Seroprevalence to Measles Virus after Vaccination or Natural Infection in an Adult Population, in Italy

Abstract

An increase in measles cases worldwide, with outbreaks, has been registered in the last few years, despite the availability of a safe and highly efficacious vaccine. In addition to an inadequate vaccination coverage, even in high-income European countries studies proved that some vaccinated people were also found seronegative years after vaccination, thus increasing the number of people susceptible to measles infection. In this study, we evaluated the immunization status and the seroprevalence of measles antibodies among 1092 healthy adults, either vaccinated or naturally infected, in order to investigate the persistence of anti-measles IgG. Among subjects who received two doses of measles vaccine, the neutralizing antibody titer tended to decline over time. In addition, data collected from a neutralization assay performed on 110 healthy vaccinated subjects suggested an inverse correlation between neutralizing antibody titers and the time elapsed between the two vaccinations, with a significant decline in the neutralizing titer when the interval between the two doses was ≥11 years. On the basis of these results, monitoring the serological status of the population 10-12 years after vaccination could be important both to limit the number of people who are potentially susceptible to measles, despite the high efficacy of MMR vaccine, and to recommend a booster vaccine for the seronegatives.

Keywords: measles virus; neutralizing antibodies; seroprevalence; vaccine.

Figure 1

Flow diagram of the study population. Schematic representation of the study population enrolled in the study with the relative number of subjects in each group.

Figure 2

Age-specific measles IgG prevalence categorized into different age groups. Subjects over 43 years old were included into the same group.

Figure 3

Seroprevalence of measles antibodies after vaccination over-time. Antibody response in vaccinees was analyzed 8–18 years after complete vaccination. The number of seropositive and seronegative subjects was plotted.

Figure 4

Differences in neutralizing antibody titers between subjects vaccinated with two doses of measles vaccine and naturally infected subjects are shown. The whiskers represent the values from the 5th to the 95th percentiles; the median, the 25th and 75th percentiles are depicted by the horizontal lines in the boxes. Individual data points are shown; outlier values are shown as black circles or squares. GMTs are shown above the population columns. p-value of the GMT between the two groups is ≤0.00001.

Figure 5

Time elapsed between the second dose of vaccine and the serological test (years). Effects of negative correlation based on the time elapsed between the second dose of measles vaccine and the last measles investigation test on neutralizing antibody response. The whiskers represent the values from the 5th to the 95th percentiles; the median, the 25th and 75th percentiles are depicted by the horizontal lines in the boxes. Individual data points are shown; outlier values are shown as black circles. GMTs are shown above the population columns. P-value of the GMT between the first (1–11) and second (12–14) group is <0.05.

Figure 6

Effect of time elapsed between the two doses of measles vaccine on the neutralizing antibody response. The whiskers represent the values from the 5th to the 95th percentiles; the median, the 25th and 75th percentiles are depicted by the horizontal lines in the boxes. Individual data points are shown; outlier values are shown as black circles or squares. GMTs are shown above the population columns. The difference in GMTs between the first (1–6) and the third (≥11) group is statistically significant (p ≤ 0.05).

Figure 7

Differences in neutralizing antibody titers in naturally infected subjects born before (A) and after (B) 1977 (one year after the introduction of measles vaccine in Italy). The whiskers represent the values from the 5th to the 95th percentiles; the median, the 25th and 75th percentiles are depicted by the horizontal lines in the boxes. Individual data points are shown; outlier values are shown as black circles or squares. GMTs are shown above the population columns. Difference in GMT between the two groups is not significant (p > 0.05).