Safety and immunogenicity of a meningococcal B recombinant vaccine when administered with routine vaccines to healthy infants in Taiwan: A phase 3, open-label, randomized study

Nan-Chang Chiu, Li-Min Huang, Arnold Willemsen, Chiranjiwi Bhusal, Ashwani Kumar Arora, Zenaida Reynoso Mojares, Daniela Toneatto, Nan-Chang Chiu, Li-Min Huang, Arnold Willemsen, Chiranjiwi Bhusal, Ashwani Kumar Arora, Zenaida Reynoso Mojares, Daniela Toneatto

Abstract

Neisseria meningitidis is associated with high mortality and morbidity in infants and children worldwide. This phase 3 study (NCT02173704) evaluated safety and immunogenicity of a 4-component serogroup B recombinant meningococcal vaccine (4CMenB) co-administered with routine vaccines in Taiwanese infants. In total, 225 healthy infants were randomized (2 : 1 ) to receive 4CMenB and routine vaccines (4CMenB+Routine) or routine vaccines only (Routine group) at 2, 4, 6 and 12 months of age. Routine vaccines were diphtheria-tetanus-acellular pertussis-inactivated poliovirus-Haemophilus influenzae type b, 13-valent pneumococcal, hepatitis B, measles-mumps-rubella and varicella vaccines. Immune responses to 4CMenB components (factor H binding protein [fHbp], Neisserial adhesin A [NadA], porin A [PorA] and Neisseria heparin-binding antigen [NHBA]) were evaluated at 1 month post-primary and post-booster vaccination, using human serum bactericidal assay (hSBA). Reactogenicity and safety were also assessed. A sufficient immune response was demonstrated for fHbp, NadA and PorA, at 1 month post-primary and booster vaccination. In the 4CMenB+Routine group, hSBA titers ≥5 were observed in all infants for fHbp and NadA, in 79% and 59% of infants for PorA and NHBA, respectively, at 1 month post-primary vaccination and in 92-99% of infants for all antigens, at 1 month post-booster vaccination. In the 4CMenB+Routine group, hSBA geometric mean titers for all antigens increased post-primary (8.41-963) and post-booster vaccination (17-2315) compared to baseline (1.01-1.36). Immunogenicity of 4CMenB was not impacted by co-administration with routine pediatric vaccines in infants. Reactogenicity was slightly higher in the 4CMenB+Routine group compared with Routine group, but no safety concerns were identified.

Keywords: Neisseria meningitidis; co-administration; immunogenicity; infant; safety; serogroup B meningococcal vaccine.

Figures

Figure 1.
Figure 1.
Focus on patient section
Figure 2.
Figure 2.
Participant flowchart. Footnotes: N, number of infants; 4CMenB, 4-component serogroup B recombinant meningococcal recombinant vaccine; M, month; DTaP-IPV-Hib, combined diphtheria, tetanus, acellular pertussis, inactivated poliovirus types 1, 2, 3 and Haemophilus influenzae type b vaccine, PCV13, 13-valent pneumococcal conjugate vaccine; HepB, hepatitis B vaccine; MMR, measles, mumps and rubella vaccine; Varicella, varicella vaccine; WC, withdrawal of consent; AE, adverse event; O, other; LFU, lost to follow-up; PV, protocol violation. According to the Taiwanese Immunization Program for Infants, the first 2 doses of HepB are given at 0 (M0) and 1 month (M1) of age.
Figure 3.
Figure 3.
Participants in the 4CMenB+Routine group with hSBA titers ≥5 against each of the indicator strains for the four vaccine antigens (full analysis set). Footnotes: 4CMenB, 4-component serogroup B recombinant meningococcal vaccine; hSBA, human serum bactericidal assay; M, month; fHbp, factor H-binding protein; NadA, Neisserial adhesin A; PorA, porin A; NHBA, Neisseria heparin-binding antigen. Note: Error bars represent 95% confidence intervals. Dotted horizontal lines represent the criteria for assessment of sufficient immune response at 1 month post-primary (M7) and post-booster (M13) vaccination. The immune response was considered sufficient if the lower limit of the 95% confidence intervals for the percentage of infants with hSBA titers ≥5 post-primary or booster vaccination was above 70% at M7 or 75% at M13, respectively.

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