Safety, reactogenicity and immunogenicity of a novel pneumococcal protein-based vaccine in adults : a phase I/II randomized clinical study

Background: New vaccines containing highly conserved Streptococcus pneumoniae proteins such as pneumolysin toxoid (dPly) and histidine-triad protein D (PhtD) are being developed to provide broader protection against pneumococcal disease. This study evaluated the safety, reactogenicity and immunogenicity of different pneumococcal protein-containing formulations in adults. Methods: In a phase I double-blind study (www.clinicaltrials.gov: NC100707798), healthy adults (18-40 years) were randomized (1:2:2:2:2:2:2) to receive two doses of one of six investigational vaccine formulations 2 months apart, or a single dose of the control 23-valent pneumococcal polysaccharide vaccine (23PPV; Pneumovax23 (TM), Sanofi Pasteur MSD) followed by placebo. The investigational formulations contained dPly alone (10 or 30 mu g), or both dPly and PhtD (10 or 30 mu g each) alone or combined with the polysaccharide conjugates of the 10-valent pneumococcal non-typeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV; Synflorix (TM), GlaxoSmithKline Vaccines). Two groups primed with a formulation containing dPly and PhtD (10 or 30 mu g each) continued to the follow-up phase II study (NCT00896064), in which they received a booster dose at 5-9 months after primary vaccination. Results: Of 156 enrolled and vaccinated adults, 146 completed the primary immunization and 43 adults received a booster dose. During primary and booster vaccination, for any formulation, 39.5 degrees C (oral temperature) was reported. Unsolicited adverse events considered causally related to vaccination were reported following 39.5 degrees C (oral temperature) was reported. Unsolicited adverse events considered causally related to vaccination were reported following <= 33.3% of investigational vaccine doses. No serious adverse events were reported for adults receiving investigational vaccine formulations. Formulations containing dPly with or without PhtD were immunogenic for these antigens; polysaccharide conjugate-containing formulations were also immunogenic for those 10 polysaccharides. Conclusion: Investigational vaccine formulations containing dPly and PhtD were well tolerated and immunogenic when administered to healthy adults as standalone protein vaccine or combined with PHiD-CV conjugates.A