Immunogenicity and Safety of an Investigational Combined Haemophilus influenzae Type B-Neisseria meningitidis Serogroups C and Y-Tetanus Toxoid Conjugate Vaccine
Neisseria meningitidis serogroups B, C, and Y cause most meningococcal disease in industrialized countries. A Haemophilus influenzae type b-meningococcal serogroups C and Y-tetanus toxoid conjugate vaccine (HibMenCY-TT) was evaluated. A total of 1104 infants (randomized 3:1:1) were vaccinated at 2, 4, and 6 months with HibMenCY-TT, MenC-CRM197 + Hib-TT, or Hib-TT. At 12 to 15 months, HibMenCY-TT and MenC-CRM-primed children received HibMenCY-TT; Hib-TT-primed received N. meningitidis serogroup B Hib-outer membrane protein complex. Antibody concentrations and rabbit/human complement serum bactericidal antibody titers (rSBA/hSBA) were determined. Safety was monitored after each dose (diary cards for first 31 days) until 6 months postdose 4. Postdose 3, rates of antipolyribosylribitol phosphate ≥ 1 μg/mL and rSBA-MenC ≥1:128 in HibMenCY-TT recipients were noninferior to licensed controls. Percentages reaching 0.15 μg/mL (1.0 μg/mL postdose 3) and antipolyribosylribitol phosphate GMC were significantly higher after HibMenCY-TT than Hib-TT postdose 2 and postdose 3. The GMC remained significantly higher before and after dose 4. Proportions of HibMenCY-TT recipients with rSBA ≥ 1:8 were 95.6% (MenC), 98.6% (MenY) postdose-2, ≥ 99% for MenC/Y postdose 3 and 4; hSBA ≥ 1:4 were 95.5% (MenC), 89.8% (MenY) postdose 2, >97% for MenC/Y postdose 3 and 4. HibMenCY-TT had a similar safety profile to control vaccines. HibMenCY-TT induced noninferior Hib and MenC responses compared with monovalent Hib and MenC conjugates with a comparable safety profile. Bactericidal antibodies against MenC/Y were induced after 2 doses of HibMenCY-TT.
[Show abstract] [Hide abstract] ABSTRACT: The highest incidence of meningococcal disease occurs in infants younger than 1 year of age. However, in the US, prior to June 2012, there was no meningococcal vaccine licensed for use in this age group. In the US, where both serogroups C and Y contribute substantially to the overall epidemiology of invasive meningococcal disease, a vaccine combining these capsular polysaccharides was developed. We review the newly licensed HibMenCY-TT (MenHibrix™, GlaxoSmithKline Biologicals, Rixensart, Belgium), a novel vaccine containing Haemophilus influenzae type b (Hib) and serogroups C and Y Neisseria meningitidis conjugated to tetanus toxoid. We describe the vaccine, summarize the clinical trial data, and describe the patient populations recommended to receive HibMenCY-TT as their primary vaccination against Hib. Phase II and III clinical trials found HibMenCY-TT to be well tolerated, safe, and immunogenic when administered at 2, 4, 6, and 12–15 months of age for primary vaccination against both Hib and serogroups C and Y meningococcal disease. In October 2012, the Advisory Committee on Immunisation Practice in the US recommended HibMenCY-TT vaccination for infants at increased risk of meningococcal disease. HibMenCY-TT may be given concomitantly with other routine infant vaccines. It induces antibodies against Hib as well as bactericidal activity against meningococcal serogroup C and Y without increasing the number of injections required. As meningococcal disease epidemiology is dynamic, global surveillance remains essential. In the future, other countries may also benefit from the addition of HibMenCY-TT into their vaccine armamentarium against meningococcal disease.0Comments 0Citations
- "...unologic value suggested by marked rises in anti-PRP GMC and MenC and Y GMTs after the third dose . ..."Importantly, this study also assessed the immunogenicity after two doses of HibMenCY-TT in infancy and found rSBA titers ≥8 against MenC and Y in 94% and 83%, respectively, suggesting protection from serogroups C and Y meningococcal disease may be afforded as early as 5 months of age with this schedule. However, for all three HibMenCY antigens a 6-month dose still has immunologic value suggested by marked rises in anti-PRP GMC and MenC and Y GMTs after the third dose .
