Pneumococcal vaccine response in immunodeficiency diagnostics (polysaccharide)

In immunodeficiency diagnostics, the assessment of vaccine responses should always include responses to a 23-valent pneumococcal polysaccharide vaccine, as these antibody concentrations are prone to be the lowest in the immunodeficiencies causing susceptibility to infection. 

Patients with hereditary deficiencies in the ability to form antibodies to polysaccharide antigens suffer from repeated infections caused by encapsulated bacteria (e.g. Streptococcus pneumoniae). 

Instructions for selecting a pneumococcal antibody assays

Restrictions on the interpretation of pneumococcal polysaccharide vaccine response

The antibody response to a pneumococcal polysaccharide vaccine is formed within 4 weeks of vaccination. For this reason, a serum sample should be extracted no earlier than 4 weeks after vaccination, but no later than within 2 months.

Based on the concentration of antibodies produced by the polysaccharide vaccine, it is not possible to conclude whether the vaccinated individual is protected against pneumococcal diseases. The limit value of 0.35 µg/ml used to interpret vaccine responses does not reflect the individual’s level of protection. The limit value is used as a diagnostic criterion to assess the patient's ability to form antibodies against polysaccharide antigens. 

If the patient has previously received a pneumococcal conjugate vaccine, the response to the pneumococcal polysaccharide vaccine should only be interpreted against serotypes not included in the conjugate vaccine. These include 2, 8, 10A, 11A, 12F, 15B, 17F, 20 and 33F. The response is interpreted with the 6296 S-SpnAbNV test.

Interpretation of pneumococcal polysaccharide vaccine response 

The 6297 S-SpnAbVT test (serotypes 1, 4, 5, B, 7F, 9V, 14, 18C, 19F, 23F) is used to measure polysaccharide vaccine response when the patient has received a pneumococcal polysaccharide vaccine but no pneumococcal conjugate vaccine. This is because the determined serotypes are included in both vaccines.

The vaccine response is interpreted as normal if the antibody concentration of more than half of the 10 serotypes examined (6 to 10) is above 0.35 µg/ml.  

When the patient has received both a polysaccharide vaccine and a conjugate vaccine, the vaccine response to the polysaccharide vaccine is assessed based on the 6296 S-SpnAbNV test.

The vaccine response is interpreted as normal if the antibody concentration of more than half of the 9 serotypes examined (5 to 9) is above 0.35 µg/mL. 

Interpretation of borderline cases

In borderline cases, it is also assessed how much of the serotypes identified in the research subject have antibodies exceeding the limit value below which only 5 percent of the antibody concentrations in the control group fall [1]. 

The vaccine response is considered normal if, in more than half of the serotypes studied, the antibody concentration is greater than the serotype-specific antibody concentration corresponding to the 5% percentile.

In case of borderline laboratory findings, clinical symptoms are crucial in the diagnosis of immunodeficiency.

Significance of limit values in immunodeficiency diagnostics

Based on current knowledge, there is reason to use the 0.35 µg/mL concentration as the limit value for normal vaccine response in diagnosing immunodeficiency. 

Similar, strict limit values for the interpretation of vaccine responses have also been used in British studies demonstrating the efficacy of IgG replacement therapy in significantly extending the patient’s life [2]. The higher limit values apparent in American literature are based on unpublished materials [3]. 

In clinical work, serious side effects of long-term IgG replacement therapy have been particularly detected in patients whose vaccine response has been interpreted based on the least strict criteria.

In the next few years, the Finnish Institute for Health and Welfare aims to collect comprehensive Finnish patient data and use this as the basis for improving the precision of the limit value used for interpreting the results of the 6297 S-SpnAbVT and 6296 S-SpnAbNV tests, possibly per individual serotypes. 

Reference data used in interpreting polysaccharide vaccine response

The reference value data is based on measured antibody concentrations in Finnish children (2-6 years old, n = 56; 7-17 years old, n = 33) and adults (over 18 years old, n = 61) before and after pneumococcal polysaccharide vaccination. 

The reference values table contains the geometric mean concentrations (GMC) of the pneumococcus IgG class antibody concentrations. The percentile indicates the concentration below which 5 per cent of the control group concentrations fall. The increase factor is calculated before and after using the ratio of the vaccine’s geometric mean concentration. 

References

1.    Borgers H, Moens L, Picard C, Jeurissen A, Raes M, Sauer K, Proesmans M, De Boeck K, Casanova JL, Meyts I, Bossuyt X. Laboratory diagnosis of specific antibody deficiency to pneumococcal capsular polysaccharide antigens by multiplexed bead assay. Clin Immunol. 2010 Feb;134(2):198– 205. 
 
2.    Seppänen M, personal communication with Prof. Helen Chapel, Oxford, Prof. Dinakantha Kumararatne, Cambridge, Prof. Stephen Jolles, Cardiff.
 
3.    Beck SC. Making sense of serotype-specific pneumococcal antibody measurements. Ann Clin Biochem 2013 June; 50(6):517–9.

 

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