The Influence of Sex, Body Mass Index, and Age on Cellular and Humoral Immune Responses Against Measles After a Third Dose of Measles-Mumps-Rubella Vaccine

Abstract

Background: A third dose of measles-mumps-rubella vaccine (MMR3) is recommended in mumps outbreak scenarios, but the immune response and the need for widespread use of MMR3 remain uncertain. Herein, we characterized measles-specific immune responses to MMR3 in a cohort of 232 healthy subjects.

Methods: Serum and peripheral blood mononuclear cells (PBMCs) were sampled at day 0 and day 28 after MMR3. Measles-specific binding and neutralizing antibodies were quantified in sera by enzyme-linked immunosorbent assay and a microneutralization assay, respectively. PBMCs were stimulated with inactivated measles virus, and the release of cytokines/chemokines was assessed by a multiplex assay. Demographic variables of subjects were examined for potential correlations with immune outcomes.

Results: Of the study participants, 95.69% and 100% were seropositive at day 0 and day 28, respectively. Antibody avidity significantly increased from 38.08% at day 0 to 42.8% at day 28 (P = .00026). Neutralizing antibodies were significantly enhanced, from 928.7 at day 0 to 1289.64 mIU/mL at day 28 (P = .0001). Meanwhile, cytokine/chemokine responses remained largely unchanged. Body mass index was significantly correlated with the levels of inflammatory cytokines/chemokines.

Conclusions: Measles-specific humoral immune responses, but not cellular responses, were enhanced after MMR3 receipt, extending current understanding of immune responses to MMR3 and supporting MMR3 administration to seronegative or high-risk individuals.

Keywords: MMR vaccine; MMR3; cellular immunity; humoral immunity; measles virus.

Figure 1.

Study design. A total of 232 participants with 2 prior documented measles-mumps-rubella (MMR) vaccines enrolled and completed 2 visits for blood draw at day 0 (before the receipt of third dose of MMR vaccine [MMR3]) and day 28 after MMR3. Before the blood draw at day 0, demographic and clinical information, including sex, height, weight (for the calculation of body mass index [BMI]), race, ethnicity, vaccine history, dates of previous MMR vaccination, and age of study participants were collected. Serum and peripheral blood mononuclear cells (PBMCs) were isolated from blood samples obtained at day 0 and day 28. Measles virus–specific humoral immune responses were assessed in serum. Meanwhile, cellular immune responses were assessed in the supernatant of cell culture of PBMCs incubated with measles virus. Demographic and clinical variables were associated with both humoral and cellular immune responses to determine whether or not there is a correlation between these variables and immune response outcomes.

Figure 2.

Humoral responses in serum isolated from participants at day 0 and day 28. A, Sample index, a ratio of optical density in serum-added well over kit-provided calibrator, of measles virus (MeV)–specific antibodies at day 0 and day 28. A sample index >1.1 (dashed line) is considered a positive MeV-specific response. Ten participants had a sample index <1.1 at day 0, whereas at day 28, all participants had a sample index >1.1. B, Avidity index (%), a ratio of optical density in serum-added well with and without dimethylamine wash buffer, of MeV-specific antibodies at day 0 and day 28. An avidity index >30% (dashed line) is considered high avidity. C, Neutralization activity of MeV-specific antibodies at day 0 and day 28. Neutralization antibody of >120 mIU/mL (dashed line) is considered as seroprotection.

Figure 3.

Influence of body mass index (BMI) on the release of interleukin 1β (IL-1β), interleukin 6 (IL-6), tumor necrosis factor alpha (TNF-α), and interleukin 8 (IL-8) from peripheral blood mononuclear cells (PBMCs) isolated at day 0 and day 28. PBMCs were either cultured in cell culture media or stimulated with measles virus (MeV) (multiplicity of infection = 0.5) suspended in cell culture media for 48 hours. The cytokines/chemokines detected in the culture supernatant upon MeV stimulation was subtracted from the background detected in the supernatant of PBMCs cultured in cell culture media. The Benjamini and Hochberg procedure was applied to assess the influence of BMI on the normalized levels of these cytokines/chemokines. After multiple testing correction, a false discovery rate–adjusted P value (referred to as q value) < .2 is considered statistically significant.