Carrier Cuts Into Immunity

Vaccines that share common proteins can be less effective when they are given to children in combination, according to a report in this month's Infection and Immunity. The reduced protection does not yet warrant concern from parents and physicians, but experts say that the finding highlights the possibility of adverse interactions between vaccines.

Infants typically receive multiple vaccinations at one time, which reduces the number of physician visits. Many of these vaccines combine a common "carrier" protein called tetanus toxoid with an innocuous carbohydrate capsule derived from a pathogen. The protein triggers the immune system to create antibodies to the pathogen. A team led by Ron Dagan, a pediatric infectious disease specialist at Soroka University Medical Center in Beer-Sheva, Israel, wanted to know if a new pneumococcal vaccine based on tetanus toxoid would change infants' immune responses to the standard regimen of vaccines, including those for diphtheria, tetanus, pertussis (DTP), and Haemophilus influenzae type B, which protects against meningitis.

The researchers administered either a tetanus or diphtheria version of the vaccine or a placebo in combination with standard rounds of vaccinations to a group of 75 infants in both Israel and Finland. The new tetanus-based vaccine reduced Haemophilus type B antibodies in all the children, but the drop was statistically significant only in the Israelis. After the third dose, only 83% of the Israeli infants had Haemophilus antibody concentrations considered necessary for long-term protection. Dagan suggests that the difference between the two groups may be caused by the fact that Israeli DTP vaccine contains twice the tetanus toxoid as those given to Finnish infants.

Dagan's group is not sure what lowers the infants' immune responses. The most likely theory, they say, is that multiple tetanus toxoid vaccines may produce antibodies that respond to the combination of the capsular pathogen and its carrier. This could reduce the number of antibodies that target the pathogen.

The finding shows that "carrier overload is not just a theoretical concern," says Sheldon Kaplan, a pediatric infectious disease specialist at Baylor College of Medicine in Houston, Texas. As a possible remedy, the researchers propose that future vaccines contain less-concentrated antigens, or rely on less common or new proteins.