vaccine response

A novel study has found that the presence of maternal antibodies in an infant’s serum, which are transferred via the placenta in the third trimester of pregnancy, can reduce the infant’s immune response to postnatal vaccination. Additionally, the vaccine response was influenced by infant age at first vaccination, with older infants showing increased responsiveness.

 

Immunization against infectious diseases, such as smallpox, polio, diphtheria, pertussis, measles, and tetanus, is perhaps one of the most successful public heath interventions in human history. However, current immunization schedules vary with regard to infant age at first vaccination. Moreover, inactivated vaccines, such as those for tetanus, diphtheria, pertussis, polio, and hepatitis B, are considered safe for use during pregnancy, which may increase maternal antibody levels and subsequently diminish the infant immune response to vaccines.

Although numerous studies demonstrate that the presence of maternally acquired antibodies in an infant’s serum can reduce the immune response to vaccines, there is inadequate data regarding the extent of the decrease, the vaccines that are most affected, and the factors that are responsible for the reduced response.

A recent study combined serological data from 32 randomized clinical trials involving a total of 7630 infants from 17 countries. The individual studies were carried out in Spain, France, Germany, Greece, Poland, the Czech Republic, Finland, Mali, Nigeria, Chile, Nicaragua, Argentina, the Dominican Republic, the Philippines, Korea, Russia, and Australia. The age of the children at the time of enrollment ranged from 5-20 weeks, with an average age of 9 weeks. Boys comprised 51.2% of the infants enrolled. The infants were vaccinated according to one of four schedules:  6, 10, and 14 weeks; 2, 3, and 4 months; 2, 4, and 6 months; 3, 4, and 5 months. Antibodies in the infants’ serum to specific vaccine antigens were measured before vaccination, 1 month after the third priming dose of vaccination, before the booster vaccine dose, and 1 month after the booster dose.

Infants with preexisting antibodies had a reduced response to the priming dose for 20 of the 21 vaccine antigens tested, which included vaccine antigens for polio, pertussis, diphtheria, tetanus, hepatitis B, pneumococci, meningococci, and Haemophilus influenzae. The one exception was the serotype 7F pneumococcal polysaccharide, which protects against a commonly occurring serotype of Streptococcus pneumoniae. The largest reduction in infant antibody response was observed for the inactivated polio vaccine where a two-fold increase in maternal antibody levels led to 20–28% lower post-vaccination antibody levels.

For conjugate vaccines, such as the pneumococcal vaccines PCV7 and PCV10, where the primary antigens may be conjugated to protein molecules from the diphtheria or tetanus bacteria, pre-existing anti-diphtheria and anti-tetanus maternal antibodies were found to lower the infant immune response to the corresponding pneumococcal antigens.

The study also found that for each month added to an infant’s age at first immunization, there was a 10–71% increase in the post-vaccination antibody levels for 18 of the 21 vaccine antigens tested. The largest increase of 71% per month of age increase was observed for antibodies to the type b polysaccharide capsule of Haemophilus influenzae.

Lower antibody levels in infants before the administration of booster vaccine doses at 12–24 months of age were also linked to pre-existing maternal antibody levels for 16 vaccine antigens. Similarly, lower antibody levels at the pre-booster stage were linked to infant age at first vaccination. Lower antibody levels after booster vaccination were still associated with pre-existing maternal antibody levels for diphtheria, pertussis, polio, and half the pneumococcal serotypes. And with higher infant age at first vaccination, infant antibody levels at the post-booster stage were significantly enhanced for 9 of the 21 vaccine antigens examined.

Antibodies in the serum decay over periods ranging from a few days to a few months. Therefore, by delaying the first immunization step, maternal antibody interference can be reduced. The study estimated that for pertussis it was possible to offset 2–5 fold higher pre-existing maternal antibody levels owing to prenatal immunization by delaying the first immunization step by 2.2–5.04 weeks. Similarly, for diphtheria and tetanus, by delaying the first immunization step by 2.6–5.9 and 1.7–3.9 weeks, respectively, it was possible to neutralize the effects of pre-existing maternal antibodies.

These results demonstrate the importance of the timing of the first immunization step for vaccine-induced immunity in young children. This has serious implications for the design of both prenatal and infant immunization schedules. Many countries have extensive prenatal immunization programs, and delaying the first postnatal immunization step may be beneficial in such cases. However, the time delay may need to be optimized so infants derive the protective effects of maternal antibodies in their first few months but also develop robust immunity by subsequent immunization when maternal antibodies start to wane.

 

Written By: Usha B. Nair, Ph.D.
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