[Source: Proceedings of the National Academy of Sciences of the United States of America, full page: (LINK). Abstract, edited.]
Decreased humoral immunity to mumps in young adults immunized with MMR vaccine in childhood
Mohammed Ata Ur Rasheed, Carole J. Hickman, Marcia McGrew, Sun Bae Sowers, Sara Mercader, Amy Hopkins, Vickie Grimes, Tianwei Yu, Jens Wrammert, Mark J. Mulligan, William J. Bellini, Paul A. Rota, Walter A. Orenstein, Rafi Ahmed, and Srilatha Edupuganti
PNAS first published September 3, 2019 / DOI: https://doi.org/10.1073/pnas.1905570116
Contributed by Rafi Ahmed, July 18, 2019 (sent for review April 2, 2019; reviewed by Rino Rappuoli and Robert Seder)
The live-attenuated mumps-measles-rubella (MMR) vaccine has been highly successful in the United States since its introduction 47 years ago. However, for the past decade, mumps outbreaks have been occurring among young adults who were vaccinated as children. Waning immunity has been proposed as a key contributing factor to mumps resurgence. In our sample (n = 71) of 18- to 23-year-old college students, the majority had detectable mumps IgG antibodies by enzyme-linked immunosorbent assay (ELISA) but the magnitude was lower than rubella. Neutralizing antibody titers were 6-fold lower to a circulating genotype G mumps strain versus the vaccine strain. Ten percent of our participants had no detectable memory B cells to mumps. Strategies are needed to improve immunity to the mumps vaccine.
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.
mumps, measles, rubella – MMR vaccine – memory B cells (MBCs) – plaque reduction -neutralization titers – IgG ELISA
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Author contributions: M.A.U.R., C.J.H., W.J.B., W.A.O., R.A., J.W., and S.E. designed research; M.A.U.R., C.J.H., M.M., S.B.S., S.M., A.H., V.G., and S.E. performed research; M.A.U.R., C.J.H., S.B.S., S.M., T.Y., and S.E. analyzed data; and M.A.U.R., C.J.H., J.W., M.J.M., W.J.B., P.A.R., W.A.O., R.A., and S.E. wrote the paper.
Reviewers: R.R., GlaxoSmithKline; and R.S., NIH.
The authors declare no conflict of interest.
This article contains supporting information online at www.pnas.org/lookup/suppl/doi:10.1073/pnas.1905570116/-/DCSupplemental.
Published under the PNAS license.
Keywords: Mumps; Vaccines; Serology; Seroprevalence; Immunoglobulins.