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Comparison of 13 acellular pertussis vaccines: overview and serologic response
K M Edwards1, B D Meade, M D Decker
1Department of Pediatrics, Food and Drug Administration, Rockville, MD, USA.
Insights
This study compared 13 diphtheria-tetanus-acellular pertussis (DTaP) vaccines against whole-cell pertussis vaccines in infants. Most DTaP vaccines showed superior antibody responses to pertussis antigens compared to whole-cell vaccines.
Area of Science:
- Pediatric Infectious Diseases
- Vaccinology
- Immunology
Background:
- Whole-cell pertussis vaccines have been associated with adverse events.
- Diphtheria-tetanus-acellular pertussis (DTaP) vaccines offer a potentially safer alternative.
- Variations in DTaP vaccine composition and manufacturing exist.
Purpose of the Study:
- To compare the immunogenicity of 13 different diphtheria-tetanus-acellular pertussis (DTaP) vaccines against a licensed whole-cell pertussis (WCL) vaccine.
- To assess antibody responses to specific pertussis antigens (pertussis toxin, filamentous hemagglutinin, fimbriae, pertactin) and diphtheria and tetanus toxoids.
Main Methods:
- Healthy infants received one of the study vaccines at 2, 4, and 6 months of age.
- Serum samples were collected before immunization and one month after the third dose.
- Antibody levels were measured using Chinese hamster ovary cell toxin neutralization assays and agglutination tests.
Main Results:
- All vaccines induced significant increases in antibodies against their respective antigens.
- Post-immunization antibody titers varied significantly among the DTaP vaccines.
- The majority of DTaP vaccines elicited antibody responses equal to or greater than the WCL vaccine for most antigens.
- For pertussis toxin (PT), antibody levels correlated poorly with antigen quantity, suggesting formulation impacts immunogenicity.
Conclusions:
- DTaP vaccines can stimulate immune responses exceeding those of licensed whole-cell vaccines for measured antibodies.
- Pertussis toxin (PT) immunogenicity depends on factors beyond antigen concentration, such as antigen derivation and formulation.
- No single DTaP vaccine was consistently the most or least immunogenic across all evaluated antigens.
Objective:
To compare the immunogenicity of a licensed conventional whole-cell (WCL) and 13 diphtheria-tetanus-acellular pertussis (DTaP) vaccines that differed in source, method of manufacture, and included antigens; all vaccines included diphtheria and tetanus toxoids.
Methods:
Healthy infants were enrolled through six university-based vaccine and treatment evaluation units and were randomized to receive one of the study vaccines at 2, 4, and 6 months of age. Sera were obtained before the first immunization and 1 month after the third immunization and were analyzed for antibody to pertussis toxin (PT), filamentous hemagglutinin, fimbriae, pertactin, and diphtheria and tetanus toxins. Chinese hamster ovary cell toxin neutralization assays were performed, and levels of agglutinating antibodies were determined.
Results:
Of 2342 infants enrolled, 1942 contributed usable preimmunization and postimmunization serum specimens. Each vaccine produced significant increases in antibodies directed against the included antigens; postimmunization antibody titers differed significantly among the DTaP vaccines. For each evaluated antigen, the majority of DTaP vaccines produced antibody responses that equaled or exceeded those produced by WCL. For some antigens (eg, PT), mean antibody levels by vaccine correlated poorly with the quantity of antigen included in each vaccine; for others (eg., fimbriae), there was a close correlation.
Conclusion:
Although serologic correlates of pertussis immunity are not defined, it is clear that DTaP vaccines can stimulate immune responses that exceed those of licensed whole-cell vaccine with respect to the measured antibodies. Particularly for PT, immunogenicity seems to depend on factors in addition to antigen concentration, possibly including antigen derivation and formulation. No DTaP was most or least immunogenic with respect to all included antigens.