Long-term Dynamics of Measles Virus-Specific Neutralizing Antibodies in Children Vaccinated Before 12 Months of Age

Abstract

Background: Measles is a highly contagious disease, presenting a significant risk for unvaccinated infants and adults. Measles vaccination under the age of 12 months provides early protection but has also been associated with blunting of antibody responses to subsequent measles vaccinations and assumed to have lower vaccine effectiveness.

Methods: Our study included children who received an early measles, mumps, and rubella (MMR) vaccination between 6 and 12 months of age (n = 79, given in addition to the regular MMR vaccination schedule at 14 months and 9 years) and a group without additional early vaccination (n = 44). We evaluated measles virus (MeV)-specific neutralizing antibodies before vaccination at 14 months and up to 6 years thereafter using a plaque reduction neutralization test according to the standard set by the World Health Organization.

Results: We found a significant association between age of first MMR and MeV-specific neutralizing antibody levels later in life. Although most children who received early vaccination seroconverted after the first dose, children vaccinated before 8.5 months of age exhibited a markedly faster antibody decay and lost their protective neutralizing antibody levels over 6 years.

Conclusions: Routine vaccination of infants under 8.5 months of age may lead to blunted MeV-specific antibody responses to subsequent MMR vaccination. Early MMR vaccination should only be considered during measles outbreaks or in other situations of increased risk of MeV infection. Clinical Trials Registration. EudraCT 2013-003078-28.

Keywords: MMR vaccine; early infant vaccination; immunity; long-term immune protection; measles.

Graphical Abstract

This graphical abstract is also available at Tidbit: https://tidbitapp.io/institutional-portal/clinical-infectious-diseases/tidbits/long-term-dynamics-of-measles-virus-specific-neutralizing-antibodies-in-children-vaccinated-before-12-months-of-age/update

Figure 1.

Measles virus–specific neutralizing antibody levels measured 6 years after MMR-1 (at 14 months of age) with the GMC and 95% CIs for the different age groups. The dashed line represents the cutoff for protection against measles (0.12 IU/mL). Early-vaccinated children who had no MeV-specific antibodies detected at 14 months of age are highlighted in orange. Children who did not receive early vaccination are represented by triangles. The LLOQ for the PRNT was established at 0.03 IU/mL. There were 3 values below the LLOQ in the age group 5.5–6.5 months, 1 value for 6.5–7.5 months, and 4 values for 7.5–8.5 months. Abbreviations: GMC, geometric mean concentration; LLOQ, lower limit of quantitation; MeV, measles virus; MMR, measles, mumps and rubella; PRNT, plaque reduction neutralization test.

Figure 2.

Scatterplots with Loess curves depicting the age-dependent variations in MeV-specific neutralizing antibody levels following MMR vaccination. Each point on the scatterplots represents an antibody level plotted to the age of first MMR vaccination. The dashed line represents the serological protection threshold for measles (0.12 IU/mL). Orange-colored points indicate children who were early-vaccinated but were below the cutoff of protection at 14 months of age (n = 7). Children who did not receive early vaccination are represented by triangles. The Loess curves provide a smoothed representation of the observed trends. The orange Loess curve includes the subgroup of children who were early-vaccinated but were below the cutoff of protection at 14 months of age, while the gray Loess curve excludes these data points. The P values indicate the evidence of a correlation between age at first MMR vaccination and MeV-specific neutralizing antibody levels at the given time points as calculated by the asymptotic general independence test. Significance levels: *P ≤ .05, **P ≤ .01, and ***P ≤ .001. Abbreviations: MeV, measles virus; MMR, measles, mumps and rubella.

Figure 3.

The model-predicted MeV-specific neutralizing antibody level averages shown as error bars with 95% CI of the different age groups. The dashed line represents the cutoff for protection against measles (0.12 IU/mL). In fitting this model, the children who received an early vaccination but were seronegative at 14 months were excluded. Abbreviations: MeV, measles virus; MMR, measles, mumps and rubella.