Maternal antibodies may dampen infant's response to early vaccines

A new study suggests that maternal antibodies passed to babies in the last trimester of pregnancy may actually interfere with the infant's own immune response to vaccines administered in the first few months of life.

The study, titled "The Influence of Maternally Derived Antibody and Infant Age at Vaccination on Infant Vaccines Responses" and published in JAMA Pediatrics, found that high levels of maternal antibodies lingering in the infant at the time of immunization reduced their response to those vaccines.

"It is advisable to review and update vaccination status at the beginning of pregnancy and all women should follow their physician's advice on immunization strategies," Merryn Voysey, senior statistician and NIHR Doctoral Research Fellow at the Nuffield Department of Primary Care Health Services at the University of Oxford and study co-author, told Medical Economics. "Current vaccination policies are safe and effective. Our report provides important data that may be used to model the impact of modifications to the timing of vaccinations, and identifies an important issue for consideration by researchers and policymakers in developing new vaccines."

The report notes that vaccine response was also influenced by the infant's age at the time of first vaccination. Immunization schedules vary depending on infant ages, and the passing of maternal antibodies after vaccination for certain diseases is well established in previous studies. However, inactivated vaccines that are often used during pregnancy--including tetanus, pertussis and hepatitis B--may increase maternal antibodies while weakening the infant's own immune response to their own vaccination, according to the report.

The level of antibodies transferred through the placenta during the third trimester is dependent on a number of factors, including gestational age at birth, how well the placenta was functioning, and the mother's own serum antibody levels. After delivery, any antibodies transferred to the infant start to wane, but the process can take weeks to months depending on the level of antibodies initially transferred.

Many countries now encourage maternal vaccines like Dtap during the third trimester to protect infants until they can receive their own vaccine. The study authors suggest that this practice could "leave children more susceptible to disease later in infancy and increase transmission rates to unvaccinated cohorts."

Next: Study findings

Study findings

The study evaluated data from 32 randomized clinical trials collected from more than 7,000 infants in 17 countries. Antibodies were measured both before and after vaccination, after vaccination and before and after booster doses of any vaccines. Ages of the children involved in the study ranged from five weeks to 20 weeks, with vaccinations administered on four separate schedules:6, 10 and 14 weeks; 2, 3 and 4 months; 2, 4 and 6 months; and 3, 4 and 5 months.

The research team found that infants who were positive for antibodies prior to vaccination had a reduced response to nearly all-20 out of 21-of the antigens tested. The exception was the antigen for Streptococcus pneumonia, according to the report. The vaccine with the greatest response reduction was the inactivated polio vaccine. For that vaccine, response in infants with higher maternal antibody level had post-vaccination antibody levels that were 20% to 28% lower than infants with no or low maternal antibody levels. Conjugated vaccines were also found to have lower post-vaccination responses.

Decreased antibody levels after booster vaccinations at 12 months to 24 months of age were also noted in 16 of the vaccines, and lower antibodies levels prior to booster vaccination correlated to the age at which the infant received initial vaccination.

Infant age at vaccination was an important factor, according to the report, with each month adding to the vaccination schedule correlating to a 10% to 71% increase in antibody levels for most of the antigens. The greatest increase in response over increased age at administration occurred with the Haemophilus influenza vaccine, according to the study.

In comparing vaccination schedules, the study also found that wider spacing of second and third doses of vaccines allowed more time for maternal antibodies to decay and mediated interference.

The report suggests that by delaying first immunization, interference with the infant's own immune response from maternal antibodies could be reduced. Researchers estimated that high maternal antibody levels could be mitigated by a delay of between 1.7 weeks and 5.9 weeks, depending on the vaccine being administered. 

The study cautions that while delaying infant immunization may be beneficial in some ways, it would have to be carefully coordinated and thoroughly studies to make sure the protective effects of maternal antibodies are balanced with the development of their own immune responses.

Voysey said the results have important implications for research on the effects of maternal vaccines on the immune response and protection offered to infants, but are not at a stage where the recommendations in the study should impact clinical practice.