Fever as a Marker of Reactogenicity of an Acellular Pertussis-Containing Hexavalent Vaccine (HEXAVAC®) in a Large-Scale, Open, Randomized Safety Study in Healthy French Infants

Abstract

Objective: New multivalent vaccines simplify childhood immunisation schedules and can increase vaccination coverage. However, they must have a reactogenicity profile which is acceptable and comparable with that of previously available vaccines. The objective of this trial was to assess the incidence of fever of 40.0°C or higher following vaccination with HEXAVAC® or concomitant PENTACOQ® and HBVAXPRO™.

Study design: This was an open, randomised, pragmatic, post-licensure multicentre trial performed in France. Infants were randomly assigned to receive either a single injection of a hexavalent, aP-containing vaccine (HEXAVAC®) or separate injections of a pentavalent, wP-containing vaccine (PENTACOQ®) and Hepatitis B vaccine (HBVAXPRO™) at 2, 3 and 4 months of age. Both groups received a HEXAVAC® booster at 12-18 months of age.

Results and discussion: 7151 infants were enrolled in 389 centres. During the combined 3-day periods following the primary series injections, the incidence of fever of 40.0°C or higher with HEXAVAC® was not greater than with [PENTACOQ® and HBVAXPRO™]. The incidence of fever at thresholds of 38.0°C, 38.5°C, 39.0°C and 39.5°C was significantly lower in the HEXAVAC group. The vaccine attributable risk for fever of 40.0°C following the booster injection with HEXAVAC® was statistically acceptable.

Conclusion: The incidence of fever of 40.0°C higher in this study was very low and similar in both groups (HEXAVAC® or [PENTACOQ® + HBVAXPRO™] as a 3-dose primary series). Fever ≥ 38.0°C and ≤ 39.5°C was significantly less frequent following administration of HEXAVAC®. The incidence of fever of 40.0°C or higher following a HEXAVAC® booster dose was low in all infants studied.