Immunogenicity and safety of the Haemophilus influenzae type b and Neisseria meningitidis serogroups C and Y-tetanus toxoid conjugate vaccine co-administered with human rotavirus, hepatitis A and 13-valent pneumococcal conjugate vaccines: results from a phase III, randomized, multicenter study in infants

Abstract

This phase III, open-label, randomized study (NCT01978093) evaluated the immunogenicity and safety of co-administered Haemophilus influenzae type b-Neisseria meningitidis serogroups C and Y-tetanus toxoid conjugate vaccine (Hib-MenCY-TT) with human rotavirus vaccine (HRV), hepatitis A vaccine (HAV) and 13-valent pneumococcal conjugate vaccine (PCV13). We randomized 600 infants (1:1) to receive 4 doses of Hib-MenCY-TT at 2, 4, 6 and 12-15 months of age or 3 doses of Hib vaccine conjugated to N. meningitidis outer membrane protein complex (Hib-OMP) at 2, 4 and 12-15 months of age. All infants received HRV at 2 and 4 months of age, PCV13 at 2, 4, 6 and 12-15 months of age, HAV at 12-15 and 18-21 months of age, and diphtheria-tetanus-acellular pertussis-hepatitis B-inactivated poliovirus vaccine at 2, 4 and 6 months of age. We measured immune responses against HRV, HAV and Hib with enzyme-linked immunosorbent assays, and against MenC/MenY with serum bactericidal assays using human complement. The 4-dose vaccination series with Hib-MenCY-TT induced a robust immune response against Hib, which was non-inferior to that induced by a 3-dose vaccination series with Hib-OMP, and against MenC and MenY. Hib-MenCY-TT did not interfere with immune responses to concomitantly administered HRV, PCV13 and HAV. We did not identify any safety concern. In conclusion, we showed that 4-dose vaccination series with Hib-MenCY-TT during infancy did not interfere with immune responses of co-administered HRV, PCV13 and HAV, induced robust immune responses against Hib, MenC and MenY, and had a clinically acceptable safety profile.

Keywords: serogroups C and Y; type b; co-administration; hepatitis A; human rotavirus; infant; vaccination.

Figure 1.

Participant flow chart. ATP, according-to-protocol; TVC, total vaccinated cohort; HAV, hepatitis A vaccine; N, number of participants.

Figure 2.

Incidence of solicited local symptoms reported in the 4-day interval following vaccination (primary and booster total vaccinated cohorts). Hib-MenCY-TT, Haemophilus influenzae type b and Neisseria meningitidis serogroups C and Y-tetanus toxoid conjugate vaccine; Hib-OMP, Hib vaccine conjugated to N. meningitidis outer membrane protein complex; PCV13, 13-valent pneumococcal conjugate vaccine; DTaP-HBV-IPV, diphtheria-tetanus-acellular pertussis-hepatitis B surface antigen-inactivated poliovirus vaccine; HAV, hepatitis A vaccine; 95% CI, 95% confidence interval.

Figure 3.

Incidence of solicited general symptoms reported in the 4-day interval following vaccination (primary and booster total vaccinated cohorts). 95% CI, 95% confidence interval.

Figure 4.

Focus on the patient.

Figure 5.

Study design. Hib-MenCY-TT, Haemophilus influenzae type b and Neisseria meningitidis serogroups C and Y-tetanus toxoid conjugate vaccine; Hib-OMP, Hib vaccine conjugated to N. meningitidis outer membrane protein complex; HRV, human rotavirus vaccine; PCV13, 13-valent pneumococcal conjugate vaccine; DTaP-HBV-IPV, diphtheria-tetanus-acellular pertussis-hepatitis B surface antigen-inactivated poliovirus vaccine; HAV, hepatitis A vaccine; M, month; W, WeeksThe first 200 participant were enrolled in the blood sample sub-cohort 3, the next 200 participant were enrolled in the blood sample sub-cohort 2 and the last 200 participant were enrolled in the blood sample sub-cohort 1. An extended safety follow-up was done up to the start of the Booster phase. If a participant did not return for the M10–13 timepoint, the study personnel reviewed the participant’s electronic medical records and/or contacted the participant’s parent/guardian by phone to obtain the safety information.