afety and immunogenicity of an investigational vaccine containing wo common pneumococcal proteins in toddlers : A phase II andomized clinical trial

Background: To provide broader protection against pneumococcal disease, new vaccines containing conserved Streptococcus pneumoniae proteins are being developed. This study assessed the safety, reactogenicity and immunogenicity of four formulations containing pneumococcal proteins pneumolysin toxoid (dPly) and histidine triad protein (PhtD) in toddlers. Methods: In this phase II, multicenter, observer-blind study (www.clinicaltrials.gov: NCT00985751) conducted in the Czech Republic, toddlers (12–23 months) were randomized (1:1:1:1:1) to receive one of four investigational vaccine formulations (10 or 30 g each of dPly and PhtD, alone or in combination with polysaccharide conjugates from the pneumococcal non-typeable Haemophilus influenzae proteinD conjugate vaccine [PHiD-CV]), or the licensed PHiD-CV, in a 2-dose primary series plus booster at study months 0, 2 and 6. Solicited local and general symptoms were recorded within seven days postvaccination, unsolicited symptoms within 31 days post-vaccination, and serious adverse events (SAEs) during the entire study period. Antibody concentrations against the vaccine components were measured pre-vaccination, one month post-dose 2, preand one month post-booster. Results: 257 toddlers were enrolled and vaccinated. Percentages of solicited local and general symptoms following the different investigational formulations were generally within the same ranges as for PHiDCV. After each dose, grade 3 fever (>40.0 ◦C, rectal measurement) was reported for maximum one toddler in each group with no differences between investigational formulations and PHiD-CV during primary vaccination. 23 SAEs were reported for 17 toddlers, with distribution balanced between all groups except the group receiving 30 g dPly/PhtD with PHiD-CV-conjugates (no SAEs reported). None of the SAEs were considered to be vaccine-related. For all pneumococcal protein-containing formulations, anti-PhtD and anti-Ply antibody geometric mean concentrations increased from pre-vaccination to post-dose 2 and from preto post-booster vaccination. Conclusion: All investigational vaccine formulations were well-tolerated and immunogenic when administered to toddlers as a 2-dose primary vaccination followed by a booster dose. Abbreviations: AE, adverse event; anti-PD, NTHi protein D antibody; ATP, ccording-to-protocol; CI, confidence interval; dPly, pneumolysin toxoid; ELISA, nzyme-linked immunosorbent assay; GMC, geometric mean concentration; GMT, eometric mean titer; LU, Luminex units; OPA, opsonophagocytic activity; PCV, neumococcal conjugate vaccine; PHiD-CV, 10-valent pneumococcal non-typeable aemophilus influenzae protein D conjugate vaccine; PhtD, histidine-triad protein D; ly, pneumolysin; PS-conjugates, capsular polysaccharide conjugates; SAE, serious dverse event; TVC, total vaccinated cohort. ∗ Corresponding author at: University Hospital, Sokolská 581, 500 05 Hradec rálove, Czech Republic. Tel.: +420 602488620; fax: +420 495833800. E-mail addresses: prymula@fnhk.cz (R. Prymula), pazdiora@fnplzen.cz P. Pazdiora), Magali.x.traskine@gsk.com (M. Traskine), jrueggeberg@doctors.org.uk J.U. Rüggeberg), dorota.d.borys@gsk.com (D. Borys). ttp://dx.doi.org/10.1016/j.vaccine.2014.03.066 264-410X/© 2014 Published by Elsevier Ltd. © 2014 Published by Elsevier Ltd.