The ABCs of DTaP, Hib, HBV and IPV

There has been licensure recently of two combination vaccines for use in pediatrics.

Although combinations of vaccines are not new, the urgency to develop these products has become greater with the increasing number of immunizing agents in our armamentarium. Although there has been general acceptance for the increasing number of injections given to infants, these need to be minimized. This is particularly true as there are more vaccines in the pipeline.

Combinations are not new. When we think of combinations we often forget that diphtheria, tetanus and petussis were given as individual vaccines before they finally were combined. This was a happy union as it was found the addition of the pertussis antigen enhanced the response to the other two components. Oral polio vaccine contained three vaccines that had to be combined in such a way that there be no interference between the types. When the vaccines were given singly, there was a defined order so as not to decrease the take of the subsequent dose of a different strain. In trivalent oral polio vaccine, they were not combined in the same quantity to decrease the likelihood of interference. Similarly, measles-mumps-rubella vaccine does not contain equal quantities of the components for the same reason. The addition of the varicella component to produce the MMRV vaccine contains far more varicella vaccine virus than the monovalent varicella vaccine.

Besides interference, the obvious concern is whether reactions to the individual components might be additive. This would make the combination unacceptable. Combination vaccines are evaluated for reactivity before being submitted for licensure. In the case of MMRV, nine out of 10,000 doses were accompanied by febrile convulsions, compared with MMR with a rate of four out of 10,000 in those receiving the first dose. It is noted that the first dose is given during the time that febrile convulsions are most common. Thus, in the June meeting of the Advisory Committee on Immunization Practices, it was recommended that there be no preference expressed for giving MMRV or MMR and varicella vaccine in separate doses. Usually, combinations are recommended over giving multiple single vaccines requiring extra injections.

Objections to combo vaccines

For reasons that to me are irrational, there have been objections to “overloading the immune system” by giving multiple antigens simultaneously.

There are no data to support this belief. It is based on the mistaken notion that because vaccines are identified by the name of the organism or antigen that is administered that it is the only antigen in the preparation.

In fact, one can demonstrate an immune response to multiple components of vaccines, including the many antigens that may comprise a microorganism.

This also is true of the food or inhalants to which we eat or breathe. Many years ago, we were trying to determine the best way of preventing “non-specific” reactivity in serum we were testing by ELISA (J Clin Micro. 1998. 25:987). In the process, we tested the serum from 40 infants between ages 7 and 24 months and found that almost all of them had high levels of antibody against cow’s milk proteins. It was not a single cow milk protein but cow’s milk proteins. Probably the greatest challenge to the immune system occurs around the time of birth. Imagine the fetus safely tucked away in its mother’s uterus being exposed to relatively few antigens with which the mother had been in contact, being exposed to all the new antigens encountered in passing through the maternal genital tract, or taking its first breath of air!

When introducing new combinations of vaccines, harmonizing these with existing vaccines is important. It would be desirable to have vaccines produced by different manufacturers compatible. Extra doses of some components are given in certain combinations. Usually we rely on immunological correlates of protection when these are reliable rather than additional clinical trials to ensure immunologic compatibility.

Using combinations may lead to conflict concerning reimbursement and may complicate record keeping. Switching from the vaccines you currently are using to new products may lead to some confusion, as may switching doctors. The cost of using combinations must be considered in the decision as to whether to use these products (MMWR. 1999;48(rr05)1-15).

This preamble leads us to a consideration of the use of two new combination products, Pentacel, which contains DTaP, IPV and Hib, and Pediarix, which contains DTaP, IPV and hep B. Wherever possible, one should use the same brand for the series. Because of the shortage of Hib-containing vaccines (MMWR. 2007;56(50);1318-1320), a booster should not be given at 12 months to immunocompetent children who are not at increased risk. Pentacel should not be used in lieu of monovalent vaccines for these children. For those at increased risk, either monovalent Hib vaccine or Pentacel may be given at 12 to 15 months. If the latter is used, a booster of DTaP at 15 to 18 months is not needed.

The general guidelines on administering these vaccines can be found on pages 31 and 32 of the 2006 Red Book.