Safety and immunogenicity of two acellular pertussis vaccines with different pertussis toxoid and filamentous hemagglutinin content in infants 2-6 months old.

The optimal composition and antigen content of acellular pertussis vaccines is not known. Two vaccines with different quantities of pertussis toxoid (10 and 20 micrograms) and filamentous hemagglutinin (5 and 20 micrograms) and identical 69 kD protein (3 micrograms) and fimbriae 2 and 3 (5 micrograms) combined with diphtheria and tetanus toxoids were compared in a randomized, double-blind study in 2,050 infants undergoing their primary immunization series at 8 centers in the US and Canada. A 6:1 increased antigen to lower antigen allocation was used; 96% of infants received 3 doses and completed the study. A 'clinically significant' local reaction was reported in 3-6% of participants after each dose. Erythema was the most common reaction occurring in 3-5% of infants after the second or third dose. A clinically significant systemic adverse reaction was reported in 28-34% of vaccinees (or vaccinated children) after each dose; fever (7-18%) and fussiness (12-17%) were most common. There were no differences in adverse events between the 2 vaccine formulations. Antibody responses were measured in 292 infants at 1 center. At 7 months, geometric mean anti-filamentous hemagglutinin antibody titers were higher in recipients of the higher antigen content vaccine (p < 0.001) whereas recipients of the lower antigen content formulation had higher anti-fimbriae antibody (p < 0.001) and agglutinin titers (p < 0.05). No differences were detected in anti-pertussis toxin or other antibody responses between the formulations. We conclude that increasing the antigen content of the acellular pertussis vaccine had a variable effect on antibody response but was not associated with increased adverse reactions.