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Immune Deficiency Testing and Functional Antibody Assessment to guide vaccination

Functional antibody testing evaluates how well the immune system produces protective IgG antibodies after vaccination or natural exposure. It is an important part of assessing humoral (antibody‑mediated) immune function, especially in adults with recurrent or severe bacterial infections. This testing helps determine whether the immune system can respond effectively to protein antigens (tetanus), conjugate vaccines (Hib), and polysaccharide antigens (pneumococcal serotypes). A full 10 ml clotted blood sample is required. Pneumococcal serotype‑specific results may take up to 4 weeks.

Who May Benefit From This Testing

Functional antibody testing is considered when there is concern about reduced immune function, including:

  • recurrent sinus, ear or chest infections
  • recurrent pneumonia or bronchiectasis
  • poor response to previous vaccines
  • suspected primary immunodeficiency (e.g., specific antibody deficiency, CVID)
  • secondary immunodeficiency due to medications or haematological conditions

This is a targeted diagnostic test, not a routine screening investigation.

Understanding Functional Antibody Results

Hib IgG

  • Reported in µg/mL
  • <1.0 µg/mL suggests suboptimal protection

Tetanus toxoid IgG

  • Reported in IU/mL
  • <0.16 IU/mL is considered low

Pneumococcal serotype‑specific IgG

  • Protective threshold: ≥0.35 µg/mL
  • A poor response is suggested when ≥4 of 12 serotypes fall below protective levels
  • If raw data are provided, count serotypes <0.35 µg/mL

These results help identify whether the immune system responds normally to protein, conjugate and polysaccharide antigens.

Vaccination as Part of Assessment

Vaccination is used both to treat and test immune function.

  • PCV13 (conjugate) may be followed by PPSV23 (polysaccharide) when indicated
  • PPSV23 should not be repeated within 5 years
  • Menitorix (Hib/MenC) boosts Hib and tetanus responses because it is a tetanus‑conjugated vaccine
  • Revaxis may be used when tetanus IgG is low but Hib IgG is adequate

Intervals between pneumococcal doses are typically 4 weeks or longer.

Repeating Antibody Levels

Post‑vaccination antibody levels should be checked 4–6 weeks after the final dose. Patients with good responses may be re‑tested after 12 months, as some lose protection over time. Patients with poor responses to multiple pneumococcal serotypes should be referred to immunology with full pre‑ and post‑vaccination results.

REFERENCES

  • BSACI Primary Immunodeficiency Guideline https://www.bsaci.org/guidelines
  • ESID Diagnostic Criteria for Antibody Deficiency https://esid.org/Working-Parties/Registry/Diagnosis-criteria
  • UKHSA Green Book – Pneumococcal Chapter https://www.gov.uk/government/publications/pneumococcal-the-green-book-chapter-25
  • WHO Position Paper on Pneumococcal Vaccines https://www.who.int/publications/i/item/who-wer9620
  • South Tees NHS – Specific Antibody Responses https://www.southtees.nhs.uk/services/pathology/tests/specific-antibody-responses

Last reviewed: February 2026

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