Safety and Immunogenicity of a Pentavalent Vaccine Compared With Separate Administration of Licensed Equivalent Vaccines in US Infants and Toddlers and Persistence of Antibodies Before a Preschool Booster Dose: A Randomized, Clinical Trial

Department of Public Health, San Antonio Metropolitan Health District, San Antonio, Texas, USA.
PEDIATRICS (Impact Factor: 5.47). 02/2009; 123(1):301-12. DOI: 10.1542/peds.2007-3317
Source: PubMed


Our goal was to compare the safety and immunogenicity of a combination vaccine (DTaP(5)-IPV-Hib; Pentacel) with that of its separately administered, US-licensed equivalent vaccines (diphtheria, tetanus, 5-component acellular pertussis vaccine [DTaP(5); Daptacel], inactivated poliovirus vaccine [IPV; IPOL], and Haemophilus influenzae type b [Hib] vaccine [ActHIB]), when administered to infants and toddlers concomitantly with other routinely recommended vaccines and to assess antibody persistence from the fourth dose in toddlers to the fifth (preschool) DTaP(5) dose.
In this randomized, multicenter study, 1939 healthy infants were immunized at 2, 4, and 6 months of age with 1 of 3 lots of DTaP(5) coadministered with IPV and Hib vaccines or 1 lot of DTaP(5)-IPV-Hib combination vaccine. Subsequently, 849 of these study participants were given a fourth dose of DTaP(5) and Hib vaccines or a fourth dose of DTaP(5)-IPV-Hib at 1 to 16 months of age. Safety was monitored throughout the study, and blood specimens were obtained to assess antibody responses.
DTaP(5)-IPV-Hib elicited similar or fewer solicited injection-site and systemic reactions as compared with the separate administration of US-licensed DTaP(5), IPV, and Hib vaccines. Seroresponse and seroprotection rates elicited by DTaP(5)-IPV-Hib were noninferior to US-licensed equivalent vaccines after the infant series and after the fourth dose. Children immunized with DTaP(5)-IPV-Hib had higher antibody geometric mean concentrations to pertussis toxoid and filamentous hemagglutinin; children immunized with the separate vaccines had higher responses to pertactin. Hib antibody responses to Hib polysaccharide were nearly identical in the DTaP(5)-IPV-Hib and separate-vaccine groups. Persistence of antibodies to the fifth (preschool) dose was also similar between groups.
DTaP(5)-IPV-Hib combination vaccine was shown to be immunogenic and well tolerated. No clinically important differences in the safety or immunologic profiles were noted for DTaP(5)-IPV-Hib versus the separately administered, US-licensed equivalent vaccines. DTaP(5)-IPV-Hib is a suitable replacement for separately administered DTaP, IPV, and Hib vaccines.

