Safety and immunogenicity of fractional dose intradermal injection of two quadrivalent conjugated meningococcal vaccines

Abstract

BackgroundVaccination with conjugated meningococcal vaccines is the best way to prevent invasive meningococcal disease. Changes in serogroup epidemiology have led to the inclusion of quadrivalent vaccines in the national immunization programs of several countries, but vaccines are frequently in short supply. Intradermal administration has the potential to increase vaccine availability through dose reduction, without sacrificing efficacy. It has never before been investigated for glycoconjugate meningococcal vaccines. MethodsDifferent fractional doses of two quadrivalent meningococcal conjugate vaccines (MenACWY-CRM197 (Menveo®) and MenACWY-TT (Nimenrix®)) were administered intradermally to sequential groups of 4 participants, according to an adaptive dose escalation design, starting at 1/10th of the original dose. Booster doses were given after 4–6 months based on interim serology results using a multiplex bead-based assay (MIA). Final analyses were based on serum bactericidal antibody titers (rSBA). ResultsA total of 12 subjects were enrolled (average 25 years old, range 19–48). MenACWY-CRM197 became unavailable during the course of the study and was only evaluated for a 1/10th dose. This dose resulted in less than complete seroprotection for serogroup A but complete protection against the other serogroups. MenACWY-TT was evaluated for a 1/10th and 1/5th dose level. Both fractional doses of MenACWY-TT resulted in complete seroprotection against all vaccine serogroups. Geometric mean titers 1 month after vaccination were lower and decayed faster in the MenACWY-CRM197 group. Adverse events were mild and there were no serious adverse events. ConclusionFractional intradermal vaccination against meningococcal disease with quadrivalent conjugate vaccine appears to be safe and effective in our small dose finding study. Tetanus toxoid conjugated vaccine (Nimenrix®) shows a trend towards higher antibody levels compared to CRM197-conjugated vaccine (Menveo®). The 1/5th fractional dose of MenACWY-TT appears to result in higher antibody levels than does the 1/10th dose. These results can be used for a larger non-inferiority study.This trial was registered in clinicaltrials.gov under NCT01782066.