Persistence of Mumps Antibodies after 2 Doses of Measles-Mumps-Rubella Vaccine
ABSTRACT Since 1990, most US schoolchildren have received a second dose of measles-mumps-rubella vaccine (MMR2) at kindergarten entry. The objective of the present study was to evaluate the short- and long-term mumps immunogenicity of MMR2.
At enrollment in 1994-1995, children (n=308) in a rural Wisconsin health maintenance organization received MMR2 at age 4-6 years. A comparison group of older children (n=308) was vaccinated at age 9-11 years. Serum samples were collected over 12 years. Mumps antibody levels were evaluated by plaque-reduction neutralization (lowest detectable titer, 10).
Before MMR2, the geometric mean titer (GMT) for the younger group was 33; no subject was seronegative, but 16% had the lowest detectable titer. In response to MMR2, the GMT tripled to 97, and the proportion with low titers diminished to 3%. Four-fold boosts occurred among 54%, but only 3% were positive for immunoglobulin M. Twelve years after MMR2, the GMT declined to 46, the proportion with titers<or=10 was not significantly different from the pre-MMR2 proportion, and 5% were seronegative. The older group showed similar patterns, and at age 17 years both groups had comparable antibody levels.
The mumps antibody response to MMR2 was vigorous, but over a 12-year period titers declined to levels similar to pre-MMR2 titers. No advantage was apparent in delaying MMR2 from kindergarten to middle school.
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ABSTRACT: Since 1990, most schoolchildren in the United States have received a second dose of measles-mumps-rubella vaccine (MMR2) at kindergarten entry. Elimination of endemic rubella virus circulation in the United States was declared in 2004. The objective of the current study was to evaluate the short- and long-term rubella immunogenicity of MMR2. At enrollment in 1994-1995, children (n = 307) in a rural Wisconsin health maintenance organization received MMR2 at age 4-6 years. A comparison group of older children (n = 306) was vaccinated at age 9-11 years. Serum specimens were collected during a 12-year period. Rubella antibody levels were evaluated by plaque-reduction neutralization (lowest detectable titer, 1:10). Before administration of MMR2 in the kindergarten group, 9% of subjects were seronegative, 60% had the lowest detectable titer, and the geometric mean titer (GMT) was 1:13. One month after administration of MMR2, 1% were seronegative, 6% had the lowest detectable titer, and the GMT was 1:42. Four-fold boosts occurred in 62% of subjects, but only 0.3% were immunoglobulin M positive. Twelve years after MMR2 administration, 10% were seronegative, 43% had the lowest detectable titer, and the GMT was 1:17. The middle-school group showed similar patterns. Rubella antibody response to MMR2 was vigorous, but titers decreased to pre-MMR2 levels after 12 years. Because rubella is a highly epidemic disease, vigilance will be required to assure continued elimination.The Journal of Infectious Diseases 09/2009; 200(6):888-99. DOI:10.1086/605410 · 5.78 Impact Factor
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ABSTRACT: In 2006 the United States experienced the largest nationwide mumps epidemic in 20 years, primarily affecting college dormitory residents. Unexpected elements of the outbreak included very abrupt time course (75% of cases occurred within 90 days), geographic focality (85% of cases occurred in eight rural Midwestern states), rapid upward and downward shift in peak age-specific attack rate (5-9-year olds to 18-24-year olds, then back), and two-dose vaccine failure (63% of case-patients had received two doses). To construct a historical context in which to understand the recent outbreak, we reviewed US mumps surveillance data, vaccination coverage estimates, and relevant peer-reviewed literature for the period 1917-2008. Many of the unexpected features of the 2006 mumps outbreak had been reported several times previously in the US, e.g., the 1986-1987 mumps resurgence had extremely abrupt onset, rural geographic focality, and an upward-then-downward age shift. Evidence suggested recurrent mumps outbreak patterns were attributable to accumulation of susceptibles in dispersed situations where the risk of endemic disease exposure was low and were triggered when this susceptible population was brought together in crowded living conditions. The 2006 epidemic followed this pattern, with two unique variations: it was preceded by a period of very high vaccination rates and very low disease incidence and was characterized by two-dose failure rates among adults vaccinated in childhood. Data from the past 80 years suggest that preventing future mumps epidemics will depend on innovative measures to detect and eliminate build-up of susceptibles among highly vaccinated populations.Vaccine 10/2009; 27(44):6186-95. DOI:10.1016/j.vaccine.2009.06.109 · 3.49 Impact Factor
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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.Immunology 09/2010; 131(1):33-9. DOI:10.1111/j.1365-2567.2010.03263.x · 3.74 Impact Factor