Avidity indices (AI) were calculated as the percent of antibody that remained bound following NaSCN elution, using an interpolation optical density (OD) value of 0

Avidity indices (AI) were calculated as the percent of antibody that remained bound following NaSCN elution, using an interpolation optical density (OD) value of 0.5 Units (Interpolation valueNaSCN/ Interpolation TSHR valuePBS/FCS) 100. produced strong opsonophagocytic activity against 4 of 8 serotypes and 30% produced high avidity serotype-specific IgG antibodies to 10 of 23 serotypes at 2 weeks post- Pneumovax. Responses were protective for most serotypes that cause disease in western countries while responses to most of the epidemiologically relevant serotypes for developing countries were low. == Conclusion == This is the first comprehensive study evaluating the functional antibody response to Pneumovax in 12-month old infants. Pneumovax induced functional antibody responses to several serotypes causing disease in Western countries but induced poorer responses to serotypes that are responsible for the majority of disease in developing countries. Pneumovax may be of benefit in some populations but further studies are required before this can be recommended in developing countries. Keywords:pneumococcal polysaccharide vaccine, antibody, opsonophagocytosis, avidity, function, serotype, Pneumovax, 23vPPV == Introduction == Streptococcus pneumoniaeis the most common cause of bacterial pneumonia, non-epidemic meningitis, bacteraemia and otitis media in children. In developing countries an estimated one million deaths per year in children under 5 years of age are attributable to pneumococcal disease1. More than 90 serotypes have been described based on the capsular polysaccharide structure of pneumococcus2. Pneumovax, a 23-valent pneumococcal polysaccharide vaccine (23vPPV), contains the 23 pneumococcal serotypes that cause up to 90% of invasive pneumococcal disease (IPD) in unvaccinated children less than 5 years of age in the USA3and 83% of IPD in children under 5 years of age in Fiji4. Immunization with 23vPPV induces production of anti-capsular IgG antibodies by T-cell independent mechanisms. Protection againstS. pneumoniaeis mediated by opsonophagocytosis of the organism in the presence of complement and Flavin Adenine Dinucleotide Disodium serotype-specific antibody5,6. Current opinion suggests that whilst 23vPPV provides immune protection in children greater than 2 years of age, the polysaccharide-specific T-independent response is poorly developed in younger children due to immaturity of the infant immune system characterized by the lack of a functional splenic marginal zone7. Consequently, the WHO and national health authorities do not advocate the use of 23vPPV in children under 2 years of age. Nevertheless, Indigenous Australian children receive 23vPPV at 18 months following a 3 dose pneumococcal conjugate vaccine (PCV7; Prevenar) primary series and the use of 23vPPV following a primary series with PCV7 has been shown to boost the response to Prevenar serotypes and be immunogenic for non-PCV7 serotypes810. However the capacity of infants <2 years of age to produce functional antibody responses to purified polysaccharide antigens remains uncertain. The serotype-specific IgG response to 23vPPV is one of the main tests used to investigate children with suspected immune deficiency. However, data on the normal immune response to 23vPPV are limited11,12. Expert guidelines for the interpretation of an adequate response to 23vPPV in the context of evaluation of immunocompetence and Specific Antibody Deficiency (SAD)13are Flavin Adenine Dinucleotide Disodium available. In children aged 25 years, it has been suggested that an adequate response to the 23vPPV be defined as a post- immunization titer 1.3 g/ml and/or a four-fold or greater increase from the pre-immunization titer for 50% Flavin Adenine Dinucleotide Disodium of serotypes tested13,14. Importantly, however, these criteria were derived from small study cohorts, selected patient populations, or studies examining IgG responses to a limited number of serotypes using an older generation ELISA. We have recently characterised the serotype-specific IgG response following 23vPPV in 12 month old children15. We found that 95% of infants generated an adequate antibody response to polysaccharide antigens (as defined by current expert guidelines13), although some serotypes were poorly immunogenic in the majority of infants with less than 30% of infants mounting adequate IgG responses Flavin Adenine Dinucleotide Disodium to serotypes 6B, 14 and 23F following immunization15. This was the first detailed evaluation of serotype-specific IgG responses to polysaccharide antigens in infants less than 2 years of age, and moreover, was the only study to assess infant antibody responses using the 3rdgeneration WHO ELISA16which is known to offer higher specificity and correlate more closely with the functional opsonophagocytic assay (OPA)17,18. Nevertheless, the functional activity of serotype-specific IgG produced by infants less.