
Comprehensive Immune Evaluation:
- IgG, IgA, IgM, IgE
- Lymphocyte subpopulations
- Memory B cells
Management:
- Antibiotic prophylaxis
- Immunoglobulin replacement
Specialist referral:
- Assess for complications (e.g., bronchiectasis, autoimmune disease)
KEY TAKEAWAYS
- Use both protein and polysaccharide vaccines for diagnostic vaccination
- Pneumovax 23 is crucial for identifying immune deficiencies
- 23-serotype assay is more accurate than 13-serotype
- Prevenar 13 may confound Pneumovax 23 results
- Repeat tests for unexpected results
- Correct interpretation ensures timely diagnosis and better outcome