Immunogenicity and Safety Evaluation of a New Syringe Presentation of Reduced Antigen Content Diphtheria-Tetanus-Acellular Pertussis Vaccine in Healthy Adolescents: Results from a Randomized Trial
Background: GlaxoSmithKline Vaccines' reduced antigen content diphtheria-tetanus-acellular pertussis vaccine (dTpa), indicated for booster vaccination in children, adolescents and adults, has been licensed in >70 countries worldwide. It has been available as a single dose vial or a prefilled disposable syringe without a needle. The syringe presentation was recently replaced by a prefilled syringe with tip cap and plunger stopper manufactured with different components. The present study compared the immunogenicity and safety of dTpa in the new and previous syringe presentations.
Methods: Phase IV, randomized, controlled, single-blind, multicenter, parallel-group study in Mexico and Chile (NCT01362322). Healthy adolescents aged 10–15 years who had previously received 5 or 6 doses of DTP-combination vaccines, were randomized (1:1) to receive a dTpa booster in the new (dTpa-new, N=335) or previous (dTpa-previous, N=336) syringe presentation. Antibodies against diphtheria (D), tetanus (T) and pertussis antigens (pertussis toxoid [PT], filamentous hemagglutinin [FHA] and pertactin [PRN]) were measured pre- and 1 month post-booster. Non-inferiority of dTpa-new vs dTpa-previous was shown if the upper limits (ULs) of the 95% confidence intervals (CIs) for the post-booster geometric mean concentration (GMC) ratios (dTpa-previous/dTpa-new) for antibodies to the 5 dTpa antigens were ≤1.5 (primary objective). Solicited and unsolicited symptoms were recorded for 4 and 31 days post-booster, respectively. Serious adverse events (SAEs) were recorded up to study end.
Results: The per-protocol immunogenicity cohort comprised 321 dTpa-new and 319 dTpa-previous subjects. Non-inferiority of dTpa-new vs dTpa-previous was shown for all antigens (range of ULs of 95% CIs for GMC ratios: 1.03–1.13; Table). One month post-booster, immune responses were in similar ranges for all antigens in both groups (Table).
Solicited and unsolicited symptoms were reported at similar rates in both groups, with no large swelling reactions (diameter >100 mm). One SAE (injury, not assessed as vaccine-related) was reported in the dTpa-new group.
Conclusion: Changing the syringe presentation did not impact the immunogenicity and safety profiles of dTpa in adolescents.
M. De La O,
A. Lepetic, GSK: Employee, Salary and Stock options as a part of my job agrement
K. Hardt, GSK: Employee and Shareholder, Salary
G. Jayadeva, GSK: Employee and Shareholder, Salary
S. Kuriyakose, GlaxoSmithKline Pharmaceuticals: Employee, Salary
H. H. Han, GSK: Employee and Shareholder, Salary
N. Pavia-Ruz, GSK: Investigator, Research support