UBC Faculty Research and Publications

Factors Affecting Antibody Responses to Immunizations in Infants Born to Women Immunized Against Pertussis in Pregnancy and Unimmunized Women : Individual-Participant Data Meta-analysis Abu-Raya, Bahaa; Maertens, Kirsten; Munoz, Flor M.; Zimmermann, Petra; Curtis, Nigel; Halperin, Scott A.; Rots, Nynke; Barug, Daan; Holder, Beth; Rice, Thomas F.; Kampmann, Beate; Leuridan, Elle; Sadarangani, Manish

Abstract

Background: Exploring factors that affect immune responses to immunizations in infants born to women immunized with tetanus-diphtheria-acellular-pertussis (Tdap) in pregnancy compared with unimmunized women is important in designing immunization programs. Methods: Individual-participant data meta-analysis of 8 studies reporting post7 immunization immunoglobulin G (IgG) levels to vaccine antigens in infants born to either women immunized with Tdap in pregnancy or unimmunized women, using mixed-effects models. Results: In infants of Tdap-immunized women, two-fold higher levels of anti11 pertussis toxin (PT) and anti-diphtheria-toxoid (DT) IgG pre-primary immunization were associated with 9% and 10% lower post-primary immunization levels, (geometric mean ratio [GMR], PT: 0.91; 95% CI, 0.88-0.95,n=494, DT: 0.9; 0.87- 0.93,n=519). Timing of immunization in pregnancy did not affect post-primary immunization anti-Bordetella pertussis, anti-tetanus-toxoid (TT) and anti-DT IgG levels. Spacing of infant immunization did not affect post-primary immunization anti- B. pertussis and anti-DT levels. In infants of Tdap-immunized women, two-fold higher levels of anti-PT and anti-filamentous haemagglutinin (FHA) IgG pre-primary immunization were associated with lower post-booster immunization levels, (GMR, PT: 0.91; 0.85-0.97,n=224, FHA: 0.92; 0.85-0.99,n=232). Timing of immunization in pregnancy did not affect post-booster immunization anti-Bordetella pertussis, anti22 tetanus-toxoid (TT) and anti-DT IgG levels. Spacing of infant immunization did not affect post-booster immunization anti-PT, anti-pertactin (PRN), anti-TT and anti-DT IgG levels. In infants of unimmunized women, two-fold higher 25 IgG levels of some vaccine antigens pre-primary immunization were associated with 8-17% lower post-primary immunization levels (GMR, PT 0.92, 95% CI:0.88-0.97, n=373; FHA:0.88, 95% CI:0.85-0.92,n=378; PRN:0.84, 95% CI:0.81-0.88, n=367; TT:0.88, 95% CI:0.83- 0.93, n=241; DT: 0.83, 95% CI:0.79-0.87,n=278). Two-fold higher levels of anti- FHA IgG pre-primary immunization were associated with 8% lower post-booster immunization levels (GMR, 0.92; 95% CI: 0.86-0.99,n=138). Discussion: Increased IgG levels pre-primary immunization is associated with reduced post-primary and post-booster immunization levels for some antigens in infants of women immunized or unimmunized in pregnancy, but their clinical significance is uncertain.

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