For the past decade, mumps outbreaks have been occurring among young adults who were vaccinated as children, leaving researchers puzzled.

After all, the live-attenuated mumps-measles-rubella (MMR) vaccine has been extremely effective in the United States for nearly 50 years. One hypothesis is that waning immunity could be playing a role, according to a report in Proceedings of the National Academy of Science.

Researchers from Emory University and the CDC sought to test that theory. In a sample of 71 college students aged 18 to 23 years, most of the subjects had detectable mumps immunoglobulin G (IgG) antibodies by enzyme-linked immunosorbent assay (ELISA). The study team notes, however, that the magnitude was lower than for rubella.

“Neutralizing antibody titers were 6-fold lower to a circulating genotype G mumps strain versus the vaccine strain,” the researchers report. “Ten percent of our participants had no detectable memory B cells to mumps. Strategies are needed to improve immunity to the mumps vaccine.”

The article points out that, in the last 10 years, mumps outbreaks in the U.S. usually have occurred in close-contact, high-density settings such as colleges, often affecting young adults; many of those patients had the recommended two doses of MMR vaccine.

In addition to waning vaccine-induced immunity, the study team notes that there appears to be a variation between the strain of mumps virus now circulating and the vaccine strain, which is part of the MMR childhood vaccine.

“Overall, the MMR vaccine has been great, with a 99 percent reduction in measles, mumps and rubella disease and a significant reduction in associated complications since its introduction,” explains Sri Edupuganti, MD, MPH, associate professor of medicine (infectious diseases) at Emory University School of Medicine and medical director of the Hope Clinic of Emory Vaccine Center. “What we’re seeing now with these mumps outbreaks is a combination of two things—a few people were not making a strong immune response to begin with, and the circulating strain has drifted away from the strain that is in the vaccine.”

The college students studied were living in a nonoutbreak area. They were assayed for antibodies and memory B cells (MBCs) to mumps, measles, and rubella.

Results showed that seroprevalence rates of mumps, measles, and rubella, as determined by ELISA, were 93%, 93%, and 100%, respectively. The index standard ratio indicated that the concentration of IgG was significantly lower for mumps than for rubella, however.

“High IgG avidity to mumps Enders strain was detected in sera of 59/71 participants who had sufficient IgG levels,” the authors write. “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 researchers note that most of the participant—80%—received their second MMR vaccine 10 or more 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,” the authors conclude.

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