August 1996
BETHESDA, Md. — A Food and Drug Administration (FDA) advisory committee agreed that a three-component acellular pertussis vaccine is safe and effective for the primary series.
The diphtheria-tetanus-acellular pertussis (DTaP) vaccine (Infanrix), manufactured by SmithKline Beecham, contains chemically inactivated pertussis toxin, filamentous hemagglutinin and pertactin. Safety and efficacy trials conducted in Germany and Italy concluded that the vaccine had an efficacy rate between 84% and 89%.
Members of the FDA's Vaccines and Related Biological Products Advisory Committee were satisfied that the trials clearly demonstrated the vaccine's efficacy when administered to children at 2 months, 4 months and 6 months of age.
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Overall, the DTaP vaccine was far less reactogenic than the whole cell vaccine, according to the results of the Italian trial, yet a trend toward increasing reactogenicity emerged with successive doses.
Reports of swelling and rectal temperatures of 38°C or higher increased with each successive dose of DTaP. This progression was not seen among children who received whole cell vaccine or the diphtheria-tetanus control.
The trend toward progressing reactogenicity is not unique to Infanrix and has been seen with other acellular pertussis vaccines, said Barbara Howe, MD, director of clinical research and development and medical affairs, anti-infectives/biologicals, SmithKline Beecham. Despite the trend, the acellular vaccine is still less reactogenic than whole cell pertussis vaccines.
The increased reactogenicity is not necessarily related to the pertussis component. The SmithKline Beecham vaccine has higher content of diphtheria and tetanus antigens than other DTP vaccines used in the United States, although they are equivalent to other vaccines used in Europe.
The advisory committee agreed that Infanrix is safe for the first three doses, but stressed the need for more data regarding the use of the vaccine for the full five-dose immunization series. SmithKline Beecham indicated that it is continuing the German trials, following children through the full five-dose series.
As committee members discussed whether the data supported labeling the vaccine for use at the fourth and fifth doses, others questioned the practicality of licensing the vaccine only for the first three doses.
To date, one other DTaP vaccine (Tripedia, Connaught) has been before the advisory committee, which determined it is safe and effective for the infant doses. The FDA has not yet made a decision on licensure of that vaccine, but the proposed label would allow its use for all five doses.
If the use of Infanrix were to be limited to the three primary doses, providers would be forced to use another product for the entire series or to use two different vaccines. In addition, Howe said, the Advisory Committee on Immunization Practices considers the fourth dose as part of the primary series and therefore it should not be separated from the three infant doses.
Regarding simultaneous administration of Infanrix with other routine immunizations, SmithKline Beecham presented data showing that administering its DTaP vaccine along with hepatitis B, Haemophilus influenzae type b and oral polio vaccines did not reduce the immune response to any antigen.
For more information, see:
- Greco D, Salmaso S, Mastrantonio P, et al. A controlled trial of two acellular vaccines and one whole-cell vaccine against pertussis. N Engl J Med. 1996;334:341-48.
- Schmitt H-J, Wirsing Von König CH, Neiss A, et al. Efficacy of acellular pertussis vaccine in early childhood after household exposure. JAMA 1996;275:37-41.
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