Immunogenicity of a reduced schedule of pneumococcal conjugate vaccine in healthy infants and correlates of protection for serotype 6B in the United Kingdom.

Background: Pneumococcal conjugate vaccine (PCV) was introduced in the United Kingdom immunization schedule in September 2006. This study was conducted to establish the immunogenicity of licensed PCV (Prevenar) at a reduced, 2 priming dose schedule (2+1) and to evaluate functional responses in the context of vaccine effectiveness.

Methods: Infants were randomized to receive PCV at 2 and 3 months or 2 and 4 months of age. Boosters were administered at the same time as Haemophilus influenzae type B/meningococcal C conjugate and Measles, Mumps and Rubella or with Measles, Mumps and Rubella alone (www.ClinicalTrials.gov NCT00197808).

Results: PCV at 2/3 months of age was poorly immunogenic and recruitment to this arm was terminated. PCV at 2/4 months of age resulted in lower than expected responses to serotypes 6B and 23F. Functional analysis of serotype 6B by OPA revealed that an enzyme-linked immunosorbent assay cutoff of 0.2 microg/mL was a better predictor of OPA positivity than a cut off of 0.35 microg/mL. PCV booster responses were excellent and no interference from concomitant vaccines was noted.

Conclusions: An interval of at least 8 weeks is required when starting PCV vaccination at 2 months of age although not all serotypes are equally immunogenic. Correlates of protection derived from enzyme-linked immunosorbent assay values may not be equally appropriate for all serotypes as illustrated by results for 6B in this study.