[Show abstract] [Hide abstract] ABSTRACT: A pooled analysis was conducted of 1257 toddlers who received a fourth dose of Haemophilus influenzae type b-Neisseria meningitidis serogroups C and Y-tetanus toxoid conjugate vaccine (HibMenCY-TT) or Hib conjugate vaccine (Hib polysaccharide conjugated to N. meningitidis outer membrane protein) coadministered with measles-mumps-rubella (MMR) and varicella (VAR) vaccines (NCT00134719/NCT00289783). Noninferiority of immunological responses to MMR and VAR was demonstrated between groups and incidences of MMR- and VAR-specific solicited symptoms were similar, indicating that HibMenCY-TT can be coadministered with MMR and VAR.0Comments 4Citations
- "...Hib and anti-meningococcal serogroups C and Y immune responses and had an acceptable safety profile.4,5 Here, pooled analysis of data from these studies demonstrated noninferiority of immunological res..."In 2 randomized controlled studies, 3 doses of HibMenCY-TT in infancy followed by 1 dose at 12 to 15 mo of age induced robust anti-Hib and anti-meningococcal serogroups C and Y immune responses and had an acceptable safety profile.4,5 Here, pooled analysis of data from these studies demonstrated noninferiority of immunological responses to MMR and VAR when concomitantly administered with the fourth dose of HibMenCY-TT compared with coadministration with a fourth dose of monovalent Hib-OMP.
[Show abstract] [Hide abstract] ABSTRACT: Meningococcal diseases are serious threats to global health, and new vaccines specifically tailored to meet the age-related needs of various geographical areas are required. This paper focuses on the meningococcal conjugate vaccines developed by GSK Biologicals. Two combined conjugate vaccines were developed to help protect infants and young children in countries where the incidence of meningococcal serogroup C or serogroup C and Y disease is important: Hib-MenC-TT vaccine, which offers protection against Haemophilus influenzae type b and Neisseria meningitidis serogroup C diseases, is approved in several countries; and Hib-MenCY-TT vaccine, which adds N. meningitidis serogroup Y antigen, is currently in the final stages of development. Additionally, a tetravalent conjugate vaccine (MenACWY-TT) designed to help protect against four meningococcal serogroups is presently being evaluated for global use in all age groups. All of these vaccines were shown to be highly immunogenic and to have clinically acceptable safety profiles.0Comments 15Citations
- "... 4 (ATP cohort for Persistence Year 1), Results of this table were previously published    . Table 5: rSBA-MenA, rSBA-MenC, rSBA-MenW-135, and rSBA-MenY antibody response one month  ..."1389.5 [1205.0–1602.2] N: numbers of subjects with available data, 95% CI: 95% confidence interval, GMT: Geometric Mean Titre, %: percentage of subjects with titre within the specified range, PD3: one month after dose 3 (ATP Cohort for Immunogenicity), Pre-D4: just prior dose 4 (ATP Cohort for Persistence), PD4: one month after dose 4 (ATP Cohort for Immunogenicity), PD4 (Y1): one year after dose 4 (ATP cohort for Persistence Year 1), Results of this table were previously published    . Table 5: rSBA-MenA, rSBA-MenC, rSBA-MenW-135, and rSBA-MenY antibody response one month   or 42 days  after one dose of MenACWY-TT in toddlers (ATP immunogenicity cohort).
