Combination vaccine including Hib, MenC and tetanus toxoid works well in preterm infants

Omenaca F. Pediatr Infect Dis J. 2011; doi: 10.1097/INF.0b013e3182293a82

A combination vaccine including Haemophilus type b, Neisseria meningitidis serogroup C and tetanus toxoids appears as effective in preterm infants as with full-term infants, according to a recent study published online.

The combined Hib-MenC-TT conjugate vaccine (Hib-MenC-TT, Menitorix, GlaxoSmithKline Biologicals) was immunogenic and well tolerated in preterm infants when compared with full-term infants when co-administered with other routine pediatric vaccines.

Results of the open, controlled, multicenter study conducted in Spain indicate no significant differences between the two preterm groups regarding immunogenicity or reactogenicity. The data support the routine vaccination of premature infants at the recommended chronological age with Hib-MenC-TT co-administered with diphtheria-tetanus-acellular pertussis combination vaccines and a seven-valent pneumococcal conjugate vaccine (PCV7, Prevenar, Pfizer) at 2, 4 and 6 months of age, with a booster dose in the second year of life.

“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,” the researchers wrote in the study.

The investigators 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 Hib-MenC-TT, DTaP-hepatitis B (HepB)-inactivated polio vaccine (DTaP-HepB-IPV, Infanrix Penta, GlaxoSmithKline) 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.

Hib-MenC-TT vaccine contained 5 mcg Hib polyribosylribitol phosphate (PRP) and 5 mcg MenC polysaccharides each conjugated to TT. Hib-MenC-TT was administered intramuscularly (IM) into the left anterolateral thigh. DTaP-HepB-IPV, DTaP-IPV/Hib and PCV7 were given IM into the right anterolateral thigh, according to the study.

At one month post-vaccination with the three-dose primary series, “the percentage of subjects with seroprotective anti-PRP antibody concentrations (>0.15 mcg/mL) was >99% in all groups. Prior to the booster dose, the percentage of subjects who continued to have anti-PRP concentrations >0.15 mcg/mL was 89.5% in the preterm 1 group; 86.3% in the preterm 2 group; and 90.0% in the full-term group,” the authors wrote.

Marked increases in anti-PRP antibody GMCs were also seen with booster vaccination, with post-booster anti-PRP GMCs .47 mcg/mL in all groups. Postbooster anti-PRP GMCs were between 3.7 and 5.5-fold higher than post-dose three concentrations. All subjects had anti-PRP concentrations >1.0 mcg/mL after the booster dose.

Eligible infants were aged 8 weeks through 12 weeks at the time of the first vaccination. Children born after 36 weeks’ gestation were enrolled in the full-term group. The preterm group comprised children born at <36 weeks’ gestation and was comprised of two groups: preterm 1 included infants born <31 weeks’ gestation and preterm 2 included infants born between 31 and 36 weeks’ gestation.

According to the literature, infants born before 36 weeks’ gestation are at greater risk of morbidity from vaccine-preventable diseases because of the relative immaturity of their immune system. In addition, some vaccine antigens may be less immunogenic at lower gestational age, according to the researchers.

Disclosures: GlaxoSmithKline Biologicals was the funding source and was involved in all stages of the study conduct and analysis. GSK Biologicals also funded all costs associated with the development and the publishing of the present manuscript.

Dr. Omenaca received payments for lectures from GSK and his institution received grants for studies from GSK, Pfizer and INC research. Dr. Aristegui received payments for grants, travels to meetings and consultancy from GSK. Dr Tejedor and his institution received investigator fees. Dr. Moreno-Perez received payments for travel to meetings and for lectures from GSK, Pfizer and Sanofi and for board membership from Astra Zeneca. Dr. Ruiz-Contreras received payment for lectures and a study grant for this study from GSK.Dr. Merino and his institution received payments for working on clinical assays from GSK, he also received consulting fees, travel support from GSK and payment for expert testimonies on conferences from GSK and Pfizer. Dr. Muro Brussi and Dr Sa´nchez-Tamayo have no conflicts of interest to declare. Dr. Castro Fernandez and Dr Cabanillas both received investigator fees from the Fundacion para la Invigacion. Drs Peddiraju, Mesaros and Miller are employees of GlaxoSmithKline Biologicals. Drs Miller and Mesaros report ownership of stock options.

Dimitris A. Kafetzis

The risk of vaccine-preventable diseases is particularly elevated among preterm infants and may be attributed to both immune system immaturity and potential compromised immunogenicity derived from vaccine antigens in this particular population. Consequently, varied immune responses to vaccines are observed among preterm infants, thus potentially leading to their inadequate immunization. In particular, such vaccination failure has been previously reported for Hib among preterm infants, posing them at increased risk for being infected. Most recently, the combined Hib-MenC-TT vaccine (Hib-MenC-TT, Menitorix, GlaxoSmithKline Biologicals GSK) has been adopted as a booster dose in Hib and MenC-vaccinated infants in the UK and Australia. The evaluation of the immunogenicity and safety of Hib-MenC-TT in preterm infants, particularly when administered concomitantly with other routine pediatric vaccines, is vitally important in order to secure the immunization profile of this high risk population group.

The study of interest presents an open, controlled, multicenter study which comparatively assessed the immunogenicity and safety following vaccination with Hib-MenC-TT, DTaP-HepB-IPV, and PCV7 at 2 to 4-6 months of age, followed by a booster at 16-18 months of age, among preterm and full-term infants. The study findings support that preterm infants did not differ from their full-term counterparts with respect to seroprotection rates or geometric mean concentrations at 1 month following either the vaccination or booster dates evaluated. However, it is noteworthy that anti-HBs geometric mean concentrations were significantly lower among premature infants aged younger than 31 weeks at birth. In addition, the Hib-MenC-TT vaccine was well tolerated among premature and full-term infants, alike. Finally, no serious vaccine-related adverse events were reported.

As a result, it is upheld that the study provides support in favor of the use of the Hib-MenC-TT vaccine among preterm infants at the recommended chronological age. Specifically, when administered concomitantly with other routine pediatric vaccines preterm infants, Hib-MenC-TT had elevated immunogenicity and low reactogenicity. Moreover, seroprotection rates against Hib and MenC following vaccination exceeded 99.0% in preterm infants. In addition, the booster Hib-MenC-TT dose resulted in marked increases in antibody concentrations/titers, indicating effective induction of immune memory. Due to the open-ended study design applied, future randomized trials are necessary to confirm the present study findings.

Dimitris A. Kafetzis, MD, PhD
Infectious Diseases in Children Editorial Board member

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