Immunogenicity of the Booster Dose of 2 Investigational Protein-Based Pneumococcal Vaccine Formulations in Toddlers: A Phase II Randomized Trial

Abstract

Background. We have previously shown that primary vaccination with 2 formulations of an investigational pneumococcal vaccine containing each of the highly conserved pneumococcal proteins pneumolysin toxoid (dPly) and histidine‐triad protein D (PhtD) at either 10 μg (PHiD‐CV/dPly/PhtD‐10) or 30 μg (PHiD‐CV/ dPly/PhtD‐30) combined with polysaccharide conjugates of 10‐valent pneumococcal conjugate vaccine (PHiD‐CV, GSK Vaccines [not licensed in USA]) induced robust immune responses in infants in Europe. Here, we present immunogenicity results following administration of a booster dose of these 2 vaccine formulations in the same study. Methods. In this phase II, multicenter, observer‐blind trial (NCT01204658) in Europe, 576 infants aged 6‐14 weeks were randomized 1:1:1:1 to receive primary and booster vaccinations (at ages 2, 3, 4 and 12‐15 months) with either PHiD‐CV/dPly/ PhtD‐10, PHiD‐CV/dPly/PhtD‐30, PHiD‐CV or 13‐valent pneumococcal conjugate vaccine (PCV13, Pfizer), co‐administered with DTPa‐HBV‐IPV/Hib. Immune responses were assessed pre‐ and 1 month post‐booster. Results. All vaccinees had post‐booster anti‐Ply and anti‐PhtD antibody concentrations ≥ assay cut‐off (12 and 17 EL.U/mL, respectively), except for PhtD in PHiD‐CV vaccinees: 96.1% of toddlers. Increases in geometric mean antibody concentrations (GMCs) from pre‐ to post‐booster timepoint were observed (Table 1). For each of the 10 common vaccine pneumococcal serotypes, ≥96.9% of toddlers had post‐booster antibody concentrations ≥0.2 μg/mL; GMCs are shown in Table 1. Pneumococcal opsonophagocytic activity (OPA) seemed to be similar between PHiD‐CV/dPly/PhtD‐10, PHiD‐CV/dPly/PhtD‐30 and PHiD‐CV recipients (except for 9V geometric mean OPA titers in PHiD‐CV/dPly/PhtD‐10 versus PHiD‐CV group) (Table 2). Post‐booster anti‐protein D GMCs tended to be lower in the protein‐based formulations groups than in the PHiD‐CV group (Table 1). Conclusion. PHiD‐CV/dPly/PhtD‐10 and PHiD‐CV/dPly/PhtD‐30 induced booster responses to Ply and PhtD. No interference with immune responses to pneumococcal conjugates was observed when combining dPly and PhtD with the 10 PHiDCV polysaccharide conjugates. (Table Presented) .