Decreased humoral immunity to mumps in young adults immunized with MMR vaccine in childhood

Abstract

In the past decade, multiple mumps outbreaks have occurred in the United States, primarily in close-contact, high-density settings such as colleges, with a high attack rate among young adults, many of whom had the recommended 2 doses of mumps-measles-rubella (MMR) vaccine. Waning humoral immunity and the circulation of divergent wild-type mumps strains have been proposed as contributing factors to mumps resurgence. Blood samples from 71 healthy 18- to 23-year-old college students living in a non-outbreak area were assayed for antibodies and memory B cells (MBCs) to mumps, measles, and rubella. Seroprevalence rates of mumps, measles, and rubella determined by IgG enzyme-linked immunosorbent assay (ELISA) were 93, 93, and 100%, respectively. The index standard ratio indicated that the concentration of IgG was significantly lower for mumps than rubella. High IgG avidity to mumps Enders strain was detected in sera of 59/71 participants who had sufficient IgG levels. The frequency of circulating mumps-specific MBCs was 5 to 10 times lower than measles and rubella, and 10% of the participants had no detectable MBCs to mumps. Geometric mean neutralizing antibody titers (GMTs) by plaque reduction neutralization to the predominant circulating wild-type mumps strain (genotype G) were 6-fold lower than the GMTs against the Jeryl Lynn vaccine strain (genotype A). The majority of the participants (80%) received their second MMR vaccine ≥10 years prior to study participation. Additional efforts are needed to fully characterize B and T cell immune responses to mumps vaccine and to develop strategies to improve the quality and durability of vaccine-induced immunity.

Keywords: IgG ELISA; MMR vaccine; memory B cells (MBCs); mumps, measles, rubella; plaque reduction neutralization titers.

Conflict of interest statement

The authors declare no conflict of interest.

Figures

Fig. 1.

Index Standard Ratio (ISR) of IgG antibodies to mumps, measles and rubella are shown in 71 participants. Mean, median, and range are as follows: 2.72, 2.79, and 0.25 to 5.55 for mumps; 3.24, 3.18, and 0.43 to 7.66 for measles; and 3.67, 3.61, and 1.25 to 5.87 for rubella. Horizontal lines represent mean with SEM. P values were determined comparing 3 groups using unpaired t test. The dotted line represents the limit of detection.

Fig. 2.

Neutralizing antibody titers to mumps Jeryl Lynn versus genotype G strain. Antibody titers were determined by plaque reduction neutralization. The PRN end titer was determined to be the highest dilution of serum that gave 50% or higher plaque reduction compared with the average number of plaques formed in the absence of serum by using the Kärber formula. The geometric mean titer of 69 participants for JL was 217 compared with 35 for genotype G (Error bars are 95% CI, 174 to 270 for JL and 27 to 45 for genotype G). P values were determined comparing 2 groups using unpaired t test.

Fig. 3.

Frequency distribution of neutralizing antibody titers to mumps JL or genotype G. PRN titers (PRNT) to the JL vaccine strain are shown in red and PRN titers to genotype G are shown in blue. The PRN end titer was determined for each strain based on the highest dilution of serum that resulted in 50% or higher plaque reduction compared with plaques formed in the absence of serum. The number of participants with a given titer to each strain is represented in the table (Lower).

Fig. 4.

Mumps-, measles-, and rubella-specific memory B cells. The frequency of antigen-specific IgG-secreting MBCs was measured in PBMCs of healthy participants after short-term culture and reported as percent of total IgG-secreting cells. Dots represent individual participants. Horizontal lines represent mean with SEM and the horizontal dotted line represents the limit of detection. Baseline influenza-specific MBCs in the same individuals were determined using the seasonal influenza vaccine as the antigen.