Should Pneumococcal Serotype 3 Be Included in Serotype-Specific Immunoassays?

Abstract

Since the introduction of the 13-valent pneumococcal conjugate vaccine, a number of studies have demonstrated the limited efficacy of the pneumococcal serotype 3 component of this vaccine. Evidence from seven countries (Denmark, France, Greece, Portugal, Sweden, UK, US) shows limited or no effectiveness of the 13-valent pneumococcal conjugate vaccine against serotype 3 invasive pneumococcal disease and carriage. The serotype 3 capsule has some unique characteristics that may serve to explain this lack of efficacy-capsular polysaccharide is abundantly expressed, leading to a greater thickness of capsule, and free capsular polysaccharide may be released during growth. The serotype 3 component of the Luminex multiplex assay demonstrates inferior inter-laboratory reproducibility than other components and results may not be reliable. This communication outlines this evidence and discusses whether it is necessary to include serotype 3 in the assay in the future.

Keywords: Streptococcus pneumoniae; conjugate vaccine; immunoassay; multiplex; serotype 3.

Figure 1

Chart showing mean serotype 3 specific IgG concentration compared to percentage agreement between labs for the UK National External Quality Assessment Service for Immunology, Immunochemistry and Allergy (UK NEQAS IIA) pneumoccocal antibody serotype-specific immunoassay distributions between 2016–2018. Positive results are those assigned a concentration greater than the correlate of protection (0.35 μg/mL) by that laboratory and negative results are those equal to or lower than the correlate of protection. Percentage of agreement equals the percentage of laboratories assigning the same result, with 50% being the lowest possible.