Elsevier

Vaccine

Volume 37, Issue 32, 26 July 2019, Pages 4460-4467
Vaccine

Antibody persistence and booster response following MenACWY-CRM vaccination in children as assessed by two different assay methods

https://doi.org/10.1016/j.vaccine.2019.06.076Get rights and content
Under a Creative Commons license
open access

Highlights

  • We evaluated 4-year antibody persistence in MenACWY-CRM-primed infants/toddlers.

  • hSBA/rSBA titers for all serogroups were higher in primed than in naïve children.

  • A 2-dose series in toddlers induced higher persistence than 4 doses given during infancy.

  • A booster dose at 60 months of age was immunogenic and well-tolerated in all children.

  • We found no correlation between rSBA and hSBA titers in different age groups.

Abstract

Background

The quadrivalent meningococcal conjugate vaccine MenACWY-CRM has been shown to be immunogenic and well-tolerated in infants and toddlers. We evaluated antibody persistence for up to 4 years after vaccination with MenACWY-CRM in the first years of life and response to a booster dose administered at 60 months of age.

Methods

This was phase 3b, open-label, multicenter extension trial (NCT01148017). We assessed by hSBA and rSBA the persistence of antibody responses to serogroups ACWY in 203 healthy 60-month-olds receiving 4 doses of MenACWY-CRM during infancy (ACWY-4 group), or 2 doses at 12/13 and 15 months or 1 dose at 18 months of age (ACWY-2 group). We administered a MenACWY-CRM dose to 224 primed and 45 naïve 60-month-olds and evaluated safety and antibody response 1 month later.

Results

Antibody persistence measured by both assays was higher in primed than naïve 60-month-olds. The percentages of primed children with hSBA titers ≥8 was low for serogroup A (6–25%) and moderate for serogroups C (27–43%), Y (69–74%) and W (56–69%). For all serogroups, hSBA antibody geometric mean titers (GMTs) tended to be higher in the ACWY-2 than the ACWY-4 group. Post-booster/single dose, ≥96% of primed and ≥73% of naïve children had hSBA titers ≥8 against each serogroup, and hSBA GMTs were higher in primed children. The booster dose was well-tolerated and no safety concern was identified. We further assessed persistence using rSBA across different age groups and detected no overall correlation between rSBA and hSBA titers.

Conclusions

Primary vaccination of infants/toddlers with MenACWY-CRM resulted in moderate antibody persistence against serogroups C, W and Y for up to 4 years after the last priming dose. Regardless of priming schedule, a MenACWY-CRM booster dose at 60 months of age induced a robust immune response against all serogroups and was well-tolerated in all children.

Keywords

Persistence
hSBA
rSBA
MenACWY-CRM
Meningococcal
Booster

Abbreviations

AE
adverse event
ATP
according-to-protocol
CI
confidence interval
CRM
non-toxic cross-reacting mutant of diphtheria toxin isolated from cultures of Corynebacterium diphtheria strain C7 (β197)
D
day
fHbp
factor H binding protein
GMT
geometrical mean titers
hSBA
serum bactericidal assay using human complement
IMD
invasive meningococcal disease
MenACWY-CRM
quadrivalent meningococcal conjugate vaccines containing each of meningococcal groups A, C, Y and W capsular polysaccharides
rSBA
serum bactericidal assay using baby rabbit complement
SAE
serious adverse event

Cited by (0)

1

Present address; Moderna Therapeutics, Cambridge, United States.