- [Show abstract] [Hide abstract] ABSTRACT: Meningococcal disease incidence is highest in children younger than 2 years of age, yet there is no US-licensed vaccine for this age group. A phase III study evaluated the immunogenicity and safety of an investigational Haemophilus influenzae type b (Hib)-Neisseria meningitidis serogroups C and Y-tetanus toxoid conjugate vaccine (HibMenCY). A total of 4180 infants were randomly assigned to receive the HibMenCY at the ages of 2, 4, 6, and 12 to 15 months or the licensed Hib tetanus toxoid conjugate vaccine (ActHIB) at 2, 4, and 6 months and Hib conjugated to N meningitidis outer membrane protein (PedvaxHIB) at 12 to 15 months. Routinely scheduled vaccines were coadministered. Serum bactericidal activity using human complement and anti-polyribosylribitol phosphate antibodies were assessed in 991 subjects. Local and systemic adverse reactions were recorded for 4 days after each dose. The percentage of HibMenCY recipients with serum bactericidal assay using human complement titers of 1:8 or higher after dose 3 was 98.8% for N meningitidis serogroup C (MenC) and 95.8% for N meningitidis serogroup Y (MenY). After dose 4, the percentages were 98.5% and 98.8%, respectively. The percentage of HibMenCY recipients with postdose 3 anti-polyribosylribitol phosphate antibody levels of ≥ 1.0 μg/mL was noninferior to that of control (96.3% vs 91.2%). After dose 4, MenC and MenY serum bactericidal assay using human complement antibody titers increased 12-fold over pre-dose 4 levels. Incidence of pain, redness, and swelling at the HibMenCY injection sites tended to be lower than with Hib type b after the first 3 doses and after the fourth dose. Rates of systemic symptoms were similar across groups. The HibMenCY was immunogenic against MenC and MenY and induced anti-polyribosylribitol phosphate antibody levels noninferior to those of licensed Hib conjugate vaccine. The safety profile of the HibMenCY was clinically acceptable and comparable to Hib conjugate vaccine.0Comments 22Citations
- [Show abstract] [Hide abstract] ABSTRACT: The highest rates of invasive meningococcal disease occur in children under 2 years of age, yet as of early 2011 no vaccine was licensed for the youngest infants. However, a novel vaccine consisting of capsular polysaccharides from Haemophilus influenzae type b (Hib) and Neisseria meningitidis serogroups C and Y conjugated to tetanus toxoid (HibMenCY-TT; MenHibrix, GlaxoSmithKline) is in the late stages of development. In clinical trials involving more than 7800 children, HibMenCY-TT was shown to be safe and immunogenic when administered at 2, 4, 6 and 12-15 months of age. Anti-polyribosylribitol phosphate antibody responses were noninferior to those elicited by licensed monovalent Hib vaccines, and most vaccinees developed bactericidal antibodies against N. meningitidis serogroups C and Y. The majority of subjects retained antibody responses as far as 3 years after vaccination. If licensed, HibMenCY-TT not only represents an incremental option for protection against invasive Hib, but also has the potential to prevent invasive meningococcal disease without increasing the number of injections.0Comments 6Citations
- [Show abstract] [Hide abstract] ABSTRACT: The safety profile of HibMenCY was compared with licensed Hib conjugate vaccines in a pooled analysis that included more than 8,500 subjects who were administered a four-dose series of HibMenCY or commercially available Hib vaccines at 2, 4, 6 and 12–15 mo of age in two primary vaccination and two fourth dose phase 3 studies. In all studies, HibMenCY or Hib vaccine was co-administered with age-appropriate, routinely recommended vaccines. In one primary and one fourth dose study (n = 4180), local and general symptoms were solicited using diary cards for 4 d after each dose. Serious adverse events (SAEs) and the occurrence of adverse events (AEs) indicating new onset of chronic disease (NOCD), rash, and conditions prompting Emergency Room (ER) visits were reported from dose 1 until 6 mo after dose 4. The incidences of solicited local and general symptoms were similar following HibMenCY and commercially available Hib vaccines. For some solicited symptoms (pain at the injection site and irritability), rates were lower in the HibMenCY group compared with the Hib control group (p value < 0.05). There were no statistically significant differences between groups in the incidences of SAEs, NOCDs, rash, or AEs leading to ER visits, with the exceptions of anemia and viral gastroenteritis, which occurred significantly less frequently in those receiving HibMenCY than those receiving commercially available Hib vaccines. In this pooled safety analysis, the safety profile of HibMenCY was similar to the safety profile of licensed monovalent Hib vaccines, despite the addition of meningococcal antigens. These studies are registered at www.clinicaltrials.gov NCT00345579 (primary vaccination study), NCT00345683 (fourth dose vaccination study) and NCT00289783 (primary and fourth dose vaccination studies)0Comments 8Citations