The Effect of Pertussis Vaccination During Pregnancy on the Binding Epitopes and Avidity of Anti–Pertussis Toxin Immunoglobulin G Antibodies in Infants and Their Mothers

BACKGROUND: Immunization during pregnancy (IP) against pertussis protects young infants, but the maternally derived antibodies blunt the quantity of infants' antibody responses to their primary vaccination. While the blunting effect has been well studied for antibody quantity, potential blunting that would affect functional characteristics of these antibodies is less studied. This study evaluated the effect of IP on the epitopes and avidity of anti-pertussis toxin (PT) immunoglobulin G (IgG) antibodies in infants and their mothers. METHODS: In this prospective open-label controlled clinical trial, 47 pregnant women received diphtheria and tetanus toxoids and acellular pertussis (DTaP) vaccine booster, and 22 pregnant women who were not vaccinated served as controls. Sixty-nine infants received hexavalent DTaP vaccine at 3 and 5 months of age. The binding strength of anti-PT IgG antibodies and their ability to inhibit epitope-specific binding of mouse monoclonal antibodies were measured with enzyme-linked immunosorbent assays in both maternal and infant samples. RESULTS: In both study groups, antibodies in cord blood showed higher epitope-specific inhibition and avidity than what was induced in infants after 2 primary vaccine doses, at age 6 months. Higher anti-PT IgG concentrations (P < .001) and epitope-specific inhibition targeting 1B7 (P = .049) and 11E6 (P = .02) were noted at age 6 months in control group infants, suggesting epitope-specific blunting in the IP group. No difference was observed in the avidity of anti-PT IgG at age 6 months between 2 study groups. The increase in avidity after vaccination was the highest in those mothers and infants with lower baseline avidity. CONCLUSIONS: IP decreased primary vaccination-induced antibody responses disproportionately against different PT epitopes in infants. CLINICAL TRIALS REGISTRATION: European Union Clinical Trial database (EudraCT no. 2019-001986-34; https://www.clinicaltrialsregister.eu).