Immunogenicity of pneumococcal conjugate vaccines in infants after two or three primary vaccinations: A systematic review and meta-analysis

Pneumococcal conjugate vaccines have been successfully used in infant vaccination programs. While most countries have used vaccination schedules with three primary immunisations and one booster dose, some countries have implemented schedules with only two primary immunisations and a booster dose. This systematic review aims to summarize evidence on immunogenicity of pneumococcal conjugate vaccines in infants comparing two and three primary immunisations before a booster dose is given. We systematically reviewed papers published between 1999 and 2011. Results from individual studies were pooled in a meta-analysis with the difference in proportion of children achieving serotype-specific ELISA antibody levels of ≥0.35 μg/ml. We estimated that about 10% less children achieve ELISA antibody levels of ≥0.35 μg/ml after two primary immunisations compared to three primary immunisations for most of serotypes included in one of the licensed pneumococcal conjugate vaccines. This difference in proportion was higher for serotypes 6B and 23F, where -49.4% (-66.0; -32.9%) and -26.9% (-37.2%; -16.6%) less children achieved protective antibody levels. These results support the notion that the majority of children are protected by two primary immunisations with pneumococcal conjugate vaccines in the first year of life. However, for serotypes 6B and 23F protection may be reduced.