The Influence of Maternally Derived Antibody and Infant Age at Vaccination on Infant Vaccine Responses An Individual Participant Meta-analysis

JAMA Pediatrics
July 2017, Vol 171, No. 7, Pages 611-716
http://archpedi.jamanetwork.com/issue.aspx

Original Investigation
The Influence of Maternally Derived Antibody and Infant Age at Vaccination on Infant Vaccine Responses An Individual Participant Meta-analysis
Merryn Voysey, MSc; Dominic F. Kelly, PhD; Thomas R. Fanshawe, PhD; et al.
JAMA Pediatr. 2017;171(7):637-646. doi:10.1001/jamapediatrics.2017.0638
Key Points
Question  What is the potential for and extent of maternal antibody interference in infant vaccine responses?
Findings  In this individual participant data meta-analysis of the serum of 7630 infants, maternal antibody concentrations and the infant’s age at first vaccination both influenced infant vaccine responses. These effects are seen for almost all antigens contained in global immunization programs, are not removed by more widely spaced schedules, and influence immune response for some vaccines even at the age of 24 months.
Meaning  Prenatal immunization programs containing multicomponent vaccines have the potential to interfere with current immunization programs; however, a delayed start to infant immunization may mitigate these inhibitory effects.
Abstract
Importance  The design of infant immunization schedules requires an understanding of the factors that determine the immune response to each vaccine antigen.
Data Sources  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  Immunogenicity trials of licensed or unlicensed vaccines administered to infants were included if antibody concentrations in infants were measured prior to the first dose of vaccine.
Data Extraction and Synthesis  The database was examined; studies that appeared to have appropriate data were reviewed.
Main Outcomes and Measures  Antigen-specific antibody concentration measured 1 month after priming vaccine doses, before booster vaccination, and 1 month after booster vaccine doses.
Results  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.