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Sex-based differences in mumps immunity after a third dose of measles-mumps-rubella vaccine
Huy Quang Quach1, Tamar Ratishvili1, Iana H Haralambieva1
1Mayo Clinic Vaccine Research Group, Mayo Clinic, Rochester, MN 55905, USA.
Background:
A third dose of measles-mumps-rubella (MMR3) vaccine is recommended for mumps outbreak control, but the magnitude and durability of MMR3-induced immunity and the effect of sex on those outcomes, remain incompletely characterized.
Methods:
A total of 214 healthy individuals with two prior MMR doses received MMR3. Blood samples were collected at baseline (D0), day 28 (D28), and 18 months (M18) post-vaccination. Mumps-specific IgG, IgG avidity, and neutralizing antibodies (nAb) were measured by IgG ELISA and plaque reduction microneutralization assay. Cytokine and chemokine secretions from peripheral blood mononuclear cells (PBMCs) were profiled using multiplex assay.
Results:
Median IgG sample index values increased from 2.12 at D0 to 2.64 at D28 (p = 0.0019), and 2.85 at M18 (p < 0.001). IgG avidity rose slightly from 79.54% at D0 to 81.88% at D28 and 86.87% at M18. nAb titers (ND50) increased from 50.48 at D0 to 67.00 at D28 (p = 0.0014), and 60.18 at M18 (p = 0.044). Despite these statistically significant changes, fold increases across time points were small (IgG: 1.15-1.13; avidity: 1.03-1.08; and nAb: 1.2-1.18). Of the 21 cytokines and chemokines analyzed, only interferon-γ induced protein 10 (IP-10/CXCL10) showed significant increase and was negatively correlated with D28/D0 changes in IgG titers (r = -0.23; p = 0.014), but not with M18 changes, avidity, or nAb responses. Biological sex significantly influenced both IgG and IP-10 responses.
Conclusions:
MMR3 conferred limited additional humoral and cellular immune benefits, with notable sex-dependent effects. These findings support MMR3 use primarily in outbreak settings and identify IP-10 as a potential biomarker associated with MMR3 immunogenicity.
Insights
A third dose of the measles-mumps-rubella (MMR3) vaccine offers limited immune benefits, with sex influencing responses. Findings support MMR3 use during mumps outbreaks and suggest IP-10 as a potential biomarker.
Area of Science:
- Immunology
- Vaccinology
- Public Health
Background:
- The third dose of the measles-mumps-rubella (MMR3) vaccine is recommended for controlling mumps outbreaks.
- However, the extent and duration of immunity induced by MMR3, and the influence of sex on these outcomes, require further investigation.
Purpose of the Study:
- To evaluate the magnitude and durability of humoral and cellular immunity following a third dose of the MMR vaccine.
- To assess the impact of biological sex on MMR3-induced immune responses.
Main Methods:
- 214 individuals received a third MMR dose (MMR3).
- Mumps-specific IgG, IgG avidity, and neutralizing antibodies (nAb) were measured at baseline, 28 days, and 18 months post-vaccination.
- Cytokine and chemokine profiles, including IP-10/CXCL10, were analyzed from peripheral blood mononuclear cells (PBMCs).
Main Results:
- MMR3 showed statistically significant but small increases in IgG, IgG avidity, and nAb titers over 18 months.
- Only IP-10/CXCL10 levels increased significantly and correlated negatively with early IgG changes.
- Biological sex significantly influenced IgG and IP-10 responses.
Conclusions:
- MMR3 provides limited additional humoral and cellular immune benefits.
- Sex-dependent effects on immune responses were observed.
- Findings support MMR3 use in outbreak settings and highlight IP-10 as a potential immunogenicity biomarker.
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