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Detection of mumps virus-specific memory B cells by transfer of peripheral blood mononuclear cells into
Corinne Vandermeulen1, Lieven Verhoye, Sunil Vaidya
1Centre for Youth Health Care, Kapucijnenvoer, Leuven, Belgium. corinne.vandermeulen@med.kuleuven.be
Abstract:
Waning immunity to mumps after one or two doses of the measles, mumps and rubella (MMR) vaccine has been described. Using a human peripheral blood lymphocyte (PBL)-severe combined immunodeficiency (SCID) mouse model, MMR vaccine recipients with undetectable and high antibody titres against mumps were compared for the presence of circulating mumps-specific memory B cells. Peripheral blood mononuclear cells (PBMC) from six donors (three subjects with undetectable and three with high antibody titres against mumps) were injected into the spleens of non-obese diabetic (NOD)-SCID mice (three mice per subject). Mice were pretreated with TMbeta1 and total body irradiation to improve engraftment. In vivo production of human antibodies against mumps was evaluated in mouse plasma on days 7, 10 and 13 with a commercial enzyme-linked immunosorbent assay (ELISA), functional reduction neutralization test. Three donors had mumps antibody titres below the detection limit (titre < 230) and three had high antibody titres (range 5700-7300). None of the mice injected with PBMC from subjects with undetectable antibody titres showed detectable human antibody titres, despite the presence of cell-mediated immunity in two of the three donors. Seven out of nine mice injected with PBMC from subjects with high antibody titres acquired detectable antibody titres for mumps in their plasma. PBMC from vaccinees without detectable serum antibodies against mumps virus were unable to induce secretion of anti-mumps antibodies in the blood of recipient mice, whereas PBMC from vaccinees with high antibody titres were able to do so. This observation suggests that the frequency of mumps-specific memory B cells is very low in vaccinees with undetectable antibody titres. These individuals may therefore be at risk of developing mumps disease upon encounter with wild-type virus.
Insights
Waning immunity to mumps after the measles, mumps, and rubella (MMR) vaccine may be linked to low levels of mumps-specific memory B cells. Individuals with undetectable antibody titres showed no antibody production in a mouse model, suggesting potential risk for mumps infection.
Area of Science:
- Immunology
- Vaccinology
- Virology
Background:
- Waning immunity to mumps following measles, mumps, and rubella (MMR) vaccination is a recognized concern.
- The presence and function of mumps-specific memory B cells in vaccine recipients with varying antibody titers require further investigation.
Purpose of the Study:
- To investigate the presence and function of mumps-specific memory B cells in individuals with undetectable versus high antibody titers after MMR vaccination.
- To assess the capacity of peripheral blood mononuclear cells (PBMC) from these individuals to induce anti-mumps antibody production in vivo.
Main Methods:
- A human peripheral blood lymphocyte (PBL)-severe combined immunodeficiency (SCID) mouse model was utilized.
- PBMCs from MMR vaccine recipients with undetectable (<230) and high (5700-7300) mumps antibody titers were injected into NOD-SCID mice.
- In vivo production of human anti-mumps antibodies was measured using ELISA and functional reduction neutralization tests.
Main Results:
- Mice injected with PBMCs from donors with undetectable mumps antibody titers did not produce detectable human antibodies against mumps.
- Seven out of nine mice receiving PBMCs from donors with high antibody titers developed detectable mumps-specific antibodies.
- PBMCs from vaccinees with undetectable antibody titers failed to induce anti-mumps antibody secretion in recipient mice.
Conclusions:
- The frequency of mumps-specific memory B cells is significantly lower in MMR vaccinees with undetectable antibody titers.
- Individuals with undetectable mumps antibody titers post-vaccination may be at increased risk of mumps disease upon exposure to wild-type virus.
- This study highlights the importance of memory B cell assessment in understanding vaccine effectiveness and potential immune gaps.
