Rubella virus-specific humoral immune responses and their interrelationships before and after a third dose of measles-mumps-rubella vaccine in women of childbearing age

• Published in: Vaccine Vol. 38; no. 5; pp. 1249 - 1257
• Main Authors: Haralambieva, Iana H., Ovsyannikova, Inna G., Kennedy, Richard B., Goergen, Krista M., Grill, Diane E., Chen, Min-hsin, Hao, Lijuan, Icenogle, Joseph, Poland, Gregory A.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Ltd 29.01.2020; Elsevier Limited
• Subjects: Adult; Age; Allergy and Immunology; Antibodies; Antibodies, Neutralizing - immunology; Antibodies, Viral - immunology; Antibody; Antibody Affinity; Antibody response; Antigens; Avidity; B-lymphocytes; Biobanks; Enrollments; Enzyme-Linked Immunosorbent Assay; Female; females; Humans; Humoral; Humoral immunity; Immune response; Immune response (humoral); Immune system; Immunity; Immunity, Humoral; Immunoglobulin G; Immunoglobulin G - immunology; Immunological memory; Lymphocytes B; Measles; Measles-Mumps-Rubella Vaccine; Measles-Mumps-Rubella Vaccine - administration & dosage; Medical records; Memory cells; Minnesota; Mumps; Neutralization Tests; Neutralizing; neutralizing antibodies; Rubella; Rubella - immunology; Rubella - prevention & control; Rubella Vaccine; Rubella virus - immunology; seroprevalence; Test systems; Vaccination; Vaccines; Viral; Viruses; women; Womens health; United States > US; Minnesota; Rubella; Humoral; Antibody; Viral; Measles-Mumps-Rubella Vaccine; Immunity; Rubella Vaccine
• ISSN: 0264-410X; 1873-2518; 1873-2518
• DOI: 10.1016/j.vaccine.2019.11.004

In the U.S., measles, mumps, and rubella vaccination is recommended as two vaccine doses. A third dose of measles-mumps-rubella (MMR) vaccine is being administered in certain situations (e.g., identified seronegativity and during outbreaks). We studied rubella-specific humoral immunity (neutralizing antibody, enzyme-linked immunosorbent assay/ELISA IgG titer and antibody avidity) and the frequencies of antigen-specific memory B cells before and after a third dose of MMR-II in 109 female participants of childbearing age (median age, 34.5 years old) from Olmsted County, MN, with two documented prior MMR vaccine doses. The participants were selected from a cohort of 1117 individuals if they represented the high and the low ends of the rubella-specific antibody response spectrum. Of the 109 participants, we identified four individuals (3.67% of all study participants; 7.14% of the low-responder group) that were seronegative at Baseline (rubella-specific ELISA IgG titers <10 IU/mL), suggesting a lack of protection against rubella before receipt of a third MMR vaccine dose. The peak geometric mean neutralizing antibody titer one month following the third dose of MMR vaccine for the cohort was 243 NT50 (CI; 241, 245), which is expected for a cohort with two doses of MMR, and the peak geometric mean IgG titer was 150 IU/mL (CI; 148, 152) with no seronegative individuals at Day 28. One-third of all subjects (31.8% for the neutralizing antibody; 30.8% for the IgG titer) experienced a significant boost (≥4-fold) of antibody titers one month following vaccination. Antibody titers and other tested immune-response variables were significantly higher in the high-responder group compared to the low-responder group. The frequencies of rubella-specific memory B cells were modestly associated with the antibody titers. Our study suggests the importance of yet unknown inherent biologic and immune factors for the generation and maintenance of rubella-vaccine-induced humoral immune responses.