Effects of Maternal Measles Antibodies on Response After Infant MMR Vaccination

Results of a study published in the Journal of the Pediatric Infectious Diseases Society showed for the first time that pre-existing low-avidity neutralizing maternal measles antibodies do not interfere with the development of high concentrations of high-avidity measles antibodies in children immunized at age 12 months.

This study recruited 103 full-term infants born at the British Columbia Women’s Hospital between 2005 and 2008. Infants were followed from birth until 24 months, with blood samples collected at birth; before measles, mumps, and rubella (MMR) vaccine at age 12 months; and at age 24 months. However, not all infants supplied all 3 samples or had a sufficient sample at each time.

Results of neutralizing antibody kinetics showed that of 83 of 84 infants had maternal measles antibodies at birth, with geometric mean concentrations of 1591 mIU/mL (95% CI, 1284-1972 mIU/mL). This decreased to 13 mIU/mL (95% CI, 10-16 mIU/mL) before immunization at age 12 months. At aged 24 months, geometric mean concentrations increased to 2508 mIU/mL (95% CI, 2138-2941 mIU/mL; P ≤.001 for all comparisons).

Results of the effects of maternal measles antibodies on neutralizing antibody concentrations showed that for infants with maternal measles antibodies at 12 months, the geometric mean concentrations at birth was 3452 mIU/mL (95% CI, 1634-7295 mIU/mL). This was significantly higher than the birth geometric mean concentrations of those with no detectable antibodies at 12 months: 1333 mIU/mL (95% CI, 1039-1709 mIU/mL; P =.01). Of the 103 total infants, 16 had maternal measles antibodies present at age 12 months before MMR vaccination, with geometric mean concentrations of 145 mIU/mL (95% CI, 59-357 mIU/mL). However, 6 infants were excluded from further testing. For the remaining 10 infants, the geometric mean concentrations was 84 mIU/mL (95% CI, 43-164 mIU/mL) before vaccination. At age 24 months, the geometric mean concentrations for these 10 infants showed a significant boost after measles vaccine, pre- vs postvaccination geometric mean concentrations (P =.002). The geometric mean concentrations at 24 months for children vaccinated in the presence or absence of maternal antibodies were not significantly different.

In terms of immunoglobulin G (IgG) antibody avidity kinetics, at birth, the median avidity index was 1.9 in 83 infant samples. This decreased to a median of 0.0 in 99 samples at age 12 months, before immunization. Postimmunization, the median avidity index increased significantly to 1.8 in 98 infants measured at age 24 months (P <.001, before vs after immunization).

Results of the effects of maternal antibodies on IgG antibody avidity were as follows: at 12 months, avidity index was negative in all samples and the median increased significantly at 24 months in response to measles immunization, and this was equivalent in those with and without maternal antibodies with median avidity index of 1.8 and 1.9, respectively (P <.001, before vs after immunization for both groups; P =.4, with vs without maternal antibodies).

Investigations of the correlation between neutralizing antibody and immunoglobulin G antibody avidity found that at birth, 6 infants had avidity index despite detectable neutralizing antibodies in 5 of 6 of these infants. At 12 months, avidity index was negative in all infants, including 10 with detectable neutralizing antibodies. For infants with high concentrations of neutralizing antibodies, the avidity index was still below detection. However, infants with similar concentrations of neutralizing antibodies detected at birth or age 24 months had positive avidity index. Further, although significant positive correlation between plaque reduction neutralization concentrations and avidity index at birth and at age 24 months (r=0.2 and r=0.3, respectively; P ≤.03 for both) existed, correlation at age 12 months was low (r=0.05; P =.6).

According to investigators, this work, “suggests the possibility that vaccine-induced measles maternal antibodies lose avidity at a faster rate than antibodies induced by natural disease, opening the possibility of effective immunization in infants aged <12 months.” They also stated that this phenomenon requires further investigation.

Reference

Collins CA, Gelinas L, Yasukawa LL, et al. Measles maternal antibodies with low avidity do not interfere with the establishment of robust quantity and quality antibody responses after the primary dose of measles, mumps, and rubella vaccine administered at 12-months of age. [published online October 23 2019]. J Pediatric Infect Dis Soc. doi: 10.1093/jpids/piz074.