Maternal antibody concentrations significantly inhibited infant antigenic responses to priming vaccines and subsequent boosters, according to a large-scale study of all vaccine types, published in JAMA Pediatrics. A team of investigators from the United Kingdom, Canada, and the United States found a continuing inhibitory effect to vaccines given in early infancy that favored a better response in older infants. Interference in antigenic responses from preexisting antibodies was seen in carrier protein vaccines to diphtheria and tetanus, as well as in conjugate vaccines to a range of other childhood diseases.
The investigators had access to antibody data from GlaxoSmithKline for 21 antigens collected from 19 large-cohort studies across 17 countries other than the United States. Initial vaccines were administered at between 5 and 20 weeks (mean age, 9.0 weeks; standard deviation, 2.3 weeks), according to 4 different schedules: 6, 10, and 14 weeks; 2, 3, and 4 months; 2, 4, and 6 months; or 3, 4, and 5 months.
A strong inhibitory response from preexisting maternal antibodies was reported in 20 of 21 priming vaccines, with the single exception of 7F serotype pneumococcal polysaccharide. The largest effect was observed on antibodies to inactivated polio vaccine, which were inhibited by 20% to 28% because of a 2-fold higher preexisting antibody level from maternal transmission. Likewise, binary analysis indicated a reduction in response to the polio vaccine of 36% to 60%.
The maternal inhibition of antibodies continued beyond boosters for most vaccines, and could still be measured at 12 to 24 months, which the authors noted indicated a need to reevaluate current vaccine dosing schedules.
In 18 of the 21 vaccines evaluated, infants who received the priming vaccines at an older age had greater antibody postvaccine titers, ranging from 10% to 71% higher for each additional month of age. “While most vaccines work better in older infants/children than in younger infants, the timing must be planned carefully to give maximum protection when it is most needed,” explained coauthor Merryn Voysey, MSc, senior statistician and National Institute for Health Research doctoral research fellow at the Nuffield Department of Primary Care Health Sciences, University of Oxford, United Kingdom. Ms Voysey told Infectious Disease Advisor that, “the timing has to be carefully planned based on disease risk at different ages and the levels of (protective) antibody from the mother/vaccine schedule.”
Infectious Disease Advisor asked whether, if the schedules were changed, maternal antibodies would provide enough early immunogenicity. “There is good evidence that maternal immunization can provide protection against pertussis in the first few months of life. We don’t yet have studies that compare different schedules head to head, and this is the work that is needed to inform policy changes,” Ms Voysey responded.
The challenge to delaying the current schedule for many priming vaccines is to avoid giving subsequent boosters closer together. “The best immune responses are achieved when the vaccine doses are separated by at least 4 weeks and so crowding of doses close together is unlikely to be considered,” Ms Voysey said.
Voysey M, Kelly DF, Fanshawe TR, et al. The influence of maternally derived antibody and infant age at vaccination of infant vaccine responses: an individual participant meta-analysis [published online May 15, 2017]. JAMA Pediatr. doi: 10.1001/jamapediatrics.2017.0638