Immunogenicity, reactogenicity, and immune memory after primary vaccination with a novel Haemophilus influenzae-Neisseria meningitidis serogroup C conjugate vaccine

Abstract

We evaluated two formulations of a new combined Haemophilus influenzae type b (Hib)-meningococcal serogroup C (MenC)-tetanus toxoid (TT) conjugated vaccine and two formulations of a new MenC-TT vaccine (trials 711202/001 and 711202/008; clinical trial register numbers NCT00135486 and NCT00135564 [www.ClinicalTrials.gov]). A total of 520 healthy infants were randomized to receive primary vaccination (at 2, 3, and 4 months) with either MenC-TT plus diphtheria-tetanus-acellular pertussis (DTPa)-hepatitis B virus (HBV)-inactivated poliovirus (IPV)/Hib, Hib-MenC-TT plus DTPa-HBV-IPV, or MenC-CRM(197) plus DTPa-HBV-IPV/Hib (control). At 12 to 15 months, subjects received a polysaccharide challenge with meningococcal polysaccharide C plus a DTPa-HBV-IPV/Hib booster. Immune responses were assessed 1 month after dose 2, 1 month after dose 3, and prior to and 1 month after the booster. After primary vaccination, there was no difference between groups in seroprotection rates as measured by titers of serum bactericidal antibody (SBA) to MenC (> or = 1:8) or concentrations of anti-polyribosyl ribitol phosphate (PRP) antibody (> or = 0.15 microg/ml). Prior to the booster, there was no difference between groups in SBA seroprotection rates, whereas anti-PRP seroprotection rates were significantly higher after priming with Hib-MenC-TT. Booster doses induced large increases in SBA and anti-PRP antibodies in primed groups, indicating successful priming with induction of immune memory. Reactogenicity and safety were similar in all groups during the primary and booster phases. A novel combined Hib-MenC-TT conjugate vaccine induced MenC and Hib responses comparable to those induced by licensed monovalent vaccines. A Hib-MenC-TT conjugate vaccine provides vaccination against two major pathogens in a single injection and is a suitable candidate for use in primary or booster vaccination schedules.

Figures

FIG. 1.

Vaccination schedule. Blood samples were collected before the first primary vaccine dose, 1 month after the second primary vaccine dose, 1 month after the third primary vaccine dose, and before and 1 month after the booster dose.

FIG. 2.

Subjects enrolled and reasons for elimination from analyzed cohorts.

FIG. 3.

Incidence of solicited local and general symptoms, with 95% CIs, within the 8-day follow-up period after primary vaccination. Results are shown for all primary doses combined, for the MenC or Hib-MenC injection site, and for the total cohort receiving primary vaccination.

FIG. 4.

Incidence of solicited local and general symptoms, with 95% CIs, within the 4-day follow-up period after booster vaccination. Local symptoms occurred at the Infanrix hexa injection site. Results are shown for the total cohort receiving the booster vaccination. Infanrix hexa plus one-fifth dose of Mencevax (Men ACWY) was given as a booster to all subjects.