Haemophilus Influenzae Type b-Neisseria Meningitidis Research Articles

Safety and immunogenocity of a novel combined Haemophilus influenzae type b–Neisseria meningitidis serogroups A and C-tetanus-toxoid conjugate vaccine in healthy Chinese children aged 6 months to 5 years old

A novel combined Haemophilus influenzae type b-Neisseria meningitidis serogroups A and C-tetanus-toxoid conjugate vaccine (Hib-MenAC vaccine) has been developed to protect children against diseases caused by Hib, MenA, and MenC. This study investigated the safety and immunogenicity of the Hib-MenAC vaccine administered in 2-dose series to children aged 6–23 months and in a single dose to children aged 2–5 y. A randomized, positive-controlled, non-inferiority clinical trial was conducted for 1200 healthy participants in each age group. Within each age group, participants were randomly allocated to the Hib-MenAC group or the control group at a ratio of 1:1. Adverse reactions were recorded within 28 d after each dose. Blood samples were obtained to assess immunogenicity on day 0 and at 28 d after a complete vaccination course. For the investigational vaccine, the incidence of total adverse reactions in vaccinees aged 6–23 months was 46.8% and that in vaccinees aged 2–5 y was 29.8%. Most adverse reactions were mild or moderate. One non-fatal serious adverse event occurred in the Hib-MenAC group, but was unrelated to vaccination. The seroconversion rate to the 3 components reached 94.0%, and the proportion of vaccinees with rSBA titers ≥ 1:8 and PRP ≥ 0.15 g/mL reached 97.0% in both age groups. The safety and immunogenicity of the Hib-MenAC vaccine were non-inferior when compared to the licensed vaccines. It was concluded that the novel vaccine would be expected to protect children against all of the targeted diseases.

MenHibrix

To review the immunogenicity and safety of the Haemophilus influenzae type b-Neisseria meningitidis serogroups C and Y tetanus toxoid conjugate vaccine (Hib-MenCY-TT) for infants and toddlers. Studies conducted in humans and limited to publication in English were identified through a MEDLINE (January 2000 to September 2013) search using the terms Hib-MenCY-TT, MenHibrix, and Haemophilus influenzae type b-Neisseria meningitidis serogroups C and Y tetanus toxoid conjugate vaccine. Clinical trial registries, Web sites, and reference citations from publications identified were reviewed for additional sources. Randomized controlled trials were included to evaluate the safety and immunogenicity of Hib-MenCY-TT. Epidemiological data and recommendations from the Advisory Committee on Immunization Practices (ACIP) were also reviewed. Hib-MenCY-TT is available for primary vaccination of infants as a 4-dose series at 2, 4, 6, and 12 to 15 months of age. Hib-MenCY-TT has comparable immunogenicity to licensed Hib vaccines and produces high levels of N meningitidis antibodies against serogroups C and Y. The most common adverse events were pain and redness at the injection site, drowsiness, and irritability. Hib-MenCY-TT has been demonstrated to be a safe and immunogenic vaccination for prevention of disease caused by N meningitidis serogroups C and Y and H influenzae type b in healthy infants and toddlers. Currently, the ACIP recommends the use of Hib-MenCY-TT specifically in high-risk infants aged 6 weeks to 18 months. Hib-MenCY-TT provides the first therapeutic option for vaccination of infants as young as 6 weeks of age who are at increased risk for meningococcal disease.

Combined Haemophilus Influenzae Type B-Neisseria Meningitidis Serogroup C Vaccine Is Immunogenic and Well Tolerated in Preterm Infants When Coadministered With Other Routinely Recommended Vaccines

Preterm infants are at greater risk of morbidity from vaccine-preventable diseases. Therefore, their responses to vaccination are of particular interest. In this open, controlled, Spanish multicenter study, we assessed immunogenicity and safety following primary vaccination of 163 preterm infants (n = 56, <31 weeks' gestation; n = 107, 31-36 weeks' gestation) and 150 full-term infants (>36 weeks' gestation), with Haemophilus Influenzae type B (Hib)-MenC-TT, DTaP(diphtheria-tetanus-acellular pertussis vaccine)-HepB-IPV, and PCV7 at 2 to 4-6 months of age followed by booster vaccination at 16 to 18 months of age. Serum bactericidal activity (rabbit complement) against MenC, and antibodies to Hib and hepatitis b (anti-HBs) were determined. Local/general symptoms were assessed after each vaccination via diary cards. Serious adverse events were recorded throughout the study. There were no statistically significant differences between preterm and full-term infants in either Hib or MenC seroprotection rates or geometric mean concentrations at 1 month postdose 3, before or 1 month postbooster. Postdose 3, >99% of participants had seroprotective anti-HBs antibody concentrations. Anti-HBs geometric mean concentrations was significantly lower in the <31-week group compared with other groups and this difference persisted until 16 to 18 months of age. Hib-MenC-TT vaccine was well tolerated at all ages. There was one death caused by meningococcal serogroup-B sepsis (full term). No serious adverse events were assessed by the investigator as being vaccine related. Hib-MenC-TT vaccine had a similar immunogenicity and safety profile in preterm and full-term infants. These results demonstrate that preterm infants can be safely vaccinated with Hib-MenC-TT at the recommended chronologic age without impacting the responses to the Hib and MenC antigens.

