Detection of mumps virus‐specific memory B cells by transfer of peripheral blood mononuclear cells into immune‐deficient mice

Abstract

Summary 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 TMβ1 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.

Immunoinformatics Approach for Epitope-Based Peptide Vaccine Design and Active Site Prediction against Polyprotein of Emerging Oropouche Virus

“…Hebeis et al demonstrated that the activation of virus-specific memory B-cells to secrete immunoglobulin G (Ig G) is autonomous of cognate or bystander T-cell help [ 68 ]. The role of virus-specific B-cell memory has been found in mumps virus [ 69 ], human influenza virus [ 70 ], rotavirus [ 71 , 72 ], and dengue virus [ 73 ].…”

The resurgence of mumps and pertussis

“… 23,25 Finally, there is limited evidence that with the waning of antibodies, also memory B cells disappear and the long-term protection can not be guaranteed anymore. 26 These studies indicate that mumps vaccines appear to be less immunogenic than initially assumed. This implies that the primary immune response is able to eliminate mumps, but that the protection lasts less long than originally thought.…”

Estimates of Mumps Seroprevalence May Be Influenced by Antibody Specificity and Serologic Method

“…Furthermore, the nature of the immune response to mumps seems to be inherently weak by some measures. Besides inducing typically low levels of neutralizing antibody, multiple reports indicate that the frequency of mumps-specific memory B-cells is also very low (35,58,59). It may be reasonable to try to improve the neutralizing antibody response by (re)directing it toward HN rather than NP, but other effects of antibodies, such as complement fixation, should not be overlooked (60,61).…”