Combination Vaccine Found Safe and Effective for Infants

ROCHESTER, N.Y., Oct. 4 -- A combination vaccine that adds hepatitis B and polio virus to the standard DTP vaccine was found safe and just as immunogenic as the customary five separate shots, according to a 22-center study.

The combination vaccine, Pediatrix (diphtheria, tetanus, pertussis [DTaP], hepatitis B, and polio virus), approved in 2002, is made by GlaxoSmithKline, which supported this study and participated in its design and data collection.

Streamlining an infant's immunization schedule from a total of 15 shots over the three checkups to nine shots will help promote parent compliance, timely vaccination, and fewer administration errors, Michael Pichichero, M.D., of the University of Rochester, and colleagues, wrote in the Journal of Pediatrics.

The study overturns findings from a previous study that suggested problems when two specific vaccines, recommended for two-, four-, and six-month checkups, were given at the same time.

The vaccines concerned were Pediatrix (diphtheria, tetanus, pertussis [DTaP], hepatitis B, and polio virus) and Prevnar, a pneumococcal 7-valent conjugate vaccine (PCV-7).

Earlier studies had found that when the combination vaccine and the pneumonia vaccine were given together, a suboptimal immune response was produced against pertussis in the combination vaccine, along with more uncomfortable reactions, such as fever and swelling at the injection site, Dr. Pichichero said.

The pneumonia vaccine, Prevnar (Lederle laboratories), was approved in 2000, about two years before the combination vaccine, Pediatrix, was licensed.

A total of 575 healthy two-month-olds were enrolled at 22 sites nationwide. Each infant was randomly assigned to one of three groups:

• Combination vaccine, in which infants were given three vaccines, including Pediatrix (DTaP, HepB, IPV), a second vaccine to protect against Haemophilus influenzae type B (HiB), and a third, Prevnar for PCV-7.
• Separate vaccines, in which infants received five independent vaccines including DTaP, HepB, IPV for polio virus, HiB, and PVC-7.
• Staggered vaccines, which was the same as the combination group, except that PCV-7 was delayed by two weeks at every appointment, thereby requiring six office visits, instead of three.

Blood samples were collected before the study began, and again at seven months. Parents were given a diary and were asked to record temperatures, general symptoms such as fussiness, or loss of appetite, and pain or swelling at the injection site.

Immunogenicity in the combination vaccine group was noninferior to that of the separate and staggered vaccine groups with seroprotective rates for diphtheria, tetanus, and poliovirus and to geometric mean concentrations for pertussis, the researchers said.

Seroprotective rates for HepB and Hib were not different between groups, and seropositivity for PCV-7 was high in all groups.

Overall, irritability was the most frequently reported general symptom in all the groups and was significantly higher for the combination vaccine infants.

Fever rates above 101.3 F were significantly higher in the combination vaccine group. Fever lasted for only a day in all the groups.

Overall, medical advice was sought for fever after eight vaccine doses in eight different infants, three in the combination group. However, no group differences were observed in rates of symptoms for which parents sought medical advice.

Local reactions were significantly higher in the combination vaccine group compared with the staggered vaccine group for pain or swelling. None of the local symptoms at any injection site led to a medical visit.

Immunogenicity for the combined vaccine given along with HiB and PCV-7 vaccines as a three-dose primary series was at least as good at that of the separately administered vaccines with respect to DTaP, and polio-virus antibody response. Furthermore, the researchers said, seroprotection rates for hepatitis B were above 98% for all the groups.

Although inconsistent differences in the response to pertussis had been observed in smaller clinical trials of PCV-7 given with the combination vaccine, importantly, the immune response for all criteria, including whooping cough, was similar to the separate and staggered groups, the researchers said.

This study put to rest earlier reservations by showing that the combined vaccine is just as safe and effective as separate shots, and that concerns about pertussis immunity have been dispelled, the researchers concluded.

The CDC's Advisory Committee on Immunization Practices, along with the American Academy of Pediatrics, endorse the use of parenteral combination vaccines if licensed and indicated for the patient's age, instead of their equivalent component vaccines.

Interpretation of data, writing of the manuscript, and decision to submit the paper for publication was made by the authors with contribution from GlaxoSmithKline. No form of payment was provided to any of the authors in conjunction with development of this manuscript.

Dr. Pichichero reported that he has received research grants and/or honoraria from GlaxoSmithKline, Sanofi Pasteur Inc, Wyeth, and Merck for vaccine-related research. Co-author Henry H. Bernstein, DO, has been a recipient of grant/research funding from GlaxoSmithKline. Mark M. Blatter, M.D., serves on the Speakers' Bureaus for Sanofi Pasteur and GlaxoSmithKline. He has received grant/research funding from GlaxoSmithKline, Sanofi Pasteur, Wyeth, Merck MedImmune, and Chiron Lode Schuerman, M.D., is an employee of GlaxoSmithKline and has stock options at the company. Brigitte Cheuvart, Ph.D., is an employee of GlaxoSmithKline. Sandra J. Holmes, Ph.D., is a former employee of and previous consultant for GlaxoSmithKline.