PALO ALTO, Calif. - New evidence suggests that the immunocompetence of the host develops gradually over the first year of life, and that maternal antibodies are not the sole reason for the failure of measles vaccine in children 6 months and younger.
Because of this failure, measles vaccine is recommended for administration between 12-15 months, but this leaves children 6-12 months of age at risk for disease. Past studies showed a high failure rate of measles vaccination in infants younger than 12 months. Poor immunogenicity was associated with the persistence of antibodies acquired transplacentally from mothers whose measles immunity was induced by natural infection.
Therefore, further investigation is required when considering lowering the recommended age of measles immunization for infants whose mothers have vaccine-induced immunity, according to the results of a recent study.
"This is an immune maturation issue," said senior author of the study Yvonne A. Maldonado, MD, associate professor, department of pediatrics, division of infectious disease, Stanford University School of Medicine, Stanford, Calif.
"The vaccine can be used in children at 6 months during an epidemic situation, but it is not considered in the regular dosing schedule," she said.
The purpose of the study was to assess whether there are intrinsic immunologic barriers to immunization of infants younger than 12 months with measles vaccine or whether neutralization of the vaccine virus by passive antibodies constitutes the only significant obstacle to early vaccination.
The recommendation to immunize children at 12-15 months of age was made to ensure that all infants had lost passive antibody when immunized and that optimal herd immunity was achieved. In contrast to the first three decades after measles vaccine was introduced, most infants are now born to mothers who have vaccine-induced measles immunity rather than natural infection, said Maldonado, who is also a member of the National Vaccine Advisory Committee.
Healthy infants without documented chronic illnesses who were 6, 9 or 12 months old were en rolled as they were seen for their well-child visit at the Palo Alto Medical Foundation. A total of 87 healthy infants were enrolled in the study, but two infants never participated after consent was given. Thirteen infants provided only the initial blood sample and 72 infants (6-month-olds, n=25; 9-month-olds, n=24; 12-month-olds, n=10) provided both the initial and follow-up samples. However, not all T cell and B cell assays were performed for each sample.
Children born before 36 weeks' gestation whose birth weight was less than 2,500 g or who had chronic underlying illnesses were excluded.
Infants 6 months and 9 months of age were immunized with measles vaccine (Attenuvax, Merck) while 12-month-old infants were given measles-mumps-rubella vaccine (MMR, Merck & Co.).
Blood samples were collected from infants before vaccination and 12 weeks later. Samples were also taken from infants who did not respond to initial measles vaccination and were given the combination vaccine, MMR.
Healthy adults who received at least one measles vaccination were also evaluated. No measles cases were reported in the geographic area during the study.
Before immunization, measles neutralizing antibody titers were determined in 65 infants; 12 of the 23 6-month-old infants had detectable passive antibodies compared with seven of 20 9-month-old infants and none of 22 12-month-olds.
There were no statistical differences in measles geometric mean titers (GMTs) before vaccination when comparing 6-month-old and 9-month-old infants born to the oldest mothers (born before 1957; n=17) and the youngest mothers (born after 1963; n=13).
Only 10 of the 23 infants 6 months of age had seropositive titers after vaccination compared with 17 of the 20 infants 9 months old, and 21 of the 12-month-old infants.
In contrast, age-related differences were observed among infants who had no detectable passive antibodies by plaque reduction neutralization (PRN) assay prior to immunization. Among these infants, the measles GMTs after vaccination were lower in 6-month-old infants compared with 9-month-old infants and 12-month-old infants lacking detectable passive antibody prior to vaccination.
Six infants who had primary measles vaccine failure at 6 months of age or 9 months of age were evaluated for neutralizing antibodies up to two years after revaccination with M-M-R. According to the study results, their GMTs increased significantly from 4.7 to 403 (P=0.02).
The seroconversion rate, defined as a fourfold rise in antibody titer, in the 6-month-old infants was only 67%, and only 36% of these infants achieved seroprotective neutralizing antibody titers of 120 or higher after vaccination, compared with 100% of 9- and 12-month-old infants lacking detectable passive antibody prior to vaccination.
The deficiency of the humoral immune response to measles vaccine among 6-month-old infants without detectable passive antibodies in this study, compared with that among 9- or 12-month-old infants, indicates that some component of the immune response to measles antigens undergoes maturation late in the first year of life.
This study also suggests that postnatal maturation of the immune system is also likely to restrict the immunogenicity of measles vaccine in 6-month-old infants. The next phase will be to determine the specific mechanism of why an infant's immune response does not work as well at 6 months of as 9 months of age.
Interference from passively acquired antibodies among infants younger than 12 months has been observed, according to the results. Mothers born before 1957 who had measles immunity from natural disease transferred more neutralizing antibodies to their infants than mothers with vaccine-induced immunity.
Because most women of childbearing age in the United States are now immunized against measles, infants lose measles neutralizing antibody sooner after birth and could benefit from measles vaccination before 12 months of age to provide active immunity against infection. "Eventually 9 months of age may be a good age to vaccinate for the first time," she said.
For your information:
- Gans HA, Arvin AM, Galinus J, et al. Deficiency of the humoral immune response to measles vaccine in infants immunized at age 6 months. JAMA 1998;280:527-531.
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