Combination Vaccine Produces Lower Immune Response Than Vaccines Administered Separately

The development of immunogenic vaccines against major diseases of childhood has dramatically decreased the rates of invasive disease, according to background information in the article. Since the introduction of a monovalent serogroup C meningococcal glycoconjugate vaccine (MenC) into the United Kingdom routine immunization schedule in November 1999, group C meningococcal disease has decreased by 87 percent in the ages targeted for vaccination, with estimated vaccine efficacy of 90 percent. Within 2 years of the introduction of a 7-valent pneumococcal glycoconjugate vaccine into the recommended infant schedule in the United States, there was a 69 percent reduction in culture-positive invasive pneumococcal disease in children younger than 2 years.

The advent of these efficacious and safe vaccines has increased pressure on crowded infant immunization schedules. Infants in the United States receive up to 20 separate vaccine injections over 5 immunization encounters at ages 2, 4, 6, 12, and 18 months to protect against disease due to hepatitis B, diphtheria, tetanus, pertussis, polio, measles, mumps, rubella, varicella, H influenzae type b, and pneumococcus. The inclusion of MenC would add a further 3 to 4 doses to the U.S. regimen. The development of combination vaccines has become a priority. The combining of pneumococcal and meningococcal conjugate vaccines has the potential to spare U.S. infants up to 4 extra injections by age 18 months and to decrease parental and clinician concerns about the number of vaccinations in early childhood.

Jim P. Buttery, F.R.A.C.P., formerly of the University of Oxford, Churchill Hospital, Headington, Oxford, U.K., and colleagues conducted a study to determine the immunogenicity and safety of a combination 9-valent pneumococcal-group C meningococcal conjugate candidate vaccine (Pnc9-MenC). The phase 2 randomized controlled trial was conducted from August 2000 to January 2002 and enrolled 240 healthy infants aged 7 to 11 weeks from 2 U.K. centers, with home follow-up visits at ages 2, 3, 4, and 5 months. Infants received Pnc9-MenC (n = 120) or monovalent group C meningococcal conjugate vaccine (MenC) (n = 120) administered in addition to routine immunizations (diphtheria and tetanus toxoids and whole-cell pertussis [DTwP], Haemophilus influenzae type b (Hib) polyribosylribitol phosphate-tetanus toxoid protein conjugate, oral polio vaccine).

The researchers found: "Pnc9-MenC combination vaccine administered to infants at ages 2, 3, and 4 months demonstrated reduced group C meningococcal immunogenicity compared with MenC vaccine. The immunogenicity of concomitantly administered Hib and DTwP vaccines was also diminished. The Pnc9-MenC vaccine was safe and immunogenic for all contained pneumococcal serotypes."

"These results highlight the unpredictability of immune responses to individual vaccine antigens after incorporating multiple antigens into combination vaccines and underline the importance of assessing the immunogenicity of all coadministered vaccine antigens in prelicensure trials. The Pnc9-MenC vaccine as tested may not be a suitable replacement for individual MenC or pneumococcal glycoconjugate vaccines," the authors conclude.

(JAMA. 2005;293:1751-1758. Available post-embargo at jama.com)

Editor's Note: This study was funded by Wyeth Vaccines. For financial disclosure information, please see the JAMA article. Dr. Buttery is now with the Department of General Medicine, Murdoch Children's Research Institute, University of Melbourne Department of Paediatrics, Royal Children's Hospital, Melbourne, Australia.