The immunogenicity of pneumococcal polysaccharides in infants and children: A meta-regression

The immunogenicity of plain (not conjugated) pneumococcal polysaccharides in children and infants was reviewed using a systematic literature search. Immunogenicity was defined as the fold-increase in serotype specific antibody concentration after a single dose of plain polysaccharide vaccine in unprimed subjects. Meta-regression was used to calculate the influence of study treatments including subject age, sampling time, dosage, immunization route, vaccine composition and study location. Immunogenicity increased with age for all serotypes, and the increase was more rapid in the first 11 months of life. Study location was the next most significant study variable, with higher responses in countries with lower GDP. A flat dose–response curve was observed over a range from 5 to 50 μg polysaccharide. Serotypes 6A, 6B, 14, 19F and 23F were significantly less immunogenic than serotypes 2, 3, 4, 7F, 8, 9N, 9V and 18C in 11 month old children, but continued to increase in immunogenicity with age until reaching similar levels at 6 years. Some proposed T-independent immune mechanisms could explain the differences in serotype immunogenicity.

► The immunogenicity of plain (unconjugated) pneumococcal polysaccharides has matured for many serotypes by 11 months of age.
► The immunogenicity of plain (unconjugated) pneumococcal polysaccharides is higher in countries with a lower GDP.
► At 11 months of age serotypes 6A, 6B, 14, 19F and 23F are significantly less immunogenic than serotypes 2, 3, 4, 7F, 8, 9N, 9V and 18C.
► Two immune mechanisms, complement C3 modification and T-independent regulation, give predictions consistent with the differences in serotype immunogenicity.