An experimental vaccine that combines coverage for nine strains of pneumococcus and a single meningococcal strain appears to be less effective than a meningitis vaccine alone, and also decreases the immunogenicity of some other vaccinations given concomitantly, according to a recent report.
The study results provide a cautionary tale for vaccine makers and pediatricians, said John Bradley, M.D., director of the division of infectious disease at Children's Hospital, San Diego, who was asked to comment on the findings.
“It is not easy to put together a vaccine that has all these components,” he said. “When you mix them all together you don't get the nice brisk responses you expect when you administer each separately, and we're probably further off from a single vaccine than we were all hoping,” added Dr. Bradley, who is a member of the American Academy of Pediatrics Committee on Infectious Diseases.
Lead author Jim P. Buttery, M.D., agreed that the study showed the technical difficulty of building a single-shot package. “Each new antigen is successively more difficult,” he said in an interview with this newspaper.
The phase II trial compared Wyeth's Pnc9-MenC vaccine with the company's MenC vaccine alone (JAMA 2005;293:1751–8). MenC (Meningitec) is not used in the United States, and it's not likely that the Pnc9-MenC combination would be sold here, as the strains it covers are not as prevalent.
There is great interest in combination vaccines. Dr. Buttery and his associates noted that if a combination meningococcal/pneumococcal vaccine was adopted, it could spare U.S. infants up to four extra injections by 18 months, and U.K. infants two to three injections at each visit.
Dr. Buttery led the study while at Churchill Hospital in Oxford, England. He is now with Murdoch Children's Research Institute, the University of Melbourne (Australia).
In the trial, Dr. Buttery and his colleagues enrolled 240 healthy infants aged 7–11 weeks at two United Kingdom hospitals from August 2000 to January 2002.
Children who had known immunosuppression, previous vaccination, or confirmed invasive meningococcal or pneumococcal disease were excluded.
They were divided into two groups: 120 received the Pnc9-MenC vaccine, and 120 received MenC, a monovalent group C meningococcal conjugate vaccine. MenC is the standard in the United Kingdom. There is no separate pneumococcal injection. Both groups also were given diphtheria and tetanus toxoids and whole-cell pertussis, Haemophilus influenzae type b (Hib), polyribosylribitol phosphate-tetanus toxoid protein conjugate, and oral polio vaccine.
Vaccinations were given at ages 2, 3 and 4 months—an accelerated schedule, compared with the United States. Home follow-up visits were conducted at 2, 3, 4, and 5 months of age.
At 5 months, serum samples indicated that the combination vaccine was less immunogenic than the MenC vaccine. Antibody concentrations for Hib and diphtheria were lower for infants who received the combination. Dr. Buttery and his colleagues said the effect on diphtheria was unexpected, but he noted that the antibodies were still in the protective range. There was no difference between the groups for tetanus antibodies.
More children in the combination group had to forego second or third vaccinations because of prolonged crying or fever.
The study might not be applicable to U.S. practice because of the accelerated schedule—only a month of separation between each dose—and because of the different vaccinations used. For instance, whole-cell pertussis and oral polio are not usually given in the United States, Dr. Bradley said.
But he said it was important the study was published, especially since it was sponsored by a drug company and was published even though it had negative findings.
Dr. Buttery, who has acted as a consultant for Wyeth and received other assistance from the company, said in an interview that though he is not privy to company decisions, a phase III study “may not occur.”
He and his colleagues concluded that, “The reduced immunogenicity of the serogroup C meningococcal component of Pnc9-MenC as well as concomitantly administered Hib and diphtheria may limit its further development.”