title: Mumps-specific cross-neutralization by MMR vaccine-induced antibodies predicts protection against mumps virus infection.
abstract: Similar to other recent mumps genotype G outbreaks worldwide, most mumps patients during the recent mumps genotype G outbreaks in the Netherlands had received 2 doses of measles, mumps and rubella (MMR) vaccine during childhood. Here, we investigate the capacity of vaccine-induced antibodies to neutralize wild type mumps virus strains, including mumps virus genotype G.
  
  
  
  In this study, we tested 105 pre-outbreak serum samples from students who had received 2 MMR vaccine doses and who had no mumps virus infection (n=76), symptomatic mumps virus infection (n=10) or asymptomatic mumps virus infection (n=19) during the mumps outbreaks. In all samples, mumps-specific IgG concentrations were measured by multiplex immunoassay and neutralization titers were measured against the Jeryl Lynn vaccine strain and against wild type genotype G and genotype D mumps virus strains.
  
  
  
  The correlation between mumps-specific IgG concentrations and neutralization titers against Jeryl Lynn was poor, which suggests that IgG concentrations do not adequately represent immunological protection against mumps virus infection by antibody neutralization. Pre-outbreak neutralization titers in infected persons were significantly lower against genotype G than against the vaccine strain. Furthermore, antibody neutralization of wild type mumps virus genotype G and genotype D was significantly reduced in pre-outbreak samples from infected persons as compared with non-infected persons. No statistically significant difference was found for the vaccine strain. The sensitivity/specificity ratio was largest for neutralization of the genotype G strain as compared with the genotype D strain and the vaccine strain.
  
  
  
  The reduced neutralization of wild type mumps virus strains in MMR vaccinated persons prior to infection indicates that pre-outbreak mumps virus neutralization is partly strain-specific and that neutralization differs between infected and non-infected persons. Therefore, we recommend the use of wild type mumps virus neutralization assays as preferred tool for surveillance of protection against mumps virus infection.
authors.affiliation: Centre for Infectious Disease Control, National Institute for Public Health and the Environment (RIVM), P.O. Box 1, 3720 BA Bilthoven, The Netherlands; Department of Viroscience, Erasmus University Medical Centre, P.O. Box 2040, 3000 CA Rotterdam, The Netherlands. Electronic address: sigrid.gouma@rivm.nl.
authors.forename: Sigrid
authors.initials: S
authors.lastname: Gouma
authors.affiliation: Centre for Infectious Disease Control, National Institute for Public Health and the Environment (RIVM), P.O. Box 1, 3720 BA Bilthoven, The Netherlands. Electronic address: hinke.ten.hulscher@rivm.nl.
authors.forename: Hinke I
authors.initials: HI
authors.lastname: Ten Hulscher
authors.affiliation: Centre for Infectious Disease Control, National Institute for Public Health and the Environment (RIVM), P.O. Box 1, 3720 BA Bilthoven, The Netherlands. Electronic address: tessa.schurink@rivm.nl.
authors.forename: Tessa M
authors.initials: TM
authors.lastname: Schurink-van 't Klooster
authors.affiliation: Centre for Infectious Disease Control, National Institute for Public Health and the Environment (RIVM), P.O. Box 1, 3720 BA Bilthoven, The Netherlands. Electronic address: hester.de.melker@rivm.nl.
authors.forename: Hester E
authors.initials: HE
authors.lastname: de Melker
authors.affiliation: Department of Medical Microbiology, University Medical Centre Utrecht, P.O. Box 85500, 3508 GA Utrecht, The Netherlands. Electronic address: G.J.Boland@umcutrecht.nl.
authors.forename: Greet J
authors.initials: GJ
authors.lastname: Boland
authors.affiliation: Centre for Infectious Disease Control, National Institute for Public Health and the Environment (RIVM), P.O. Box 1, 3720 BA Bilthoven, The Netherlands. Electronic address: patricia.kaaijk@rivm.nl.
authors.forename: Patricia
authors.initials: P
authors.lastname: Kaaijk
authors.affiliation: Centre for Infectious Disease Control, National Institute for Public Health and the Environment (RIVM), P.O. Box 1, 3720 BA Bilthoven, The Netherlands. Electronic address: cecile.van.els@rivm.nl.
authors.forename: Cécile A C M
authors.initials: CACM
authors.lastname: van Els
authors.affiliation: Centre for Infectious Disease Control, National Institute for Public Health and the Environment (RIVM), P.O. Box 1, 3720 BA Bilthoven, The Netherlands; Department of Viroscience, Erasmus University Medical Centre, P.O. Box 2040, 3000 CA Rotterdam, The Netherlands. Electronic address: m.koopmans@erasmusmc.nl.
authors.forename: Marion P G
authors.initials: MPG
authors.lastname: Koopmans
authors.affiliation: Centre for Infectious Disease Control, National Institute for Public Health and the Environment (RIVM), P.O. Box 1, 3720 BA Bilthoven, The Netherlands. Electronic address: rob.van.binnendijk@rivm.nl.
authors.forename: Rob S
authors.initials: RS
authors.lastname: van Binnendijk
mesh_terms: D057134:Antibodies, Neutralizing / Q000097:blood*; D000914:Antibodies, Viral / Q000097:blood*; D056738:Cross Protection; D004196:Disease Outbreaks; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D022542:Measles-Mumps-Rubella Vaccine / Q000627:therapeutic use*; D009107:Mumps / Q000517:prevention & control*; D009109:Mumps virus / Q000235:genetics; D009426:Netherlands; D009500:Neutralization Tests
chemical_list: D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D007074:Immunoglobulin G; D022542:Measles-Mumps-Rubella Vaccine
keywords: Asymptomatic infection; Correlate of protection; IgG antibodies; MMR vaccination; Mumps virus; Strain-specific neutralization