Abstract
Polysaccharide responsiveness is tested by measuring antibody responses to polysaccharide vaccines to diagnose for humoral immunodeficiency. A common assumption is that this responsiveness is biased by any previous exposure to the polysaccharides in the form of protein-coupled polysaccharide vaccines, such as those used in many childhood vaccination programmes.To examine this assumption, we investigated the effect of protein-coupled polysaccharide vaccination on subsequent polysaccharide responsiveness.HIV-infected adults (n = 47) were vaccinated twice with protein-coupled polysaccharides and six months later with pure polysaccharides. We measured immunoglobulin G responses against three polysaccharides present in only the polysaccharide vaccine (non-memory polysaccharides) and seven recurring polysaccharides (memory polysaccharides). Responsiveness was evaluated according to the consensus guidelines published by the American immunology societies.Impaired responsiveness to non-memory polysaccharides was more frequent than to memory polysaccharides (51% versus 28%, P = 0.015), but the individual polysaccharides did not differ in triggering sufficient responses (74% versus 77%, P = 0.53). Closer analysis revealed important shortcomings of the current evaluation guidelines. The interpreted responseś number and their specificities influenced the likelihood of impaired responsiveness in a complex manor. This influence was propelled by the dichotomous approaches inherent to the American guidelines. We therefore define a novel more robust polysaccharide responsiveness measure, the Z-score, which condenses multiple, uniformly weighted responses into one continuous variable. Using the Z-score, responsiveness to non-memory polysaccharides and memory-polysaccharides were found to correlate (R2 = 0.59, P<0.0001).We found that polysaccharide responsiveness was not biased by prior protein-coupled polysaccharide vaccination in HIV-infected adults. Studies in additional populations are warranted.
Highlights
Polysaccharide responsiveness is tested by measuring antibody responses to polysaccharide vaccines
Responsiveness was evaluated based on American consensus guidelines [1]: An adequate response to an individual polysaccharide was defined as a post-immunisation IgG concentration of at least 1.3 mg/ml or at least four fold over baseline and a person was defined as having impaired responsiveness if less than 70% of individual responses were adequate
A pre-vaccination IgG concentration above 1.3 mg/ml entails an insufficient response if the post-vaccination IgG concentration is below 1.3 mg/ml
Summary
Polysaccharide responsiveness is tested by measuring antibody responses to polysaccharide vaccines. The test forms a cornerstone in diagnosing humoral immunodeficiency [1,2,3,4]. The reason is that childhood vaccination schemes commonly include the same polysaccharides, which are used for testing, but in protein-coupled form. This may be problematic because the dominant perception in the field is that all future responses to protein-coupled polysaccharides - even without the protein moiety – will describe protein responsiveness rather than polysaccharide responsiveness [5]. It is difficult to test polysaccharide responsiveness and to acknowledge the dominant perception. The key question is to which extent the dominant perception is correct
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