A phase II randomized controlled trial of a multicomponent meningococcal serogroup B vaccine, 4CMenB, in infants (II)

Abstract

The licensed meningococcal serogroup B vaccine, 4CMenB (Bexsero^®), contains recombinant membrane proteins (rMenB) and outer membrane vesicles (OMV) of the New Zealand serogroup B strain. We investigated whether reducing the OMV and/or protein content influences 4CMenB immunogenicity and reactogenicity in healthy two month-old infants. Six formulations were studied: 4CMenB, rMenB with 0, ¼ or ½ the OMV dose in 4CMenB, a half-dose of 4CMenB or a prelicensure formulation of 4CMenB, as a 4-dose primary/booster series, concomitantly with routine vaccines (DTaP-HBV-IPV/Hib and 7-valent pneumococcal conjugate) at 2, 3, 4 and 12 months of age. Immunogenicity was assessed as serum bactericidal activity measured with human complement (hSBA) against indicator strains for Men B vaccine antigens before and after the 2,3,4-month series and 12-month dose. Parents recorded solicited reactions for 7 days after each vaccination, and any adverse events throughout the study period. All formulations elicited robust immune response against rMenB components at 5 months, there was some evidence of OMV and protein dose-dependence for Men B indicator strains tested. Titers waned up to the 12-month dose, which elicited further strong responses, which were still OMV and protein dose-dependent. Groups with no, or low-dose OMV displayed slightly lower reactogenicity profiles, but all formulations were generally well-tolerated, high fever was rare and transient, and only three transient SAEs were considered possibly vaccine-related. Decreasing or removing the OMV content reduced reactogenicity of 4CMenB to a certain extent, but had an unacceptable negative impact on the immunogenicity profile. Trial: Clinicaltrials.gov NCT00937521

Keywords: :

• infants
• meningococcal
• serogroup B
• vaccination
• outer membrane vesicles

10.4161/hv.29218

Conflicts of interest

SE has received research grants from Crucell, GSK and Pfizer, and honoraria for consultancy work with Novartis and GSK. RP has received research grants and honoraria from Novartis, GSK, Pfizer, Baxter and Sanofi Pasteur. GVZ received study fees from Novartis. FX, MB, PD and DT are full-time employees of Novartis Vaccines and Diagnostics.

Acknowledgments

The authors are grateful to all the parents who gave permission for their children to participate in this clinical trial, all the investigator physicians from the various study sites in Argentina, Chile, Czech Republic, Hungary and Italy, and Drs Valentina Montinaro, Valentina Preti, Fabio Meneghin, and Francesca Penagini (all from the University of Milan, Italy) for their assistance in performing the study. The authors are also grateful to Dr Keith Veitch (keithveitch communications, Amsterdam, Netherlands) for preparing an initial draft manuscript and providing subsequent editorial assistance.

Authors’ contributions

SE, RP, GVZ, MB, PD and DT participated in the conception and design of the trials. SE, RP and GVZ managed study sites and enrolled participants. DT, MB and PD performed study management for the study sponsor, FX performed all statistical operations. All authors were involved in the interpretation of analyzed data and the decision to submit for publication, and commented and developed the manuscript from the initial draft.

Funding statement

The study was fully financed by Novartis Vaccines and Diagnostics. The study sponsor designed the study with the study investigators, drafted the protocol, supplied all materials, analyzed sera, collated data and performed all statistical analyses.