Mumps Virus Nucleoprotein and Hemagglutinin-Specific Antibody Response Following a Third Dose of Measles Mumps Rubella Vaccine

Donald R Latner; Amy Parker Fiebelkorn; Marcia McGrew; Nobia J Williams; Laura A Coleman; Huong Q McLean; Steven Rubin; Carole J Hickman

doi:10.1093/ofid/ofx263

Mumps Virus Nucleoprotein and Hemagglutinin-Specific Antibody Response Following a Third Dose of Measles Mumps Rubella Vaccine

Open Forum Infect Dis. 2017 Dec 8;4(4):ofx263. doi: 10.1093/ofid/ofx263. eCollection 2017 Fall.

Authors

Donald R Latner¹, Amy Parker Fiebelkorn¹, Marcia McGrew¹, Nobia J Williams¹, Laura A Coleman^{2

3}, Huong Q McLean², Steven Rubin⁴, Carole J Hickman¹

Affiliations

¹ National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia.
² Center for Clinical Epidemiology and Population Health, Marshfield Clinic Research Foundation, Marshfield, Wisconsin.
³ Novartis Institutes for Biomedical Research, Cambridge, Massachusetts.
⁴ Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, Maryland.

Abstract

Background: Recent mumps outbreaks among 2-dose measles mumps rubella (MMR) vaccine recipients have raised questions regarding the potential benefits of a third dose of vaccine (MMR3). If MMR3 provides a sustained elevation in mumps antibody, it may be beneficial for certain at-risk groups or as an outbreak control measure.

Methods: Sera were collected immediately prior to MMR3 and at 1 month and 1 year post-MMR3 from 656 healthy adults aged 18-28 years in a nonoutbreak setting. Immunoglobulin G (IgG) was measured by enzyme-linked immunosorbent assay (ELISA) using whole mumps virus (commercial ELISA), hemagglutinin (HN; major neutralizing target), and nucleoprotein (NP; immunodominant) antigens. ELISA measurements were compared with in vitro plaque reduction neutralization (PRN) titers, and baseline antibody was compared with post-MMR3 levels.

Results: There were modest but statistically significant (P < .05) increases in mumps antibody at 1 month post-MMR3 by all 3 ELISA methods and by PRN titer. At 1 year post-MMR3, mumps antibody declined toward baseline but remained elevated (P < .05). The correlation between PRN titers and ELISA measurements was poor (r² = .49), although sera with the highest amount of HN IgG also had the highest PRN titers.

Conclusions: Individuals with the lowest baseline PRN titers had the largest increase in frequency of samples that became positive for HN and NP by ELISA. A third dose of MMR may benefit certain individuals with a low level of mumps virus-neutralizing antibody, especially in the context of an outbreak or other high-risk setting. Additionally, poor correlation among serologic tests does not allow effective prediction of PRN titer by ELISA.

Keywords: hemagglutinin; immunization; mumps; mumps immunogenicity; nucleoprotein; third-dose measles mumps rubella (MMR) vaccine; vaccine preventable disease.