Download full-text


Available from: Fernando R Noriega
  • Source
    • "For example, injection site reactions might be hypothesized to be less common after receiving a single combination vaccine than after receiving the equivalent vaccinations on the day (e.g. [19]). In studying injection site reactions , then, Pentacel should be analyzed separately from separate vaccination with DTaP, Hib, and IPV, because the effect of Pentacel is hypothesized to be different from the effects of the individual components. "
    [Show abstract] [Hide abstract]
    ABSTRACT: As vaccine hesitancy has increased in the United States, various authors have begun proposing alternatives to the Advisory Committee on Immunization Practices' recommended childhood immunization schedule. Because parents may believe the safety claims made by such authors, evaluations of the safety of alternative vaccination schedules are needed. However, comparing the safety of different vaccination schedules has numerous methodologic challenges. These challenges include defining vaccination history, defining safety, appropriately modeling interactions between vaccines, and appropriately handling age effects. Failure to properly address these challenges can result in biased results.
    Preview · Article · Mar 2013 · Vaccine
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: To evaluate the clinical utility of diphtheria and tetanus toxoids and acellular pertussis adsorbed and inactivated poliovirus vaccine ([DTaP-IPV]; Kinrix) and diphtheria and tetanus toxoids and acellular pertussis adsorbed,inactivated poliovirus and Haemophilus b conjugate (tetanus toxoid conjugate)vaccine ([DTaP-IPV/Hib]; Pentacel) in the schedule for pediatric immunizations. PubMed was searched (1966-April 2009) using the key words Kinrix and Pentacel. Subject headings included vaccines, combined; diphtheria-tetanus-pertussis vaccine; diphtheria-tetanus-acellular pertussis vaccines; poliovirus vaccine, inactivated; and Haemophilus influenzae type b polysaccharide vaccine tetanus toxin conjugate. The search was limited to English-language publications involving humans. Product labeling was obtained from GlaxoSmithKline and Sanofi Pasteur. The Centers for Disease Control and Prevention (CDC) Web site was searched for relevant recommendations published June 2008-October 2009. Phase 2 and 3 clinical trials evaluating immunogenicity and safety of DTaP-IPV and DTaP-IPV/Hib were reviewed. Published trials were supplemented with abstracts, review articles, manufacturer product labeling, and CDC recommendations. DTaP-IPV is immunogenic compared to its component vaccines,with no effect of concomitantly administered measles, mumps, and rubella vaccine.Although injection site pain has occurred more with the combination vaccine, its use would reduce by 1 the number of injections given when a child is 4-6 years old.DTaP-IPV/Hib is immunogenic and safe compared to separate vaccines.Immunogenicity to 7-valent pneumococcal conjugate vaccine and hepatitis B(HepB) vaccine is not affected by concomitant administration. DTaP-IPV/Hib decreases injections by up to 7 when given at 2, 4, 6, and 15-18 months of age. It fits into the schedule more easily than DTaP-HepB-IPV (Pediarix), the other DTaP containing combination vaccine indicated for the primary infant series. DTaP-IPV and DTaP-IPV/Hib combination vaccines are immunogenic and safe when given to infants and children. They reduce the number of required injections. Combination vaccines are encouraged to promote timely vaccination and complete immunization schedules.
    Preview · Article · Mar 2010 · Annals of Pharmacotherapy
  • [Show abstract] [Hide abstract]
    ABSTRACT: To evaluate the safety and immunogenicity of a diphtheria, tetanus, acellular pertussis and Haemophilus infuenzae Type b (DTaP/Hib) combination vaccine first developed by a Chinese manufacturer, a randomized, two-stage, parallel controlled, single center clinical trial was conducted in Dafeng, Jiangsu Province of China. A total of 720 infants were enrolled and randomly assigned to two groups with a 2:1 allocation. In Stage I, 480 subjects in Group T were administered with 3 doses of the DTaP/Hib vaccine at 3, 4 and 5 months of age, respectively, while 240 subjects in Group C received separate licensed DTaP vaccine and Hib conjugate vaccine on the same schedule. In Stage II, 633 primed toddlers (431 of Group T and 202 of Group C) were given a booster dose at 18 months of age. Sera samples were collected at pre-dose 1, 4 weeks post-dose 3, pre-dose 4 and 4 weeks post-dose 4, respectively. Levels of protective antibodies were measured by Enzyme Linked Immunoadsorbent Assay (ELISA). Immunogenicity was evaluated with regard to geometric mean concentrations (GMCs), seroconversion rates and seroprotection rates of the antibodies. Solicited adverse reactions were recorded for 3 days after each dose; unsolicited adverse events and serious adverse events were monitored for 28 days after vaccination. Results showed that seroconversion rates of anti-pertussis toxoid (PT), anti-filamentous hemagglutinin (FHA), anti-diphtheria toxoid (DT), anti-tetanus toxid (TT) and anti-polyribosyl-ribitol-phosphate (PRP) in Group T (Stage I: 98.06%, 97.33%, 100%, 100%, 98.79%; Stage II: 99.18%, 83.42%, 99.18%, 63.32%, 85.05%) were comparable to that of Group C (Stage I: 95.26%, 93.16%, 100%, 100%, 98.42%; Stage II: 98.89%, 83.89%, 98.33%, 53.89%, 76.67%). Nearly 100% of the subjects in both groups achieved seroprotective levels of anti-DT (> or = 0.1IU/ml), anti-TT (> or = 0.1IU/ml) and anti-PRP (> or = 0.15 microg/ml) after primary and booster vaccination. The frequencies of local induration, swelling and redness as well as general reactions such as fever, diarrhea and anaphylaxis were low and acceptable in both groups. In conclusion, the DTaP/Hib vaccine was demonstrated to be non-inferior to the control vaccines on safety and immunogenicity. There could be a bright future for the DTaP/Hib vaccine to be widely used in the universal vaccination of Chinese children.
    No preview · Article · Jun 2010 · Vaccine
Show more