IMMUNE RESPONSE AND ONE-YEAR ANTIBODY PERSISTENCE AFTER A FOURTH DOSE OF A NOVEL HAEMOPHILUS INFLUENZAE TYPE B AND NEISSERIA MENINGITIDIS SEROGROUPS C AND Y-TETANUS TOXOID CONJUGATE VACCINE (HibMenCY) AT 12 TO 15 MONTHS OF AGE

A total of 236 infants received a fourth Haemophilus influenzae type b-Neisseria meningitidis serogroups C and Y-tetanus toxoid conjugate vaccine (HibMenCY) dose at 12 to 15 months. One month later, the proportion with anti-PRP antibody > or =1.0 microg/mL and bactericidal titers > or =1:8 to MenC and MenY was 98.9%, 96.9%, and 95.4%, respectively. One year later, anti-PRP concentrations > or =0.15 microg/mL, and MenC and MenY bactericidal titers > or =1:8 persisted in 100%, 96.6%, and 83.8%, respectively. The safety profile of HibMenCY was comparable to Hib.

REACTOGENICITY AND IMMUNOGENICITY OF COMBINED HAEMOPHILUS INFLUENZAE TYPE B-MENINGOCOCCAL SEROGROUP C CONJUGATE VACCINE BOOSTER DOSE COADMINISTERED WITH MEASLES, MUMPS, AND RUBELLA VACCINEHIB-MENC-TT BOOSTER WITH ROUTINE MMR VACCINE

A booster dose of Haemophilus influenzae type b-Neisseria meningitidis serogroup C conjugate (Hib-MenC-TT) vaccine simultaneously administered with measles, mumps, and rubella (MMR) vaccine in 13- to 14-month-old Spanish toddlers, primed with 3 doses of a combined Diphteria-Tetanus-Acellular Pertusis DTPa-Hib-containing vaccine and a MenC-CRM197 conjugate vaccine, had a good reactogenicity profile and induced similar Hib and MenC booster responses and MMR seropositivity rates as the vaccines given alone.

Randomized Trial to Assess Immunogenicity and Safety of Haemophilus influenzae Type b and Neisseria meningitidis Serogroups C and Y–Tetanus Toxoid Conjugate Vaccine in Infants

Study assessed the immunogenicity and safety of an investigational Haemophilus influenzae type b-Neisseria meningitidis serogroups C and Y-tetanus toxoid conjugate vaccine (HibMenCY-TT) in infants. In a single-blinded, controlled study, 609 infants were randomized 1:1 to receive primary vaccination (2, 4, and 6 months) with either HibMenCY-TT or monovalent Haemophilus influenzae type b tetanus toxoid conjugate vaccine (Hib-TT), co-administered with combined diphtheria-tetanus-acellular pertussis-hepatitis B-inactivated poliovirus vaccine and 7-valent pneumococcal conjugate vaccine. A second control group of 3- to 5-year-old children received a single dose of licensed meningococcal ACWY polysaccharide vaccine (MPSV4). Immunogenicity was measured before and 1 month after dose 3/MPSV4 using human (hSBA) and rabbit complement bactericidal assays (rSBA) and enzyme-linked immunosorbent assay assays for IgG antibodies to MenC and MenY polysaccharides. Anti-polyribosylribitol phosphate antibody concentrations were measured 1 month after the third dose. Safety was also assessed. One month after primary vaccination statistically significantly more HibMenCY-TT than Hib-TT vaccines had anti-PRP antibody concentrations > or =1.0 microg/mL (93.5% vs. 85.8%). The percentage of HibMenCY-TT recipients with hSBA titers > or =1:8 (MenC: 95.9%, MenY: 89.4%) was statistically significantly higher than for MPSV4 recipients (MenC: 30.2%, MenY: 47.5%). The percentage of subjects reporting any severe (grade 3) symptom within 4 days of each vaccination was: 11.5% (HibMenCY-TT) and 24.8% (Hib-TT) (group difference, 13.27%, 95% CI: [7.22;19.29], P < 0.001). The investigational HibMenCY-TT vaccine was well tolerated and immunogenic in infants, induced Hib immune responses that were comparable to licensed Hib-TT vaccine, and induced high levels of bactericidal antibodies against N. meningitidis serogroups C and Y.

Serum Anticapsular Antibody Response in the First Week after Immunization of Adults and Infants with the Haemophilus influenzae type b-Neisseria meningitidis Outer Membrane Protein Complex Conjugate Vaccine

Eight healthy adults and 48 infants 2 and 4 months old were immunized with Haemophilus influenzae type b-Neisseria meningitidis outer membrane protein complex conjugate vaccine (PRP-OMP) to evaluate antibody kinetics in the first days after immunization. Five adults (63%) had some decrease in antibody, although the geometric mean did not decrease significantly. With one exception, the nadir occurred on postimmunization day 3. Seven had an antibody increase by day 7. Of the children, 6 (75%) of 8 and 17 (77%) of 23 had a decrease in antibody in serum obtained on day 2-3 after the first or second dose, respectively, the magnitude of which directly correlated with the preimmunization antibody concentration. However, the geometric mean did not decrease significantly. Within 1 week of immunization, 85% of infants had an increase in antibody, significantly greater after the second dose than after the first. A high concentration of maternally derived antibody before immunization correlated negatively with antibody response. Thus, a transient decrease in antibody occurs in most adults and infants 2-3 days after immunization with PRP-OMP followed by a prompt increase by day 7.