Deidentified individual participant data from GlaxoSmithKline clinical trials were obtained through Clinical Study Data Request. The data were requested on January 2, 2015, and final data were received on April 11, 2016.
Study Selection: The database was examined; studies that appeared to have appropriate data were reviewed.
Main Outcomes and Measures: A total of 7630 infants from 32 studies in 17 countries were included. Mean (SD) age at baseline was 9.0 (2.3) weeks; 3906 (51.2%) were boys. Preexisting maternal antibody inhibited infant antibody responses to priming doses for 20 of 21
antigens. The largest effects were observed for inactivated
polio vaccine, where 2-fold higher maternal antibody concentrations resulted in 20% to 28% lower postvaccination antibody concentration (geometric mean ratios [GMRs], type 1: 0.80; 95% CI, 0.78-0.83; type 2: 0.72; 95% CI, 0.69-0.74; type 3: 0.78; 95% CI, 0.75-0.82). For acellular
pertussis antigens, 2-fold higher maternal antibody was associated with 11% lower postvaccination antibody for
pertussis toxoid (GMR, 0.89; 95% CI, 0.87-0.90) and filamentous
hemagglutinin (GMR, 0.89; 95% CI, 0.88-0.90) and 22% lower
pertactin antibody (GMR, 0.78; 95% CI, 0.77-0.80). For
tetanus and
diphtheria, these estimates were 13% (GMR, 0.87; 95% CI, 0.86-0.88) and 24% (GMR, 0.76; 95% CI, 0.74-0.77), respectively. The influence of maternal antibody was still evident in reduced responses to booster doses of acellular
pertussis, inactivated
polio, and
diphtheria vaccines at 12 to 24 months of age. Children who were older when first immunized had higher antibody responses to priming doses for 18 of 21
antigens, after adjusting for the effect of maternal antibody concentrations. The largest effect was seen for polyribosylribitol
phosphate antibody, where responses were 71% higher per month (GMR, 1.71; 95% CI, 1.52-1.92).
Conclusions and Relevance: Maternal antibody concentrations and infant age at first vaccination both influence infant
vaccine responses. These effects are seen for almost all
vaccines contained in global immunization programs and influence immune response for some
vaccines even at the age of 24 months. These data highlight the potential for maternal immunization strategies to influence established infant programs.