Measles, Mumps, and Rubella Antibody Patterns of Persistence and Rate of Decline Following the Second Dose of the MMR Vaccine Open Access

Seagle, Emma E. (2017)

Permanent URL: https://etd.library.emory.edu/concern/etds/sf268600b?locale=en
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Abstract

Previous studies of the measles, mumps, and rubella (MMR) vaccine have reported a high degree of individual variation in patterns of waning antibody immunity, yet none have defined the degree of variation that exists. We utilized data from a 12 year longitudinal study of Wisconsin children vaccinated with the second dose of MMR (MMR2) at 4-6 years of age to identify patterns of seropositivity and antibody persistence for each antigen following receipt of MMR2, compare antibody kinetic patterns across antigens, and estimate the rate of decline in antibody levels using correlated data methods. Of the 313 study participants who received MMR2, 302 had measles antibody data and 296 had mumps and rubella data. The majority of participants remained seropositive for the follow-up period for all three antigens (96% measles, 88% mumps, 79% rubella). Among the 291 individuals with defined antibody persistence trends for all 3 antigens, 41 (14%) had the same trend categorization for measles, mumps, and rubella (2 stable, 18 declining, 17 variable, and 4 other), 188 (65%) had the same trend for 2 of the 3 antigens, and 62 (21%) had discordant trends for all three antigens. Among the individuals characterized as having a "declining trend" for measles, antibodies were high post-MMR2 (1 month post GMT: 3892.7 mIU/mL), but declined an average of 9.7% per year among those with the same baseline titer and no response to MMR2 (<2 fold increase), adjusting for sex. Those with MMR2 response of ≥2 fold experienced a slower decline (6.3% per year among those with 2-4 fold increase and 7.4% per year among those with ≥4 fold increase). Mumps rate of decline was 9.2% per year, adjusting for MMR2 response and baseline titer. Rubella antibodies declined an average of 2.6% per year among those who received MMR1 at age 12-15 months, and 5.9% per year among those who received MMR1 >15 months, adjusting for baseline rubella titer and MMR2 response. The high variation in persistence trends coupled with the fast rate of decline within a subset of individuals may impact herd immunity and individual susceptibility, particularly in outbreak scenarios.

Table of Contents

Chapter I. Background.................................................................................................1

Measles, Mumps, and Rubella Overview..........................................................................1

The MMR Vaccine.........................................................................................................3

Immunological Response and Vaccine Effectiveness .........................................................5

Vaccine Failure and Outbreaks.......................................................................................6

Antibody Persistence Following Vaccination......................................................................7

Measles Antibody Persistence........................................................................................8

Mumps Antibody Persistence........................................................................................10

Rubella Antibody Persistence........................................................................................12

Persistence and Clinical Factors....................................................................................13

Marshfield Clinic Research Foundation Studies of Antibody Persistence...............................14

Current Analytic Methods used to Evaluate Antibody Persistence.......................................15

References.................................................................................................................16

Chapter II. Manuscript.................................................................................................22

Title..........................................................................................................................22

Authors.....................................................................................................................22

Abstract....................................................................................................................22

Introduction...............................................................................................................23

Methods....................................................................................................................24

Study population and procedures..................................................................................24

Analysis....................................................................................................................25

Descriptive patterns....................................................................................................25

Estimating rate of antibody decline within "declining trend"..............................................27

Sensitivity analysis.....................................................................................................28

Results.....................................................................................................................28

Seropositivity patterns................................................................................................29

Persistence trends......................................................................................................29

Decline in antibody titers among those with declining trend..............................................30

Discussion.................................................................................................................32

References.................................................................................................................37

Manuscript Tables and Figures......................................................................................40

Chapter III. Public Health Implications...........................................................................50

Implications of Pattern and Trend Analysis......................................................................50

Implications of Waning Immunity...................................................................................51

Moving Forward...........................................................................................................51

References..................................................................................................................53

Appendix....................................................................................................................54

Supplemental Manuscript Materials and Tables ................................................................54

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